Brief Report: Changing Characteristics Among In-Hospital HIV Deaths: An 11-Year Retrospective Review of a Regional Hospital in South Africa.

BACKGROUND: Elevated HIV-associated mortality persists, despite a notable decline with the expansion of antiretroviral therapy (ART). In South Africa, the relative majority of deaths occur in health facilities, providing an opportunity to track decedent characteristics. SETTING: We analyzed data from 14,870 adult patients who died between 2008 and 2018 at Klerksdorp/Tshepong Hospital Complex in South Africa. METHODS: Recorded data included demographics, causes of death, HIV status, ART, and tuberculosis (TB) history. We present summary statistics and results from linear, log-binomial, and multinomial regressions to quantify changes over time. RESULTS: Over the study period, the median age of decedents with HIV in the hospital increased from 39.3 to 43.4 years, and there was a switch to male predominance (46%-54%). Those who died at a younger age (<40 years) remained more likely to be HIV-positive than the older age group, despite the overall proportion of HIV-positivity decreasing over time. The proportion of decedents with HIV ever started on ART increased from 21% to 67%. The proportion of HIV patients dying from TB and AIDS-defining illnesses decreased from 31% to 22%. CONCLUSIONS: We noted a shift in deaths over time to more men and older individuals, whereas the burden of HIV was heaviest on the younger age groups. Advanced HIV disease remained an important cause of mortality. We also observed an increase in less-traditional opportunistic illnesses among those with HIV, including malignancy, cardiovascular disease, and kidney disease. The high proportion of patients on ART who died prematurely requires further research and interventions.

Undiagnosed Pulmonary Tuberculosis (TB) and Coronavirus Disease 2019 (COVID-19) in Adults Dying at Home in a High-TB-Burden Setting, Before and During Pandemic COVID-19: An Autopsy Study.

BACKGROUND: Missing or undiagnosed patients with tuberculosis (TB) or coronavirus disease 2019 (COVID-19) are of concern. Identifying both infections in patients with no diagnosis prior to death contributes to understanding the burden of disease. To confirm reports of global reduction in TB incidence, a 2012 autopsy study of adults dying at home of natural causes in a high-TB-burden setting was repeated, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assessments after the first COVID-19 surge in South Africa. METHODS: Adult decedents who died at home with insufficient information to determine cause of death, no recent hospitalization, and no current antemortem TB or COVID-19 diagnosis were identified between March 2019 and October 2020 with a 4-month halt during lockdown. A standardized verbal autopsy followed by minimally invasive needle autopsy (MIA) was performed. Biopsies were taken for histopathology from liver, bilateral brain and lung; bronchoalveolar lavage fluid was collected for Xpert (MTB/RIF) and mycobacterial culture, and blood for human immunodeficiency virus (HIV) polymerase chain reaction (PCR) testing. After the start of the COVID-19 pandemic, a nasopharyngeal swab and lung tissue were subjected to SARS-CoV-2 PCR testing. RESULTS: Sixty-six MIAs were completed in 25 men and 41 women (median age, 60 years); 68.2% had antemortem respiratory symptoms and 30.3% were people with HIV. Overall, TB was diagnosed in 11 of 66 (16.7%) decedents, and 14 of 41 (34.1%) in the COVID-19 pandemic were SARS-CoV-2 positive. CONCLUSIONS: Undiagnosed TB in adults dying at home has decreased but remains unacceptably high. Forty percent of decedents had undiagnosed COVID-19, suggesting that estimates of excess deaths may underestimate the impact of SARS-CoV-2 on mortality.

Impact and cost-effectiveness of the national scale-up of HIV pre-exposure prophylaxis among female sex workers in South Africa: a modelling analysis.

