An HIV-1 risk assessment tool for women aged 15-49 in African countries: A pooled analysis across 15 nationally representative surveys.

BACKGROUND: Women in Africa disproportionately acquire HIV-1. Understanding which women are most likely to acquire HIV-1 can guide focused prevention with pre-exposure prophylaxis (PrEP). Our objective is to identify women at highest risk of HIV-1 and estimate PrEP efficiency at different sensitivity levels. METHODS: Nationally representative data were collected from 2015-2019 from 15 population-based household surveys. This analysis included women aged 15-49 who tested HIV-1 sero-negative or had recent HIV-1. Least absolute shrinkage and selection operator regression models were fit with 28 variables to predict recent HIV-1. Models were trained on the full population and internally cross-validated. Performance was evaluated using area under the receiver-operating-characteristic curve (AUC), sensitivity, and number needed to treat (NNT) with PrEP to avert one infection. RESULTS: Among 209,012 participants 248 had recent HIV-1 infection, representing 118 million women and 402,000 (95% CI: 309,000-495,000) new annual infections. Two variables were retained in the model: living in a subnational area with high HIV-1 viremia and having a sexual partner living outside the home. Full-population AUC was 0.80 (95% CI: 0.76-0.84); cross-validated AUC was 0.79 (95% CI: 0.75-0.84). At a sensitivity of 33%, up to 130,000 cases could be averted if 7.9 million women were perfectly adherent to PrEP; NNT would be 61. At a sensitivity of 67%, up to 260,000 cases could be averted if 25.1 million women were perfectly adherent to PrEP; the NNT would be 96. CONCLUSIONS: This risk assessment tool was generalizable, predictive, and parsimonious with tradeoffs between reach and efficiency.

HIV Prevalence and Associated Factors Among Men in South Africa 30 Years into the Epidemic: The Fifth Nationwide Cross-Sectional Survey.

We investigated HIV prevalence and associated factors among men ≥ 15 years in South Africa using data from a 2017 nationwide cross-sectional survey. HIV prevalence was 10.5% among 6 646 participants. Prevalence increased from 4.1% in the younger men (15-24 years), 12.5% in young men (25-34 years) to 12.7% in older men (≥ 35 years). Odds of being infected with HIV were lower among younger men who had secondary level education and those who reported poor/fair self-rated health. Young and older men of other race groups had lower odds of HIV infection. Odds of infection were lower among young men who had moderate/high exposure to HIV communication programmes. Men not aware of their HIV status had higher odds of HIV infection, including older men who never married. Improved access to education, behavioral change programmes, and awareness of HIV status are necessary to reduce the risk of HIV infection among Black African men.

Association Between ART Adherence and Mental Health: Results from a National HIV Sero-Behavioural Survey in South Africa.

This paper assesses the levels of antiretroviral treatment (ART) adherence and mental health distress among study participants in a national behavioural HIV-sero prevalence study South Africa. The study was a cross-sectional population-based multi-stage stratified cluster random survey, (SABSSM V, 2017). Structured questionnaires were used to collect information on socio-demographics, HIV knowledge, perceptions, HIV testing and HIV treatment history. Study participants were tested for HIV infection, antiretroviral use, viral suppression, and ART drug resistance. A total of 2155 PLHIV aged 15 years or older who were on ART were included in the study. Incidence of either moderate or severe mental health distress was 19.7%. Self-reported ART adherence among study participants with no, mild, moderate, or severe mental distress was 82%, 83%, 86% and 78%, respectively. The adjusted odds ratio for ART non-adherence was 0.58 (95% CI 0.24; 1.40) for mild mental distress, 0.82 (95% CI 0.35; 1.91) for moderate mental distress and 2.19 (95% CI 1.14; 4.19) for severe mental distress groups compared to the no mental health distress group. The other factors that were associated with ART non-adherence in adjusted models included education level, alcohol use and province/region of residence. The study revealed that mental health remains a challenge to ART adherence in South Africa. To improve ART adherence, HIV continuum of care programs should include screening for mental health among people living with HIV.

Potential Impact and Cost-Effectiveness of Condomless-Sex-Concentrated PrEP in KwaZulu-Natal Accounting for Drug Resistance.

INTRODUCTION: Oral preexposure prophylaxis (PrEP) in the form of tenofovir-disoproxil-fumarate/emtricitabine is being implemented in selected sites in South Africa. Addressing outstanding questions on PrEP cost-effectiveness can inform further implementation. METHODS: We calibrated an individual-based model to KwaZulu-Natal to predict the impact and cost-effectiveness of PrEP, with use concentrated in periods of condomless sex, accounting for effects on drug resistance. We consider (1) PrEP availability for adolescent girls and young women aged 15-24 years and female sex workers, and (2) availability for everyone aged 15-64 years. Our primary analysis represents a level of PrEP use hypothesized to be attainable by future PrEP programs. RESULTS: In the context of PrEP use in adults aged 15-64 years, there was a predicted 33% reduction in incidence and 36% reduction in women aged 15-24 years. PrEP was cost-effective, including in a range of sensitivity analyses, although with substantially reduced (cost) effectiveness under a policy of ART initiation with efavirenz- rather than dolutegravir-based regimens due to PrEP undermining ART effectiveness by increasing HIV drug resistance. CONCLUSIONS: PrEP use concentrated during time periods of condomless sex has the potential to substantively impact HIV incidence and be cost-effective.

Towards achieving the 90-90-90 HIV targets: results from the south African 2017 national HIV survey.

BACKGROUND: Measuring progress towards the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 treatment targets is key to assessing progress towards turning the HIV epidemic tide. In 2017, the UNAIDS model estimated that 75% of people living with HIV (PLHIV) globally knew their HIV positive status, 79% of those who knew their status were on antiretroviral therapy (ART), and 81% of those who knew their HIV status and were on ART had a suppressed viral load. The fifth South African national HIV sero-behavioural survey collected nationally representative data that enabled the empirical estimation of these 90-90-90 targets for the country stratified by a variety of key factors. METHODS: To evaluate progress towards achievement of the 90-90-90 targets for South Africa, data obtained from a national, representative, cross-sectional population-based multi-stage stratified cluster random survey conducted in 2017 were analysed. The Fifth South African National HIV Prevalence, Incidence, Behaviour and Communication Survey (SABSSM V), collected behavioural and biomarker data from individuals residing in households from 1000 randomly selected Small Area Layers (SALs), across all nine provinces of the country. Structured questionnaires were used to collect socio-demographic data, knowledge and perceptions about HIV, and related risk behaviours. Blood samples were collected to test for HIV infection, antiretroviral use, and viral suppression (defined as < 1000 copies/ml). Weighted proportions of study participants aged 15 years and older who tested HIV positive were computed for those who reported awareness of their status (1st 90), and among these, those who were currently on ART (2nd 90) and of these, those who were virally suppressed (3rd 90). RESULTS: Among persons 15 years and older who were HIV positive, 84.8% were aware of their HIV positive status, of whom 70.7% were currently on ART, with 87.4% of these estimated to have suppressed viral load at the time of the survey. These estimates varied by sex, age, and geo-location type. Relatively higher percentages across all three indicators for women compared to men were observed: 88.7% versus 78.2% for those aware of their status, 72.3% versus 67.7% for on ART, and 89.8% versus 82.3% for viral suppression. Knowing one's positive HIV status increased with age: 74.0, 85.8, and 88.1% for age groups 15-24 years old, 25-49 years old and 50-64 years old, although for those 65 years and older, 78.7% knew their HIV positive status. A similar pattern was observed for the 2nd 90, among those who knew their HIV positive status, 51.7% of 15 to 24 year olds, 70.5% of those aged 25-49 years old, 82.9% of those aged 50-64 years old and 82.4% of those aged 65 years or older were currently on ART. Viral suppression for the above mentioned aged groups, among those who were on ART was 85.2, 87.2, 89.5, and 84.6% respectively. The 90-90-90 indicators for urban areas were 87.7, 66.5, and 87.2%, for rural settings was 85.8, 79.8, and 88.4%, while in commercial farming communities it was 56.2, 67.6 and 81.4%. CONCLUSIONS: South Africa appears to be on track to achieve the first 90 indicator by 2020. However, it is behind on the second 90 indicator with ART coverage that was ~ 20-percentage points below the target among people who knew their HIV status, this indicates deficiencies around linkage to and retention on ART. Overall viral suppression among those on ART is approaching the target at 87.4%, but this must be interpreted in the context of low reported ART coverage as well as with variation by age and sex. Targeted diagnosis, awareness, and treatment programs for men, young people aged 15-24 years old, people who reside in farming communities, and in specific provinces are needed. More nuanced 90-90-90 estimates within provinces, specifically looking at more granular sub-national level (e.g. districts), are needed to identify gaps in specific regions and to inform provincial interventions.

Predictors of knowledge about tuberculosis: results from SANHANES I, a national, cross-sectional household survey in South Africa.

BACKGROUND: South Africa is one of the 22 high tuberculosis burden countries that contribute 80% of the global tuberculosis cases. Tuberculosis is infectious and due to its rapid and easy transmission route poses a threat to population health. Considering the importance of social and psychological factors in influencing health outcomes, appraising knowledge and awareness of tuberculosis, remain vital for effective tuberculosis control. The main aim of this study was to investigate the factors that predict knowledge about tuberculosis among 18-64 year old adults in South Africa. METHODS: A cross-sectional survey method was used. Multi-stage disproportionate, stratified cluster sampling was used to select households within enumeration areas stratified by province and locality type. Based on the Human Sciences Research Council 2007 master sample, 500 Enumerator Areas representative of the socio-demographic profile of South Africa were identified and a random sample of 20 households was randomly selected from each Enumerator Area, yielding an overall sample of 10,000 households. The tuberculosis module contained in the South African National Health And Nutrition Examination Survey I was the only module that examined the social determinants of an infectious disease. This module was questionnaire-based with no biomarkers obtained to screen for the presence of tuberculosis disease among the participants. Data was collected by administering a researcher developed individual level questionnaire. Simple and multiple linear regression was used to determine the independent variables associated with tuberculosis knowledge. RESULTS: Half the sample (52.6%) was female and the majority of the respondents were black African (76.5%). More than two thirds (68.0%) resided in urban areas, 56.9% did not complete high school and half were not in formal employment. Significant predictors of tuberculosis knowledge were race, sex, completion of high school, being in employment, having a diagnosis of the disease in ones' life-time and learning about tuberculosis from television, brochures, health workers, and teachers. CONCLUSIONS: To reduce the burden of tuberculosis in South Africa, media campaigns targeting both rural and urban communities should include conveying accurate information about the disease. Policy makers should also address structural barriers that vulnerable communities face.

New insights into HIV epidemic in South Africa: key findings from the National HIV Prevalence, Incidence and Behaviour Survey, 2012.

This article presents key findings from the 2012 HIV prevalence, incidence and behaviour survey conducted in South Africa and explores trends in the HIV epidemic. A representative household based survey collected behavioural and biomedical data among people of all ages. Chi-squared test for association and formal trend tests (2002, 2005, 2008 and 2012) were used to test for associations and trends in the HIV epidemic across the four surveys. In 2012 a total of 38 431 respondents were interviewed from 11 079 households; 28 997 (67.5%) of 42 950 eligible individuals provided blood specimens. HIV prevalence was 12.2% [95% CI: 11.4-13.1] in 2012 with prevalence higher among females 14.4% than males 9.9%. Adults aged 25-49 years were most affected, 25.2% [95% CI: 23.2-27.3]. HIV prevalence increased from 10.6% [95%CI: 9.8-11.6] in 2008 to 12.2% [95% CI: 11.4-13.1] in 2012 (p < 0.001). Antiretroviral treatment (ART) exposure doubled from 16.6% in 2008 to 31.2% in 2012 (p < 0.001). HIV incidence in 2012 among persons 2 years and older was 1.07% [95% CI: 0.87-1.27], with the highest incidence among Black African females aged 20-34 years at 4.5%. Sexual debut before 15 years was reported by 10.7% of respondents aged 15-24 years, and was significantly higher among male youth than female (16.7% vs. 5.0% respectively, p < 0.001). Reporting of multiple sexual partners in the previous 12 months increased from 11.5% in 2002 to 18.3% in 2012 (p < 0.001). Condom use at last sex dropped from 45.1% in 2008 to 36.2% in 2012 (p < 0.001). Levels of accurate HIV knowledge about transmission and prevention were low and had decreased between 2008 and 2012 from 31.5% to 26.8%. South Africa is on the right track with scaling up ART. However, there have been worrying increases in most HIV-related risk behaviours. These findings suggest that there is a need to scale up prevention methods that integrate biomedical, behavioural, social and structural prevention interventions to reverse the tide in the fight against HIV.

Role of the epithelium in human papillomavirus and human immunodeficiency virus infections in the female genital tract.

Background: Two-thirds of people living with human immunodeficiency virus type 1 (HIV-1) infection reside in Sub-Saharan Africa, where there are the highest prevalence and incidence rates of human papillomavirus (HPV) infection. Both infections are sexually transmitted and enter the body via the epithelium. This review describes the extent of involvement of the epithelium in each infection in the female genital tract. Methods: A narrative review was conducted on the role of the epithelium in HPV and HIV-1 infections. Results: An intact epithelial barrier is the predominant form of protection against viral entry and infection, including from HIV-1 and HPV. HPV is an intraepithelial pathogen, and thus, its growth and amplification, which are dependent on squamous cell differentiation, occur in the epithelium. It gains entry to the basal cells of the stratified squamous epithelium via micro-abrasions or other epithelial injuries that expose the basement membrane. HIV-1, conversely, passes through the epithelium to infect subepithelial tissues. Following deposition of the HIV-1-containing inoculum into the lumen, the virus enters the mucosa through breaks in the epithelial barrier within hours of infection. Further, HIV-1 penetrates the epithelium via various mechanisms, including paracellular passage or across epithelial cells through transcytosis. The capture of the virus from the mucosal surface by intraepithelial and/or subepithelial target cells has also been documented. Conclusions: Epithelial disruption is the major pathogenetic pathway in HIV-1 and HPV infections. Therefore, biochemical compounds that strengthen the epithelial barrier must be prioritized to prevent these infections.

Determinants of psychological distress among individuals who are aware of their HIV serostatus in South Africa: findings from the 2017 national HIV prevalence, incidence, behavior, and communication survey.

Introduction: Psychological distress is a growing public health challenge among people living with HIV. This study investigated the prevalence of psychological distress among individuals who know their HIV positive or negative serostatus in South Africa using 2017 data from a nationwide cross-sectional household-based population survey. Methods: The data for this secondary analysis was collected using a multi-stage stratified cluster randomized sampling design. Multivariable backward stepwise generalized linear regression models were fitted to determine factors associated with psychological distress as measured by the Kessler Scale (K10) among HIV-positive and HIV-negative individuals who know their serostatus in South Africa. Results: Of 18,662 participants, psychological distress was 27.4% (95% CI: 25.3-29.7) among those HIV-positive and 20.1% (95% C: 18.8-21.4) among those HIV-negative. The odds of psychological distress were significantly higher among HIV-positive individuals who rated their health as fair/poor [AOR = 1.22 (95% CI: 1.09-1.35), p < 0.001], and the odds were lower among those residing in rural formal/farm areas [AOR = 0.85 (95% CI: 0.78-0.93), p < 0.001], and those with tertiary education level [AOR = 0.88 (95% CI: 0.78-0.99), p = 0.033]. The odds of psychological distress in HIV-negative individuals were significantly higher among females than males [AOR = 1.09 (95% CI: 1.05-1.14), p < 0.001], high-risk alcohol drinkers [AOR = 1.26 (95% CI: 1.02-1.57), p = 0.035] and hazardous alcohol drinkers [AOR = 1.09 (95% CI: 1.01-1.18), p = 0.028] than abstainers and those who rated their health as fair/poor rather than excellent/good [AOR = 1.18 (95% CI: 1.10-1.26), p < 0.001]. Conclusion: The study underscores the importance of addressing, alcohol misuse and socio-structural inequalities linked to gender and race-based disparities, such as low educational attainment and unemployment, as critical factors associated with psychological distress in the study population.

Prevalence of subclinical pulmonary tuberculosis in adults in community settings: an individual participant data meta-analysis.

BACKGROUND: Subclinical pulmonary tuberculosis, which presents without recognisable symptoms, is frequently detected in community screening. However, the disease category is poorly clinically defined. We explored the prevalence of subclinical pulmonary tuberculosis according to different case definitions. METHODS: We did a one-stage individual participant data meta-analysis of nationally representative surveys that were conducted in countries with high incidence of tuberculosis between 2007 and 2020, that reported the prevalence of pulmonary tuberculosis based on chest x-ray and symptom screening in participants aged 15 years and older. Screening and diagnostic criteria were standardised across the surveys, and tuberculosis was defined by positive Mycobacterium tuberculosis sputum culture. We estimated proportions of subclinical tuberculosis for three case definitions: no persistent cough (ie, duration ≥2 weeks), no cough at all, and no symptoms (ie, absence of cough, fever, chest pain, night sweats, and weight loss), both unadjusted and adjusted for false-negative chest x-rays and uninterpretable culture results. FINDINGS: We identified 34 surveys, of which 31 were eligible. Individual participant data were obtained and included for 12 surveys (620 682 participants) across eight countries in Africa and four in Asia. Data on 602 863 participants were analysed, of whom 1944 had tuberculosis. The unadjusted proportion of subclinical tuberculosis was 59·1% (n=1149/1944; 95% CI 55·8-62·3) for no persistent cough and 39·8% (773/1944; 36·6-43·0) for no cough of any duration. The adjusted proportions were 82·8% (95% CI 78·6-86·6) for no persistent cough and 62·5% (56·6-68·7) for no cough at all. In a subset of four surveys, the proportion of participants with tuberculosis but without any symptoms was 20·3% (n=111/547; 95% CI 15·5-25·1) before adjustment and 27·7% (95% CI 21·0-36·4) after adjustment. Tuberculosis without cough, irrespective of its duration, was more frequent among women (no persistent cough: adjusted odds ratio 0·79, 95% CI 0·63-0·97; no cough: adjusted odds ratio 0·76, 95% CI 0·62-0·93). Among participants with tuberculosis, 29·1% (95% CI 25·2-33·3) of those without persistent cough and 23·1% (18·8-27·4) of those without any cough had positive smear examinations. INTERPRETATION: The majority of people in the community who have pulmonary tuberculosis do not report cough, a quarter report no tuberculosis-suggestive symptoms at all, and a quarter of those not reporting any cough have positive sputum smears, suggesting infectiousness. In high-incidence settings, subclinical tuberculosis could contribute considerably to the tuberculosis burden and to Mycobacterium tuberculosis transmission. FUNDING: Mr Willem Bakhuys Roozeboom Foundation.

Tobacco smoking clusters in households affected by tuberculosis in an individual participant data meta-analysis of national tuberculosis prevalence surveys: Time for household-wide interventions?

Tuberculosis (TB) and non-communicable diseases (NCD) share predisposing risk factors. TB-associated NCD might cluster within households affected with TB requiring shared prevention and care strategies. We conducted an individual participant data meta-analysis of national TB prevalence surveys to determine whether NCD cluster in members of households with TB. We identified eligible surveys that reported at least one NCD or NCD risk factor through the archive maintained by the World Health Organization and searching in Medline and Embase from 1 January 2000 to 10 August 2021, which was updated on 23 March 2023. We compared the prevalence of NCD and their risk factors between people who do not have TB living in households with at least one person with TB (members of households with TB), and members of households without TB. We included 16 surveys (n = 740,815) from Asia and Africa. In a multivariable model adjusted for age and gender, the odds of smoking was higher among members of households with TB (adjusted odds ratio (aOR) 1.23; 95% CI: 1.11-1.38), compared with members of households without TB. The analysis did not find a significant difference in the prevalence of alcohol drinking, diabetes, hypertension, or BMI between members of households with and without TB. Studies evaluating household-wide interventions for smoking to reduce its dual impact on TB and NCD may be warranted. Systematically screening for NCD using objective diagnostic methods is needed to understand the actual burden of NCD and inform comprehensive interventions.

A phase IIa trial of the new tuberculosis vaccine, MVA85A, in HIV- and/or Mycobacterium tuberculosis-infected adults.

RATIONALE: Novel tuberculosis (TB) vaccines should be safe and effective in populations infected with Mycobacterium tuberculosis (M.tb) and/or HIV for effective TB control. OBJECTIVE: To determine the safety and immunogenicity of MVA85A, a novel TB vaccine, among M.tb- and/or HIV-infected persons in a setting where TB and HIV are endemic. METHODS: An open-label, phase IIa trial was conducted in 48 adults with M.tb and/or HIV infection. Safety and immunogenicity were analyzed up to 52 weeks after intradermal vaccination with 5 × 10(7) plaque-forming units of MVA85A. Specific T-cell responses were characterized by IFN-γ enzyme-linked immunospot and whole blood intracellular cytokine staining assays. MEASUREMENTS AND MAIN RESULTS: MVA85A was well tolerated and no vaccine-related serious adverse events were recorded. MVA85A induced robust and durable response of mostly polyfunctional CD4(+) T cells, coexpressing IFN-γ, tumor necrosis factor-α, and IL-2. Magnitudes of pre- and postvaccination T-cell responses were lower in HIV-infected, compared with HIV-uninfected, vaccinees. No significant effect of antiretroviral therapy on immunogenicity of MVA85A was observed. CONCLUSIONS: MVA85A was safe and immunogenic in persons with HIV and/or M.tb infection. These results support further evaluation of safety and efficacy of this vaccine for prevention of TB in these target populations.

Healthcare seeking patterns for TB symptoms: Findings from the first national TB prevalence survey of South Africa, 2017-2019.

BACKGROUND: Although tuberculosis (TB) symptoms have limited sensitivity they remain an important entry point into the TB care cascade. OBJECTIVES: To investigate self-reported healthcare seeking for TB symptoms in participants in a community-based survey. METHODS: We compared reasons for not seeking care in participants reporting ≥1 of four TB screening symptoms (cough, weight loss, night sweats, fever) in the first South African national TB prevalence survey (2017-2019). We used logistic regression analyses to identify sociodemographic and clinical characteristics associated with healthcare seeking. RESULTS: 5,168/35,191 (14.7%) survey participants reported TB symptoms and 3,442/5168 had not sought healthcare. 2,064/3,442(60.0%) participants intended to seek care, 912 (26.5%) regarded symptoms as benign, 399 (11.6%) reported access barriers(distance and cost), 36 (1.0%) took other medications and 20(0.6%) reported health system barriers. Of the 57/98 symptomatic participants diagnosed with bacteriologically confirmed TB who had not sought care: 38(66.7%) intended to do so, 8(14.0%) regarded symptoms as benign, and 6(10.5%) reported access barriers. Among these 98, those with unknown HIV status(OR 0.16 95% CI 0.03-0.82), p = 0.03 and those who smoked tobacco products(OR 0.39, 95% CI 0.17-0.89, p = 0.03) were significantly less likely to seek care. CONCLUSIONS: People with TB symptoms delayed seeking healthcare, many regarded symptoms as benign while others faced access barriers. Those with unknown HIV status were significantly less likely to seek care. Strengthening community-based TB awareness and screening programmes together with self-screening models could increase awareness of the significance of TB symptoms and contribute to improving healthcare seeking and enable many people with TB to enter the TB care cascade.

Adult HIV-1 incidence across 15 high-burden countries in sub-Saharan Africa from 2015 to 2019: a pooled analysis of nationally representative data.

BACKGROUND: Harmonised population-based surveys with recent HIV-1 infection testing algorithms permit pooled cross-sectional estimation of HIV incidence across multiple countries. We aimed to estimate adult HIV-1 incidence rates and number of new infections by sex, age, and subregion in sub-Saharan Africa. METHODS: We analysed data from 13 Population-Based HIV Impact Assessment (PHIA) surveys and two additional population-based surveys done between 2015 and 2019 in 15 sub-Saharan African countries. HIV-seropositive samples from adults aged 15-59 years were tested for recent HIV-1 infection by use of an algorithm consisting of the HIV-1 limiting antigen avidity enzyme immunoassay, HIV-1 viral load, and qualitative detection of antiretroviral agents. Data were pooled across countries; sampling weights were incorporated to represent all adults in the 15 national populations. Analyses accounted for the complex sample designs. HIV incidence rates, incidence rate differences, and number of new annual infections were estimated. FINDINGS: Among 445 979 adults sampled, 382 had recent HIV-1 infection. The estimated HIV-1 incidence rate was 3·3 per 1000 person-years (95% CI 2·6-4·0) among women and 2·0 per 1000 person-years (1·2-2·7) among men (incidence rate difference 1·3 per 1000 person-years, 95% CI 0·3-2·3). Among adults aged 15-24 years, the incidence rate was higher for women (3·5 per 1000 person-years) than men (1·2 per 1000 person-years; difference 2·3, 95% CI 0·8-3·8), but infection rates were similar between sexes in all other age groups. The HIV-1 incidence rate was 7·4 per 1000 person-years (95% CI 5·0-9·7) in southern sub-Saharan Africa, 2·3 per 1000 person-years (1·7-2·9) in the eastern subregion, and 0·9 per 1000 person-years (0·6-1·2) in the western and central subregion. 689 000 (95% CI 546 000-833 000) new HIV cases were estimated annually among the 265 million susceptible adults (61·6% in women). INTERPRETATION: HIV-1 incidence and number of new infections differed by age, sex, and subregion. Approaches for risk stratification are needed to guide comprehensive HIV-1 prevention. FUNDING: National Institutes of Health.

The HIV care continuum for sexually active transgender women in three metropolitan municipalities in South Africa: findings from a biobehavioural survey 2018-19.

BACKGROUND: Despite high HIV prevalence in transgender women in sub-Saharan Africa, to our knowledge no study presents data across the HIV care continuum for this population in the region. The aim of this study was to estimate HIV prevalence and present data to develop the HIV care continuum indicators for transgender women in three South African metropolitan municipalities. METHODS: Biobehavioural survey data were collected among sexually active transgender women in the metropolitan municipalities of Johannesburg, Buffalo City, and Cape Town, South Africa. Transgender women (aged ≥18 years, self-reporting consensual sex with a man in the 6 months before the survey) were recruited using respondent-driven sampling (RDS). An interviewer-administered questionnaire was used to determine awareness of HIV status; blood specimens were collected on dried blood spots to test for HIV antibodies, antiretroviral treatment (ART) exposure, and viral load suppression. Population-based estimates of HIV 95-95-95 cascade indicators were derived by use of individualised RDS weights with RDS Analyst software. Multivariate stepwise backward logistic regression modelling was used to determine factors associated with each cascade indicator. All eligible participants were included in the final analysis. FINDINGS: Between July 26, 2018, and March 15, 2019, we enrolled 887 sexually active transgender women: 323 in Johannesburg, 305 in Buffalo City, and 259 in Cape Town. HIV prevalence was highest in Johannesburg where 229 (74·1%) of 309 tests were positive (weighted prevalence estimate 63·3%, 95% CI 55·5-70·5), followed by Buffalo City where 121 (43·7%) of 277 were positive (46·1%, 38·7-53·6), and then Cape Town where 122 (48·4%) of 252 were positive (45·6%, 36·7-54·7). In Johannesburg, an estimated 54·2% (95% CI 45·8-62·4) of transgender women with HIV knew their positive status, in Cape Town this was 24·2% (15·4-35·8), and in Buffalo City this was 39·5% (27·1-53·4). Among those who knew their status, 82·1% (73·3-88·5) in Johannesburg, 78·2% (57·9-90·3) in Cape Town, and 64·7% (45·2-80·2) in Buffalo City were on ART. Of those on ART, 34·4% (27·2-42·4) in Johannesburg, 41·2% (30·7-52·6) in Cape Town, and 55·0% (40·7-68·4) in Buffalo City were virally suppressed. INTERPRETATION: Innovative strategies are needed to inform efforts to diagnose and to treat transgender women living with HIV promptly to achieve viral load suppression. Differentiated HIV services tailored to transgender women of race groups other than Black South African, and those with low education attainment and low outreach exposure, innovative testing, and adherence strategies should be developed to improve the HIV cascade for South African transgender women. FUNDING: The US President's Emergency Plan For AIDS Relief and US Centers for Disease Control and Prevention.

Seroprevalence survey of anti-SARS-CoV-2 antibody and associated factors in South Africa: Findings of the 2020-2021 population-based household survey.

Population-based serological testing is important to understand the epidemiology and estimate the true cumulative incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to inform public health interventions. This study reports findings of a national household population SARS-CoV-2 serosurvey in people 12 years and older in South Africa. This cross-sectional multi-stage random stratified cluster survey undertaken from November 2020 to June 2021 collected sociodemographic data, medical history, behavioural data, and blood samples from consenting participants. The samples were tested for SARS-CoV-2 antibodies using the Roche ElecsysAnti-SARS-CoV-2 chemiluminescence immunoassay (CLIA) Total Antibody Test. The survey data were weighted by age, race, sex, and province with final individual weights benchmarked against the 2020 mid-year population estimates and accounted for clustering. Descriptive statistics summarize the characteristics of participants and seroprevalence. Logistic regression analyses were used to identify factors associated with seropositivity. From 13290 survey participants (median age 33 years, interquartile range (IQR) 23-46 years), SARS-CoV-2 seroprevalence was 37.8% [95% Confidence Interval (CI) 35.4-40.4] and varied substantially across the country's nine provinces, and by sex, age and locality type. In the final adjusted model, the odds of seropositivity were higher in women than in men [aOR = 1.3 (95% CI: 1.0-1.6), p = 0.027], and those living with HIV (self-report) [aOR = 1.6 (95% CI: 1.0-2.4), p = 0.031]. The odds were lower among those 50 years and older compared to adolescents 12-19 years old [aOR = 0.6 (95% CI: 0.5-0.8), p<0.001] and in those who did not attend events or gatherings [aOR = 0.7 (95% CI: 0.6-1.0), p = 0.020]. The findings help us understand the epidemiology of SARS-CoV-2 within different regions in a low-middle-income country. The survey highlights the higher risk of infection in women in South Africa likely driven by their home and workplace roles and also highlighted a need to actively target and include younger people in the COVID-19 response.

Association of diabetes, smoking, and alcohol use with subclinical-to-symptomatic spectrum of tuberculosis in 16 countries: an individual participant data meta-analysis of national tuberculosis prevalence surveys.

Background: Non-communicable diseases (NCDs) and NCD risk factors, such as smoking, increase the risk for tuberculosis (TB). Data are scarce on the risk of prevalent TB associated with these factors in the context of population-wide systematic screening and on the association between NCDs and NCD risk factors with different manifestations of TB, where ∼50% being asymptomatic but bacteriologically positive (subclinical). We did an individual participant data (IPD) meta-analysis of national and sub-national TB prevalence surveys to synthesise the evidence on the risk of symptomatic and subclinical TB in people with NCDs or risk factors, which could help countries to plan screening activities. Methods: In this systematic review and IPD meta-analysis, we identified eligible prevalence surveys in low-income and middle-income countries that reported at least one NCD (e.g., diabetes) or NCD risk factor (e.g., smoking, alcohol use) through the archive maintained by the World Health Organization and by searching in Medline and Embase from January 1, 2000 to August 10, 2021. The search was updated on March 23, 2023. We performed a one-stage meta-analysis using multivariable multinomial models. We estimated the proportion of and the odds ratio for subclinical and symptomatic TB compared to people without TB for current smoking, alcohol use, and self-reported diabetes, adjusted for age and gender. Subclinical TB was defined as microbiologically confirmed TB without symptoms of current cough, fever, night sweats, or weight loss and symptomatic TB with at least one of these symptoms. We assessed heterogeneity using forest plots and I2 statistic. Missing variables were imputed through multi-level multiple imputation. This study is registered with PROSPERO (CRD42021272679). Findings: We obtained IPD from 16 national surveys out of 21 national and five sub-national surveys identified (five in Asia and 11 in Africa, N = 740,815). Across surveys, 15.1%-56.7% of TB were subclinical (median: 38.1%). In the multivariable model, current smoking was associated with both subclinical (OR 1.67, 95% CI 1.27-2.40) and symptomatic TB (OR 1.49, 95% CI 1.34-1.66). Self-reported diabetes was associated with symptomatic TB (OR 1.67, 95% CI 1.17-2.40) but not with subclinical TB (OR 0.92, 95% CI 0.55-1.55). For alcohol drinking ≥ twice per week vs no alcohol drinking, the estimates were imprecise (OR 1.59, 95% CI 0.70-3.62) for subclinical TB and OR 1.43, 95% CI 0.59-3.46 for symptomatic TB). For the association between current smoking and symptomatic TB, I2 was high (76.5% (95% CI 62.0-85.4), while the direction of the point estimates was consistent except for three surveys with wide CIs. Interpretation: Our findings suggest that current smokers are more likely to have both symptomatic and subclinical TB. These individuals can, therefore, be prioritised for intensified screening, such as the use of chest X-ray in the context of community-based screening. People with self-reported diabetes are also more likely to have symptomatic TB, but the association is unclear for subclinical TB. Funding: None.

