26th Meeting

BE IT FURTHER RESOLVED that PACHA recommends that nevirapine prophylaxis is an acceptable therapy until more effective antiviral therapy that does not induce drug resistance becomes available.

BE IT FURTHER RESOLVED that PACHA recommends that the Secretary of HHS take all necessary steps to expedite clinical trials on novel simple, effective, and affordable treatments to prevent MTCT during delivery.

Presidential Advisory Council on HIV/AIDS

International Subcommittee

Draft Motion

Improving Prevention of Mother-to-Child Transmission (PMTCT) Efforts Globally

WHEREAS, the President’s Emergency Plan for AIDS Relief (PEPFAR), building on the significant work accomplished under the President’s 2002 International Mother and Child HIV Prevention Initiative, calls for the rapid scaleup of PMTCT activities that promote improved access and efficacy of prevention efforts; and

WHEREAS, increasing numbers of women in their childbearing years are becoming HIV-infected, the majority living in communities without adequate access to prevention activities—such as those in the United States that have reduced pediatric infections from perinatal transmission to under 1 percent annually; and

WHEREAS, significant progress has been made in the global battle to reduce MTCT through strategies such as enhancing safe deliveries, breastfeeding avoidance, and short-course ARV therapy, it is recognized that treatment of the mother with highly active antiretroviral therapy (HAART) during pregnancy and the breastfeeding period will be required to achieve a reduction of transmission that resembles the U.S. success; and

WHEREAS, utilization of HAART reduces the viral burden in the mother thus reducing transmission to the infant and allows recovery of the immune system producing a healthier mother and more likely a healthier baby thereby reducing the number of orphaned or vulnerable children; and

WHEREAS, the President’s Emergency Plan requires special attention be paid to mothers and children and the scaling up of ARV therapy;

BE IT RECOMMENDED that U.S. Government Departments and their implementing agencies involved in HIV/AIDS activities globally intensify their efforts to secure HAART for pregnant and breastfeeding women through the provision of effective medications, the training of nurses and midwives to manage medication therapies, and the monitoring and evaluation of the health of the mother, the child, and the prevention of new HIV infections.

Presidential Advisory Council on HIV/AIDS

International Subcommittee

Draft Motion

Call for Ensuring Broader Programs of AIDS Prevention in Implementing
the President’s Emergency Plan for AIDS Relief (PEPFAR)

WHEREAS, Uganda has achieved the greatest degree of HIV prevalence decline of any country and remains the only country with a generalized epidemic that has experienced significant HIV prevalence decline; and

WHEREAS, President Bush has heralded the Uganda ABC prevention model as the most effective model for prevention of sexually transmitted HIV in generalized epidemics (those of sub-Saharan Africa and the Caribbean) and has made it the centerpiece of the prevention component of PEPFAR; and

WHEREAS, recent research published in Science, British Medical Journal, The Lancet, and the Journal of International Development, among others, shows that the ABC model is indeed the best prevention strategy for generalized epidemics and that decline in casual sex (the B component of ABC) is the single most important factor accounting for success in Uganda; and

WHEREAS, there is great institutional and bureaucratic resistance to conducting AIDS prevention in ways that differ from the programs of the past two decades; and

WHEREAS, the first two components of ABC are not being adequately supported by foreign donors, including USAID, in Uganda itself, as concluded by U.S. Senator Brownback, among others, after a recent trip to Uganda; and

WHEREAS, the National Strategic Framework for HIV/AIDS Activities in Uganda (2003/04–2005/06) and Uganda’s current national Monitoring and Evaluation Draft Plan

contain no specific objectives or impact indicators related to the first two components of ABC, only to condoms, yet earlier plans were replete with these A and B objectives and indicators;

BE IT RESOLVED that PACHA use its influence to ensure that the Uganda ABC model be implanted just as the President and the Congress intended, as evidenced in the language of the bill and of the Smith and Pitts Amendments, which suggest equal balance between A, B, and C components in programmatic attention and in levels of resource allocation;

BE IT FURTHER RESOLVED that PACHA recommends to the President that basic program indicators be required of all PEPFAR-funded AIDS prevention projects and programs, indicators associated with all three intended components: abstinence, mutual faithfulness, and correct and consistent condom use. Indicators for condom use are already found in prevention programs. Those for the first two components should at a minimum include the following program indicators, recommended by PEPFAR:

For A: 1. Percentage of never-married young men and women aged 15–24 who have
            never had sex

2. Percentage of young never-married women and men aged 15–24 who have had sexual intercourse in the last 12 months, of all young never-married respondents surveyed

For B: 3. Percentage of women and men aged 15–49 who had sex with more than one
            partner in the last 12 months.

Mr. Mason introduced the next presenter, Dr. Murray Lumpkin of the FDA. He congratulated the Council for having passed a visionary resolution requiring that PEPFAR purchase high-quality drugs for the PEPFAR program, one result of which is the fast-track approval process in place at FDA, which Dr. Lumpkin will now explain.

Presentation

“PEPFAR and FDA,” by Murray M. Lumpkin, M.D., Acting Deputy Commissioner, FDA, HHS

Dr. Lumpkin noted that in the world market, there are many HIV/AIDS drug products, but the question is whether they should be purchased. These products include counterfeits, illegitimate knockoffs, and legitimate knockoffs. The challenges to FDA include how to ensure that products purchased under PEPFAR are quality products and at the same time to ensure that PEPFAR gets the best value for the dollar in drug-purchasing efforts to help treat the largest number of patients. In addition, there is the ethical issue of two standards, which was addressed by the PACHA resolution, i.e., how can we ask other countries to give their people drugs we don’t use in the United States?

FDA has initiated an expedited marketing application review process, which is more than just expedition. This process began in May 2004, when former HHS Secretary Tommy Thompson announced that FDA would implement a new, expedited review process for certain drugs to ensure that the United States could provide safe, effective quality drugs under the PEPFAR program.

Key elements of the expedited tentative approval are:

• FDA is not changing its standards. Efficacy, safety, and manufacturing quality, including inspections, are all intact.
• However, the process is newly and very explicitly open to all manufacturers, not just those in the United States. A tentative approval program has assisted the generic industry in the United States for years, allowing them to apply to manufacture and market generics before the U.S. patent on the drug they are “copying,” in a bioequivalent way, has expired. In that way, they are positioned, the day the patent does expire, to “hit the market.”
• In addition—another breakthrough—PEPFAR has told potential applicants that if they win tentative approval, they can have access to PEPFAR programs, and when the U.S. patents have expired, have access to the U.S. market as well.
• To help the process, FDA has provided guidance to the potential applicants, including the PEPFAR list of approved HIV/AIDS drugs. Most of these are single dose, but the guidance also says that if the applicants wish to apply to combine drugs and provide a fixed-dose combination (FDC), FDA will welcome the application and, further, will not require the applicant to prove that using previously approved drugs in combination is safe and effective because “FDA has seen enough data on this.” However, bioequivalence must be shown.

FDA guidance for companies was posted on www.fda.gov on May 17, 2004. It outlines scenarios for review of different applications and provides a list of generics of the few fixed-dose drugs already available and of those not available in the United States. It also describes the components of a high-quality marketing application.

FDA’s commitment to this program includes expedited review in approximately 8 weeks of completed marketing applications. Because such a process normally takes 6 months, this is “significant,” Dr. Lumpkin noted, particularly since it includes inspections of manufacturing plants, many of which are expected to be located overseas.

Preapplication activities include spending time and effort up front to help potential manufacturers work through the complex nature of scientific and regulatory questions they will encounter. This will be particularly helpful to companies with little or no experience with the FDA.

FDA is also working with PEPFAR and drug regulatory authorities in the 15 focus countries to conduct train-the-trainer sessions and training about general marketing applications and the approval process, about assessment of current good manufacturing practices (CGMP) and current good clinical practices (CGCP), and about postmarket adverse-event reporting. FDA is interested in postmarket adverse-event reporting because it wants to learn from new data on the safety and efficacy of drugs marketed under the fast-track program.

Planned for April is a large training program in the United States for regulatory authorities from the 15 focus countries. Dr. Lumpkin emphasized that even if FDA approves an application, local authorities will also need to approve the manufacturer’s bid to market within their national borders. FDA will show other authorities how it handles marketing authorization and is also working on a confidentiality agreement that will allow FDA and signatory countries to share data and documentation.

Dr. Lumpkin said critical components of the program are FDA’s plan to conduct preapproval and CGCP and CGMP inspections to ensure the integrity of the data in the marketing applications and of drug product quality during manufacturing. FDA is even prepared to conduct mock inspections to help manufacturers that have little or no experience with the agency.

Dr. Lumpkin confirmed that FDA has already received applications under the program and that they are under review. FDA cannot provide a list, but companies can make the fact of their applications public. In December, the U.S. generic company Barr received full approval for manufacture of didanosine delayed-release capsules. In January, tentative approvals were given to Aspen of South Africa to manufacture lamivudine (150 mg)/ziovudine (300 mg FDC), copackaged with nevirapine (200 mg). U.S. patents block the marketing of these generics in the United States. FDA inspectors have conducted a full inspection of Aspen facilities.

Question and Answer Period

Dr. Judson commented that the FDA fast-track approval program seems like a sensible and medically justified answer to those who would say we’re using FDA to shield our own pharmaceutical industry. Has that issue been diffused? Dr. Lumpkin said getting angry comments is part of working at FDA. Press reports were mixed when the news about the Aspen approval broke, but many were favorable. Everything comes down to the fact that if U.S. dollars are being used in the program, they should be spent on drugs that meet high standards. The expedited process also opens high standards approval to more companies.

Dr. Yogev complimented FDA for a superb job and asked if we need to push interested companies into doing the right studies more quickly. Dr. Lumpkin noted that FDA is very proactive and open to meeting with and helping interested companies. For the PEPFAR fast-track program, the studies required are for bioequivalence. When companies submit clinical data, FDA will travel to the site to make sure the trial was real. Trials do not need to be conducted in the United States. He added that FDA worked very closely and quickly with Aspen. Approval was granted within 2 weeks of receipt of completed applications.

Mr. Mason also congratulated FDA. He noted that under PEPFAR, 155,000 people in 15 countries are in treatment. A remaining issue is the fact that FDA currently cannot discuss pending or failed applications. Dr. Lumpkin said the authorizing Act for FDA prevents this type of information sharing, for the most part, but FDA is exploring confidentiality agreements with counterpart agencies, including the World Health Organization. He added that the agency is very close to a confidentiality agreement with the South African Government. Without such agreements, a change in the FDA Act would be required. 

Dr. Sullivan said once FDA review of an application has been completed, FDA should be able to release information about that application, particularly if it is denied. Should PACHA make such a recommendation? Dr. Lumpkin noted that FDA is permitted to do this under exemptions granted by Congress for pediatric drug applications. The Council could use this as an example. His concern is whether companies would be deterred from applying, although this hasn’t seemed to be a problem for pediatric drug manufacturers.

Dr. Sullivan asked the International Subcommittee to review this issue and report back to the full Council. There was some discussion of whether generic companies would be deterred from making applications to the FDA. Dr. Sullivan said he believes the generic industry is not that fragile, and we shouldn’t aid and abet the marketing of unsafe drugs anywhere.

Ms. Ivantic-Doucette expressed concern about PEPFAR’s purchasing poor-quality malaria and tuberculosis (TB) drugs. Dr. Lumpkin said FDA is very willing to look at expedited approval for high-quality malaria and TB drugs as well.

Announcement

Mr. Grogan noted that PACHA is updating and improving its Web site and asked Council members to volunteer to review the progress made to date, at HHS, sometime in late February or early March. Interested members should provide their contact information to Mr. Grogan.

Lunch

AFTERNOON SESSION

Dr. Sullivan reconvened the Council meeting.

International Subcommittee Report, Continued

Mr. Mason introduced Dr. Lynn A. Paxton to give a presentation on tenofovir.

“CDC Safety and Efficacy Trials of Tenofovir for HIV Prophylaxis,” by Lynn Paxton, M.D., M.P.H., Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, CDC

Dr. Paxton gave a PowerPoint slide presentation on:

• The rationale for HIV prophylaxis
• Tenofovir
• Tenofovir studies, including an extended safety trial on MSM in the United States and safety and efficacy trials in injecting drug users (IDUs) in Thailand and in heterosexuals in Botswana
• CDC/NIH consultations in December 2004.

