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.5 SARS-CoV-2 wave in South Africa (May - June 2022). STUDY DESIGN: A prospective field evaluation compared the SARS-CoV-2 Antigen Rapid test from Hangzhou AllTest Biotech (nasal swab) and the Standard Q COVID-19 Rapid Antigen test from SD Biosensor (nasopharyngeal swab) to the Abbott RealTime SARS-CoV-2 assay (nasopharyngeal swab) on samples collected from 540 study participants. RESULTS: Overall 28.52% (154/540) were SARS-CoV-2 RT-PCR positive with median cycle number value of 12.30 (IQR 9.30-19.40). Out of the 99 successfully sequenced SARS-CoV-2 positive samples, 18 were classified as BA.4 and 56 were classified as BA.5. The overall sensitivities of the AllTest SARS-CoV-2 Ag test and Standard Q COVID-19 Ag test were 73.38% (95% CI 65.89-79.73) and 74.03% (95% CI 66.58-80.31) and their specificities were 97.41% (95% CI 95.30-98.59) and 99.22% (95% CI 97.74-99.74) respectively. Sensitivity was >90% when the cycle number value was <20. The sensitivity of both rapid tests was >90% in samples infected with Omicron sub-lineage BA.4 and BA.5. CONCLUSION: Accuracy of tested rapid antigen tests that target the nucleocapsid SARS-CoV-2 protein, were not adversely affected by BA.4 and BA.5 Omicron sub-variants.

Depression symptoms, HIV testing, linkage to ART, and viral suppression among women in a high HIV burden district in KwaZulu-Natal, South Africa: A cross-sectional household study.

Achieving the UNAIDS 90-90-90 targets by 2020 is contingent on identifying and addressing mental health challenges that may affect HIV testing and treatment-related behaviors. This study is based on survey data from KwaZulu-Natal, South Africa (2014-2015). HIV positive women who reported higher depression scores had a lower odds of having tested previously for HIV (15-25 years: AOR = 0.90, 95% CI [0.83, 0.98]; 26-49 years: AOR = 0.90, 95% CI [0.84, 0.96]). Because HIV testing behavior represents a gateway to treatment, the findings suggest mental health may be one challenge to attaining the UNAIDS 90-90-90 targets.

Factors associated with HIV in younger and older adult men in South Africa: findings from a cross-sectional survey.

OBJECTIVE: This study investigated the behavioural, psychosocial and biological factors associated with HIV in a younger group of men (15 to 24 years) compared with an older group of men (25 to 35 years). DESIGN: A household-based, cross-sectional study was conducted. SETTING: Men were randomly selected using a two-stage random sampling method in KwaZulu-Natal, South Africa, between June 2014 and June 2015. PARTICIPANTS: Overall, we interviewed 1472 younger men and 1138 older men. Only participants who could speak English or Zulu, were able to provide informed consent and who were expected to be living in the study area for the next 12 months were enrolled into the study. PRIMARY AND SECONDARY OUTCOMES: HIV status was the primary outcome for the study. Men's HIV status was derived from blood samples collected in the study which were tested for HIV antibodies. RESULTS: HIV prevalence was higher among older men (35.4%, 95% CI: 31.7 to 39.1) than younger men (7.6%, 95% CI: 6.2 to 9.4, p<0.01). Older men, who completed secondary school had a lower likelihood of being HIV positive (adjusted OR (AOR): 0.41, 95% CI: 0.27 to 0.63, p<0.001) and those with greater food insecurity had a higher likelihood of being HIV positive (AOR: 1.57, 95% CI: 1.05 to 2.34, p=0.04). Younger men with a higher number of lifetime sexual partners had a higher likelihood of being HIV positive (AOR: 1.04, 95% CI: 0.99 to 1.09, p=0.09). CONCLUSION: Given that the HIV prevalence is higher in the older men, community based interventions need to target older men for medical circumcision and support HIV positive men to improve their material conditions early. For younger men intervening to reduce HIV risk behaviours at a young age before these behaviours become entrenched should be central to HIV prevention programmes.

Coital frequency and condom use in age-disparate partnerships involving women aged 15 to 24: evidence from a cross-sectional study in KwaZulu-Natal, South Africa.

OBJECTIVE: This study examines the role of age-disparate partnerships on young women's HIV risk by investigating coital frequency and condom use within age-disparate partnerships involving women aged 15 to 24. DESIGN: A community-based, cross-sectional study was conducted. SETTING: Participants were randomly selected using a two-stage random sampling method in uMgungundlovu district, KwaZulu-Natal, South Africa, between June 2014 and June 2015. PARTICIPANTS: A total of 1306 15-24-year-old women in an ongoing heterosexual partnership were included in the analysis. Participants had to be a resident in the area for 12 months, and able to provide informed consent and speak one of the local languages (Zulu or English). PRIMARY AND SECONDARY OUTCOME MEASURES: Sexual frequency was assessed by asking participants how many times they had sex with each partner in the past 12 months. The degree of condomless sex within partnerships was assessed in the survey by asking participants how often they used a condom with their partners. RESULTS: Age-disparate partnerships were associated with a higher order category (once, 2-5, 6-10, 11-20, >20) of coital frequency (adjusted OR (aOR) 1.32, p<0.05, 95% CI 1.02 to 1.71) and with sex on more than 10 occasions (aOR 1.48, p<0.01, 95% CI 1.12 to 1.96) compared with age-similar partnerships. Age-disparate partnerships were also more likely to involve sex on more than 10 occasions with inconsistent condom use (aOR 1.43, p<0.05, 95% CI 1.04 to 1.96) in the previous 12 months. CONCLUSION: The finding that increased sexual activity is positively associated with age-disparate partnerships adds to the evidence that age-disparate partnerships pose greater HIV risk for young women. Our study results indicate that interventions to reduce risky sexual behaviour within age-disparate partnerships remain relevant to reducing the high HIV incidence rates among adolescent girls and young women.

Misdiagnosis of HIV infection during a South African community-based survey: implications for rapid HIV testing.

INTRODUCTION: We describe the overall accuracy and performance of a serial rapid HIV testing algorithm used in community-based HIV testing in the context of a population-based household survey conducted in two sub-districts of uMgungundlovu district, KwaZulu-Natal, South Africa, against reference fourth-generation HIV-1/2 antibody and p24 antigen combination immunoassays. We discuss implications of the findings on rapid HIV testing programmes. METHODS: Cross-sectional design: Following enrolment into the survey, questionnaires were administered to eligible and consenting participants in order to obtain demographic and HIV-related data. Peripheral blood samples were collected for HIV-related testing. Participants were offered community-based HIV testing in the home by trained field workers using a serial algorithm with two rapid diagnostic tests (RDTs) in series. In the laboratory, reference HIV testing was conducted using two fourth-generation immunoassays with all positives in the confirmatory test considered true positives. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value and false-positive and false-negative rates were determined. RESULTS: Of 10,236 individuals enrolled in the survey, 3740 were tested in the home (median age 24 years (interquartile range 19-31 years), 42.1% males and HIV positivity on RDT algorithm 8.0%). From those tested, 3729 (99.7%) had a definitive RDT result as well as a laboratory immunoassay result. The overall accuracy of the RDT when compared to the fourth-generation immunoassays was 98.8% (95% confidence interval (CI) 98.5-99.2). The sensitivity, specificity, positive predictive value and negative predictive value were 91.1% (95% CI 87.5-93.7), 99.9% (95% CI 99.8-100), 99.3% (95% CI 97.4-99.8) and 99.1% (95% CI 98.8-99.4) respectively. The false-positive and false-negative rates were 0.06% (95% CI 0.01-0.24) and 8.9% (95% CI 6.3-12.53). Compared to true positives, false negatives were more likely to be recently infected on limited antigen avidity assay and to report antiretroviral therapy (ART) use. CONCLUSIONS: The overall accuracy of the RDT algorithm was high. However, there were few false positives, and the sensitivity was lower than expected with high false negatives, despite implementation of quality assurance measures. False negatives were associated with recent (early) infection and ART exposure. The RDT algorithm was able to correctly identify the majority of HIV infections in community-based HIV testing. Messaging on the potential for false positives and false negatives should be included in these programmes.

Strengthening HIV surveillance: measurements to track the epidemic in real time.

Surveillance for HIV as a public health initiative requires timely, detailed and robust data to systematically understand burden of infection, transmission patterns, direct prevention efforts, guide funding, identify new infections and predict future trends in the epidemic. The methods for HIV surveillance have evolved to reliably track the epidemic and identify new infections in real time. Initially HIV surveillance relied primarily on the reporting of AIDS cases followed by measuring antibodies to HIV to determine prevalence in key populations. With the roll-out of antiretroviral therapy (ART) resulting in better survival and the corresponding increase in HIV prevalence, the landscape of surveillance shifted further to track HIV prevalence and incidence within the context of programmes. Recent developments in laboratory assays that potentially measure and differentiate recent versus established HIV infection offer a cost-effective method for the rapid estimation of HIV incidence. These tests continue to be validated and are increasingly useful in informing the status of the epidemic in real time. Surveillance of heterogeneity of infections contributing to sub-epidemics requires methods to identify affected populations, density, key geographical locations and phylogenetically linked or clustered infections. Such methods could provide a nuanced understanding of the epidemic and prioritise prevention efforts to those most vulnerable. This paper brings together recent developments and challenges facing HIV surveillance, together with the application of newer assays and methods to fast-track the HIV prevention and treatment response.

