Viral genetic heterogeneity in HIV-1-infected individuals is associated with increasing use of HAART and higher viremia

Objective: To assess the correlation between the outgrowth of mutant viruse s (viral genetic heterogeneity), highly active antiretroviral therapy (HAAR T), and plasma HIV-1 RNA in a population-based observational cohort study. Design: The study population consisted of 42 HIV-1-infected individuals rec eiving at least two nucleotide reverse transcriptase (RT) inhibitors and on e or more protease inhibitors at study entry. There were no restrictions on antiretroviral therapy after enrollment Methods: Plasma samples were obtained from subjects at baseline, at therapy changes, and at quarterly intervals for quantitation of HIV-1 RNA levels a nd for sequence determination of the entire protease coding region and the first 235 codons of the reverse transcriptase coding region. Data were anal yzed using the generalized estimating equation method for longitudinal data and using linear regression analysis. Results: With increased time on HAART there were significant increases in t he number of total HIV-1 mutations in the regions sequenced (P = 0.010). Th ere were significant correlations between the increases in the plasma HIV-1 RNA levels and the numbers of total mutations and reverse transcriptase mu tations (P = 0.007 and 0.021, respectively). Conclusions: The number of HIV-1 mutations increased over time. Failure of HAART in this study population was correlated with outgrowth of virus with numerous mutations in the reverse transcriptase and protease coding regions . Phenotypic results correlated with genotypic results, showing decreased s usceptibility to antiretrovirals over time in the majority of this populati on during HAART. Both synonymous and non-synonymous mutations were observed , with a higher incidence of non-synonymous mutations occurring at codons a ssociated with drug resistance. (C) 2000 Lippincott Williams & Wilkins.