The rationale for HIV prophylaxis:

• There is a need for biomedical interventions to complement existing HIV prevention strategies, given 14,000 new HIV infections each day globally and 40,000 new HIV infections annually in the United States.
• To date, we have no effective HIV vaccines or microbicides.
• Systemic HIV infection is not immediate, so prophylaxis could prevent or modify viral replication and spread.
• HIV prophylaxis could function as an “oral” vaccine or microbicide.
• Treatment medications are used as prophylaxis for bacteria, fungi, and the malaria parasite.
• HIV prophylaxis has been shown effective in reducing perinatal transmission (a 50 percent reduction in risk from single doses of nevirapine to mother and infant as well as use of combination drugs in the United States).
• Postexposure prophylaxis is recommended by HHS for occupational exposure (81 percent risk reduction from AZT) as well as for sexual and parenteral exposures (guidelines in press).

Dr. Paxton showed how studies in monkeys have demonstrated efficacy of tenofovir prophylaxis in at least these animal models. There are no human efficacy studies.

History of tenofovir (TDF):

• TDF is a highly potent ARV produced by Gilead and approved by FDA in 2001 for use in HIV-infected persons.
• TDF has been used in more than 15,000 patients in clinical trials and more than 200,000 patients in clinical settings.
• There is a low incidence of side effects.
• TDF can be given through once-a-day dosing with long serum half-life.
• Low levels of induced resistance (or a relatively high genetic barrier) have been seen.

Primary concerns regarding TDF prophylaxis include:

Some evidence of behavioral disinhibition, although previous vaccine trials showed decreases in risk behaviors in MSM and IDUs.

Toxicities in HIV-infected persons, including decreased renal function, decreased bone mineral density, and gastrointestinal episodes, although longer studies in humans have shown that these effects tend to level off over time and less than
1 percent of those studied stop taking TDF due to these side effects; in addition, these toxicities might be less in non-HIV-infected persons.

Selection for resistant viruses in persons who do not become infected.

Dr. Paxton said CDC will closely monitor behaviors, toxicities, and resistance in upcoming trials.

Trials planned, underway, or suspended (possibly temporarily) include:

The Gates Foundation’s Family and Health International (FHI) efficacy trial in female sex workers in Cameroon (currently on hold), Nigeria, and Ghana, as well as a planned study of high-risk heterosexual men in Malawi

An NIH-funded University of California at San Francisco/Gates-funded Australia efficacy trial in female sex workers in Cambodia, presently on hold

A CDC nonhuman primate study in progress

A CDC extended safety study in American MSM (just beginning)

CDC safety and efficacy studies in IDUs in Thailand and heterosexuals in Botswana (to begin at the end of February 2005).

Dr. Paxton noted that the French equivalent of CBS’ “60 Minutes” did an “inflammatory” show on the study in Cameroon, and the study is now on hold. Administrative irregularities have been found but no violations of consent or issues of safety. The Cameroon Minister of Health has come out strongly in support of the study.

Dr. Paxton also stated that a small but vocal HIV/AIDS advocacy movement led by ACT UP PARIS is against the trials in Cambodia and has made accusations that sex workers are too vulnerable to be involved. In addition, demands have been made for lifetime care of persons involved in the study. Dr. Paxton added there is division in the advocacy movement over what ACT UP PARIS has done.

The CDC’s extended safety trial is being conducted at two sites: the AIDS Research Consortium of Atlanta (ARCA) and the San Francisco Department of Public Health (SFDPH). The study objectives and design are to assess clinical, laboratory, and behavioral safety as well as adherence and acceptability through a randomized double-blind placebo-controlled Phase II extended safety study with 1:1 TDF/placebo over 24 months with safety committee review of data at 6, 12, and 18 months.

Study objectives, design, and status:

Objective—to assess clinical, laboratory, and behavioral safety, as well as adherence and acceptability

Design—400 HIV-negative MSM, 25 percent men of color; 9-month delay in enrollment of 200 men to assess behavioral changes once TDF prophylaxis has begun; close monitoring of seroconverters for resistance and clinical outcomes; adverse events and access to HIV care if infected, managed through physician referral

Status—protocol is currently at the review board, with a start date in February 2005.

Dr. Paxton characterized the study as small, adding that CDC does not expect many seroconverters, and there is anecdotal evidence that prophylaxis lowers viral setpoint for subsequent infections.

What CDC TDF studies planned in Thailand and Botswana have in common:

Both involve Phase II/III randomized double-blind placebo-controlled safety and efficacy trials with 1:1 TDF/placebo.

Phase II safety trials (200 person-years followed by DSMB review [single DSMB for both studies]); if safety criteria met, will roll into Phase III efficacy trials.

There will be screening, enrollment, and monthly and quarterly visits, including interviews, physical exams, labs, HIV testing, risk-reduction counseling, adherence assessments, and side effects monitoring.

CDC will be looking at the following endpoints—HIV seroconversion, adverse events, risk behaviors, adherence, and altered viral load setpoint in seroconverters.

For seroconverters, CDC will look at viral loads, CD4 counts, and ARV resistance.

The planned start date is in February 2005.

Dr. Paxton outlined the differences between the two studies, noted critical components, and provided information about how the trials in Thailand are being coordinated with Global AIDS Program (GAP) activities and the trials in Botswana are being coordinated with PEPFAR/GAP activities.

A report is due out soon on the result of consultations between the CDC and the NIH on the implications of successful TDF prophylaxis trials. Dr. Paxton said the consultation involved:

Impact of demonstrated efficacy in one trial on other trials

HHS recommendations for TDF use in the United States, for acceptable efficacy level, differing transmission routes, and unstudied populations

Monitoring for usage, increased risk behavior, HIV incidence, adverse events

Impact on existing HIV prevention program, domestically and internationally

Impact on future vaccine and microbicide trials

Future HIV prophylaxis research with other ARVs, less frequent dosing schedules, and other delivery systems.

Within 18 months the CDC will have the results of efficacy trials. Dr. Paxton noted that some MSM are beginning to use TDF as part of a three-V-way party use of Viagra, Valium, and Viread (TDF). CDC is trying to get the word out that this is risky behavior.

In the ongoing process of considering the potential impact of TDF, the CDC has developed a communications strategy that includes factsheets; questions and answers; outreach and posting on the CDC Web site; identification and preparation of CDC, site-specific, and third-party spokespersons to respond to media inquiries; targeted outreach to key media and opinion leaders; and ongoing monitoring of and response to media coverage.

In conclusion, Dr. Paxton said the CDC strongly believes that assessment of TDF as an HIV prophylaxis is a rational next step in HIV prevention research; the CDC will be conducting complementary studies in the prevention of homosexual, parenteral, and heterosexual transmission; and HIV prophylaxis represents our best hope for an effective biomedical HIV prevention tool in the near future.

Dr. Paxton added that if TDF works as a prophylaxis, it will be a good weapon in the prevention arsenal. However, even if it is proven effective, not everyone will be able to use it. Therefore, we need to continue to try to develop a vaccine and microbicides. In addition, using protection such as condoms continues to be critical.

Question and Answer Period

Ms. Ivantic-Doucette noted she believes in TDF but feels cautious and thinks it is important to have high ethical considerations in working with vulnerable populations. Are there alternatives to using sex workers in such studies? She mentioned that in Kenya there are 30,000 nurses, 15 percent of whom are infected, and they would make a good study.

Dr. Paxton noted the Cambodia sex workers study is not a CDC study. She agreed that all studies need to be held to high ethical standards. The sex worker populations were chosen because they are the most affected. A basic tenet of research is that its modality is conducted in a community for that community’s ultimate benefit. You do have to be ever vigilant. As scientists, we have to think about what is the best thing to do. Politics should not be our primary concern. She added that the idea of working with nurses in Kenya is interesting.

Dr. McKinnell asked about the real-world relevance of TDF prophylaxis, in terms of adherence, if we’re successful. Would there be a problem with compliance? Dr. Paxton responded that a 50 percent reduction would translate into really large numbers, adding that TDF’s long half-life might help, although that is not really known at this point.

Dr. Sweeney asked what percentage of people actually engages in prevention. She also asked about cost and resistance factors. Dr. Paxton said we do have better modalities, like the condom, that are available right now. She noted many people don’t use them either. She thinks that the more choices we give people, the more likely we are to find a prevention method they will use. She said TDF’s cost is falling, and is currently about 80 cents. While that may seem affordable to us, that is still out of reach of many in the developing world. In the trials it’s inevitable that someone will become positive while using TDF. CDC hopes there won’t be much resistance, but we don’t know. That’s why we’re doing the studies.

Dr. Judson asked about the origins of the CDC’s and other prophylaxis studies. Dr. Paxton said the Buenos Aires conference was the beginning, then TDF’s manufacturer started thinking about it, as well as the Gates Foundation. She added she believes we will not be able to treat our way out of the epidemic, that TDF may provide secondary and tertiary prevention possibilities, and that she thinks there will be some disinhibition. “Those in greatest need are least likely to comply. They are also the least likely to be able to afford it.”

Dr. Bowers-Stephens asked whether there will be a placebo in the U.S. safety trial. Dr. Paxton said no. Participants will be asked a number of questions including about the use of condoms.

Dr. Primm said the primate studies seem to indicate that route of exposure has an effect on effectiveness, and Dr. Paxton confirmed that the CDC studies will be looking at that.

Mr. Mason then introduced Ambassador John Miller to give a presentation on human trafficking and HIV/AIDS.

Presentation

“Human Trafficking,” by Ambassador John Miller, Director, Office to Monitor

and Combat Trafficking in Persons, U.S. Department of State

Ambassador Miller said he was here to share information and to ask for the Council’s help. He was accompanied by Laura Lederer of the State Department’s Global Affairs Office.

Most Americans would be surprised to find out that there is slavery in the 21st century, but in fact there is, with 800,000 men, women, and children trafficked every year into slavery over international borders. There is also domestic servitude.

The challenge to control global and domestic trafficking extends to every nation in the world. Trafficking for sex slavery is rampant and mostly affects girls. He has met many girls and young women who have suffered, and he knows their stories, such as the story of Katia from Czechoslovakia, who left her home with her 2-year-old after a failed marriage and went to work in Amsterdam. There, she was taken by traffickers who threatened her 2-year-old’s life unless she became a sex worker.

Prostitution is drawing women all over the world into sex slavery. Patterns show transnational travel and implications for the HIV/AIDS epidemic worldwide. Ambassador Miller recalled one young female victim in Cambodia who was dying of AIDS. When she was younger, she had been taken from her village by a man who she thought would marry her, but it turned out that she had been sold. She was put to work as a sex worker to pay off her debts. The only way she became free of her slavery was to get sick.

Ambassador Miller said he needs the Council’s help because of the tie-in between trafficking, sex slavery, and HIV/AIDS. Many in the sex trade want to leave their jobs. Many are in danger. He concluded that he is impressed by the human trafficking resolution before the Council because it attempts to link human trafficking and HIV/AIDS.

Dr. McIlhaney asked for permission to show a few slides of data relevant to the resolution.

Slide 1: Brothels and Core Transmitter Connection. “Asian countries with the highest HIV prevalence (2–3 percent of their 15–49-year-old population)…all have brothel-based female sex workers (FSW) as a dominant factor.” (From the WHO HIV/AIDS in Asia and the Pacific Region 2001 report.)

Slide 2: HIV Transmission in Thailand: FSW to Client to General Population. “The noted success of Thailand, with its 100 percent condom program for all commercial and casual sex, has not had much effect on the slow but steady transmission of HIV from infected male clients of FSW to their regular sex partners (wives and girlfriends).” (From the same report cited above.)

Slide 3: Chart: HIV Prevalence in General Populations and FSW by Asian Country. An example was given of 2.8 percent prevalence in the general population of Cambodia but 38 percent among FSW, with 16–78 percent condom use by FSW.

Dr. McIlhaney concluded there is a direct relationship between sex workers and HIV prevalence. He thanked his coauthors of the resolution: Dr. Jane Hu, Dr. McKinnell, and Ms. Lederer. Ms. Lederer added that the heart of the resolution is that we want all the U.S. Government agencies to see the link and address it.

Question and Answer Period

Dr. Primm wondered about slavery in Saudi Arabia and East Africa. Ambassador Miller said his Office prepares an annual report on slavery around the world. The U.S. Justice Department also prepares a report on the United States. In Africa, there is a huge sex slavery tie between Nigeria and Italy. In the Middle East, there is quite a bit of domestic servitude slavery and some sex slavery. We need to focus more on demand and destination countries, like Italy and the United States. Next year we hope to do better.