INTRODUCTION: In 2016, South Africa (SA) initiated a national programme to scale-up pre-exposure prophylaxis (PrEP) among female sex workers (FSWs), with ∼20,000 PrEP initiations among FSWs (∼14% of FSW) by 2020. We evaluated the impact and cost-effectiveness of this programme, including future scale-up scenarios and the potential detrimental impact of the COVID-19 pandemic. METHODS: A compartmental HIV transmission model for SA was adapted to include PrEP. Using estimates on self-reported PrEP adherence from a national study of FSW (67.7%) and the Treatment and Prevention for FSWs (TAPS) PrEP demonstration study in SA (80.8%), we down-adjusted TAPS estimates for the proportion of FSWs with detectable drug levels (adjusted range: 38.0-70.4%). The model stratified FSW by low (undetectable drug; 0% efficacy) and high adherence (detectable drug; 79.9%; 95% CI: 67.2-87.6% efficacy). FSWs can transition between adherence levels, with lower loss-to-follow-up among highly adherent FSWs (aHR: 0.58; 95% CI: 0.40-0.85; TAPS data). The model was calibrated to monthly data on the national scale-up of PrEP among FSWs over 2016-2020, including reductions in PrEP initiations during 2020. The model projected the impact of the current programme (2016-2020) and the future impact (2021-2040) at current coverage or if initiation and/or retention are doubled. Using published cost data, we assessed the cost-effectiveness (healthcare provider perspective; 3% discount rate; time horizon 2016-2040) of the current PrEP provision. RESULTS: Calibrated to national data, model projections suggest that 2.1% of HIV-negative FSWs were currently on PrEP in 2020, with PrEP preventing 0.45% (95% credibility interval, 0.35-0.57%) of HIV infections among FSWs over 2016-2020 or 605 (444-840) infections overall. Reductions in PrEP initiations in 2020 possibly reduced infections averted by 18.57% (13.99-23.29). PrEP is cost-saving, with $1.42 (1.03-1.99) of ART costs saved per dollar spent on PrEP. Going forward, existing coverage of PrEP will avert 5,635 (3,572-9,036) infections by 2040. However, if PrEP initiation and retention doubles, then PrEP coverage increases to 9.9% (8.7-11.6%) and impact increases 4.3 times with 24,114 (15,308-38,107) infections averted by 2040. CONCLUSIONS: Our findings advocate for the expansion of PrEP to FSWs throughout SA to maximize its impact. This should include strategies to optimize retention and should target women in contact with FSW services.

Understanding drivers of female sex workers' experiences of external/enacted and internalised stigma: findings from a cross-sectional community-centric national study in South Africa.

To deepen our understanding of sex work stigma, and to its drivers and their interrelation, we conducted an analysis using structural equation modelling of the South African National Sex Worker Survey. We enrolled 3005 women in sex work using multi-stage sampling across all South Africa's provinces. Experience of external/enacted and internalised stigma was widespread. Non-partner rape, intimate partner violence and partner controlling behaviour (often expressions of external/enacted stigma) compounded internalised stigma. These experiences of violence, other manifestations of external/enacted stigma and food insecurity, were key drivers of internalised stigma, and often had an impact on mental health. We found that considerable protection against stigma emanated from viewing sex work positively. This resistance to stigma provided opportunities to shift the narrative. Reducing sex workers' exposure to external/enacted stigmatising behaviour, including by enabling more to work indoors, and providing greater protection from partner violence and rape, are critical for better health and well-being. Ending the criminalisation of sex work is foundational for safer working conditions and better health outcomes for sex workers, similarly providing adequately funded mental and physical health and social care through sex work specific programmes.

Yield of Facility-based Targeted Universal Testing for Tuberculosis With Xpert and Mycobacterial Culture in High-Risk Groups Attending Primary Care Facilities in South Africa.

BACKGROUND: We report the yield of targeted universal tuberculosis (TB) testing of clinic attendees in high-risk groups. METHODS: Clinic attendees in primary healthcare facilities in South Africa with one of the following risk factors underwent sputum testing for TB: human immunodeficiency virus (HIV), contact with a TB patient in the past year, and having had TB in the past 2 years. A single sample was collected for Xpert-Ultra (Xpert) and culture. We report the proportion positive for Mycobacterium tuberculosis. Data were analyzed descriptively. The unadjusted clinical and demographic factors' relative risk of TB detected by culture or Xpert were calculated and concordance between Xpert and culture is described. RESULTS: A total of 30 513 participants had a TB test result. Median age was 39 years, and 11 553 (38%) were men. The majority (n = 21734, 71%) had HIV, 12 492 (41%) reported close contact with a TB patient, and 1573 (5%) reported prior TB. Overall, 8.3% were positive for M. tuberculosis by culture and/or Xpert compared with 6.0% with trace-positive results excluded. In asymptomatic participants, the yield was 6.7% and 10.1% in symptomatic participants (with trace-positives excluded). Only 10% of trace-positive results were culture-positive. We found that 55% of clinic attendees with a sputum result positive for M. tuberculosis did not have a positive TB symptom screen. CONCLUSIONS: A high proportion of clinic attendees with specific risk factors (HIV, close TB contact, history of TB) test positive for M. tuberculosis when universal testing is implemented.

