Moderate Levels of Pre-Treatment HIV-1 Antiretroviral Drug Resistance Detected in the First South African National Survey

Abstract

BackgroundIn order to assess the level of transmitted and/or pre-treatment antiretroviral drug resistance to HIV-1, the World Health Organization (WHO) recommends that regular surveys are conducted. This study’s objective was to assess the frequency of HIV-1 antiretroviral drug resistance in patients initiating antiretroviral treatment (ART) in the public sector throughout South Africa.MethodsA prospective cross-sectional survey was conducted using probability proportional to size sampling. This method ensured that samples from each province were proportionally collected, based on the number of patients receiving ART in each region. Samples were collected between March 2013 and October 2014. Pol sequences were obtained using RT-PCR and Sanger sequencing and submitted to the Stanford Calibrated Population Resistance tool v6.0.ResultsA total of 277 sequences were available for analysis. Most participants were female (58.8%) and the median age was 34 years (IQR: 29–42). The median baseline CD4-count was 149 cells/mm3 (IQR: 62–249) and, based on self-reporting, participants had been diagnosed as HIV-positive approximately 44 days prior to sample collection (IQR: 23–179). Subtyping revealed that 98.2% were infected with HIV-1 subtype C. Overall, 25 out of 277 patients presented with ≥1 surveillance drug resistance mutation (SDRM, 9.0%, 95% CI: 6.1–13.0%). Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were the most numerous mutations detected (n = 23). Only two patients presented with a protease inhibitor (PI) mutation. In four patients ≥4 SDRMs were detected, which might indicate that these patients were not truly ART-naïve or were infected with a multi-resistant virus.ConclusionsThese results show that the level of antiretroviral drug resistance in ART-naïve South Africans has reached moderate levels, as per the WHO classification. Therefore, regular surveys of pre-treatment drug resistance levels in all regions of South Africa is highly recommended to monitor the changing levels of pre-treatment antiretroviral drug resistance.

Assessment of HIV transfusion transmission risk in South Africa: a 10‐year analysis following implementation of individual donation nucleic acid amplification technology testing and donor demographics eligibility changes

“…Ten percent of the recently acquired HIV infections in donors had sequences consistent with transmitted drug resistance, similar to the finding of 9% ART drug‐resistant HIV in the first South African national survey of pretreatment resistance . There were too few non–subtype C cases to investigate any differences in drug resistance prevalence between subtypes.…”

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

“…One population-based study in South Africa found evidence of DRM in 7% of ART-naïve patients in rural KwaZulu-Natal in 2012, similar to our findings of DRMs in 8% of our 2014 North West population sequenced pre-treatment. Clinical cohort studies in sub-Saharan Africa have found a similar prevalence of drug resistance mutations in 6-11% of ART-naïve patients [11,20,22]. If our study participants reported ART initiation accurately, 8% would represent the baseline estimate of transmitted resistance in the population, most of which was NNRTI only (63.0%), with fewer mutations representing PI/ NRTI resistance (25.5%) and even fewer being single PI resistance (11.5%).…”

“…For these patients, DRM could lead to first-line failure. Recent studies have demonstrated that the prevalence of transmitted and acquired drug resistance is increasing in RSA [20]. The cost in a program as large as South Africa's makes baseline DRM testing prior to ART initiation to inform regimen selection largely infeasible; however NHLS has instituted alert reports for adherence counseling and DRM testing should be made available when treatment failure is evident.…”

“…While known factors contribute to virological failure (intermittent adherence to medication resulting in nonsuppressive drug levels in a setting of ongoing viral replication, transmitted resistance), it remains unknown what proportion of those undergoing virological failure can be attributed to each factor. Studies in sub-Saharan Africa have found drug resistance mutations in 6-14% of ARTnaïve patients [11,19,20], and 84-89% of those with virological failure who initiated ART ≥12 months prior [19,21]. Results from a systematic review and metaanalysis estimated a prevalence of pretreatment nonnucleotide reverse-transcriptase inhibitor (NNRTI) resistance of 11% in southern Africa [22].…”

Improving our understanding of antibiotic resistance: The relevance of surveillance at the population level

“…The approach of understanding the microbial resistance levels in the general population is not new: for example, it is being applied in HIV drug resistance surveillance. [10] In view of the enormous challenge posed by the surge in antibiotic resistance in SA and globally, new strategies are needed to improve our understanding of the antibiotic resistance landscape.…”