Ms. Ivantic-Doucette noted the TDF prophylaxis studies that involve sex workers and asked if we do some things through research design or inadvertently that we shouldn’t. Ambassador Miller said not every trafficking victim is an HIV/AIDS victim and vice versa.

Ms. Smith asked which is the lead agency on this issue and how are its efforts being coordinated with those of private organizations? Ambassador Miller said President Bush formed a Presidential Task Force on Trafficking Victims, and now he chairs an intergovernmental group on the subject with representation from all the major U.S. agencies. The positive news is that Governments around the world are waking up to
the problem, and today there are more cases and more shelters than ever before. Nongovernmental organizations involved include the International Justice Mission, the Salvation Army, and Shared Hope.

Ms. Shoemaker asked what individuals can do to help. The Ambassador said media coverage of the issues has been helpful in increasing public awareness. Individuals can help by keeping their eyes and ears open and reporting to local law enforcement those they believe are involved in trafficking or are victims. More civic and religious groups need to get involved as well.

Dr. Green thanked the Ambassador for his passionate presentation. He asked how one goes about abolishing the sex trade, and how one identifies the sex trade in Africa, where there is “a lot of transactional sex.” The Ambassador said there are no easy answers, but addressing causes, such as poverty, would help. He noted the Swedish success story, which began when the Government decided to arrest anyone procuring and trafficking. Although the problem of sexual slavery and prostitution hasn’t been eliminated there, the number of victims going into Sweden has dropped dramatically. In Korea, 1 million women signed a petition against the sex trade, and then the Korean National Assembly passed legislation to provide job training and education to sex workers. In a short period of time many sex shops and brothels have been closed. In the United States, the Justice Department has tripled its prosecutions, and agencies now have foreign language programs to reach out to victims, including migrants. We are also setting up shelters in most major cities.

Dr. Sullivan said he needs to understand why this subject is being brought to this Council. He added that the resolution needs a lot of work. He objected to the resolution’s language regarding health professionals. He asked that more information be provided on the effect that curbing trafficking would have on reducing HIV/AIDS. He asked that the International Subcommittee respond.

Mr. Mason said Dr. McIlhaney of the International Subcommittee would work with the Prevention Subcommittee on the issues outlined by Dr. Sullivan, then bring the resolution back to the full Council.

Break

International Subcommittee Report, Continued

Mr. Mason then welcomed Dr. Anthony Fauci, noting that he had the pleasure of traveling to Africa with him in December of 2003. He noted Dr. Fauci’s extraordinary career and dedication, and said if a cure for HIV/AIDS is ever found, it will be due in large measure to Dr. Fauci.

Presentation

“Presentation to PACHA on HIVNET 012,” by Anthony Fauci, M.D., Director, National Institute of Allergy and Infectious Diseases, NIH

Dr. Fauci said the focus of his talk today will be the HIVNET 012 clinical trial performed several years ago and subsequently published to show the safety and efficacy of nevirapine, as well as confusing news reports containing a series of allegations about the trial.

Using a PowerPoint presentation, Dr. Fauci reminded the Council of the epidemic’s global numbers, including the fact that the highest concentration of infection and illness is in sub-Saharan Africa. He noted that about 2.2 million children are living with HIV/AIDS, that in 2004 there were about 640,000 new infections among children due primarily to infection during mothers’ pregnancy, labor, and delivery or via breastfeeding, and that in 2004, there were 510,000 HIV/AIDS-related child deaths.

Dr. Fauci noted the targets for ARV drugs are reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and fusion/entry inhibitors. He noted that state-of-the-art drugs in the developed world have had a major impact not only on newly diagnosed HIV/AIDS patients but on HIV/AIDS-related deaths.

In Africa, Dr. Fauci has seen firsthand the dichotomy between people who need drugs and those who are getting drugs. For example, in sub-Saharan Africa only 8 percent of people who need drugs get them. For mother-to-child transmission (MTCT), he added, the most effective strategy will be availability of potent, combination ARV therapy in the entire HIV-infected population. However, that is not feasible today in many countries in the developing world.

Dr. Fauci showed slides that contained important dates for key studies in understanding confusion that has arisen regarding nevirapine and MTCT. First, nevirapine was approved by the FDA for safety and efficacy in 1996—longer ago than many news reports seem to indicate. It was the first in a new class of drugs—non-nucleoside reverse transcriptase inhibitors. Pediatric approval was granted in September of 1998.

Scientists saw that nevirapine might be a way to give a brief-course therapy to prevent MTCT through one dose to mother, one to baby. In 1997, the HIVNET 012 randomized study began. The trial took place in Uganda, and the results were published in The Lancet in 1999 as “Intrapartum and Neonatal Single-Dose Nevirapine Compared with Zidovudine for Prevention of Mother to Child Transmission of HIV-1 in Kampala, Uganda: HIVNET 012 Randomised Trial” (Laura A. Guay et al.).

In 2003, an 18-month followup study of the HIVNET 012 Randomised Trial (J. Brooks Jackson et al.) was published in The Lancet, showing that nevirapine blocked HIV transmission through breastfeeding. Earlier, the South African SAINT trial (“The SAINT Trial: Nevirapine versus ZDV +3TC in Prevention of Peripartum HIV Transmission,” University of KwaZulu-Natal Medical School, Congella, South Africa) had preliminarily concluded that both nevirapine and ZDV + 3TC were effective, “with results comparable to those observed with NVP (nevirapine) in HIVNET 012 and with ZDV/3TC” in another study. No drug-related maternal or pediatric serious adverse events were reported.

A Thai study released soon after didn’t address whether nevirapine alone was effective in blocking transmission, but it did add data to what was known about the safety of nevirapine in a single dose. Again, no serious adverse effects were found. Dr. Fauci emphasized that the safety of nevirapine in a single dose has been corroborated in multiple studies.

In 2004, G. Jourdain et al. published the results of their study in The New England Journal of Medicine (“Intrapartum Exposure to Nevirapine and Subsequent Maternal Responses to Nevirapine-Based Antiretroviral Therapy”). Dr. Fauci summarized the results of the study, emphasizing the finding of resistance mutations, but also noting the importance of clinical relevance:

In an observational study in Thailand, immunocompromised women (CD4+
T-cell counts <250/mm to the third) received either intrapartum NVP (n+221) or no intrapartum NVP (n=48), and then began NVP-containing HAART.

At day 10, 32 percent of mothers receiving intrapartum NVP had resistance mutations.

At 6 months, mothers on NVP-containing HAART achieved maximal virologic suppression (<50 HIV RNA copies/ml) as follows—no intrapartum NVP (n=40), 68 percent; intrapartum NVP, no NVP resistance mutations (n=119),
52 percent; intrapartum NVP, NVP resistance mutations (n=61), 38 percent.

The groups had similar clinical improvement and equivalent increases in
CD4+ T-cell counts.

The key points here are that there was some resistance, but clinically the team didn’t see any difference. The question was, is this genotypic resistance a show stopper? The researchers concluded it was not.

Later in 2004, Hoosen Coovadia, M.D., published an article in The New England Journal of Medicine entitled “Antiretroviral Agents—How Best to Protect Infants from HIV and Save Their Mothers from AIDS.” Dr. Fauci emphasized Dr. Coovadia’s conclusion that the Jourdain et al. study findings “are not a reason to abandon single-dose nevirapine for the prevention of MTCT. … Single-dose nevirapine is a regimen of striking simplicity, efficacy, and affordability.”

Addressing the toxicity of nevirapine, Dr. Fauci quoted the FDA’s January 19, 2005, advisory, which noted that while clinically symptomatic and asymptomatic liver toxicity has been observed with long-term use of nevirapine in combination with other HIV drugs, symptomatic liver toxicity has not been reported with the use of single doses of nevirapine to the mother and child.

Dr. Fauci showed two slides of critical chronological points in the HIVNET 012 study and related studies, as well as Boehringer Ingelheim’s filing in 2001 with FDA for permission to expand use of nevirapine in the United States to MTCT. In 2002, site visits to Kampala turned up procedural issues with regard to a HIVNET 012 followup study. Later that year, Division of AIDS (DAIDS) staff unanimously concluded that the procedural issues identified had no bearing on the proven safety and efficacy of the single-dose nevirapine regimen. Plans were made and carried out for a series of DAIDS remonitorings. In 2003, DAIDS published an “Omnibus” report of its findings, and in 2004, allegations began to appear in the press, beginning with the Associated Press (AP), that U.S. officials knew of drug risks in the study, that the head of DAIDS, Dr. Edmund Tramont, had altered the study, and that a woman had died during the study. A firestorm of other stories and accusations followed, including in the African press. In addition, Rev. Jesse L. Jackson made a statement critical of the NIH.

Dr. Fauci emphasized that, with his approval, Dr. Tramont had reexamined everything regarding HIVNET 012. He noted that 2 years earlier, in 2002, the NIH had published a statement that “Although no evidence has been found that the conclusions of HIVNET 012 are invalid or that any trial participants were placed at an increased risk of harm, certain aspects of the collection of the primary data may not conform to FDA regulatory requirements.” Dr. Fauci called these technical difficulties in the study that wouldn’t pass FDA muster.

Dr. Fauci then examined four allegations about HIVNET 012 and provided facts.

Allegation 1: NIH officials were warned that research on nevirapine was flawed and may have underreported thousands of severe reactions including deaths.

Fact: This statement is absolutely false. Monitoring reports of HIVNET 012 found no additional serious adverse reactions related to nevirapine. The original published study and the multiple subsequent reviews of the HIVNET 012 trial found only a very small number of serious adverse reactions that potentially might be due to nevirapine.

Allegation 2: NIH officials chose not to inform the White House in the spring of 2002 about safety issues concerning nevirapine.

Fact: There is no truth to this allegation. No direct report to the White House was necessary because there were no new data that changed the conclusion of the initial HIVNET 012 report, that is, that single-dose nevirapine is a safe and effective regimen for blocking mother-to-infant HIV transmission.

Allegation 3: There has been scientific and administrative misconduct by staff within NIAID’s DAIDS.

Fact: These allegations have been assessed by the NIH Office of the Director and have been found to be completely without merit. To address the issues of the scientific validity of the study, the NIH has contracted with the Institute of Medicine (IOM) to conduct an additional independent review of HIVNET 012.

Allegation 4: Dr. Tramont inappropriately “altered” a remonitoring report related to HIVNET 012.

Fact: These allegations are false. As Director of the NIAID DAIDS, Dr. Tramont had the overall responsibility for generating a remonitoring report of HIVNET 012. He edited several subreports (initially drafted by several DAIDS staff members) to make sure that the final omnibus report accurately reflected the entire remonitoring process.

Dr. Fauci concluded his presentation by showing Dr. Tramont’s impressive vitae, adding that Dr. Tramont can’t respond himself to these allegations due to an ongoing personnel dispute and the restrictions of the Privacy Act.

Question and Answer Period

Dr. McKinnell asked if there is any way to sensitize the news media. Dr. Fauci said his experience with this situation is very discouraging. The result has been terrible in sub-Saharan Africa, particularly in South Africa.

Ms. Clements asked Dr. Fauci how we can tackle the myths such as that the virus is manmade and is intentionally being used to destroy Africans and African Americans. Dr. Fauci said that, in general, many people don’t know the history of how African Americans actually have been mistreated in the past. Continuing education and leadership is needed from black community leaders. The NIH has also tried to help, doing damage control by talking to various African Ambassadors. Also, the U.S. State Department has issued a misinformation bulletin on the imbroglio concerning nevirapine and the HIVNET 012 study.

Ms. Singleton McDonald said she is disturbed that Dr. Fauci has to spend time defending good work. She asked how the Council can help. On a personal level, she said some Council members would like to bring African American leaders to Dr. Fauci for a presentation on the matter. Dr. Fauci said a meeting would be fine. He suggested that PACHA could view the situation as an indirect attack on the President’s $5 million program. He added that PEPFAR will be one of President Bush’s great legacies because he is responsible for saving thousands and thousands of African babies. That fact should come through loud and clear.

Ms. Rock noted that she works with 076 study moms and babies, and she agrees the Council needs to do something to help rectify misinformation about effective MTCT therapies here and abroad. She said one way to approach that is to wait for the IOM report. Dr. Yogev noted that a resolution on MTCT and nevirapine is already in front of the full Council and that it might help.

Dr. Primm commented that no one in the press talked about how nevirapine has saved many lives. That needs to be a main message in presentations to African American leaders and, subsequently, to the community at large. Dr. Fauci speculated that the press has not covered the drug’s beneficial effects because it’s not a story for them. He noted the whole matter was never reported in either The New York Times or The Washington Post.