Sex work and young women: a cross sectional study to understand the overlap of age and sex work as a central tenet to epidemic control in South Africa.

Adolescent girls and young women (AGYW) engaging in sex-for-money transactions are at risk of HIV infection. A better understanding of the demographic, socio-economic factors and risks of HIV acquisition is required to guide appropriate public health interventions targeting young sex workers in South Africa. A cross-sectional survey of Female Sex Workers (FSWs), using a chain referral sampling method, was conducted across 12 sites in South Africa in 2019. Three thousand and five participants were enrolled and interviewed assessing demographic characteristics, sexual behaviour, substance use and HIV testing and treatment. Of 3005 women, 13.3% were ≤24 years old (young FSWs); of these, 60.0% entered sex work aged ≤19 years. Economic factors were the primary drivers of entry into sex work. HIV prevalence amongst young FSWs was 40.4%, with 12.4% recently infected. Younger FSWs were significantly less likely to know they were HIV positive (87.6% versus 92.1%), to report any ART exposure (75.2% versus 87.6%) and to be virally suppressed (58.1% versus 75.2%) compared to older FSWs. Our findings highlight that many FSWs enter sex work at a young age. It is essential to develop tailored services and interventions that improve access to HIV prevention and treatment services addressing specific needs.

Experiences of South African caregivers disclosing to their children living with HIV: Qualitative investigations.

Awareness of Human Immunodeficiency Virus (HIV) status improves health outcomes in children living with HIV, yet caregivers often delay disclosure. This qualitative investigation explored, through observation, how 30 caregivers responded to a HIV Disclosure study conducted between 2017 and 2020 at Chris Hani Baragwanath Academic Hospital, Soweto, South Africa. Caregivers were assisted in disclosing to their children, aged 7-13 years; followed by a sub-sample of caregivers providing in-depth interviews to elaborate on findings.1) Barriers to disclosure included: caregivers being ill equipped, the fear of negative consequences and children considered lacking emotional or cognitive readiness. 2) Deflecting diagnosis from their children and the need for medication, motivated caregivers to disclosure. 3) Apprehension was evident during disclosure; however, overall disclosure was a positive experience with the support of the healthcare providers. These results highlight the significant role healthcare providers' play in supporting caregivers through the disclosure process.

HIV incidence estimation among female sex workers in South Africa: a multiple methods analysis of cross-sectional survey data.

BACKGROUND: Although numerous studies have investigated HIV risk factors and shown high HIV prevalence among female sex workers in South Africa, no national HIV incidence estimate exists for this potentially important group for HIV transmission. We aimed to estimate HIV incidence among female sex workers in South Africa who could be accessed through sex worker programmes, and to refine and describe the methods that enabled analysis. METHODS: This study was embedded in a cross-sectional national survey of female sex workers who were linked to sex worker programmes. We aimed to enrol 3000 female sex workers aged at least 18 years who had sold or transacted in sex in the preceding 6 months in 12 randomly selected districts of the 22 districts with sex worker programmes, ensuring coverage of all provinces of South Africa. Women who self-reported as current victims of human trafficking were excluded from enrolment. We used a multistep process to sample districts and then hotspots, and a chain referral method to recruit participants. We collected cross-sectional data for self-reported HIV status, demographic characteristics, and exposure to violence. Two rapid tests were used to ascertain diagnostic markers, a viral load assay was used to ascertain clinical markers, and the Maxim Limiting Antigen Avidity EIA was used to ascertain infection-staging HIV markers. Given the challenges of estimating HIV incidence, especially cross-sectionally, multiple methods of estimation were adapted to our setting, leveraging the age structure of HIV prevalence, recency-of -infection biomarker results (ie, where recent infection is classified as ≤1·5 normalised optical density [ODn] on the avidity assay and viral load of ≥1000 copies per mL), and reported testing histories. FINDINGS: Of 3005 female sex workers who were enrolled and interviewed between Feb 4 and June 26, 2019, 2999 who had HIV test results were included in this analysis. The median age of participants was 32 years (IQR 27-38). 1714 (57·2%) of 2999 participants self-reported as being HIV positive, and 1447 (48·3%) of 2993 participants reported client sexual violence in the past year. The measured HIV prevalence was 62·1% (95% CI 60·3-65·7) and peaked at approximately age 40 years. Using recency-of-infection biomarker results, we obtained a base case estimate of HIV incidence of 4·60 cases per 100 person-years (95% CI 1·53-8·45) for the population. Estimates were generally consistent by method, and outlying incidence estimates calculated by self-reported testing histories were considered unreliable. Various sensitivity analyses produced estimates up to 11 cases per 100 person-years, and we did not detect differences by age and region. INTERPRETATION: We found that female sex workers have extraordinarily high HIV incidence of approximately 5 cases per 100 person-years, emphasising the need to sustain and strengthen efforts to mitigate risk and provide adequate care. The notable role that sex work has in HIV transmission demands substantial investment in ongoing epidemiological monitoring. FUNDING: South African Medical Research Council, South African National Treasury, Global Fund, South African Department of Science and Innovation, Wellcome Trust.