Safety of tenofovir gel, a vaginal microbicide, in South African women: results of the CAPRISA 004 Trial.

BACKGROUND: Tenofovir gel, used vaginally before and after coitus, reduced women's acquisition of HIV by 39%. This is a safety assessment of tenofovir gel, including renal, bone, gastrointestinal, genital and haematological parameters. METHODS: In the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004, a double-blind, randomized placebo-controlled trial, 445 of the 889 eligibly enrolled women were assigned to tenofovir gel. All participants were advised to use the gel vaginally only, with one dose of gel within 12 h before and a second dose as soon as possible after sex, with no more than two doses in 24 h. Clinical and laboratory safety data were collected at monthly and quarterly visits, respectively. Genital assessments were undertaken at enrolment and quarterly thereafter, or as indicated. RESULTS: Women assigned to tenofovir gel were exposed to an average monthly vaginal dose of 240 mg of tenofovir (six applications). In total, six women, three in each group, had mild creatinine elevations, all of which occurred in July/August 2008. The incidence of anaemia was 3.5 and 3.8 per 100 women-years in tenofovir and placebo groups, respectively (P=0.80). Of the six women (four tenofovir and two placebo) experiencing bone fractures, none were associated with abnormal phosphate or calcium values. The proportion of women with diarrhoea was higher in the tenofovir gel group (17% versus 11%; P=0.026). There was no significant increase of any genital adverse event in the tenofovir group. CONCLUSIONS: No significant renal, haematological, genital or bone effects were associated with the use of tenofovir gel. Aside from a puzzling increase in diarrhoea, tenofovir gel has an excellent safety profile.

A drug evaluation of 1% tenofovir gel and tenofovir disoproxil fumarate tablets for the prevention of HIV infection.

INTRODUCTION: More than a million people acquire HIV infection annually. Pre-exposure prophylaxis (PrEP) using antiretrovirals is currently being investigated for HIV prevention. Oral and topical formulations of tenofovir have undergone preclinical and clinical testing to assess acceptability, safety and effectiveness in preventing HIV infection. AREAS COVERED: The tenofovir drug development pathway from compound discovery, preclinical animal model testing and human testing were reviewed for safety, tolerability and efficacy. Tenofovir is well tolerated and safe when used both systemically or applied topically for HIV prevention. High drug concentrations at the site of HIV transmission and concomitant low systemic drug concentrations are achieved with vaginal application. Coitally applied gel may be the favored prevention option for women compared with the tablets, which may be more suitable for prevention in men and sero-discordant couples. However, recent contradictory effectiveness outcomes in women need to be better understood. EXPERT OPINION: Emerging evidence has brought new hope that antiretrovirals can potentially change the course of the HIV epidemic when used as early treatment for prevention, as topical or oral PrEP. Although some trial results appear conflicting, behavioral factors, adherence to dosing and pharmacokinetic properties of the different tenofovir formulations and dosing approaches offer plausible explanations for most of the variations in effectiveness observed in different trials.

Recruitment of high risk women for HIV prevention trials: baseline HIV prevalence and sexual behavior in the CAPRISA 004 tenofovir gel trial.

BACKGROUND: Young women in sub-Saharan Africa bear a disproportionate burden of HIV infection compared to men but have limited options to reduce their HIV risk. Microbicides could fill an important HIV prevention gap for sexually active women who are unable to successfully negotiate mutual monogamy or condom use. PURPOSE: This paper describes the baseline sample characteristics in the CAPRISA 004 trial which assessed the safety and effectiveness of the vaginal microbicide, 1% tenofovir gel for HIV prevention in South Africa. METHODS: This analysis assessed the baseline demographic, clinical and sexual behavior data of women screened and enrolled into the trial. The characteristics were summarized using descriptive summary measures; expressed as means and percent for categorical variables. RESULTS: HIV prevalence at screening was 25.8% [95% Confidence Interval (CI):23.9-27.7). Of the 889 eligibly enrolled women who contributed follow-up data, rural participants recruited from a family planning (FP) clinic were younger, more likely to be living apart from their regular partner, reported lower coital frequency, had lower condom use (p < 0.001). In contrast, urban participants recruited from a sexually transmitted disease (STD) clinic reported higher numbers of lifetime sexual partners, new partners in the last 30 days and receiving money in exchange for sex (p < 0.001). CONCLUSION: The populations selected provide suitable diverse target groups for HIV prevention intervention studies. TRIAL REGISTRATION: ClinicalTrials.gov: NCT 00441298.