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

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

Male circumcision and Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis: observations after a randomised controlled trial for HIV prevention

International audienceOBJECTIVE: To assess the association between male circumcision and Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis using data from a male circumcision randomised controlled trial. METHODS: We used data collected during the male circumcision trial conducted in Orange Farm (South Africa) among men aged 18-24 years. Altogether, 1767 urine samples collected during the final follow-up visit were analysed using PCR. Prevalence of N gonorrhoeae, C trachomatis and T vaginalis was assessed as a function of male circumcision using odds ratios (OR) given by univariate and multivariate logistic regression. RESULTS: In an intention-to-treat analysis, prevalence of N gonorrhoeae, C trachomatis and T vaginalis among intervention and control groups were 10.0% versus 10.3% (OR 0.97; p = 0.84), 2.1% versus 3.6% (OR 0.58; p = 0.065) and 1.7% versus 3.1% (OR 0.54; p = 0.062), respectively. The association between T vaginalis and male circumcision remained borderline when controlling for age, ethnic group, number of lifetime partners, marital status, condom use and HIV status (AOR 0.48; p = 0.069). In the as-treated analysis, this association became significant (OR 0.49, p = 0.030; AOR 0.41, p = 0.030). CONCLUSIONS: This study demonstrates for the first time that male circumcision reduces T vaginalis infection among men. This finding explains why women with circumcised partners are less at risk for T vaginalis infection than other women. The protective effect on T vaginalis is an additional argument to recommend male circumcision in Africa where it is acceptable

Surveillance of Transmitted HIV-1 Drug Resistance in Gauteng and KwaZulu-Natal Provinces, South Africa, 2005-2009

Surveillance of human immunodeficiency virus type 1 transmitted drug resistance (TDR) was conducted among pregnant women in South Africa over a 5-year period after the initiation of a large national antiretroviral treatment program. Analysis of TDR data from 9 surveys conducted between 2005 and 2009 in 2 provinces of South Africa suggests that while TDR remains low (<5%) in Gauteng Province, it may be increasing in KwaZulu-Natal, with the most recent survey showing moderate (5%-15%) levels of resistance to the nonnucleoside reverse transcriptase inhibitor drug clas

A comparison of South African national HIV incidence estimates: A critical appraisal of different methods

BACKGROUND: The interpretation of HIV prevalence trends is increasingly difficult as antiretroviral treatment programs expand. Reliable HIV incidence estimates are critical to monitoring transmission trends and guiding an effective national response to the epidemic. Methods and FINDINGS: We used a range of methods to estimate HIV incidence in South Africa: (i) an incidence testing algorithm applying the Limiting-Antigen Avidity Assay (LAg-Avidity EIA) in combination with antiretroviral drug and HIV viral load testing; (ii) a modelling technique based on the synthetic cohort principle; and (iii) two dynamic mathematical models, the EPP/Spectrum model package and the Thembisa model. Overall, the different incidence estimation methods were in broad agreement on HIV incidence estimates among persons aged 15-49 years in 2012. The assay-based method produced slightly higher estimates of incidence, 1.72% (95% CI 1.38 - 2.06), compared with the mathematical models, 1.47% (95% CI 1.23 - 1.72) in Thembisa and 1.52% (95% CI 1.43 - 1.62) in EPP/Spectrum, and slightly lower estimates of incidence compared to the synthetic cohort, 1.9% (95% CI 0.8 - 3.1) over the period from 2008 to 2012. Among youth aged 15-24 years, a declining trend in HIV incidence was estimated by all three mathematical estimation methods. CONCLUSIONS: The multi-method comparison showed similar levels and trends in HIV incidence and validated the estimates provided by the assay-based incidence testing algorithm. Our results confirm that South Africa is the country with the largest number of new HIV infections in the world, with about 1 000 new infections occurring each day among adults aged 15-49 years in 2012

HIV care coverage among HIV-positive adolescent girls and young women in South Africa: Results from the HERStory Study

Background. Health service coverage cascades measure the proportion of a population in need of a service that experienced a positive health outcome from the service, and enable tracking of progress in achieving universal health coverage and inequities in care coverage.Objectives. To investigate HIV care coverage among HIV-positive adolescent girls and young women (AGYW) living in six South African districts, compare coverage by age and socioeconomic status (SES), and investigate other associated factors including participation in a combination HIV prevention intervention.Methods. The HERStory Study was an evaluation of the combination intervention, comprising a representative household survey of AGYW aged 15 - 24 years living in six intervention districts. From September 2017 to November 2018, biological, sociodemographic and behavioural data were collected. HIV-positive status, initiation of antiretroviral therapy (ART) and viral suppression were determined through laboratory tests (enzyme-linked immunosorbent assay for HIV antibodies, antiretroviral (ARV) metabolites and viral load (VL) testing). Viral suppression was defined as a VL &lt;1 000 copies/mL. Knowledge of HIV-positive status was self-reported, and participants testing positive for ARV metabolites were assumed to have known their HIV-positive status. Unconditional HIV care cascades were created, stratified by age and SES. We used Pearson’s χ2 tests corrected for survey-based analysis to describe factors associated with knowledge of HIV status, and being on ART.Results. Of the 4 399 participants, 568 were HIV-positive (12.4%), of whom 60.8% (95% confidence interval (CI) 57.1 - 64.5) knew their status, 50.6% (95% CI 46.6 - 54.0) were on ART, and 62.1% (95% CI 58.4 - 65.9) were virally suppressed. Most participants (84.9%) were in the lower SES group, and they had better coverage than the higher SES group: 61.9% (95% CI 58.3 - 65.4) knew their status, 52.1% (95% CI 48.4 - 55.9) were on ART, and 64.9% (95% CI 61.3 - 68.4) were virally suppressed, compared with 55.0% (95% CI 42.1 - 68.0), 40.0% (95% CI 29.2 - 50.8), and 46.6% (95% CI 34.5 - 58.7), respectively. Participants aged 15 - 19 years had slightly inferior coverage to the 20 - 24-year-old group: 57.5% knew their status, 46.1% were on ART and 59.5% were virally suppressed, compared with 62.3%, 52.2% and 63.3%.Conclusions. These findings emphasise the need to close the gaps in HIV care coverage among AGYW, of whom only 61% knew their HIV-positive status and only 62% were virally suppressed. There is pro-poor inequality in HIV care coverage, with those in lower socioeconomic groups more likely to be virally suppressed

