12th Conference on Retroviruses and Opportunistic Infections Boston, Massachusetts - February 22-25, 2005

Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 22

Cissy Kityo Mutuluuza¹, S Walker², P Kaleebu³, V Robertson⁴, R Enzama¹, A Burke², D Yirrell³, A Reid⁴, P Munderi³, D Gibb², C Gilks⁵, P Mugyenyi¹, H Grosskurth³, J Hakim⁴, D Pillay⁶, and the DART Trial
¹Joint Clin Res Ctr, Kampala, Uganda; ²Med Res Council Clin Trials Unit, London, UK; ³Med Res Council/Uganda Virus Res Inst Prgm on AIDS, Entebbe, Uganda; ⁴Univ of Zimbabwe, Harare; ⁵Imperial Coll, London, UK; and ⁶Univ Coll, London, UK

BACKGROUND: DART (Development of Anti-Retroviral Therapy in Africa) is a randomized trial of monitoring strategies and planned interruptions (after 24 weeks) in 3300 symptomatic ART-naïve adults with CD4 < 200 cells/mm³ from 3 clinical sites (2 in Uganda, 1 in Zimbabwe). Of 3263 patients enrolled to October 1, 2004, 2466 (76%) have received zidovudine (ZDV)+lamivudine (3TC)+ tenofovir DF (TDF) first-line. As there are few viral load data on this regimen, we conducted a 24-week virology sub-study (n = 300).

METHODS: Plasma HIV-1 RNA was retrospectively assayed at 0, 4, 12, and 24 weeks in 100 patients at each site (50 with baseline CD4 of 1 to 99 and 50 of 100 to 199 cells/mm³) using the Roche Amplicor assay. All assays have been performed in Africa under cross-site quality assurance. Here we present results from Ugandan patients, based on available samples (intention to treat).

RESULTS: Of the 200 Ugandan adults, 68% were women, median age was 37 years, and median baseline CD4 100 cells/mm³ (IQR 36 to 144). Median HIV RNA was 333,600 copies/mL (IQR 106,000 to 662,300 copies/mL), and mean 5.4 log₁₀ copies/mL (SD 0.7). At week 24 (n = 188), 54% achieved < 50 copies/mL and 72% < 400 copies/mL (intent to treat M = F 51% and 68%, respectively). Corresponding proportions were 14% and 40% at week 4 (n = 193), and 49% and 85% at week 12 (n =187). Mean decreases from baseline were 2.5, 3.6, and 3.5 log₁₀ copies/mL at weeks 4, 12, and 24, respectively, and median CD4 increases 83 and 88 cells/mm³ at weeks 12 and 24. Six patients died before 24 weeks: 2 died before 4 weeks, the other 4 had final HIV RNA before death of < 1000 copies/mL. At 12 and 24 weeks, 10% and 19% had HIV RNA ≥ 1000 copies/mL (6% and 15% ≥ 2000 copies/mL). In the preceding 12 weeks, 28 of 37 patients with HIV RNA ≥ 1000 copies/mL at week 24 had been off ART for > 1 week (n = 4), had incomplete adherence (n = 23), became pregnant (n = 3), or had severe adverse events, grade 3/4 adverse events, or other ART-modifying adverse events (n = 6) or malaria (n = 12). Preliminary 24 week data from 100 patients in Zimbabwe are similar.

CONCLUSIONS: Triple nucleoside regimens are highly relevant in resource limited settings: 27% of DART patients have a prior diagnosis of pulmonary or extra-pulmonary tuberculosis, the latter also being the third most frequently reported WHO grade 4 event after baseline. ZDV+3TC+TDF has good virological efficacy in advanced HIV disease, comparable to that reported after HAART introduction in equivalent industrialised populations, but against a background of intercurrent illnesses. Evaluation of genotypes in those with HIV RNA ≥ 1000 copies/mL at 24 weeks, and response to 48 weeks are ongoing.

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Copyright © 2005 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.