Rev. Sanders noted that sometimes it is difficult to translate what you know into lay language, but this is something we must try to do in part to tackle mistrust.

Dr. Sullivan asked if Dr. Fauci had communicated with Rev. Jesse Jackson about his comments. Dr. Fauci said Rev. Jackson and an NIH official shared a spot on a National Public Radio show, and Rev. Jackson repeated his allegations. Dr. Sullivan said it’s possible the Council could help. Dr. Judson commented that what will change Rev. Jackson’s mind is if people he respects provide different information. Council members agreed to get back to Dr. Fauci on how they can help.

Treatment and Care Subcommittee Report and Resolutions

Treatment and Care Subcommittee Chair Dr. Reznik said the Subcommittee has a resolution regarding the President’s State of the Union address. Other issues under Subcommittee consideration include the new Medicare prescription drug benefit, the RWCA, drug resistance, and the drug pipeline. Dr. Reznik thanked former Chair Brent Minor for his fabulous leadership.

Dr. Reznik introduced the State of the Union resolution.

Presidential Advisory Council on HIV/AIDS

Treatment and Care Subcommittee

Draft Motion

State of the Union Resolution

WHEREAS, the Ryan White Comprehensive AIDS Resources Emergency (CARE) Act, first signed into law by President George Herbert Walker Bush and subsequently reauthorized in 1996 and 2000, provides primary care, treatment, and essential support services to approximately 533,000 uninsured and underinsured people living with HIV/AIDS in the United States, and

WHEREAS, the care and treatment of persons living with HIV/AIDS is a high priority for this Administration and an important part of an effective national public health strategy,

BE IT RESOLVED that the Presidential Advisory Council on HIV/AIDS (PACHA) wishes to express our sincerest gratitude to the President of the United States of America, George W. Bush, for bringing national attention to the domestic HIV/AIDS epidemic and the disproportionate impact this disease has on African American men and women by calling for the reauthorization and modernization of the Ryan White CARE Act in the State of the Union address on February 2, 2005.

Dr. Reznik then introduced the last presenter of the day.

Presentation

“The New Medicare Prescription Drug Benefit: Impact on HIV/AIDS Care,” by Christine Lubinski, Executive Director, HIV Medicine Association

Ms. Lubinksi said her goal is to give a snapshot of the new benefit and identify challenges and issues for people with AIDS who qualify.

Using PowerPoint slides, Ms. Lubinski provided Medicare 101. Medicare is:

The Federal health insurance program for the disabled and elderly (65 years plus)

Administered by the Centers for Medicare and Medicaid Services (CMS)

A national standardized health plan with eligibility, benefits, and costs to beneficiaries

An entitlement program, in which HIV/AIDS patients qualify primarily through disability.

Medicare and HIV/AIDS:

There are about 60,000–80,000 Medicare beneficiaries with HIV/AIDS.

They qualify for Medicare after approximately 2 years of disability, and currently there is no drug benefit; there is the AIDS Drug Assistance Program (ADAP).

70–85 percent of the beneficiaries also qualify for Medicaid as dual eligibles (getting full coverage from both programs), and Medicaid acts as a wraparound.

There are approximately 50,000 dual eligibles. They:

Are disabled, poor, and in the end-stage of illness

Rely on Medicaid for HIV medication

Have varied benefits based on geography

Sometimes use ADAP to supplement Medicaid medication limitations (for example, Texas covers four prescriptions per month; the rest are picked up by ADAP).

The Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of 2003 was signed into law on December 8, 2003. It is the biggest change to Medicare in 40 years. Primarily it adds a prescription drug benefit to Medicare.

The benefit starts January 1, 2006, but enrollment begins November 15, 2005 (earlier for dual eligibles).

The beneficiary chooses from a stand-alone prescription drug plan (PDP) or a managed care plan (Medicare Advantage) that includes a prescription drug plan (MA-PD), but this choice exists only if a Medicare Advantage plan is available where the patient lives.

The premium in 2006 is expected to be $35 per month, although this will vary by plan. All beneficiary costs and subsidy eligibility will be adjusted annually.

If a beneficiary is not subsidized, the plan will not cover the $250 deductible. It will cover 75 percent of the initial benefit from $251 to $2,250. It will then not cover what is called the donut hole, or annual expenses of between $2,251 and $5,100. After that, catastrophic coverage above $5,100 will be covered at 95 percent.

Generous low-income subsidies are available for beneficiaries with incomes below 135 percent of the Federal poverty level (FPL) in 2006. Those eligible for full subsidy for payment of deductibles or premiums are those who are:

Dually eligible

Receiving Supplemental Security Income (SSI)

Earning below 135 percent of the FPL with asset limits of $6,000 if single and $9,000 if in a couple.

Low-income subsidies for beneficiaries with incomes between 135 and 150 percent of FPL (2006) are available for individuals with incomes below 150 percent of FPL and asset limits of $10,000 if single and $20,000 if in a couple. This subsidy provides for a sliding scale premium and a $50 deductible.

Dual eligibles need to know that:

States will no longer receive Federal matching funds for Medicaid prescription drugs for duals.

They must switch to Medicare for drug coverage.

The impact will depend on the State’s previous Medicaid plan and Medicare drug plans available in the area.

Access is limited to the “average cost plan.”

They will be automatically enrolled in the drug plan in the fall of 2005 unless they choose another plan.

They can maintain Medicaid coverage for other health care services.

Issues and challenges for beneficiaries include:

Deciding whether to enroll if they have a choice. There are financial penalties for delayed enrollment.

Enrolling in the low-income subsidy program: Will beneficiaries know they are eligible? Will they sign up?

Comparing plans and deciding which to join when there could be wide variations in premiums, benefit design, formularies, and preferred drug lists each year.

Facing the consequences of a bad decision, such as an annual lockin.

Tracking total out-of-pocket pharmaceutical costs, which is important due to the benefit gap.

Facing formulary changes with 60 days’ notice.

Other issues include copays, which may discourage people from filling their prescriptions.

In terms of ADAP:

It cannot provide “countable” wrap-around coverage to the new drug benefit.

It will not count toward true out-of-pocket (TrOOP) costs, which trigger catastrophic coverage.

ADAP may provide supplemental coverage in the form of subsidizing premiums or copays and covering nonformulary drugs, but coverage will be costly and ongoing for ADAPs, and persons will not reach the catastrophic coverage limit.

The problem is that the new program doesn’t really help ADAP, Ms. Lubinski said. For example:

Beneficiaries could experience an erosion of drug coverage as they transition from ADAP to the new benefit.

Medicare beneficiaries with AIDS (including dual eligibles) may continue to need ADAP assistance to pay premiums and copays and to supplement inadequate formularies, if States are willing and able to do so.

Financially strapped ADAPs will experience minimal fiscal relief and new challenges as a result of the new benefit.

Formulary requirements are a problem. For example:

Plans are not required to cover all HIV antiviral drugs.

Plans are encouraged but not required to comply with Federal guidelines for HIV/AIDS treatment.

Plans are only required to cover two drugs in each therapeutic class, and the model formulary developed so far outlines four classes of HIV drugs—nucleosides, nonnucleosides, protease inhibitors, and others.

The good news is that CMS will review plan formularies to ensure they do not discriminate against certain groups of beneficiaries in their formularies or in their drug cost tiering structure.

Ms. Lubinski added she is hopeful CMS will provide proper oversight and not approve formularies that do not have all the ARV drugs, and she is hoping that the Council will support this.

In addition:

Drug plan Pharmacy and Therapeutic Committees are required to have minimal physician representation, and there is no specific requirement about consultation with HIV medical experts in formulary development.

Plans are required to send formulary information to beneficiaries in writing prior to enrollment.

Plans are required to give beneficiaries 60 days’ notice before removing a drug from the formulary. Physicians and beneficiaries may file for an exception based on medical necessity to continue receiving the drug.

Plans are not required to cover drugs for off-label indications (and there are many used for HIV/AIDS patients), but CMS has indicated it will not allow plans to have a burdensome process for requesting this kind of coverage.

There is a procedure for grievances and appeals. Early drafts of CMS regulations on it were flawed. The current regulations are somewhat better due in part to advocacy intervention. The procedure currently:

Allows an appeal for a drug not on a formulary only if the prescribing physician determines no other covered drug is as effective or there will be adverse effects.

Allows a 72-hour time frame for coverage determination under a standard appeal.

Allows an automatic expedited appeal if it is supported or initiated by a physician, and the response must be within 24 hours, initially.

Does not require, in most instances, an emergency supply of medicine pending appeal.

Permits appointed representatives, including physicians, to file an appeal on behalf of the beneficiary at all appeal levels.

Ms. Lubinski’s organization will continue to advocate for a new drug benefit that:

Ensures comprehensive coverage of HIV medications on plan formularies based on Federal HIV guidelines (at present, this is referenced in the CMS regulations but not required).

Allows ADAP to supplement benefit and count expenditures as true out-of-pocket costs (at present, this is not allowed).

Ensures coverage for off-label use of medications (at present, this is allowed but not required).

Allows all medically necessary drugs to count toward the catastrophic limit (at present, this is not allowed).

Allows dual eligibles the full range of health plans in their areas without additional premium costs, not just average cost plan (at present, this is not allowed).

Does not deny dual eligibles medications for failure to pay cost-sharing (at present, this is denied).

In addition, Ms. Lubinski advocates changing the law to allow Medicaid to supplement Medicare coverage with Federal matching funds, at least through the transitional period, to ensure continuity of care.

What PACHA can do:

Support an ADAP wraparound as countable toward out-of-pocket costs, which is an HHS policy decision.

Support requiring that drug plans cover all HIV drugs.

Support transitional Medicaid drug coverage for dual eligibles to ensure continuity of care.

Request a CMS presentation on efforts to educate and enroll Medicare beneficiaries with AIDS (particularly dual eligibles).

Monitor implementation after January 2006 by requesting ongoing reports and presentations from CMS on exceptions filed, coverage of HIV drugs, and other quality assurance measures.

Question and Answer Period

Dr. Primm noted that working with the addicted is his experience and specialty. Therefore, he is concerned about Medicare’s not paying for treatment of IDUs who need to be maintained on an alternative. This problem will extend to about 60 of his daily patients. Ms. Lubinski responded that neither Medicare nor Medicaid handles addiction very well, but at least some States will continue to pay. Dr. Primm said CMS needs to address this and correct it.

Ms. Ivantic-Doucette wondered if the only gatekeepers are physicians, when most of the delivery of care and prescribing is falling to nurse practitioners and physician assistants. Ms. Lubinski said her organization primarily represents physicians, so that’s why she referred to them when it comes to grievance and appeals. However, under the regulations, the gatekeeper can be anyone appointed by the patient. She will check the language. She added that it’s unclear to how the freestanding drug plans and the new Medicare Advantage plans will interface with Medicare regional regulations.

Dr. Reznik said the Subcommittee would request that information.

Dr. Judson commented that this benefit has turned out to be something that only Americans can understand. We started out with a political demand for a drug benefit, Congress looked at what was politically bearable, and now we have a number of regulations that are highly problematic. What is the process? Does CMS have full authority to change the regulations? Ms. Lubinksi noted that the draft regulations were subject to comment. Then final regulations were promulgated 10 days ago. CMS has said it will issue additional guidance in some areas. Now there is speculation that Congress will take another look at the law. A number of advocates are saying it should, for continuity purposes. Her opinion is Congress will take another look only if it has to and if it can narrowly control changes. PACHA can help by making sure that CMS conducts oversight and review of the drug formularies, and monitors the benefit.

Dr. Reznik said the Subcommittee is working on a motion that addresses these points and also how the benefit could free up ADAP. He asked for e-mail input from the full Council.

Ms. Shoemaker characterized the presentation as frightening, given that she is a single woman with AIDS who makes more than $6,000 per year with the help of Social Security. She gets food stamps and coverage for her Blue Cross/Blue Shield premiums. She owns her home and a car. She has no out-of-pocket money left. Now, as a survivor, she feels she is being penalized.

Ms. Clements said she is particularly concerned about the elderly. She asked if there is an upside to the new benefit. Ms. Lubinski responded that if you have no coverage at all now you’ll get some, which could be very significant. If you have no coverage at all and high drug needs, the new benefit will be significant. However, 2 million people might lose other benefits. It remains to be seen. The devil is in the details. Will the benefit be generous enough and easy enough to access? We don’t know right now. The law is very flawed. It was a sausage-making process by Congress.

