Efficacy, safety, and tolerability of long-term combination antiretroviral therapy in asymptomatic treatment-naïve adults with early HIV infection.
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.


METHODS
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.


CONCLUSIONS
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.
McMahon
Deborah K
DK
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Dinubile
Mark J
MJ
Meibohm
Anne R
AR
Marino
Deborah R
DR
Robertson
Michael N
MN
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019469:Indinavir / Q000009:adverse effects / Q000627:therapeutic use; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010342:Patient Acceptance of Health Care; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D016312:Treatment Refusal; D019562:Viral Load; D014766:Viremia; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
D019380:Anti-HIV Agents; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir