Acceptability of an annual tenofovir alafenamide implant for HIV prevention in South African women: findings from the CAPRISA 018 Phase I clinical trial.

Introduction: Long-acting HIV pre-exposure prophylaxis promises to improve uptake, adherence and persistence challenges experienced with daily oral tablets. We assessed the acceptability of an annual tenofovir alafenamide (TAF) implant in South African women enrolled from 9 July 2020 until 31 May 2022 in a Phase I trial.

Methods: Six women received one TAF implant for 4 weeks (Group 1), after which 30 women were randomized (4:1, TAF to placebo ratio) to receive 1 or 2 TAF or placebo implants for 48 weeks (Group 2), before trial discontinuation.

Drug transporter mRNA expression and genital inflammation in South African women on oral pre-exposure prophylaxis (PrEP).

Globally HIV remains a major public health problem. In sub-Saharan Africa most new HIV infections occur in adolescent girls and young women. Previously tested antiretroviral drugs as different pre-exposure prophylaxis (PrEP) formulations have shown inconsistent levels of protection against HIV in African women.

Evaluating diagnostic accuracy of an RT-PCR test for the detection of SARS-CoV-2 in saliva.

Background And Objective: Saliva has been proposed as a potential more convenient, cost-effective, and easier sample for diagnosing SARS-CoV-2 infections, but there is limited knowledge of the impact of saliva volumes and stages of infection on its sensitivity and specificity.

Methods: In this study, we assessed the performance of SARS-CoV-2 testing in 171 saliva samples from 52 mostly mildly symptomatic patients (aged 18 to 70 years) with a positive reference standard result at screening. The samples were collected at different volumes (50, 100, 300, and 500 µl of saliva) and at different stages of the disease (at enrollment, day 7, 14, and 28 post SARS-CoV-2 diagnosis).

Effectiveness of ChAdOx1 nCoV-19 and BBIBP-CorV vaccines against COVID-19-associated hospitalisation and death in the Seychelles infected adult population.

Background: The Seychelles COVID-19 vaccination campaign was initiated using two different vaccines during the first wave of the pandemic in 2021. This observational study estimated vaccine effectiveness against severe outcomes (hospitalisation and/or death) from individuals infected with COVID-19 in the Seychelles adult population during Beta and Delta variant transmission.

Methods: This nationwide retrospective cohort study included all Seychellois residents aged ≥ 18 years who tested positive by RT-PCR or rapid antigen test for COVID-19 between January 25, 2021, and June 30, 2021.

COVID-19 vaccine hesitancy in KwaZulu-Natal, South Africa: A survey of unvaccinated adults.

Background: Concerns and misconceptions surrounding coronavirus disease 2019 (COVID-19) vaccines may account for vaccine hesitancy and low uptake.

Aim: To determine prevalence of COVID-19 vaccine hesitancy, vaccine-related misconceptions, and predictors of vaccine hesitancy among South Africans.

Setting: Community setting in five districts in KwaZulu- Natal province.

Clinical outcomes with second-line dolutegravir in people with virological failure on first-line non-nucleoside reverse transcriptase inhibitor-based regimens in South Africa: a retrospective cohort study.

Background: Dolutegravir (DTG) is recommended for second-line antiretroviral therapy (ART) after virological failure on first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens in people living with HIV in low-income and middle-income countries. We compared the effectiveness of DTG versus the previously recommended ritonavir-boosted lopinavir (LPV/r) regimen for second-line treatment in South Africa.

Methods: In this retrospective observational cohort study, we used routinely collected, de-identified data from 59 primary health-care facilities in eThekwini Municipality, KwaZulu-Natal, South Africa.

Clinical Outcomes After Viremia Among People Receiving Dolutegravir vs Efavirenz-Based First-line Antiretroviral Therapy in South Africa.

Background: We aimed to compare clinical outcomes after viremia between dolutegravir vs efavirenz-based first-line antiretroviral therapy (ART) as evidence is lacking outside clinical trials in resource-limited settings.

Methods: We conducted a retrospective cohort analysis with routine data from 59 South African clinics. We included people with HIV aged ≥15 years receiving first-line tenofovir disoproxil fumarate, lamivudine, dolutegravir (TLD) or tenofovir disoproxil fumarate, emtricitabine, efavirenz (TEE) and with first viremia (≥50 copies/mL) between June and November 2020.

Host genetic variation at a locus near CHD1L impacts HIV sequence diversity in a South African population.