Mr. Minor agreed that the new benefit as currently configured is very scary. He advocated that PACHA learn the financial implications. He advocated that PACHA make sure all the needed medications are part of the program, not just two per class. Public Health Service guidelines are needed here. It’s a great role for PACHA to stand up and make sure that people continue to have access to needed medications.

Dr. Reznik promised the Council that the Subcommittee would return with a motion. He turned the meeting back over to Dr. Sullivan.

Dr. Sullivan called the day full and productive. He announced that Ms. Smith will chair Day 2.

Dr. Primm commented that he’d like to think President Bush’s mention of the RWCA came from the urgings of this Council. Dr. Sullivan said he believes President Bush is paying attention to the information he receives from PACHA but that he has a number of important sources of advice.

Ms. Singleton McDonald asked when the Council will meet the new HHS Secretary as well as the President, again. Dr. Sullivan said the new HHS Secretary, Michael Leavitt, hopes to come to the Council’s meeting tomorrow.

Dr. Sullivan then adjourned the meeting.

Adjournment

Presidential Advisory Council on HIV/AIDS
26th Meeting
Hubert Humphrey Building
200 Independence Avenue, S.W.
Room 800
Washington, DC 20201

February 8, 2005

Council Members—
Present

Louis Sullivan, M.D., Council Co-Chair
Anita Smith, Council Co-Chair
Abner Mason, Chair, International Subcommittee
David Reznik, D.D.S., Chair, Treatment and Care Subcommittee
M. Monica Sweeney, M.D., M.P.H., Chair, Prevention Subcommittee
Rosa M. Biaggi, M.P.H., M.P.A.
Cheryll Bowers-Stephens, M.D., M.B.A.
Jacqueline S. Clements
Mildred Freeman
John F. Galbraith
Edward C. Green, Ph.D.
Cheryl-Anne Hall
Jane Hu, Ph.D.
Karen Ivantic-Doucette, M.S.N., F.N.P., ACRN
Rashida Jolley
Franklyn N. Judson, M.D.
Sandra Singleton McDonald
Joe McIlhaney, M.D.
Henry McKinnell, Jr., Ph.D.
Brent Tucker Minor
Jose Montero, M.D., FACP
Dandrick Moton
Beny Primm, M.D.
Debbie Rock
Rev. Edwin Sanders
Lisa Mai Shoemaker
Ram Yogev, M.D.

Council Members—
Absent

David Greer
Prem Sharma, D.D.S., M.S.

Council Staff—
Present

Joseph Grogan, Esq., Executive Director
Dana Ceasar, U.S. Department of Health and Human Services (HHS)

DAY 2

MORNING SESSION

Welcome Remarks

Council Co-Chair Anita Smith welcomed everyone and asked that the meeting stay on schedule as much as possible, particularly so Subcommittees will have sufficient time at lunch to work on draft motions. The Council will also have presentations and a continued report by the Treatment and Care Subcommittee.

Dr. Louis Sullivan noted that the new HHS Secretary, Michael Leavitt, may come to the Council meeting around 1:45 p.m. If the Council meeting is over by then, would Council members be interested in staying to meet Mr. Leavitt? The majority of the Council indicated they would stay.

Ms. Smith then turned the meeting over to Treatment and Care Subcommittee Chair
Dr. David Reznik.

Treatment and Care Subcommittee Report, Continued from Day 1

Dr. Reznik said the themes this morning would be drug research and drug resistance. Those of us who have been working on AIDS before AIDS drugs were available know how important these drugs are to their loved ones. Now we’re stalled in new drug developments, and resistance is playing a role.

Dr. Reznik then introduced Dr. Henry (Hank) McKinnell, Jr., to present on drug research.
Dr. Reznik recalled when he was sworn in as a PACHA member. He was a little overwhelmed. When he met Dr. McKinnell at that time, he wondered to himself what he could possibly have in common with the chief executive officer (CEO) of the world’s largest pharmaceutical company. But he has seen Dr. McKinnell roll up his sleeves with PACHA and get very impassioned about an epidemic that has affected many of our lives.

Presentation

“HIV Medicines: Developing the Future,” by Hank McKinnell, Chairman and CEO, Pfizer, Inc.

Dr. McKinnell thanked Dr. Reznik for his kind introduction. He is in his third and final year with PACHA. HIV/AIDS has become a manageable disease for those with access to HIV/AIDS drugs. But since the development of highly active antiretroviral therapy (HAART) in the mid 1990s, we’ve been locked in a race, trying to keep ahead of resistance by this insidious virus. Behind his presentation are thousands of his colleagues at Pfizer who very much want to bring to the battle the next generation of drugs. We must realize the long lead times required—10–15 years. Pfizer constantly readjusts its forecasts and assumptions. Researching drugs is the most complex research process in modern society. Few researchers ever see a new medicine come out of their work. Pfizer spends $7.5 billion per year in developing new medicines. Because of the drug research industry’s unique capabilities, “we are an indispensable partner” in the fight against HIV/AIDS.

Against that backdrop Dr. McKinnell discussed a number of issues, including access to drugs, the risks and costs of developing new drugs, and the need to always put the patient at the center of drug research and development efforts.

Since 2002, PACHA and its partners in the fight against HIV/AIDS have made good progress. Early testing and treatment are more accessible thanks in part to PACHA’s call for rapid testing. Now testing should become routine and widespread. The goal of expanding Medicaid and Medicare coverage for those most in need has met with mixed success. While the new drug benefit is good, States are lowering their Medicaid funding. Reform and reauthorization of the Ryan White CARE Act (RWCA) is needed—it must continue—but we must now also stress prevention and early treatment.

Good strides have been made in increasing patient access to trained HIV/AIDS clinicians and in collaborations with nongovernmental organizations (NGOs) and patient support groups. Here, Pfizer has helped with its partnership in Kampala. Last, the large pharmaceutical companies have developed 9 of the 10 new medicines available to HIV/AIDS patients, but now we need to get these medicines to poorer nations at a lower cost.

Dr. McKinnell showed a slide of the worldwide pandemic, noting that the total number of adults and children living with HIV is 35 million to 42 million.

Dr. McKinnell ran down a list of the current U.S. Food and Drug Administration (FDA) approved medicines for HIV/AIDS—27 medicines in four classes. He said this number can increase significantly over the next 7 years. New therapies will be needed before waves of current medicines become resistant.

What does it take to discover and develop new HIV/AIDS medicines? Research-based pharmaceutical companies are the key. They have developed and brought to patients the four major classes available so far because of their unique capacity and expertise and the fact that they are the world’s largest and best source of scientific research that leads to discovery and development of medicines. He noted that there is only so much the Government, academia, the biomedical industry, and publicly funded research can do because the development process can take so long, cost so much, and has a failure cap.

Dr. McKinnell showed a slide of the general process of biomedical research and development from discovery to approval. There are several discovery approaches for each target; Phase I, II, and III trials; and then the FDA review.

There has been great consolidation in the industry. In 1988, 42 companies were members of the Pharmaceutical Manufacturers Association (PMA). In 2003, 16 were left, including Pfizer. “This business is up or out. Each medicine comes with an expiration date. Either my company continues to compete or it will get absorbed by others who do it better. Is this bad? There is great pressure to innovate or be gone.”

Dr. McKinnell lauded the FDA’s expedited review of HIV/AIDS medicines through the preapproval access, fast-track approval, and a shortened testing and review process. But additional postmarketing safety and other requirements add significant costs, so despite expedited review, cost and development times for new medicines remain substantial. For example, it costs $492 million to develop an anti-infective medicine and some $800 million to develop a medicine for chronic problems, such as high blood pressure.

Challenges in research and development of new HIV medicines include:

The complexity of the virus—the challenge of treating chronic viral disease and associated conditions

The new challenges for innovation and production that come with each new class of drug

Higher expectations—for simple treatments with fewer side effects and fixed-dose combinations (FDCs).

“This is the most complex virus we’ve ever seen. Eventually, it outsmarts all the medicines developed to date.” Each new class of drugs presents new challenges, including cost, which is mostly research and development with the exception of Fuzeon, which is also very difficult to produce, requiring 100 manufacturing steps.

Dr. McKinnell noted that even by conservative estimates of the total number of HIV patients in the United States, only 50 percent are on drug therapy, and 50 percent of those have reduced options for drug therapy. That’s not counting newly infected individuals, 10-25 percent of whom are never treated but are resistant to one drug class or another. Internationally, there is a lack of viable second-line options due to problems such as lack of health infrastructure, refrigeration, and expense. In addition, lessons learned about current regimens and resistance in the United States may not apply to developing nations. That necessitates research on all HIV subtypes. “Can you imagine 3 million people in developing nations failing treatment? It is a nightmare.”

Overall motivations for new treatment options include to:

• Improve quality of life through simpler, better tolerated regimens
• Improve tolerability and reduce short- and long-term toxicities
• Help people facing resistance
• Reduce the spread of HIV
• Improve access—domestically and internationally.

Dr. McKinnell called for expanded partnerships among stakeholders, including greater cooperation between the pharmaceutical companies. Greater cooperation would reduce costs and result in more FDCs. Expanded partnerships could also enhance vaccine research. Dr. McKinnell called for greater funding for vaccine research but added he is a skeptic. “We should behave,” he added, “like we’ll never have one.”

His vision for the future is to:

• Continue to strive to overcome daunting challenges, such as rising HIV/AIDS rates in China, India, and Russia
• Enhance prevention and education
• Continue to research and develop new treatments with needed incentives.

Concluding, Dr. McKinnell said the large pharmaceutical companies are not part of the problem; rather, they’re integral to the solution. He noted that while it’s preferable to prevent HIV infection, “we need to keep in balance risk versus incentive for new drug development. Treatment saves lives, and early treatment saves money.”

That is one reason why, he added, PACHA needs to do something about the new drug benefit’s seemingly short-sighted formulary regulations. 

Question and Answer Period

Rev. Sanders noted that we see major results from the private sector at the same time Government resources seem to be growing scarcer. Should we continue to expend large amounts of money on vaccine development, particularly when we might be able to succeed with behavioral modifications? Dr. McKinnell said adding all the money spent on HIV/AIDS from private and Government research across the board would total about $100 billion. You could ask how that might be better allocated, but you would gore some prized oxen along the way. In fact, we don’t spend enough in prevention. We should also focus on what a reasonable timeframe for research is. If you believe a vaccine is 20 years away, as he does, more resources won’t help. Scientific leads are needed. In terms of RWCA, we should put more money on rent subsidies or shortening waiting lists. More money is a cheap answer. Better allocation is an excellent project for PACHA.

Dr. Judson congratulated Dr. McKinnell for being a leader and an excellent spokesman for the industry. He asked what proportion of all money spent on HIV/AIDS medicines is coming from the Government. Dr. McKinnell responded that it must be 80 or 90 percent. Dr. Judson wondered how much the industry spends per year on marketing and on “me too” drugs. He added that it seems innovation has taken a back seat in the industry.
Dr. McKinnell said of Pfizer’s 15 percent of expenditures spent on marketing, about

3 percent is used to provide medicines free of charge and another 6-8 percent to pay bills. The balance is spent on marketing which, most often, is education of physicians and patients. He added that someone has to make the investment to make the new medicines, and that the large pharmaceutical companies have a system for doing that. For example, CCR5 represents a new class of HIV/AIDS drug therapy. It was developed in Pfizer labs. It will be available in a few years. When it is available, the company will need to recoup its investment as well as make the drug affordable and accessible. Those who can’t afford access should get it for free or at low cost. Those who can pay need to. If they don’t, it won’t be available for anyone else. The industry’s new part of this bargain is to make them available.

Dr. McKinnell added that 5 years from now, the industry will look very different than it does today. Productivity declined in the 1990s. At same time, there were many new targets. The industry strove to develop drugs for these targets but struck out a lot. Today, however, the industry is on the edge of a boom in productivity. Pfizer alone will have filed for approval of 20 new medicines by the end of 2006, including some big ones, such as CCR5, and another drug that will help lower bad and increase good cholesterol.

Dr. Reznik commented that those who are multidrug-resistant are a smaller subset of the HIV/AIDS population and that, therefore, they are less profitable as a development target. He asked if there is anything PACHA can do to encourage further development, for example, on CXCR4. He also commented that Americans are irritated by having to pay so much for drugs against the fact of drug price controls in Europe and Canada and asked, how can we help?

The U.S. Government could help, Dr. McKinnell responded. The Government needs to negotiate with foreign governments. For example, the Canadian Government tells the U.S.-based companies what they can charge, which is 30-40 percent less than what they charge in the United States. “We’ve asked the U.S. Government to address this trade issue, including putting it on the G-8 agenda.”

