Prevalence and Predictive Value of Intermittent Viremia With Combination HIV Therapy

• Published in: JAMA : the journal of the American Medical Association 2001-07, Vol.286 (2), p.171-179
• Main Authors: Havlir, Diane V, Bassett, Roland, Levitan, Diane, Gilbert, Peter, Tebas, Pablo, Collier, Ann C, Hirsch, Martin S, Ignacio, Caroline, Condra, Jon, Günthard, Huldrych F, Richman, Douglas D, Wong, Joseph K
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; antiretroviral therapy; Antiretroviral Therapy, Highly Active; Antiviral agents; Biological and medical sciences; Clinical trials; Drug Resistance, Microbial; Drug therapy; HIV; HIV - drug effects; HIV - genetics; HIV Infections - drug therapy; HIV Infections - physiopathology; HIV Infections - virology; Human immunodeficiency virus; Humans; Indinavir - therapeutic use; Lamivudine - therapeutic use; Medical sciences; Pharmacology. Drug treatments; Predictive Value of Tests; Prevalence; Proportional Hazards Models; Retrospective Studies; RNA, Viral - blood; Viral Load; Viremia - physiopathology; Virus Replication; Zidovudine - therapeutic use
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.286.2.171

CONTEXT In HIV-infected patients having virologic suppression (plasma HIV RNA 200 copies/mL). DESIGN AND SETTING Retrospective analysis of subjects in well-characterized cohorts, the AIDS Clinical Trials Group (ACTG) 343 trial of induction-maintenance therapy (August 1997 to November 1998) and the Merck 035 trial (ongoing since March 1995). PATIENTS Two hundred forty-one ACTG 343 patients, of whom 101 received triple-drug therapy throughout the study, and a small group of 13 patients from Merck 035 having virologic suppression after 6 months of indinavir-zidovudine-lamivudine. MAIN OUTCOME MEASURES Association of intermittent viremia (plasma HIV RNA >50 copies/mL with a subsequent measure 200 copies/mL) in both study groups; evidence of drug resistance in 7 patients from the small (n = 13) study group with long-term follow-up. RESULTS Intermittent viremia occurred in 96 (40%) of the 241 ACTG 343 patients of whom 32 (13%) had 2 consecutive HIV RNA values >50 copies/mL during the median 84 weeks of observation (median duration of observation after first intermittent viremia episode was 46 weeks). Of the 101 individuals receiving triple-drug therapy throughout, 29% had intermittent viremia; the proportion of episodes occurring during the maintenance period was 64% for the entire cohort and 68% for the group not receiving triple-drug therapy throughout vs 55% for those who did (P = .25). Intermittent viremia did not predict virologic failure: 10 (10.4%) of 96 patients with and 20 (13.8%) of 145 patients without intermittent viremia had virologic failure (relative risk, 0.76; 95% confidence interval [CI], 0.29-1.72). In a Cox proportional hazards model, the risk for virologic failure was not significantly greater in the ACTG 343 patients with intermittent viremia (hazard ratio, 1.28; 95% CI, 0.59-2.79). Median viral load in 10 ACTG 343 patients assessed between 24 and 60 weeks of therapy using an ultrasensitive 2.5-copies/mL detection level assay was 23 copies/mL in those with intermittent viremia