It has been previously shown that genetic variants near on chromosome 1 are associated with reduced HIV VL in African populations. However, the impact of these variants on viral diversity and how they restrict viral replication are unknown. We report on a regional association analysis in a South African population and show evidence of selective pressure by variants near on HIV RT and gag.

Single-nucleotide polymorphisms in ABC drug transporters alter expression and circulating tenofovir in healthy South African women exposed to pre-exposure prophylaxis.

We investigated if single-nucleotide polymorphisms (SNPs) in ATP-binding cassette (ABC) drug transporters alter gene expression and tenofovir disposition in South African women taking Truvada for HIV prevention. In 393 women, real-time PCR was used to determine the associations between six SNPs in ABC transporter genes, mRNA expression and circulating-tenofovir. Univariable and multivariable analyses showed that CT and TT relative to CC genotypes for the (3463C/T) SNP had significantly higher tenofovir levels.

Field evaluations of four SARS-CoV-2 rapid antigen tests during SARS-CoV-2 Delta variant wave in South Africa.

Background: Rapid antigen tests detecting SARS-CoV-2 were shown to be a useful tool in managing the COVID-19 pandemic. Here, we report on the results of a prospective diagnostic accuracy study of four SARS-CoV-2 rapid antigen tests in a South African setting.

Methods: Rapid antigen test evaluations were performed through drive-through testing centres in Durban, South Africa, from July to December 2021.

Blood monocyte and dendritic cell profiles among people living with HIV with Mycobacterium tuberculosis co-infection.

Background: Understanding the complex interactions of the immune response mediated by Mycobacterium tuberculosis and HIV co-infection is fundamental to disease biomarker discovery, vaccine, and drug development. Using flow cytometry, we characterized the frequencies and phenotypic differences in monocytes and dendritic cell populations using peripheral blood mononuclear cells from individuals with recurrent, active pulmonary tuberculosis with and without coexisting HIV infection (CAPRISA 011, Clinicaltrials.gov, NCT02114684, 29/01/2014) and compared them to samples from HIV positive individuals and healthy controls.

Associations of Social Support with Sexual Practices, Health Behaviours, and Health Outcomes Among Adolescent Girls and Young Women: Evidence From a Longitudinal Study in KwaZulu-Natal, South Africa.

Background: Several studies have reported on the benefits of social support for health behaviour, including risky sex. Social support may thus be an important resource for promoting individual health and well-being, particularly in regions where HIV rates are high and healthcare resources are scarce. However, prior research on the implications of social support for the health behaviour of young women has yielded mixed and inconclusive findings.

NK cell phenotypic profile during active TB in people living with HIV-evolution during TB treatment and implications for bacterial clearance and disease severity.

Natural killer (NK) cells, key effector cells of the innate immune system, play an important role in the clearance and control of Mycobacterium tuberculosis and HIV infections. Here, we utilized peripheral blood specimens from the Improving Retreatment Success CAPRISA 011 study to characterize NK cell phenotypes during active TB in individuals with or without HIV co-infection. We further assessed the effects of TB treatment on NK cell phenotype, and characterized the effects of NK cell phenotypes during active TB on mycobacterial clearance and TB disease severity measured by the presence of lung cavitation.

Clinical outcomes after the introduction of dolutegravir for second-line antiretroviral therapy in South Africa: a retrospective cohort study.

Background: Dolutegravir is now recommended for second-line anti-retroviral therapy (ART) in low- and middle-income countries. We compared outcomes with dolutegravir (DTG) versus the previous lopinavir/ritonavir (LPV/r) regimen in South Africa.

Methods: We used routinely collected, de-identified data from 59 South African clinics.

Performance of rapid antigen tests in identifying Omicron BA.4 and BA.5 infections in South Africa.

Background: Concerns around accuracy and performance of rapid antigen tests continue to be raised with the emergence of new SARS-CoV-2 variants.

Objective: To evaluate the performance of two widely used SARS-CoV-2 rapid antigen tests during BA.4/BA.

Experience with Contraceptive Dosage Forms and Interest in Novel PrEP Technologies in Women.

New pre-exposure prophylaxis (PrEP) strategies tailored to the needs and expectations of individuals at risk of HIV acquisition are needed. In the CAPRISA 082 prospective cohort study in KwaZulu-Natal, South Africa, sexually active women aged 18 to 30 reported, through interviewer-administered questionnaires, on their prior contraceptive experience and interest in both approved and potential future PrEP dosage forms (oral PrEP, long-acting injectable PrEP, and PrEP implants) between March 2016 and February 2018. Univariable and multivariable Poisson regression models with robust standard errors were used to detect associations between women's prior and current contraceptive use and interest in PrEP options.