Dr. Reznik said PACHA could recommend that the issue be brought up at the G-8 meeting.

Dr. McIlhaney commented that he often defends the large pharmaceutical industry’s independence and pricing, but drugs are only a holding effort until prevention works. We need to redouble our efforts in prevention. Dr. McKinnell characterized that as one of the elephants in the room. We should also track partners of those who are infected. If we were serious about zero new infections, we might think about calling for some new measures, but they might not be acceptable. He wouldn’t, however, give up on the technology, because drug development advances are being made.

Ms. Rock supported the need for people to have access to medicines and the importance of adherence, but people also need help with meeting basic needs. If basic needs aren’t met, it’s difficult for patients to continue to go the doctor and stay on medications.
Dr. McKinnell said his goal is to treat the disease early so people can stay at work, receiving an income and paying taxes. “We tend to think in terms of costs, but we need to think of the total system.”

Dr. Sullivan commented that the industry takes risks and often loses, but when it wins, losses are offset. A lot of people have trouble with that. Why is it so difficult to get other developed nations to underwrite research? Also, is there discussion of trying another model of development, such as having the Government underwrite the costs and contract with the pharmaceutical industry? Dr. McKinnell said he has considered that, but it’s not a solution. For one thing, Governments aren’t very good risk takers. Unfortunately, he said, “We’ve defined the problem in health care as its high cost. When you do that, you ration and control. If we defined the problem as the high cost of disease, everything would change. Investing in avoiding heart attacks and strokes is more rewarding than paying for heart attacks and strokes. The prevention model works.” He noted Pfizer’s partnership in prevention with Florida Medicaid that improved health outcomes by
50 percent or more as well as saved the State a lot of money.

Dr. McKinnell added that the U.S. Government needs to go to Australia, Canada, and other developed countries and say the game is over, that “You must pay your fair share. Some countries just take our technology through compulsory licensing and get a free ride.”

Dr. Sullivan asked International Subcommittee Chair Abner Mason to consider a resolution on this issue.

Dr. Yogev commented that he disagrees with a gloomy assessment of a vaccine. There have been some breakthroughs. A vaccine would be a major prevention measure. Industry doesn’t work on finding one as much as it works on other medicines because the money isn’t there. However much they may be a minority group or subset, 20,000-plus kids in the United States still need a vaccine. Dr. McKinnell responded that the CCR5 development will apply to pediatrics. He added that the industry does need to do more pediatric work. He then gave a quick history of vaccines: 40 companies used to manufacture vaccines, but a combination of product liability and Government contracting practices pushed down prices and made vaccines unattractive. All but four companies have since left the vaccine industry, including Pfizer. Now the technology for human vaccines is frozen. However, Pfizer is number one in the world today in animal health vaccine research and development.

Dr. Green asked what PACHA needs to do to take up Dr. McKinnell’s challenge to achieve zero new infections in the United States and abroad. Dr. McKinnell said routine and widespread testing would be his first recommendation. Dr. Reznik agreed, adding that it should take place in hospitals and other similar facilities. Ms. Cheryl-Anne Hall agreed, adding we also need early treatment.

Dr. Reznik introduced the next presenter, Dr. Richard D’Aquila, as a foremost expert in HIV/AIDS drug resistance.

Presentation

“Antiretroviral Drug Resistance,” by Richard T. D’Aquila, M.D., Vanderbilt University Medical Center and the Vanderbilt Meharry Center for AIDS Research, Nashville, Tennessee

Dr. D’Aquila asked members to ask questions if he becomes too technical.

Dr. D’Aquila said the heart of his presentation is this: We’re all worried for good reasons about antiretroviral (ARV) drug resistance, but has it reversed hard-fought gains in chemotherapy, is it a threat for the future, and what action is required?

HIV replication and chemotherapy is a sequential process. Current drugs tend to intervene in the process of viral entry, replication, and exit only at certain points in the sequence. What we need to do is interfere with the virus even earlier or render virions noninfectious.

The virus has many ways of getting around our defenses. It is teaching us a lot about evolution at warp speed. A great pool of variation is always present. The virus has great capacity to survive through the best variant. There is the phenomenon of escape mutants—that escape from immune pressures most common for that population. To acknowledge this could advance development of target vaccines—targeted for different immune responses.

Another important factor is the more a virus replicates on a drug, the greater the chance of resistance. This explains our historical problem with resistance: we have been using the same drugs for some time. It is critical to note, however, that mutants do get slowed down by available drugs; that is, resistance is relative, not absolute.

Does HIV resistance cause drug failure? In acyclovir-resistant herpes simplex virus (HSV), we learned the resistant virus was “fairly wimpy”, i.e., HSV does not always cause drug failure. Some of the first studies to show clinical resistance to AZT, with which Dr. D’Aquila was involved, showed that a high level of resistance was associated with drug failure, but “we couldn’t be sure lower levels of resistance harmed the AZT effect. Today, we can engineer a slightly better response if we identify mutations before choosing the next drug regimen for a patient.”

In a relatively recent paper (Deems et al.), it was shown that, generally, CD4 count declines slowly during drug failure. The norm is some loss of drug suppression, but there is still some partial drop in viral load and some benefit. An even more recent study concluded that if viral load stays below 20,000 copies/ml, there was no worsened immunocompromise. If viral load went above that level, within months there was clinical evidence of worsening compromise.

At the Comprehensive Care Center in Nashville, “we have learned to use resistance testing and other information to help patients with failing drug therapy. Decisionmaking is driven by the degree of drug resistance observed, drug side effects, and the finding that failure does not occur suddenly but rather over the course of weeks.”

Why do “failing” drugs sustain benefit? That is, why is resistance not absolute?
Dr. D’Aquila noted that:

• Drug activity against wild-type HIV results in the wild type staying suppressed.
• There is partial drug activity against resistant HIV.
• There is decreased replication capacity of resistant HIV.
• Immune response rises against antigens in the replicating resistant virus.
• There is decreased CD4 cell activation by resistant virus—statins inhibit HIV by decreasing cell proliferation.

Interestingly, in the evolution of resistant mutants for patients on drugs and patients off drugs:

• Patients on continued failing drugs experience a slow increase in both resistance and the mutant’s replicative capacity.
• Patients off drugs experience a sudden change in CD4 count and viral load that is frequently associated with a shift to wild-type (or drug-susceptible) virus (a sharp increase in viral load and decrease in CD4 count leads to damage).

Dr. D’Aquila presented one case of acute HIV infection that he called unusual, in which the newly infected patient was found to be infected with not only one mutant but several. The choice was made not to treat him with drugs. Dr. D’Aquila speculates the better choice would have been to maintain pressure on the virus, with current drugs.

How common is resistant virus in North America?

• The best data come from Richman et al. who found that 50 percent of all patients studied and 87 percent of ARV-treated patients studied had detectable viremia, but they also had been on mono or dual therapies before the advent of HAART.
• In a more recent study, Harrigan et al. showed 25 percent of patients studied who had been on later drugs, including HAART, showed resistance.
• Today’s standard is to start with more potent regimens, but no data are available yet on that.

Dr. D’Aquila said not all studies of newly infected patients in the United States and Europe show increases in resistance over time. One question is, is resistant virus less transmissible than wild-type? Some researchers think the answer is yes. However, we need to keep monitoring and to start drug therapy with triple combinations, always using the best available options to slow the spread of mutant virus.

Dr. D’Aquila said, “There’s a clear trend we are doing better, and I think we will see less resistance prevalence.”

Turning to the topic of adherence and resistance, Dr. D’Aquila showed the classic paradigm that indicates the greater the adherence the more complete the viral suppression. However, a recent paper showed that although better adherence is linear to viral suppression, it is not necessarily linear to the resistance trend. Apparently, different drugs make a difference in whether improved adherence equals better suppression as well as better resistance to drug-resistant virus.

Dr. D’Aquila showed a chart of adherence to HIV therapy in the industrialized North, with percentages of adherence as low as 53 percent in Hartford, Connecticut, and 57 percent in New York City. This has led to fears that adherence will be worse in poor areas and that more resistance will also be encountered. But a recent study of the prevalence of ARV resistance among the urban poor of San Francisco against the Nation as a whole indicated that resistance overall was lower among the urban poor with any ARV, PI, NNRTI, and RTI.

Now we are beginning to see small studies from Africa that show high adherence levels in patients on the common triple combination therapy of D4T/3TC/nevirapine (NVP).

Is average adherence enough? Dr. D’Aquila showed the results of a study in the United States (Bangsberg and Deeks) indicating that even with average adherence, HIV/AIDS drugs have had an enormous impact on morbidity and mortality. “Resistance has not yet destroyed this success.”

In summary:

• Most resistance has occurred in highly adherent patients on partially suppressive regimens.
• Potent regimens reduce resistance at all levels of adherence.
• Poverty is not an international risk factor for incomplete adherence.
• Average adherence is sufficient to impact morbidity and mortality.

In conclusion, has ARV drug resistance reversed the hard-fought gains in ARV chemotherapy? Dr. D’Aquila thinks not. Is there a threat of the future? Yes, but we must make sure that the best drugs are available to everyone according to their individual needs. In addition, there must be more research and development of HIV drugs and diagnostics, and we must continue other current priorities, including HIV pathogenesis research, observational cohort research, monitoring for resistance, and clinician and patient education in expert management of resistance. Last, there is hope for better potency from new combinations, but new drugs are also needed, including those that target the virus at an earlier stage.

Dr. D’Aquila thanked Dr. David Bangsberg for his slides and recommended Dr. Bangsberg’s 2004 Workshop on Disparities and the HIV Epidemic, available at www.mc.vanderbilt.edu/root/vumc.php?site=Workshop&doc=4557.

Question and Answer Period

In answer to questions by Dr. Judson, Dr. D’Aquila said there are ways in the lab that one could tackle replication by a nonintegrated virus. It has a short half-life. If it is not integrated in a week or 2, it’s dead. He added that the rationale for monitoring in resource-poor settings is to monitor subpopulations for patterns of emerging resistance. “We need to be able to track those newly infected, too.”

Dr. Sullivan asked for Dr. D’Aquila’s assessment of HIV/AIDS vaccine development. Dr. D’Aquila said it holds promise. “We’ve learned immune responses are targeted by alleles and that epitopes of the virus presented to the immune system will be different in population A versus population B. This raises the possibility that what might be better than working with a single antigen would be working with all clades of the virus and all parts of the operative immune system. In short, it might be better to have a vaccine cocktail of different antigens that would be recognized in most people’s immune systems.”

Ms. Ivantic-Doucette noted that PACHA is considering a resolution regarding nevirapine, and there is concern about resistance patterns in single-dose nevirapine. PACHA is also considering a resolution about MTCT and triple combination therapy. Dr. D’Aquila responded that we need to balance what we see as risk today and the great good that has come from nevirapine prophylaxis. He does advocate triple combination for prophylaxis. “Ideally, we should be using triple combination regimes. If we had all the resources we need, I would argue vigorously for treating the mother so as not to orphan the child. While we can’t eschew single-dose nevirapine right away, we should focus on developing better regimens, a combination, to minimize resistance to nevirapine.”

Responding to Dr. Yogev, Dr. D’Aquila agreed that resistance is not unique to nevirapine. However, it has a very long half-life, and one dose is present at inhibitory levels for a very long time, maybe 1 or 2 weeks. In some people, it may be longer. “If you treated with nevirapine for a week or 2, you would see high levels of resistance.” He noted a study on drug-treated patients in the United States that looked at response to a nonnucleoside-containing salvage regimen. It found that even with no evidence of resistance in the blood, responses were not good. In this study, researchers found mutant virus still present in low levels, and this was cause for compromise of the regimen.

Ms. Smith thanked all for the stimulating and engaging presentations and questions. She thanked the Treatment and Care Subcommittee.

Break

Ms. Smith reconvened the Council meeting. A Centers for Disease Control and Prevention (CDC) representative is available to answer questions stimulated by CDC Director Dr. Julie Louise Gerberding’s presentation yesterday. Then the Council will open the Public Comment period.

CDC representative Ms. Eva Seiler noted that she is still trying to get answers about syphilis incidence in the United States and will send the answers later through Mr. Grogan. The HIV/AIDS rapid test is not available for those 12 years of age or younger, but it is available for those 13 years of age or older. The manufacturer cautions about the use of the test in persons under the age of 12 because data are lacking on safety and efficacy at those age levels. A representative from the manufacturer, OraQuick, will comment on this later. Finally, once the President’s budget is released, it will show a
$4 million reduction in the proposed budget for HIV/AIDS, but CDC plans to make that up through changes in allocations to other internal programs. 

