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

Abstract

Nucleotide mixtures in human immunodeficiency virus type 1 (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 reverse transcriptase) or preantiretroviral 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 with a preventative vaccine targeting cell-mediated immunity.

Trial registration: ClinicalTrials.gov NCT00080106.

Figure 1

Comparison of ambiguous nucleotide frequency between HIV sequenced during initial viremia (tp1, ATI wk 2–8) and the end of the ATI (tp2, ATI week 16). A, Median and Wilcoxon matched-pairs signed rank test P-values for the percentage of ambiguous nucleotides within gag. B, Median and Wilcoxon matched-pairs signed rank test P-values for the percentage of ambiguous nucleotides within reverse transcriptase (RT). ATI, analytic treatment interruption.

Figure 2

Comparison of ambiguous nucleotide frequency between HIV sequenced from samples collected pre-ART versus at the end of the ATI (ATI tp2, ATI week 16). A, Median and Wilcoxon matched-pairs signed rank test P-values for the percentage of ambiguous nucleotides within gag. B, Median and Wilcoxon matched-pairs signed rank test P-values for the percentage of ambiguous nucleotides within reverse transcriptase (RT). ATI, analytic treatment interruption; ART, antiretroviral therapy.