Hepatocyte mARC1 promotes fatty liver disease.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) has a prevalence of ∼25% worldwide, with significant public health consequences yet few effective treatments. Human genetics can help elucidate novel biology and identify targets for new therapeutics. Genetic variants in mitochondrial amidoxime-reducing component 1 () have been associated with NAFLD and liver-related mortality; however, its pathophysiological role and the cell type(s) mediating these effects remain unclear.

Point-of-Care Viral Load Testing to Manage HIV Viremia During the Rollout of Dolutegravir-Based ART in South Africa: A Randomized Feasibility Study (POwER).

Background: Data are required regarding the feasibility of conducting a randomized trial of point-of-care viral load (VL) testing to guide management of HIV viremia and to provide estimates of effect to guide potential future trial design.

Setting: Two public South African clinics during the dolutegravir-based antiretroviral therapy (ART) rollout.

Methods: We randomized adults receiving first-line ART, with recent VL ≥1000 copies/mL, in a 1:1 ratio to receive point-of-care Xpert HIV-1 VL versus standard-of-care laboratory VL testing after 12 weeks.

MLX plays a key role in lipid and glucose metabolism in humans: Evidence from in vitro and in vivo studies.

Background And Aim: Enhanced hepatic de novo lipogenesis (DNL) has been proposed as an underlying mechanism for the development of NAFLD and insulin resistance. Max-like protein factor X (MLX) acts as a heterodimer binding partner for glucose sensing transcription factors and inhibition of MLX or downstream targets has been shown to alleviate intrahepatic triglyceride (IHTG) accumulation in mice. However, its effect on insulin sensitivity remains unclear.

Implementation and outcomes of dolutegravir-based first-line antiretroviral therapy for people with HIV in South Africa: a retrospective cohort study.

Background: There are few data assessing the uptake of first-line dolutegravir among men and women living with HIV in low-income and middle-income countries, and subsequent clinical outcomes in non-trial settings. We aimed to determine dolutegravir uptake in women, and the effect of dolutegravir on clinical outcomes in routine care in South Africa.

Methods: In this cohort study, we analysed deidentified data from adults receiving first-line antiretroviral therapy (ART) at 59 South African clinics from Dec 1, 2019, to Feb 28, 2022, using two distinct cohorts.

HIV incidence and associated risk factors in adolescent girls and young women in South Africa: A population-based cohort study.

Background: In sub-Saharan Africa, high HIV incidence rates in adolescent girls and young women (AGYW) persist despite extensive HIV prevention efforts.

Methods: A prospective cohort of 2,710 HIV-negative AGYW (15-24 years) in KwaZulu-Natal, South Africa were interviewed at baseline and followed-up approximately 18 months later (2014-2017). Associations between HIV seroconversion and socio-demographic and behavioural variables measured at baseline and follow-up were examined using Cox regression and a proximate determinants framework.

Impact of COVID-19 public health responses on income, food security and health services among key and vulnerable women in South Africa.

Globally, COVID-19 has impacted lives and livelihoods. Women living with HIV and/or at high risk of acquiring HIV are socially and economically vulnerable. Less is known of the impact of COVID-19 public health responses on women from key and vulnerable populations.

Vaginal microbial shifts are unaffected by oral pre-exposure prophylaxis in South African women.

Vaginal microbiota have been shown to be a modifier of protection offered by topical tenofovir in preventing HIV infection in women, an effect not observed with oral tenofovir-based pre-exposure prophylaxis (PrEP). It remains unclear whether PrEP can influence the vaginal microbiota composition. This study investigated the impact of daily oral tenofovir disoproxil fumarate in combination with emtricitabine for PrEP on the vaginal microbiota in South African women.

Clinical Evaluation of Severe Acute Respiratory Syndrome Coronavirus 2 Rapid Antigen Tests During the Omicron Wave in South Africa.

We evaluated the performance of nasal and nasopharyngeal Standard Q COVID-19 [coronavirus disease 2019] Ag tests (SD Biosensor) and the Panbio COVID-19 Ag Rapid Test Device (nasal; Abbott) against the Abbott RealTime severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assay during the Omicron (clades 21M, 21K, and 21L) wave in South Africa. Overall, all evaluated tests performed well, with high sensitivity (range, 77.78%-81.