Dose-finding study of the novel tuberculosis vaccine, MVA85A, in healthy BCG-vaccinated infants.

BACKGROUND: BCG, the only licensed tuberculosis vaccine, affords poor protection against lung tuberculosis in infants and children. A new tuberculosis vaccine, which may enhance the BCG-induced immune response, is urgently needed. We assessed the safety of and characterized the T cell response induced by 3 doses of the candidate vaccine, MVA85A, in BCG-vaccinated infants from a setting where tuberculosis is endemic. METHODS: Infants aged 5-12 months were vaccinated intradermally with either 2.5 × 10(7), 5 × 10(7), or 10 × 10(7) plaque-forming units of MVA85A, or placebo. Adverse events were documented, and T-cell responses were assessed by interferon γ (IFN-γ) enzyme-linked immunospot assay and intracellular cytokine staining. RESULTS: The 3 MVA85A doses were well tolerated, and no vaccine-related serious adverse events were recorded. MVA85A induced potent, durable T-cell responses, which exceeded prevaccination responses up to 168 d after vaccination. No dose-related differences in response magnitude were observed. Multiple CD4 T cell subsets were induced; polyfunctional CD4 T cells co-expressing T-helper cell 1 cytokines with or without granulocyte-macrophage colony-stimulating factor predominated. IFN-γ-expressing CD8 T cells, which peaked later than CD4 T cells, were also detectable. CONCLUSIONS: MVA85A was safe and induced robust, polyfunctional, durable CD4 and CD8 T-cell responses in infants. These data support efficacy evaluation of MVA85A to prevent tuberculosis in infancy. Clinical Trials Registration. NCT00679159.

Prescribing practices for presumptive TB among private general practitioners in South Africa: a cross-sectional, standardised patient study.

INTRODUCTION: Medicine prescribing practices are integral to quality of care for leading infectious diseases such as tuberculosis (TB). We describe prescribing practices in South Africa's private health sector, where an estimated third of people with TB symptoms first seek care. METHODS: Sixteen standardised patients (SPs) presented one of three cases during unannounced visits to private general practitioners (GPs) in Durban and Cape Town: TB symptoms, HIV-positive; TB symptoms, a positive molecular test for TB, HIV-negative; and TB symptoms, history of incomplete TB treatment, HIV-positive. Prescribing practices were recorded in standardised exit interviews and analysed based on their potential to contribute to negative outcomes, including increased healthcare expenditures, antibiotic overuse or misuse, and TB diagnostic delay. Factors associated with antibiotic use were assessed using Poisson regression with a robust variance estimator. RESULTS: Between August 2018 and July 2019, 511 SP visits were completed with 212 GPs. In 88.5% (95% CI 85.2% to 91.1%) of visits, at least one medicine (median 3) was dispensed or prescribed and most (93%) were directly dispensed. Antibiotics, which can contribute to TB diagnostic delay, were the most common medicine (76.5%, 95% CI 71.7% to 80.7% of all visits). A majority (86.1%, 95% CI 82.9% to 88.5%) belonged to the WHO Access group; fluoroquinolones made up 8.8% (95% CI 6.3% to 12.3%). Factors associated with antibiotic use included if the SP was asked to follow-up if symptoms persisted (RR 1.14, 95% CI 1.04 to 1.25) and if the SP presented as HIV-positive (RR 1.11, 95% CI 1.01 to 1.23). An injection was offered in 31.9% (95% CI 27.0% to 37.2%) of visits; 92% were unexplained. Most (61.8%, 95% CI 60.2% to 63.3%) medicines were not listed on the South African Primary Healthcare Essential Medicines List. CONCLUSION: Prescribing practices among private GPs for persons presenting with TB-like symptoms in South Africa raise concern about inappropriate antimicrobial use, private healthcare costs and TB diagnostic delay.