Association between viral suppression during the third trimester of pregnancy and unintended pregnancy among women on antiretroviral therapy : results from the 2019 antenatal HIV Sentinel Survey, South Africa

OBJECTIVES : About half of the pregnancies among women living with HIV (WLWH) receiving antiretroviral therapy (ART) in sub-Saharan African countries are reported to be unintended. Unintended pregnancy is associated with late initiation of antenatal care (ANC), and may delay provision of viral load monitoring services, antenatal adherence counselling and support, and other services that promote sustained viral suppression throughout pregnancy. This study examines the association between unsuppressed viral load during the third trimester of pregnancy and unintended pregnancy among women who initiated ART before pregnancy. METHODS : This was an analysis of data from a national antenatal survey conducted at 1 589 public health facilities in South Africa between 1 October and 15 November 2019. Consenting pregnant women aged 15–49 years attending ANC during the survey period were enrolled. Demographic and clinical data were collected through interview and medical record review. Pregnancy intention was assessed using two questions from the London Measure of Unplanned Pregnancy, and responses were categorized as “unintended,” “undecided,” and “intended.” Blood specimens were collected from all women and tested for HIV; and if positive, a viral load test was performed. A survey domain-based poisson regression model examined the association between unsuppressed viral load during the third trimester of pregnancy and unintended pregnancy among women who initiated ART before pregnancy. Viral suppression was defined as viral load <50 copies/mL. RESULTS : Of 10 901 WLWH with viral load data available, 63.3% (95% confidence interval (CI): 62.4%-64.1%) were virally suppressed. Among the 2 681 women (representing 24.1% of all WLWH with viral load data) who initiated ART before pregnancy and were in their third trimester at the time of enrolment, 74.4% (95% CI: 73.0%-75.8%) were virally suppressed. In the same population, the proportion virally suppressed was lower among women whose current pregnancies were unintended (72.1%, 95% CI: 70.1%-74.1%) compared to women whose pregnancies were intended (78.3%, 95% CI: 75.9%-80.5%). In multivariable analyses adjusted for age, gravity, marital status, education, location of facility and syphilis status, unintended pregnancy was associated with unsuppressed viral load during the third trimester (adjusted relative risk: 1.3, 95% CI: 1.1–1.4) among women who initiated ART before pregnancy. CONCLUSION : The identified association between unsuppressed viral load and unintended pregnancy among pregnant women who initiated ART before pregnancy highlights the need to strengthen routine assessment of fertility preferences and provision of contraceptive services to reproductive age WLWH receiving ART.The President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of cooperative agreement 5 NU2GGH001631, https:// www.cdc.gov/; World Health organization (WHO), South African Medical Research Council (SAMRC), National Department of Health (NDoH), and NICD.http://www.plosone.orgdm2022Statistic

Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa

Approximately 1 million South Africans are infected with Hepatitis C virus (HCV). The standard of care (SOC) in South Africa is combination therapy (pegylated interferon and ribavirin). HCV genotypes and/or mutations in the core/ non-structural regions have been associated with response to therapy and/or disease progression. This study examines mutations in the core (29-280 amino acids, including ~90 E1 amino acids) and NS5B (241-306 amino acids) regions on pre-treatment isolates from patients attending Johannesburg hospitals or asymptomatic South African blood donors. Diversity within known CD4+ and CD8+ T-cell epitopes was also explored. Samples grouped into subtypes 1a (N=10) 1b (N=12), 3a(N=5), 4a (N=3) and 5a(N=61). Two mutations, associated with interferon resistance–R70Q and T110N–were present in 29 genotype 5a core sequences. No resistance mutation to NS5B nucleotide inhibitors, sofosbuvir was found. Six putative CD8+ and one CD4+ T-cell epitope sequence in the core region showed binding scores of <300 IC50nM to HLA alleles frequently observed in the South African population. No known CD8+ and CD4+ T-cell epitopes were mapped in the NS5B region. The analysis begs the question whether those infected with genotype 5a will benefit better on interferon-free combination therapies. This study provides new insight into one of the lesser studied HCV genotypes and compares the diversity seen in a large pre-treatment cohort with other subtypes.Poliomyelitis Research Foundation, grant 95097.http://www.elsevier.com/locate/antiviral2017-03-31hb2016Medical Virolog