Dr. Judson said he could try to answer the syphilis question. Ms. Ivantic-Doucette repeated her concern about whether both primary and secondary rates are shown in the increases in syphilis rates noted by Dr. Gerberding yesterday. Her concern is whether latent syphilis is showing up now. Dr. Judson said the United States is still seeing a decrease in syphilis in blacks, including in the high-rate rural areas. But for gay men, rates are increasing and in the infectious stages, primary and secondary, as well as early and late latent.

Dr. Primm reminded the Council that Dr. Gerberding had also mentioned bulk purchasing of the rapid test. Ms. Seiler said it is not clear how CDC will do this, but its goal is to make the test available at cost. She added that CDC doesn’t have much experience in bulk purchasing. The goal is to make the greatest number of tests available at the best price possible.

Dr. Yogev asked whether PACHA could obtain an on-the-record statement that the CDC and FDA would allow the OraQuick test to be used in persons under the age of 12, and Ms. Seiler said that can be arranged.

Public Comment

Ms. Smith announced the opening of Public Comment. She noted each registered speaker will have 3 minutes to speak and will be reminded of their time left by timekeeper
Lt. Wanda Chestnut.

Ms. Smith called Ms. Marsha Martin, Ms. Donna Crews, and Mr. Bill McColl. No speakers rose to the microphone. Ms. Smith called Ms. Jessica Tytel, Mr. Ronald Johnson, Mr. Tony Tran, and Mr. Nguru Karugu. No speakers rose to the microphone.

Ms. Smith asked if there was anyone in the audience who had signed up but who is not on the list of names she called.

Mr. David Oxley of OraQuick Technologies rose to the microphone. He said the OraQuick oral fluid test is now available. The company also has contacted CDC about bulk purchase of 211,000 tests for FY 2005. As of the end of January 2005, 55,000 tests have been deployed. He said OraQuick strongly supports the request for bulk purchasing. He noted that State health departments don’t have access to U.S. General Services Administration (GSA) purchasing and that the company would violate GSA contract terms if it extended GSA terms directly to the States. As a consequence, the States have asked for the tests to be purchased through GSA. Now the company is waiting for further confirmation from CDC and Congress on available funding.

Dr. Samuel Jones from Nigeria then rose to the microphone. He said that up until 2 weeks ago, he was a medical officer monitoring MTCT in Africa. In Africa, pregnant women are usually first seen medically when they come to deliver. In short, the usual point of contact with mothers and their babies is the day before delivery and perhaps 2 days after. Single-dose nevirapine as a prophylaxis for MTCT answers a need, in this context. He recalled when nevirapine was discovered. He noted that Ugandans who participated in the HIVNET 012 trials of nevirapine have written a letter to Rev. Jesse Jackson about how much it is needed.

Ms. Genevieve Grapman from the Health and Gender Equity Center rose to the microphone. Her Center worked with Congress on the writing of law supporting the President’s Emergency Plan for AIDS Relief (PEPFAR). The Center was and remains specifically interested in comprehensive prevention, including but not limited to the ABC model. She stated that there is “no evidence that ABC is not being addressed in Uganda.” She said the PEPFAR implementing plan, guidelines, and 2004 operational plan require reporting on A and B. In terms of C, in Uganda today there is a shortage of condoms. She added that in sub-Saharan Africa today, HIV/AIDS is growing rapidly among young women who were not sexually active before marriage and who have been monogamous during marriage. Her Center joins Mrs. Vivian Berryhill and the U.S. Congress in supporting ABC “plus,” including addressing “D” for domestic violence.

Mr. William Arnold, CEO and Vice Chair of the Title II Community AIDS National Network and Director of the ADAP Working Group in Washington, DC, rose to the microphone. He summarized a written statement thanking the President for signaling the need for a $10 million increase in ADAP funding in the budget released February 7. However, he noted that the budget proposes only flat funding for the rest of RWCA and that, in FY 2006, ADAP will actually need an additional $250–$300 million. “Our commitment to fighting AIDS in the United States is not keeping up with either the facts of our epidemic here or the need to provide access to HIV/AIDS drugs, health care, and support.” He noted that there are now between 100,000 and 200,000 more HIV-positive Americans than when the Act and ADAP were first implemented.

While the President’s $20 million emergency funding for ADAP from FY 2005 was much appreciated, when it ends, those covered by this emergency funding will fall back into regular ADAP coverage. “How this can happen ethically in areas where ADAP programs are closed or capped, I cannot say. The present $10 million ADAP increase will not even guarantee drug coverage for the close to 2,000 folks we rescued temporarily last year from States with ADAP wait lists.” He asked for PACHA’s continued efforts and attention to the ADAP resource question, and to imagine what will happen in communities across the country when HIV-positive Americans discover their status only to also find that there is no available reliable source for providing them with the HIV/AIDS treatments that have cut AIDS death rates by more than 75 percent since 1996.

Mr. Murray Penner of the National Alliance of State and Territorial AIDS Directors (NASTAD) rose to the microphone briefly to address ADAP programs and the new Medicare drug benefit. He said NASTAD would release information February 9 about how ADAP waiting lists are beginning to grow again. This is an issue for reauthorization of the RWCA. He added that he supports Mr. Arnold’s statements about the ADAP crisis.

Medicaid cuts and changes to drug benefits are coming January 1, 2006, and NASTAD is very concerned about the impact on the ADAP program. NASTAD is also concerned about limited formularies, dual eligibles, out-of-pocket expenditures, and the need for a great deal of education about enrollment under the new program. He urged PACHA to do everything it can to make sure that HIV/AIDS patients have access to the drugs they need.

Mr. Jim Driscoll rose to the microphone as a specialist in AIDS and health care expressing his personal views about human trafficking issues and proving the relationship between trafficking and HIV/AIDS. In the past 18 months, he has interviewed scores of individuals in Asia, including in Cambodia, Myanmar, and Vietnam. Many saw the tie between human trafficking, sex slaves, sex workers, and prostitution and HIV/AIDS as a major problem. He congratulated President Bush for acknowledging the need to crack down on human trafficking. He recalled when former San Francisco Mayor Dianne Feinstein closed bath houses in the city and was attacked for lack of proof of the connection between their operation and the spread of HIV. He called for locking up pimps as a key to addressing the spread of HIV/AIDS.

Ms. Marsha Martin from AIDS Action in Washington, DC, which works in collaboration with the Health Resources and Services Administration (HRSA), rose to the podium as the last speaker. She had two handouts, one with charts showing the size and populations of the HIV epidemic in the United States in general and the estimated number of individuals who are aware of their infection but are not in care (about 250,000). She called for creating a momentum of care whereby those who are aware but not in care get into care as well as those who are unaware but are most likely infected (about another 250,000 individuals). Without this momentum, new infections will and are occurring. In short, the greater the number of HIV-positive individuals in care, the fewer new infections. Care is key to prevention. She encouraged building alliances to bring about this change in the epidemic’s dynamic. She encouraged PACHA to recognize the contributions of the FDA and of the pharmaceutical industry.

Ms. Smith announced the end of the Public Comment period.

Announcements, Breakout Sessions for Preparatory Work, Point of Order

Mr. Grogan provided instructions about where the Subcommittees would break out for lunch and preparatory work. Ms. Smith reminded the Subcommittees that they will be working on the draft motions that have been introduced. She invited members with issues or concerns about draft motions introduced by other Subcommittees to seek out the Chairs of those Subcommittees.

Mr. Mason asked as a point of order if motions not introduced on Day 1 can be introduced today.

Ms. Smith noted that, historically, PACHA has not done that.

Mr. Mason said that from the International Subcommittee’s perspective, the goal would be to congratulate the President for his extraordinary commitment to combating the epidemic on a global scale. 

Dr. Sullivan said that sounds like a followup to previous PACHA resolutions. He invited members to provide input on the idea. He said he does want to avoid debate in the full Council in order to complete the meeting in a timely fashion. He announced that Secretary Leavitt would join the Council at 1:45 p.m.

Ms. Smith adjourned the Council for its preparatory work.

Working Lunch

Break

Reconvened for Motions and Voting

Ms. Smith reconvened the Council. She said the goal will be to have completed work on all motions by Secretary Leavitt’s visit at 1:45 p.m.

International Subcommittee Report

Mr. Mason said the International Subcommittee has decided to table two of the four draft resolutions it introduced on Day 1. These are the resolutions entitled “Preventing AIDS and STDs by Curbing Human Trafficking” and “Call for Ensuring Broader Programs of AIDS Prevention in Implementing the President’s Emergency Plan for AIDS Relief (PEPFAR).” The Subcommittee will discuss these and report back to the full Council on next steps.

The Subcommittee is moving forward with the other two resolutions introduced on
Day 1: “Improving Prevention of Mother-to-Child Transmission (PMTCT) Efforts Globally,” and “Improving Prevention of Mother-to-Child Transmission (PMTCT) Efforts While Preserving Current Treatment Options for Women of Childbearing Years.”

New Draft Motion

Mr. Mason said the Subcommittee would also introduce today a new draft motion commending President Bush for his global AIDS budget. Initially, the Subcommittee thought to combine it with the Treatment and Care Subcommittee’s motion commending the President and his State of the Union address, but the two may remain separate.

First PMTCT Draft Motion Changes and Discussion

On the first draft resolution on PMTCT before the Council, Mr. Mason said the Subcommittee had made one change in the language, in the second paragraph, to “2 percent” from “1 percent.”

Dr. Montero, Ms. Ivantic-Doucette, and Dr. Reznik suggested language changes to the last paragraph. The last paragraph of the first draft resolution, on PMTCT, was altered to read: “BE IT RECOMMENDED that U.S. Government Departments and their implementing agencies involved in HIV/AIDS activities globally intensify their efforts to secure HAART for pregnant and breastfeeding women through the development of infrastructure, such as the training of nurses, midwives, and other health care workers to manage medication therapies, and the monitoring and evaluation of the impact on the health of the mother, the child, and the prevention of new HIV infections.”

Mr. Mason asked if there was further discussion. There was none. Ms. Rock made a motion that the draft resolution be accepted. She was seconded.

Passage of First Resolution on PMTCT

Mr. Mason called for a vote by a show of hands. The first resolution passed.

Second PMTCT Draft Motion Changes and Discussion

Dr. Reznik asked to clean up the language in the fifth paragraph of the second PMTCT draft resolution. Dr. Reznik said he wants to make sure Dr. Fauci is supported, as well as the work that has been done on nevirapine.

Mr. Mason called for discussion. He commented that the studies done on nevirapine weren’t perfect, and PACHA needs to give a correct impression and interpretation.

Dr. Sweeney and Dr. Sullivan suggested changes. Ms. Clements suggested changes.
Ms. Shoemaker and Dr. Reznik then suggested changes. The final change resulted in the fifth paragraph reading as follows: “WHEREAS, recent allegations related to the study which proved the safety and efficacy of nevirapine in preventing MTCT were shown to be unfounded by multiple subsequent reviews; and subsequent independent studies confirmed the results of the original study.”

Dr. Yogev also submitted changes to the draft resolution. In the third paragraph, he corrected the spelling of the word “transmission,” struck the word “the” and added the word “introduced” after “was.” In the fourth paragraph the word “major” was changed to “significant.” In the fifth paragraph, the words “as well as” were substituted for “; and subsequent.”

Mr. Mason asked if there was any further discussion. There being none he called for a vote.

Passage of the Second Resolution on PMTCT

By a show of hands, the Council passed the second resolution on PMTCT.

New Resolution

Mr. Mason read the Subcommittee’s new resolution, entitled “Commending Presidential Leadership on Global AIDS.”

“WHEREAS, the President’s Emergency Plan for AIDS Relief is a 5-year, $15 billion U.S. Government initiative to provide treatment, prevention, education, and support to people infected and affected by HIV in 15 of the hardest hit countries in the world, and

“WHEREAS, the President’s Emergency Plan has already started to show significant progress toward meeting its targeted goals for treatment with 155,000 people in treatment, and

“WHEREAS, the President’s recently announced fiscal 2006 budget has recommended $3.2 billion for the President’s Emergency Plan funding, one of the few discretionary line item increases in the President’s budget;

“BE IT HEREBY RESOLVED that PACHA commends President Bush for his continued commitment to fund the President's Emergency Plan for AIDS Relief.”

The motion was passed without discussion. Mr. Mason said this completes the report of the International Subcommittee.