Whose role is it anyways: Knowledge generation within the scope of sex work.

Research within the context of sex work is challenging. The nature of the subject matter and stigma that surrounds sex work has often privileged a homogenous, academic practice of generating knowledge. Based on the lessons and experiences of an existing sex work programme and a recently completed national public health study with female sex workers (FSWs) in South Africa, we aim to highlight the significance and successes of privileging a bottom-up, community centric approach to the design, data collection, and knowledge generation. A FSW programme provided extensive peer educator skills training and learning opportunities. Lessons were applied to the implementation of a national study on FSW across South Africa. Planning workshops with community members and sites and pre- implementation training of all site staff was undertaken. 3005 FSWs were successfully enrolled and surveyed by their peers, over 6-months. Researchers have a lot to learn from community members and should remain vigilant to the power dynamics that their privilege creates throughout the research process. Those seeking to generate knowledge should practice meaningfully engagement and include population members on the study team in roles that allow them to proactively contribute to the process and create knowledge.

The HIV Cascade of Care and Service Utilisation at Sex Work Programmes Among Female Sex Workers in South Africa.

Female sex workers (FSWs) in South Africa experience a uniquely high prevalence of HIV. We describe the HIV cascade of care (CoC) in FSWs in South Africa, and explored service utilisation at sex work programmes. A cross-sectional, study enrolled FSWs across 12 sites in South Africa. Participants were recruited using chain-referral method. Inclusion criteria: ≥ 18 years, cis-gender female, sold/transacted in sex, HIV positive. 1862 HIV positive FSWs were enrolled. 92% were known positive, 87% were on antiretroviral treatment (ART). Of those on ART, 74% were virally suppressed. Younger FSWs were significantly less likely to be on ART or virally suppressed. Female sex workers using HIV services from specialised programs were 1.4 times more likely to be virally suppressed than non-program users. The pre-COVID-19 pandemic HIV CoC amongst FSWs in South Africa shows striking improvement from previous estimates, and approaches achievement of 90:90:90 goals.

Key risk factors for substance use among female sex workers in Soweto and Klerksdorp, South Africa: A cross-sectional study.

INTRODUCTION: Sex workers in South Africa experience high levels of trauma and mental health issues, but little is known about their drug and alcohol use. This study assessed the prevalence of substance use and its key risk factors amongst female sex workers (FSWs) at two sites in South Africa. METHODS: Two cross-sectional studies were conducted, in Soweto and Klerksdorp, South Africa. Using respondent-driven sampling (RDS) 508 FSWs in Soweto and 156 in Klerksdorp were enrolled. A study-specific survey was used to collect social and demographic information, substance use, mental ill-health, and HIV status. Raw and RDS-adjusted data were analyzed using Chi-squared tests of association. Weighted and unweighted Poisson regression models were used to assess key risk factors for alcohol and drug use at both univariate and multivariate levels. RESULTS: Of the 664 FSWs, 56.2% were binge drinkers and 29.4% reported using drugs within the last year. Living in a home with regular food (RR: 1.2597, 95% CI: 1.1009-1.4413) and being HIV positive (RR: 1.1678, 95% CI: 1.0227-1.3334) were associated with a higher risk of binge drinking. Having symptoms suggestive of post-traumatic stress disorder (RR: 1.1803, 95% CI: 1.0025-1.3895) and past year physical/sexual abuse from either intimate (RR: 1.3648, 95% CI: 1.1522-1.6167) or non-intimate partners (RR: 1.3910, 95% CI: 1.1793-1.6407) were associated with a higher risk of drug use. DISCUSSION: In conclusion, our findings demonstrate a high prevalence of alcohol and drug use among FSWs in Soweto and Klerksdorp with site-specific contextual dynamics driving substance use. Site differences highlight the importance of tailoring site-specific substance use harm mitigation for this key population.

