Evaluation of HIV-1 ambiguous nucleotide frequency during antiretroviral treatment interruption.

Nucleotide mixtures in HIV-1 population sequences reflect sequence diversity. We evaluated gag and pol ambiguous nucleotide frequencies during an analytic treatment interruption (ATI) in an HIV-1 therapeutic vaccine study. The proportion of ambiguous nucleotides was significantly higher at ATI week 16 than at either the time of first detectable viremia (P<0.001 gag and P=0.03 RT) or pre-antiretroviral therapy (P=0.007 gag). No significant differences were observed in the proportion of ambiguous nucleotides between those receiving vaccine and placebo. Increased HIV diversity during the ATI may represent a potentially higher barrier to success for a therapeutic as compared to a preventative vaccine targeting cell-mediated immunity.