Abstract
BackgroundUnderstanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa.MethodsWe conducted HIV drug resistance genotyping and ART analyte testing on dried blood spots (DBS) from HIV-positive adults participating in a 2014 survey in North West Province. Among those with virologic failure (> 5000 copies/mL), we describe frequency of DRM to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI), report association of resistance with antiretroviral therapy (ART) status, and assess resistance to first and second line therapy. Analyses are weighted to account for sampling design.ResultsOverall 170 DBS samples were assayed for viral load and ART analytes; 78.4% of men and 50.0% of women had evidence of virologic failure and were assessed for drug resistance, with successful sequencing of 76/107 samples. We found ≥1 DRM in 22% of participants; 47% were from samples with detectable analyte (efavirenz, nevirapine or lopinavir). Of those with DRM and detectable analyte, 60% showed high–level resistance and reduced predicted virologic response to ≥1 NRTI/NNRTI typically used in first and second-line regimens.ConclusionsDRM and predicted reduced susceptibility to first and second-line regimens were common among adults with ART exposure in a rural South African population-based sample. Results underscore the importance of ongoing virologic monitoring, regimen optimization and adherence counseling to optimize durable virologic suppression.
Highlights
Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective
To understand the discrepancy between reported antiretroviral therapy (ART) intake and viral suppression and assess contributing factors to the low suppression rates, we assessed all HIV-positive participants for antiretroviral drug exposure and performed drug resistance testing among those not suppressed. In this manuscript we examine the potential contribution of drug resistance mutations for low viral suppression in this HIV-positive, rural South African, population-based sample, discussing implications for future programming
Among 182 seropositive participants confirmed by serial rapid testing or HIV DNA polymerase chain reaction (PCR), dried blood spots (DBS) were available for viral load and analyte testing from 170 participants (11 did not provide DBS and one had insufficient specimen for genotyping; Fig. 1)
Summary
Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa. To reap the benefits of ART and achieve widespread viral suppression, both access to and consistent adherence to medication is critical for achieving durable viral suppression and preventing drug resistance [3, 7,8,9,10]. The recent Universal Test and Treat trial in Kwa Zulu Natal noted high viral suppression rates for those on ART (85%), but an overall suppression rate of 49% among all PLHIV in 2016 [17], lower than the 2016–2017 PopART trial estimates of 63–72% virally suppressed in community cohorts [18]
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