Safety of long-term interruption of successful antiretroviral therapy: the ATHENA cohort study.

We studied the dynamics of CD4 cell counts after the interruption of virologically successful highly active antiretroviral therapy (HAART) in 139 patients. Changes in CD4 cell counts during HAART interruption followed a biphasic pattern: an initial rapid decline during the first month followed by a slow decrease. During 48 weeks of follow-up mean CD4 cell counts remained just above the mean pre-HAART level. This limits the feasibility of structured treatment interruptions for patients with low nadir CD4 cell counts.

Evaluation of nevirapine and/or hydroxyurea with nucleoside reverse transcriptase inhibitors in treatment-naive HIV-1-infected subjects.

OBJECTIVE: To examine the effect of adding nevirapine (NVP) and/or hydroxyurea (HU) to a triple nucleoside analogue reverse transcriptase inhibitor (NRTI) regimen in terms of efficacy and tolerability. METHODS: : HIV-1-infected, treatment-naive adults were randomized, using a factorial design, to add NVP and/or HU to the triple NRTI backbone of zidovudine plus lamivudine plus abacavir. Primary endpoint was treatment failure, defined as having plasma HIV RNA levels > 50 copies/ml after week 24, or discontinuation of randomized treatment. Follow-up was 72 weeks. RESULTS: For the 229 subjects, median plasma HIV-1 RNA was 4.61 log10 copies/ml and median CD4 cell count was 269 x 10 cells/l. NVP users reached plasma HIV-1 RNA < 50 copies/ml more rapidly than subjects using no NVP (log-rank test; P = 0.011). In the as-treated analysis, 21.6% of subjects using NVP versus 48.8% using no NVP reached the primary endpoint (P = 0.013). In the intent-to-treat analysis, 83.3% of subjects using HU versus 73.0% using no HU experienced treatment failure (P = 0.060), while no difference was observed in the as-treated analysis (34.5 versus 36.7%). Differences in the intent-to-treat analysis were accounted for by toxicity: 52.6% of subjects using HU experienced toxicity leading to discontinuation of randomized treatment versus 28.7% of subjects using no HU. CONCLUSION: The use of NVP in addition to a triple NRTI regimen improved both short- and long-term antiretroviral efficacy. The use of HU significantly contributed to treatment failure because of toxicity.