Effect of HIV‐1 Subtype on Virologic and Immunologic Response to Starting Highly Active Antiretroviral Therapy

Abstract

It has been proposed that subtype-related human immunodeficiency virus type 1 (HIV-1) variability may influence virologic and immunologic responses to highly active antiretroviral therapy (HAART). Studies to date, however, have described treatment outcomes predominantly in persons with subtype B infection or compared subtype B with diverse non-B subtypes grouped together. With use of data from the linked UK Collaborative Group on HIV Drug Resistance and the UK Collaborative HIV Cohort Study databases, time to viral load undetectability (viral load, <50 copies/mL), time to virologic rebound (viral load, >1000 copies/mL), and increases in the CD4 cell count were compared for a median of 39 months (interquartile range, 23-67 months) in drug-naive patients infected with subtype B (n=1550), subtype C (n=272), subtype A (n=66), circulating recombinant form AG (n=57), or subtype D (n=41) disease who started HAART. Overall, 1906 (90%) of 2116 patients achieved viral load undetectability within 12 months after they started HAART, of whom 335 (18%) subsequently experienced virologic rebound. In adjusted analyses, viral load suppression occurred more rapidly in patients infected with subtype C (hazard ratio, 1.16; 95% confidence interval, 1.01-1.33; P=.04) and subtype A (hazard ratio, 1.35; 95% confidence interval, 1.04-1.74; P=.02) relative to subtype B infection. The virologic rebound occurred marginally more rapidly in patients with subtype C infection (hazard ratio, 1.40; 95% confidence interval, 1.00-1.95; P=.05), but the hazard of virologic rebound was similar with other subtypes. Although persons with subtype B infection showed higher baseline CD4 cell counts and maintained the advantage throughout therapy, CD4 cell count recovery occurred at similar rates with all subtypes. Patients infected with prevalent non-B subtypes were as likely to achieve viral load suppression as persons infected with subtype B and showed comparable rates of CD4 cell count recovery. HAART achieves excellent outcomes regardless of the infecting subtype.