High-Levels of Acquired Drug Resistance in Adult Patients Failing First-Line Antiretroviral Therapy in a Rural HIV Treatment Programme in KwaZulu-Natal, South Africa

Abstract

ObjectiveTo determine the frequency and patterns of acquired antiretroviral drug resistance in a rural primary health care programme in South Africa.DesignCross-sectional study nested within HIV treatment programme.MethodsAdult (≥18 years) HIV-infected individuals initially treated with a first-line stavudine- or zidovudine-based antiretroviral therapy (ART) regimen and with evidence of virological failure (one viral load >1000 copies/ml) were enrolled from 17 rural primary health care clinics. Genotypic resistance testing was performed using the in-house SATuRN/Life Technologies system. Sequences were analysed and genotypic susceptibility scores (GSS) for standard second-line regimens were calculated using the Stanford HIVDB 6.0.5 algorithms.ResultsA total of 222 adults were successfully genotyped for HIV drug resistance between December 2010 and March 2012. The most common regimens at time of genotype were stavudine, lamivudine and efavirenz (51%); and stavudine, lamivudine and nevirapine (24%). Median duration of ART was 42 months (interquartile range (IQR) 32–53) and median duration of antiretroviral failure was 27 months (IQR 17–40). One hundred and ninety one (86%) had at least one drug resistance mutation. For 34 individuals (15%), the GSS for the standard second-line regimen was <2, suggesting a significantly compromised regimen. In univariate analysis, individuals with a prior nucleoside reverse-transcriptase inhibitor (NRTI) substitution were more likely to have a GSS <2 than those on the same NRTIs throughout (odds ratio (OR) 5.70, 95% confidence interval (CI) 2.60–12.49).ConclusionsThere are high levels of drug resistance in adults with failure of first-line antiretroviral therapy in this rural primary health care programme. Standard second-line regimens could potentially have had reduced efficacy in about one in seven adults involved.

Assessment of Second-Line Antiretroviral Regimens for HIV Therapy in Africa

“…In most settings, treatment is monitored clinically and with the use of CD4+ counts, with typically late detection of treatment failure, accompanied by substantial drug resistance. 3,4 Evidence supporting the WHO-recommended standardized second-line regimen (a boosted protease inhibitor and two NRTIs) is of moderate quality, 3,5 with particular uncertainty around the net contribution of NRTIs. The efficacy of NRTIs is likely to be compromised by cross-resistance from multiple mutations arising during first-line therapy, and the drugs carry well-recognized risks of toxic effects.…”

HIV Prevention Counseling Intervention Delivered During Routine Clinical Care Reduces HIV Risk Behavior in HIV-Infected South Africans Receiving Antiretroviral Therapy

“…Specifically, these individuals, like PLWH everywhere, are variably adherent to ART 8 and to safer sex practices 9–11 , despite clinic-based standard-of-care ART education and counseling and safer sex promotion. Treatment failure with continuing detectable viremia among South African PLWH on ART is not uncommon 12,13 and ART resistance has occurred in a sizable proportion of individuals who have been treated and have experienced therapeutic failure 14–19 . South African PLWH on ART who have experienced treatment failure may serve as relatively healthy but infectious vectors for transmission of drug susceptible and drug resistant virus and may contribute to the maintenance or exacerbation of South Africa’s HIV epidemic.…”

HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission

“…The prevalence of transmitted NNRTI resistance in KwaZulu-Natal has increased from below 5% in 2007 to 5%–15% in 2010 with the most commonly detected mutation being the K103NS. 23 Third, the number of patients with NNRTI mutations among those failing NNRTI-based ART is high in rural South Africa, ie, 82% in both adults 42 and children, 43 with K103NS again being the most commonly detected NNRTI mutation. Finally, the underestimation of ART resistance using conventional sequencing and the rising evidence of the clinical impact of minority NNRTI mutations remains an important consideration.…”