General Discussion

Rev. Sanders asked to participate in International Subcommittee conference calls on the two tabled International Subcommittee resolutions. Mr. Grogan will notify all members of further discussion of these resolutions. In addition, all members will receive opportunities to participate in all future conference calls by any Subcommittee.

Treatment and Care Subcommittee Report

Subcommittee Chair Dr. Reznik stated that he could complete his report in the short time before the new Secretary arrives. He wanted to comment on the Federal poverty level, which had been discussed on the previous day. For one individual, in the 48 contiguous States and the District of Columbia, the FPL is $9,310; for a family of two, it is $12,490; for three, it is $15,670. These figures will change because they were released a year ago.

Dr. Reznik then read the Treatment and Care Subcommittee version of the State of the Union resolution.

“BE IT RESOLVED that the Presidential Advisory Council on HIV/AIDS wishes to express our sincerest gratitude to the President of the United States of America, George W. Bush, for bringing national attention to the domestic HIV/AIDS epidemic and the disproportionate impact this disease has on African American men and women by calling for a reauthorization and modernization of the Ryan White CARE Act in the State of the Union Address on February 2, 2005.”

Discussion of Letter to Former HHS Secretary Tommy Thompson, Vote by Council

Ms. Smith suggested that the Council write a letter of thanks to former Secretary Thompson for his leadership.

The Council voted to approve such a letter.

Visit by HHS Officials

Dr. Sullivan introduced Christina Beato, M.D.

Dr. Beato thanked PACHA for all its hard work, including on the resolutions just passed. She noted that PACHA is here to have an impact on some of our most vulnerable populations. She asked that the focus always be prevention. Former Secretary Thompson will be pleased to receive the letter from PACHA. She has found the new Secretary to be just as warm, compassionate, and caring. He is very determined to fulfill the President’s compassionate agenda.

Dr. Sullivan commented that the new Secretary may be the twentieth to head HHS since its founding in 1953 under President Dwight D. Eisenhower.

Visit by Secretary Michael Leavitt

As Secretary Leavitt entered the room, Council members stood and applauded.

Dr. Sullivan confirmed with the Secretary that he is the twentieth person to head the department since its founding. The Council very much appreciates his taking the time to meet. PACHA is a hard-working group and has had a good meeting.

Secretary Leavitt said he aspires to know more about each Council member and how they are connected to PACHA. He asked for each member to identify themselves, who they represent, and to provide a brief statement about their PACHA connection.

Dr. Sullivan introduced Mr. Grogan as PACHA’s Executive Director who “works overtime for us.”

Ms. Shoemaker introduced herself as a person with AIDS and a motivational speaker and educator who lives outside of Traverse City, Michigan. Answering the Secretary’s question about what she teaches, she said grades 9-12, about HIV/AIDS and STDs. She added she was invited to be on the Council as a person living with AIDS.

Dr. McIlhaney introduced himself as a physician and gynecologist. His Austin, Texas, practice focuses on fertility. He became interested in HIV/AIDS and STDs when he began seeing a number of patients made sterile by sexually risky behaviors. He noted he is originally from Lubbock, Texas.

Mr. Dandrick Moton noted that for the past 6 years he has served as public relations director for a large nonprofit youth center. He lives in Arizona and is also a public speaking professor at the University of Arizona. Secretary Leavitt asked about the origins of Mr. Moton’s first name. Mr. Moton said the base is Daniel, but his mother added to it, wanting it to be unique, like he was.

Ms. Jolley said she is a Washington, DC, native who speaks to middle and senior high school students all over the country about making healthy decisions. She is also a singer, and she gave the Secretary a copy of her latest CD. She said she tries to make music that will help young people, especially young girls, make healthy decisions.

Ms. Rock said she is from Baltimore, Maryland, where she helps administer an HIV/AIDS program that provides many services to children. She said seniors and the risks they may take are of special interest, in part because her father has recently returned to the dating scene. Secretary Leavitt told a true story about an elderly couple he had met who had been married for 77 years. He told them that was inspirational, and they told him they were thinking of getting divorced but were waiting until the kids were dead.

Dr. Biaggi introduced herself and said she became interested in public health when she was hired by Catholic Charities to be a family therapist for HIV-positive people. Secretary Leavitt noted that people often find their passion through their work.

Dr. Yogev introduced himself as from Texas, south of Lubbock. He has lived in the United States for 30 years. He is a converted academician. After working with polio patients, he found his heart in the neglected area of pediatrics. His idol is Albert Schweitzer.

Dr. Jane Hu introduced herself as possibly the only Asian American in the group. She noted that in September, she started an AIDS treatment and training center in China with local Chinese doctors. She came to the Council as a politically active member of the Asian American community. She also campaigned for President Bush in 2000. She just returned from China and realizes that the United States is now her real home.

Secretary Leavitt commented that he has begun to feel the humanitarian and international outreach to the world represented by the Council and the President’s policies. He said we have a very significant stake in the domestic manifestations of this disease but also how it is affecting people and nations abroad. He recalled that when he was in China a few years ago, he and his translator went for an informal walk and began talking to people on the street about their lives. They came upon a family singing Chinese opera to each other, accompanied by a tiny cellolike instrument with one string. Soon a crowd of people had gathered, curious about the visitors. It was a magical moment and one he always remembers about China. 

Ms. Hall noted her affiliation with the Lutheran Medical Center in Brooklyn, which has a HRSA grant to develop an HIV/AIDS training program with Caribbean nations. She was born in Trinidad but emigrated 34 years ago, directly to Brooklyn.

Ms. Ivantic-Doucette introduced herself as from Marquette University. She has worked for 20 years on HIV/AIDS issues. She teaches and cares for clients, primarily African Americans in Milwaukee. She is involved with two training programs in Uganda. She has four boys, two in college. Secretary Leavitt said he grew up in a family of six boys, and he and his wife have four boys and one girl. And he just learned he is about to become a grandfather.

Dr. Green said he is originally from Washington, DC, and that he grew up in the Foreign Service. His grandfather was Ambassador to Iraq in the 1950s. He has been at Harvard’s School of Public Health for 3 1/2 years. Before that, he was primarily a U.S. Agency for International Development consultant. He thinks of himself as an Africaans, and he has spent lot of time recently on the ABC strategy. Secretary Leavitt asked what Dr. Green wrote his dissertation on, and Dr. Green told him, escaped slaves living in Surinam.

Mr. Minor commended the Secretary for taking time to come meet and learn about the individual Council members. He is originally from North Carolina. Now he lives in Alexandria, Virginia. He started Food for Friends, delivering food to people with AIDS. He has also worked as the Chair of a Title Me council. He was diagnosed with HIV/AIDS in 1987. As a gay man, he finds his affiliation with PACHA to be very gratifying, on both philosophical and deeply personal levels. Secretary Leavitt asked if Mr. Minor lives in Old Town. Mr. Minor quipped that he doesn’t get paid that much and that he lives in Arlandria. Secretary Leavitt said that although he made many trips to Washington as a Governor and has lived here now for a year, each time he leaves his house he gets lost.

Rev. Sanders introduced himself as a senior servant. He noted that his congregation has been involved in HIV/AIDS for 21 years, beginning with education. He works with HRSA, CDC, and the U.S. Justice Department. His church and its affiliated centers consider themselves to be models of faith-based participation because they are “of service.” He told the Secretary he had witnessed a miracle today because brevity is not a hallmark of PACHA members.

Dr. Bowers-Stephens said she would like to mention first that she and her husband donate time and resources to the people of Zimbabwe. She was born in North Carolina, but moved to Louisiana with her family. Her father was a dental surgeon and native of New Orleans. Secretary Leavitt noted he has a younger brother by 22 years who is just now finishing his medical residency, yet also has six sons all under the age of 8. Secretary Leavitt has quipped to his brother that his motto must be, “If there’s a harder way, I’ll find it.”

Ms. Clements introduced herself as a pre- and post-HIV test counselor and past chair of the North Carolina Governor’s advisory council on HIV/AIDS. She was married in 1980, and then her husband developed swollen lymph nodes. He was finally diagnosed with HIV/AIDS in 1986 and died in 1988. Her daughter succumbed to the same disease in 1990, at the age of 4. As far as she knows, she has had the disease for 20 years. She comes to the Council as a person whom others shunned at one time. She turns 50 this year but never thought she would. Secretary Leavitt commented on Ms. Clements’ compelling and moving story. He noted his wife’s name is also Jacqueline. He asked where Ms. Clements got her name, and she responded from her aunt, but she knows no more than that. Secretary Leavitt shared that his father’s first name is Dixie.

Ms. Singleton McDonald noted the Secretary’s compassion and warmth, adding “we need you to lead our initiatives on health.” She said she is a native of Atlanta who, in 1986, after leaving several jobs, decided to become self-employed, helping African Americans with AIDS. She then founded Outreach, Inc., the first and oldest agency in
the country serving African Americans who have HIV/AIDS. Her youngest clients are 13-year-old twins; her oldest, an 80-year-old. She is a consultant to the National Football League, working with all the teams on a public service announcement campaign about HIV/AIDS. She asked the Secretary if he would like to get involved in that movement.

Dr. Montero characterized himself as a clinician and educator, primarily with hospital patients. He has also worked with HIV/AIDS care and treatment in the Caribbean and in India. He has been to India only once but that was enough to convince him that the nation needs his help, for the population is huge, the numbers of infected high, and the potential for the epidemic to explode great.

Dr. Primm characterized himself as a senior servant of PACHA. He is from New York City, where, among many things, he is involved in addiction research and treatment. He runs a large human services conglomerate that treats about 3,000 individuals in seven clinics. He also treats battered women and children. PACHA is his second Presidential commission appointment. He is founder and chairman of the board of the Minority AIDS Council, among many other positions. Secretary Leavitt commented: “What a great way to spend your life.”

Dr. Sweeney said she is an internist with an M.S. in public health and also serves as Chair of PACHA’s Prevention Subcommittee. She is here because long before HIV had a name, she was working with it. She helps run a multiservice center for the infected and affected in the heart of Brooklyn. She was originally from the eastern shore of Virginia. Dr. Sweeney invited Secretary Leavitt to come see her in Brooklyn, and he said he will.

Dr. Reznik said he started out as a community dentist in Atlanta, and then went into oral care for HIV/AIDS patients. He is now director of one of the most comprehensive centers for HIV/AIDS, where they treat 4,700 people living with HIV/AIDS. As of this meeting, he is Chair of PACHA’s Treatment and Care Subcommittee. His mission is to ensure access to services and life-sustaining medications. Secretary Leavitt called that a remarkable mission. Dr. Reznik said he’ll cut his hair when we have a cure.

Mr. Mason said he is from Los Angeles, where he runs a nonprofit. He noted that he is the Chair of PACHA’s International Subcommittee. He grew up in Durham, North Carolina, but has spent most of his life in Massachusetts.

Ms. Smith said she is President of the Children’s AIDS Fund, which she founded with her husband in 1988. Their organization is a PEPFAR grantee under Catholic Relief Services treatment grants. They work with close to 3,000 patients in several countries. Secretary Leavitt asked if she travels often, and Ms. Smith said, very often, and in fact she leaves tonight.

Secretary Leavitt said that President Bush’s Administration commitment to the battle against HIV/AIDS is real, and the President’s intent is for the Executive Branch and advisory councils like PACHA to have a real impact. He noted that several PACHA members mentioned when they first became aware of AIDS. His first experience with it was in 1993. He had just been elected Governor, and he and his family were living in their own home, not the Governor’s mansion, when a very close neighbor and friend, Larry, became ill with AIDS. One afternoon he received a call that Larry was going to die. He went to visit Larry and asked him to explain what this disease was about. Larry then began to teach the Secretary what PACHA members know now. Regrettably that was a time when being diagnosed was a death sentence. Lots of progress has since been made. However, this epidemic is still a remarkable challenge both domestically and internationally. Secretary Leavitt said he is committed to being as helpful as he knows how to be, adding that he is open to suggestions about how he can be more helpful.

A photograph was taken of the entire Council present and Secretary Leavitt.

Announcements and Adjournment

Ms. Smith announced that members’ briefing books will be shipped to them and minutes will come shortly. She thanked Mr. Grogan and his staff. Mr. Grogan thanked Lt. Chestnut and Ms. Ceasar. He announced that there will be conference calls with the Chairs about Subcommittee and full Council meeting dates. He’ll confirm the full Council meeting dates in June with the Secretary in coming weeks. Ms. Singleton McDonald thanked everyone, including the contractors and food provider, for an excellent job.