Sexual IPV and non-partner rape of female sex workers: Findings of a cross-sectional community-centric national study in South Africa.

BACKGROUND: Globally female sex workers (FSWs) are vulnerable to violence from intimate partners, police and clients due to stigma and criminalisation. In this paper we describe South African FSWs' exposure to violence and factors associated with having been raped in the past year. METHODS: We conducted a multi-stage, community-centric, cross-sectional survey of 3005 FSWs linked to sex worker programmes in 12 sites across all nine provinces that had a SW programme. Adult women who sold sex in the preceding six months were recruited for interviews via sex worker networks. Survey tools were developed in consultation with peer educators and FSWs. RESULTS: In the past year, 70.4% of FSWs experienced physical violence and 57.9% were raped: by policemen (14.0%), clients (48.3%), other men (30.2%) and/or and intimate partner (31.9%). Sexual IPV was associated with food insecurity, entering sex work as a child, childhood trauma exposure, post-traumatic stress disorder (PTSD), drinking alcohol to cope with sex work, working more days, partner controlling behaviour, having an ex-client partner, and having no current partner to protect from ex-partners. Rape by a client, other men or policemen was associated with food insecurity, childhood trauma, PTSD, depression, using alcohol and drugs, being homeless or staying in a sex work venue, selling sex on the streets, working more days and having entered sex work as a child and been in sex work for longer. CONCLUSION: South African FSWs are very vulnerable to rape. Within the social climate of gender inequality, sex work stigma, criminalisation, and repeated victimisation, the key drivers are structural factors, childhood and other trauma exposure, mental ill-health, circumstances of sex work and, for SIPV, partner characteristics. Mostly these are amenable to intervention, with legislative change being foundational for ending abuse by policemen, enhancing safety of indoor venues and providing greater economic options for women.

Intersections of Sex Work, Mental Ill-Health, IPV and Other Violence Experienced by Female Sex Workers: Findings from a Cross-Sectional Community-Centric National Study in South Africa.

Female sex workers (FSWs) are at increased risk of mental health problems, including mood disorders and substance abuse, and we need to understand the origins of these to treat and prevent them, and particularly understand how the context in which they sell sex impacts their mental health. We conducted a multi-stage, community-centric, cross-sectional survey of 3005 FSWs linked to SW programmes in twelve sites across all nine provinces of South Africa. We interviewed adult women who had sold sex in the preceding six months, who were recruited via SW networks. We found that FSWs have very poor mental health as 52.7% had depression and 53.6% has post-traumatic stress disorder (PTSD). The structural equation model showed direct pathways from childhood trauma and having HIV+ status to mental ill-health. Indirect pathways were mediated by food insecurity, controlling partners, non-partner rape, harmful alcohol use, substance use to cope with SW, indicators of the circumstances of SW, i.e., selling location (on streets, in taverns and brothels), frequency of selling and experiencing SW stigma. All paths from childhood trauma had final common pathways from exposure to gender-based violence (non-partner rape or intimate partner violence) to mental ill-health, except for one that was mediated by food insecurity. Thus, FSWs' poor mental health risk was often mediated by their work location and vulnerability to violence, substance abuse and stigma. The potential contribution of legal reform to mitigate the risks of violence and mental ill-health are inescapable. Treatment of mental ill-health and substance abuse should be an essential element of FSW programmes.

Tuberculosis patients at the human-animal interface: Potential zooanthroponotic and zoonotic transmission.

