Effect of HIV-1 subtype on virologic and immunologic response to starting highly active antiretroviral therapy

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.