Efficacy, Safety, and Tolerability of Long-Term Combination Antiretroviral Therapy in Asymptomatic Treatment-Naïve Adults with Early HIV Infection

Abstract

Background: Initiating antiretroviral therapy in the early stages of HIV infection may afford benefits over delaying treatment. We evaluated the long-term efficacy and tolerrability of indinavir, zidovudine, and lamivudine begun in asymptomatic treatment-naïve adults with baseline CD4 counts ≥500 cells/mm³ and HIV (v)RNA levels >1000 copies/mL in an open-label, noncomparative study. Method: Proportions of participants with suppressed viremia were assessed using observed data, a model derived from generalized estimating equations counting only treatment-related discontinuations as failures (TRD=F), and a strict intention-to-treat analysis counting all noncompleters as failures (NC=F). Results: 199 participants (median age 34; 79% men; 61% White) with a median CD4 count of 574 (range 130-1204) cells/mm³ and vRNA level of 3.89 (range 2.30-6.50) log₁₀ copies/mL were followed up to 319 weeks. Overall, 142 participants (71%) discontinued the study after a median time of 112 weeks, including 4 (2%) due to unsuppressed viremia and 40 (20%) due to adverse events. After 156 weeks, 98%, 76%, and 53% of participants achieved <400 vRNA copies/mL based on observed data, TRD=F, and NC=F analyses, respectively; corresponding percentages <50 copies/mL were 93%, 72%, and 51%. Mean CD4 count increased by >250 cells/mm³ from baseline. Nausea (69%), fatigue (49%), diarrhea (37%), headache (28%), abdominal pain (28%), hematuria (27%), flank pain (26%), and hyperbilirubinemia (25%) were the most common drug-related adverse events. Conclusion: A minority of participants in this study completed follow-up. Despite durable HIV suppression in most participants remaining on treatment, treatment fatigue may interfere with long-term therapy in asymptomatic HIV-infected patients.

Keywords:

• early HIV infection
• HAART
• indinavir
• long-term efficacy
• tolerability