BACKGROUND: Human-to-animal transmission of M. tuberculosis (Mtb) is reported in South Africa but there is a paucity of epidemiological data. The aim of this One Health manuscript is to describe zooanthroponotic exposure of domestic animals to TB patients, virtually all of whom had laboratory confirmed pulmonary Mtb disease. METHODS: This cross-sectional study was nested within two TB contact tracing studies and collected data from 2017 to 2019. TB index patients and their households in three provinces of South Africa were recruited. A questionnaire was administered to households, assessing type and number of animals owned, degree of exposure of animals to humans, and veterinary consultations. For this analysis, we compared descriptive variables by animal-keeping status (animal-keeping vs non-animal keeping households), calculated the chi square and respective p-values. RESULTS: We visited 1766 households with at least one confirmed case of TB, 33% (587/1766) had livestock or companion animals. Of non-animal-owning households, 2% (27/1161) cared for other community members' livestock. Few (16%, 92/587) households kept animals in their dwelling overnight, while 45% (266/587) kept animals outside the home, but within 10 m of where people slept and ate. Most (81%, 478/587) of people in animal-owning households were willing for their animal/s to have a TB skin test, but <1% (5/587) of animals had been skin-tested; 4% (24/587) of animal-owning households had a veterinary consultation in the past six months, and 5% (31/587) reported one of their animals dying from natural causes in the prior six months. CONCLUSION: Our survey suggests that a high proportion of patients with TB live in settings facilitating close contact with domestic animal species with known susceptibility to Mtb. There is a substantial exposure of household animals to patients with TB and therefore risk of both transmission to, and spillback from animals to humans.

Community-led cross-sectional study of social and employment circumstances, HIV and associated factors amongst female sex workers in South Africa: study protocol.

BACKGROUND: In South Africa, female sex workers (FSWs) are perceived to play a pivotal role in the country's HIV epidemic. Understanding their health status and risk factors for adverse health outcomes is foundational for developing evidence-based health care for this population. OBJECTIVE: Describe the methodology used to successfully implement a community-led study of social and employment circumstances, HIV and associated factors amongst FSWs in South Africa. METHOD: A community-centric, cross-sectional, survey of 3,005 adult FSWs was conducted (January-July 2019) on 12 Sex Work (SW) programme sites across nine provinces of South Africa. Sites had existing SW networks and support programmes providing peer education and HIV services. FSWs were involved in the study design, questionnaire development, and data collection. Questions included: demographic, sexual behaviour, HIV testing and treatment/PrEP history, and violence exposure. HIV rapid testing, viral load, CD4 count, HIV recency, and HIV drug resistance genotypic testing were undertaken. Partner organisations provided follow-up services. RESULTS: HIV Prevalence was 61.96%, the median length of selling sex was 6 years, and inconsistent condom use was reported by 81.6% of participants, 88.4% reported childhood trauma, 46.2% reported physical or sexual abuse by an intimate partner and 57.4% by a client. More than half of participants had depression and post-traumatic stress disorder (52.7% and 54.1%, respectively). CONCLUSION: This is the first national survey of HIV prevalence amongst FSWs in programmes in South Africa. The data highlight the vulnerability of this population to HIV, violence and mental ill health, suggesting the need for urgent law reform. Based on the unique methodology and the successful implementation alongside study partners, the outcomes will inform tailored interventions. Our rapid rate of enrolment, low rate of screening failure and low proportion of missing data showed the feasibility and importance of community-centric research with marginalised, highly vulnerable populations.

The comorbidity of HIV, hypertension and diabetes: a qualitative study exploring the challenges faced by healthcare providers and patients in selected urban and rural health facilities where the ICDM model is implemented in South Africa.

