Ruxrungtham K, Kroon E, Ungsedhapand C, Duncombe C, Rongkavilit C, Teeratakulpisarn S, Khongphattanayothin M, Ubolyam S, Emery S, Cooper D, Lange J; Australasian Society for HIV Medicine. Conference.
Annu Conf Australas Soc HIV Med. 1999 Dec 9-11; 11: 135 (abstract no. P21).
HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Prior study HIV-NAT 002 evaluated safety and efficacy of several doses of dd/d4T in 78 treatment naive Thai HIV+ participants with baseline CD4+ counts 150-350/mm3. After 48 weeks, of 71 participants remaining on study, 68 were responding to ddI/d4T according to the protocol definition: 45/71 had HIV-1 RNA < 500 copies/ml and 23/71 had HIV-RNA < 1 log10 rise above the nadir. (Quantiplex v.2.0). These 68 were randomized to early (at week 48) vs. deferred (when failing ddI/d4T = rise in HIV-RNA >/= 1 log10 above nadir) switching to AZT/3TC. The aim of switching was to determine whether switching to an alternative double NRTI regimen before apparent failure results in better virological and immunological outcome compared to switching at the time of treatment failure. Open-label study of 96 weeks. 68 participants were randomized to early versus deferred switch from ddI/d4T to AZT/3TC. Early switchers will subsequently switch back to ddI/d4T again when failing AZT/3TC. When they fail both regimens according to above definition, participants receive hydroxyurea 500 mg BID added to the last received nucleoside combination. Follow-up was every 8 weeks for 48 weeks and every 12 weeks thereafter until week 96 + 4 weeks after any switch. 31 participants were randomized to early switch to AZT/3TC, 37 remained on ddI/d4T; 3 participants, who failed ddI/d4T by week 48 on the prior study 002, were excluded from randomization and received AZT/3TC. 67 randomized participants remain on study. (one deferred switcher lost to F/U). Both ddI/d4T and AZT/3TC are well tolerated. Three serious adverse events were reported: 1 anemia grade 4 while receiving AZT/3TC, 1 amylase grade 3 and 1 appendicitis while receiving ddI/d4T. From baseline to 48 weeks on this protocol, a total of 10/37 deferred switchers were switched to AZT/3TC because of failing ddI/d4T. Of 26 participants still on ddI/d4T at week 48 (96 weeks after starting treatment with ddI/d4T), 21 (58%) still have HIV-RNA < 500 copies/nil. Of the 31 early switchers to AZT/3TC, 21 had HIV-RNA < 500 copies/ml at baseline compared to 16 (53%) at week 48 (not significant). At baseline, mean CD4+ cells were 406/mm3 in the deferred switchers compared to 400/mm3 in the early switchers (not significant). At week 48, CD4+ cell counts were 400/mm3 vs. 323/mm3 (p=0.018). All participants are being followed for an additional 48 weeks until week 96. Both strategies (early vs. deferred switch) are well tolerated. After 48 weeks, no statistically significant difference is seen between the two strategies in number of events experienced or in suppression of HIV-RNA. Mean CD4+ cells remain higher in the deferred switchers. This may be due to less exposure to AZT (and related myelosuppression) in this group.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Anti-HIV Agents
- CD4 Lymphocyte Count
- CD4-Positive T-Lymphocytes
- Didanosine
- HIV
- HIV Infections
- HIV Protease Inhibitors
- HIV Seropositivity
- HIV-1
- Hydroxyurea
- Lamivudine
- Stavudine
- Zidovudine
- reverse transcriptase, Human immunodeficiency virus 1
Other ID:
UI: 102242808
From Meeting Abstracts