Markowitz M, Tenner-Racz K, Zhang L, Hurley A, Ramratnam B, Cao Y, Boden D, Duran M, Farthing C, Racz P, Ho DD; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 6th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 6th 1999 Chic Ill. 1999 Jan 31-Feb 4; 6th: 187 (abstract no. 636).
Aaron Diamond AIDS Research Center, New York.
38 newly-infected subjects (NIs) enrolled in 3 trials between 7/95 and 2/97. Regimens included: AZT or D4T & 3TC & either ritonavir [R] (N=12), indinavir [I] (N=12), or ritonavir/saquinavir [R/S] (N=14). All 38 responded to therapy and achieved non-detectable plasma viremia within 4.5 weeks by bDNA (<500 copies/ml N=24) or 7.1 weeks by RNA-PCR (< 400 copies/ml N=14). 27/38 [71%] remain on therapy (20-37 mos.). 20/27 [74%] have sustained complete suppression (CS) of viremia to <50 copies/ml, whereas 7/27 (26%) have intermittent detectable plasma RNA (PS) at least twice (range 2-5, median=106.5 copies). To date, mean deltaCD4 is +266 cells/microliter (CS) and + 273 cells/microliter (PS) while mean CD4/8 ratios have increased from 0.7 (CS) and 0.6 (PS) to 1.3 and 1.5 respectively. After at least 20 months of therapy, mean levels of infectious HIV from the latent reservoir are 0.11 TCID50/10(6) CD4 in CS (N=12) and 1.6 TCID50/10(6) CD4 in PS (N=4). In situ hybridization did not detect HIV-RNA in tonsil/LN obtained after 20 mos. in 9/9 CS. 6/38 (16%) withdrew early due to AE's (3 R, 1 I, 2 R/S). 5/38 (13%) discontinued therapy late (>1 year, mean 17.2 mos.); 1 (I) due to virologic failure (M184V at baseline) and 4 (R) due to AE's. In 2/4 HIV-RNA rebounded to and beyond baseline whereas the remaining 2 have had low level viremia off therapy for 14 and 21 months. Their last HIV-RNA levels were 174 and <50 copies/ml respectively. Intermittent early therapy, currently advocated as a treatment strategy, did not uniformly result in control of virus replication as 2/4 have viremia off therapy. Early combination therapy can suppress plasma viremia to persistently undetectable levels for up to and beyond three years in many but not all NIs. Occasionally detectable low-level plasma viremia appears to be biologic and not assay related, as will be discussed, and highlights the need for intensification of regimens if complete control of HIV replication is to be achieved.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Anti-HIV Agents
- HIV
- HIV Infections
- HIV Protease Inhibitors
- HIV Seropositivity
- Indinavir
- Lamivudine
- Ritonavir
- Saquinavir
- Stavudine
- Viremia
- Virus Replication
- Zidovudine
- virology
Other ID:
UI: 102195401
From Meeting Abstracts