BACKGROUND: PLWH are living longer as a result of advancement and adherence to antiretroviral therapy. As the life expectancy of PLWH increases, they are at increased risk of hypertension and diabetes. HIV chronic co-morbidities pose a serious public health concern as they are linked to increased use and need of health services, decreased overall quality of life and increased mortality. While research shows that integrated care approaches applied within primary care settings can significantly reduce hospital admissions and mortality levels among patients with comorbidities, the primary care system in South Africa continues to be challenged with issues about the delivery of quality care. METHODS: This study applied a phenomenological qualitative research design. IDIs were conducted with 24 HCPs and adults living with the comorbidity of HIV and either hypertension or diabetes across two provinces in South Africa. The objective of the research was to understand the challenges faced by HCPs and patients in health facilities where the ICDM model is implemented. The health facilities were purposively sampled. However, the HCPs were recruited through snowballing and the patients through reviewing the facilities' clinic records for participants who met the study criteria. All participants provided informed consent. The data was collected between March and May 2020. The findings were analysed inductively using thematic content analysis. RESULTS: The challenges experienced included lack of staff capacity, unclear guidelines on the delivery of integrated care for patients with HIV chronic comorbidities, pill burden, non-disclosure, financial burden, poor knowledge of treatments, relocation of patients and access to treatment. Lack of support and integrated chronic programmes including minimal information regarding the management of HIV chronic comorbidities were other concerns. CONCLUSION: The outcomes of the ICDM model need to be strengthened and scaled up to meet the unique health needs and challenges of people living with HIV and other chronic conditions. Strengthening these outcomes includes providing capacity building and training on the delivery of chronic care treatment under the ICDM model, assisted self-management to improve patient responsibility of chronic disease management and strengthening activities for comorbidity health promotion.

Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV.

BACKGROUND: Pulmonary tuberculosis (TB) in people living with HIV (PLH) frequently presents as sputum smear-negative. However, clinical trials of TB in adults often use smear-positive individuals to ensure measurable bacterial responses following initiation of treatment, thereby excluding HIV-infected patients from trials. METHODS: In this prospective case cohort study, 118 HIV-seropositive TB patients were assessed prior to initiation of standard four-drug TB therapy and at several time points through 35 days. Sputum bacillary load, as a marker of treatment response, was determined serially by: smear microscopy, Xpert MTB/RIF, liquid culture, and colony counts on agar medium. RESULTS: By all four measures, patients who were baseline smear-positive had higher bacterial loads than those presenting as smear-negative, until day 35. However, most smear-negative PLH had significant bacillary load at enrolment and their mycobacteria were cleared more rapidly than smear-positive patients. Smear-negative patients' decline in bacillary load, determined by colony counts, was linear to day 7 suggesting measurable bactericidal activity. Moreover, the decrease in bacterial counts was comparable to smear-positive individuals. Increasing cycle threshold values (Ct) on the Xpert assay in smear-positive patients to day 14 implied decreasing bacterial load. CONCLUSION: Our data suggest that smear-negative PLH can be included in clinical trials of novel treatment regimens as they contain sufficient viable bacteria, but allowances for late exclusions would have to be made in sample size estimations. We also show that increases in Ct in smear-positive patients to day 14 reflect treatment responses and the Xpert MTB/RIF assay could be used as biomarker for early treatment response.

Estimating the contribution of key populations towards HIV transmission in South Africa.

INTRODUCTION: In generalized epidemic settings, there is insufficient understanding of how the unmet HIV prevention and treatment needs of key populations (KPs), such as female sex workers (FSWs) and men who have sex with men (MSM), contribute to HIV transmission. In such settings, it is typically assumed that HIV transmission is driven by the general population. We estimated the contribution of commercial sex, sex between men, and other heterosexual partnerships to HIV transmission in South Africa (SA). METHODS: We developed the "Key-Pop Model"; a dynamic transmission model of HIV among FSWs, their clients, MSM, and the broader population in SA. The model was parameterized and calibrated using demographic, behavioural and epidemiological data from national household surveys and KP surveys. We estimated the contribution of commercial sex, sex between men and sex among heterosexual partnerships of different sub-groups to HIV transmission over 2010 to 2019. We also estimated the efficiency (HIV infections averted per person-year of intervention) and prevented fraction (% IA) over 10-years from scaling-up ART (to 81% coverage) in different sub-populations from 2020. RESULTS: Sex between FSWs and their paying clients, and between clients with their non-paying partners contributed 6.9% (95% credibility interval 4.5% to 9.3%) and 41.9% (35.1% to 53.2%) of new HIV infections in SA over 2010 to 2019 respectively. Sex between low-risk groups contributed 59.7% (47.6% to 68.5%), sex between men contributed 5.3% (2.3% to 14.1%) and sex between MSM and their female partners contributed 3.7% (1.6% to 9.8%). Going forward, the largest population-level impact on HIV transmission can be achieved from scaling up ART to clients of FSWs (% IA = 18.2% (14.0% to 24.4%) or low-risk individuals (% IA = 20.6% (14.7 to 27.5) over 2020 to 2030), with ART scale-up among KPs being most efficient. CONCLUSIONS: Clients of FSWs play a fundamental role in HIV transmission in SA. Addressing the HIV prevention and treatment needs of KPs in generalized HIV epidemics is central to a comprehensive HIV response.

