Increased detection of HIV-1 drug resistance at time of diagnosis by testing viral DNA with a sensitive assay.

Objective: HIV-1 drug resistance has been detected in 8%-24% of recently infected North Americans when assessed by consensus sequencing of plasma. We hypothesized that rates were likely higher but not detected because drug-resistant mutants are transmitted or regressed to levels below the limit of detection by consensus sequencing of HIV-1 RNA. Methods: Specimens from antiretroviral-naive individuals recently diagnosed with HIV-1 infection were compared at 15 codons to determine if testing of DNA using a sensitive oligonucleotide ligation assay (OLA) would detect drug resistance mutants not evident by consensus sequencing of serum. Results: HIV-1 drug resistance at 15 major resistance codons was greater by OLA compared with consensus sequencing: 18 of 104 vs.12 of 104 individuals (P ≤ 0.008) and 33 vs. 18 total mutations (P ≤ 0.001); increasing the rate of detection at these 15 codons by 83%. Additional mutations were detected by consensus sequencing at L33, M46, D67, V108, and K219 that were not assessed by OLA. Conclusions: The increased detection of drug-resistant HIV-1 by testing peripheral blood cells with a sensitive assay implies that both low and high levels of drug-resistant mutants are transmitted or persist in antiretroviral-naive individuals, suggesting that the clinical relevance of mutants persisting at both levels should be evaluated.