The role of drug resistance in poor viral suppression in rural South Africa: findings from a population-based study

Abstract

Background: 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. Methods:We 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.Results: Overall 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.Conclusions: DRM 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.

Tenofovir diphosphate levels in dried blood spots are associated with virologic failure and resistance to first‐line therapy in South Africa: a case–control cohort study

“…Our findings are also consistent with a clinical cohort of PWH in the United States, where TFV-DP concentrations in study participants who developed new drug resistance-associated mutations were ∼40% lower than those observed in participants who were virologically suppressed [21,24]. These results are also similar to other studies that assessed ART adherence using qualitative [31,32] and other cumulative [15,33] pharmacologic measures. For studies where quantitative measures of cumulative ART adherence were used, an analysis of young PWH in Tanzania demonstrated that participants who failed EFV and NVP treatment without resistance had hair drug concentrations below the limit of detection [15].…”

Resource and infrastructure challenges on the RESIST-2 Trial: an implementation study of drug resistance genotype-based algorithmic ART switches in HIV-2-infected adults in Senegal

“…Several studies have used DBS-based testing to perform population-level assessments of the frequency of drug resistance in HIV-1 [ 23 – 25 ] or to analyze ART outcomes in HIV-1-infected patients [ 26 – 28 ]. However, to our knowledge, no studies have attempted to use DBS testing to prospectively inform treatment decisions for HIV-1 or HIV-2-infected individuals in a programmatic setting.…”

HIV viral load suppression following intensive adherence counseling among people living with HIV on treatment at military-managed health facilities in Uganda

“…A review by WHO found sub-optimal levels of viral load suppression (VLS) among PLHIV on ART in 2013 in low and middle income countries The two most recognized barriers to viral suppression are non-adherence to treatment and age, with younger patients having higher failure rates (Bulage et al, 2017). Having less than 89% adherence to therapy increases the risk of non-suppression and development of resistance mutations as compared with perfect adherence (Bartlett, 2004;Lippman et al, 2020;von Wyl et al, 2013). Depression, alcohol use and cost of travel to the clinic have also been shown to increase risk of non-suppression in some studies (Bukenya et al, 2019;Cerutti et al, 2016;Iacob et al, 2017;Williams et al, 2016).…”