Post-trial perceptions of a symptom-based TB screening intervention in South Africa: implementation insights and future directions for TB preventive healthcare services.

BACKGROUND: Tuberculosis is a top-10 cause of under-5 mortality, despite policies promoting tuberculosis preventive therapy (TPT). We previously conducted a cluster randomized trial to evaluate the effectiveness of symptom-based versus tuberculin skin-based screening on child TPT uptake. Symptom-based screening did not improve TPT uptake and nearly two-thirds of child contacts were not identified or not linked to care. Here we qualitatively explored healthcare provider perceptions of factors that impacted TPT uptake among child contacts. METHODS: Sixteen in-depth interviews were conducted with key informants including healthcare providers and administrators who participated in the trial in Matlosana, South Africa. The participants' experience with symptom-based screening, study implementation strategies, and ongoing challenges with child contact identification and linkage to care were explored. Interviews were systematically coded and thematic content analysis was conducted. RESULTS: Participants' had mixed opinions about symptom-based screening and high acceptability of the study implementation strategies. A key barrier to optimizing child contact screening and evaluation was the supervision and training of community health workers. CONCLUSIONS: Symptom screening is a simple and effective strategy to evaluate child contacts, but additional pediatric training is needed to provide comfort with decision making. New clinic-based child contact files were highly valued by providers who continued to use them after trial completion. Future interventions to improve child contact management will need to address how to best utilize community health workers in identifying and linking child contacts to care. TRIAL REGISTRATION: The results presented here were from research related to NCT03074799 , retrospectively registered on 9 March 2017.

Prevalence and risk factors for latent tuberculosis infection among household contacts of index cases in two South African provinces: Analysis of baseline data from a cluster-randomised trial.

INTRODUCTION: Household contacts of patients with active pulmonary tuberculosis (TB) often have latent TB infection, and are at risk of progression to disease. We set out to investigate whether index TB case HIV status was linked to a higher probability of latent TB infection among household contacts. MATERIALS AND METHODS: Data were collected prospectively from participants in the intervention arm of a household cluster-randomised trial in two South Africa provinces (Mangaung, Free State, and Capricorn, Limpopo). In intervention group households, TB contacts underwent HIV testing and tuberculin skin testing (TST). TST induration was estimated at two cut-offs (≥5mm, ≥10mm). Multilevel Bayesian regression models estimated posterior distributions of the percentage of household contacts with TST induration ≥5mm and ≥10mm by age group, and compared the odds of latent TB infection by key risk factors including HIV status index case age and study province. RESULTS: A total of 2,985 household contacts of 924 index cases were assessed, with most 2,725 (91.3%) undergoing TST. HIV prevalence in household contacts was 14% and 10% in Mangaung and Capricorn respectively. Overall, 16.8% (458/2,725) had TST induration of ≥5mm and 13.1% (359/2,725) ≥10mm. In Mangaung, children aged 0-4 years had a high TST positivity prevalence compared to their peers in Capricorn (22.0% vs. 7.6%, and 20.5% vs. 2.3%, using TST thresholds of ≥5mm and ≥10mm respectively). Compared to contacts from Capricorn, household contacts living in Mangaung were more likely to have TST induration ≥5mm (odds ratio [OR]: 3.08, 95% credibility interval [CI]: 2.13-4.58) and ≥10mm (OR: 4.52, 95% CI: 3.03-6.97). There was a 90% and 92% posterior probability that the odds of TST induration ≥5mm (OR: 0.79, 95% CI: 0.56-1.14) and ≥10mm (OR: 0.77, 95% CI: 0.53-1.10) respectively were lower in household contacts of HIV-positive compared to HIV-negative index cases. CONCLUSIONS: High TST induration positivity, especially among young children and people living in Mangaung indicates considerable TB transmission despite high antiretroviral therapy coverage. Household contact of HIV-positive index TB cases were less likely to have evidence of latent TB infection than contacts of HIV-negative index cases.