Access to nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line antiretroviral therapy (ART) for HIV has been increasing in Peru since a national ART program was initiated in 2004. Between 2007 and 2009, we found a 1% prevalence of pre-ART HIV drug resistance (PDR) among antiretroviral (ARV)-naive Peruvians. Given that PDR has been associated with virologic failure (VF) of ART, in 2014-2015 we enrolled a follow-up cohort at the same institution to determine whether the rate of transmitted resistance had increased and compared virologic outcomes of those with and without PDR. Blood specimens from ARV-naive individuals were assessed for PDR to NNRTI-based ART by an oligonucleotide ligation assay (OLA) sensitive to 2% mutant within an individual's HIV quasispecies at reverse transcriptase codons M41L, K65R, K103N, Y181C, M184V, and G190A, and by Sanger consensus sequencing (CS). Rates of VF (plasma HIV RNA >200 copies/mL) were compared between those with and without PDR. Among 122 ARV-naive adults, PDR was detected by OLA in 17 (13.9%) adults. Compared with the 2007-2009 cohort, the proportion with PDR at OLA codons was significantly increased (p <.001). A total of 11 of 19 OLA mutations conferring high-level drug resistance were also detected by CS, and 8 additional participants had mutations encoding low-level resistance detected by CS for a total of 25 participants (20.5%). VF at month 6 of NNRTI-ART appeared greater in participants with versus without PDR [4/18 (22.2%) vs. 3/71 (4.2%); p =.03]. An increasing prevalence of PDR was detected among ARV-naive Peruvians. Studies are needed to determine risks of specific PDR mutations.
Bibliographical noteFunding Information:
Funds for this work came from the following organizations: National Institutes of Health, P30 AI027757 and UM1 AI106716 (L.M.F.), and The HIV Research Trust ( J.S.). The remaining authors have no conflicts to declare.
The study team acknowledges and appreciates the participants’ dedication to the study. This study was supported by The HIV Research Trust (HIVRT), CFAR P30 AI027757, and IMPAACT UM1 AI106716 awards.
© 2019, Mary Ann Liebert, Inc., publishers.
- oligonucleotide ligation assay
- pre-ART HIV drug resistant