Migrant men and HIV care engagement in Johannesburg, South Africa.

BACKGROUND: South Africa (SA) has one of the highest rates of migration on the continent, largely comprised of men seeking labor opportunities in urban centers. Migrant men are at risk for challenges engaging in HIV care. However, rates of HIV and patterns of healthcare engagement among migrant men in urban Johannesburg are poorly understood. METHODS: We analyzed data from 150 adult men (≥ 18 years) recruited in 10/2020-11/2020 at one of five sites in Johannesburg, Gauteng Province, SA where migrants typically gather for work, shelter, transit, or leisure: a factory, building materials store, homeless shelter, taxi rank, and public park. Participants were surveyed to assess migration factors (e.g., birth location, residency status), self-reported HIV status, and use and knowledge of HIV and general health services. Proportions were calculated with descriptive statistics. Associations between migration factors and health outcomes were examined with Fisher exact tests and logistic regression models. Internal migrants, who travel within the country, were defined as South African men born outside Gauteng Province. International migrants were defined as men born outside SA. RESULTS: Two fifths (60/150, 40%) of participants were internal migrants and one fifth (33/150, 22%) were international migrants. More internal migrants reported living with HIV than non-migrants (20% vs 6%, p = 0.042), though in a multi-variate analysis controlling for age, being an internal migrant was not a significant predictor of self-reported HIV positive status. Over 90% all participants had undergone an HIV test in their lifetime. Less than 20% of all participants had heard of pre-exposure prophylaxis (PrEP), with only 12% international migrants having familiarity with PrEP. Over twice as many individuals without permanent residency or citizenship reported "never visiting a health facility," as compared to citizens/permanent residents (28.6% vs. 10.6%, p = 0.073). CONCLUSIONS: Our study revealed a high proportion of migrants within our community-based sample of men and demonstrated a need for HIV and other healthcare services that effectively reach migrants in Johannesburg. Future research is warranted to further disaggregate this heterogenous population by different dimensions of mobility and to understand how to design HIV programs in ways that will address migrants' challenges.

Strategies to improve antiretroviral therapy (ART) initiation and early engagement among men in sub-Saharan Africa: A scoping review of interventions in the era of universal treatment.

OBJECTIVES: Men in sub-Saharan Africa (SSA) have lower rates of antiretroviral therapy (ART) initiation and higher rates of early default than women. Little is known about effective interventions to improve men's outcomes. We conducted a scoping review of interventions aimed to increase ART initiation and/or early retention among men in SSA since universal treatment policies were implemented. METHODS: Three databases, HIV conference databases and grey literature were searched for studies published between January 2016 to May 2021 that reported on initiation and/or early retention among men. Eligibility criteria included: participants in SSA, data collected after universal treatment policies were implemented (2016-2021), quantitative data on ART initiation and/or early retention for males, general male population (not exclusively focused on key populations), intervention study (report outcomes for at least one non-standard service delivery strategy), and written in English. RESULTS: Of the 4351 sources retrieved, 15 (reporting on 16 interventions) met inclusion criteria. Of the 16 interventions, only two (2/16, 13%) exclusively focused on men. Five (5/16, 31%) were randomised control trials (RCT), one (1/16, 6%) was a retrospective cohort study, and 10 (10/16, 63%) did not have comparison groups. Thirteen (13/16, 81%) interventions measured ART initiation and six (6/16, 37%) measured early retention. Outcome definitions and time frames varied greatly, with seven (7/16, 44%) not specifying time frames at all. Five types of interventions were represented: optimising ART services at health facilities, community-based ART services, outreach support (such as reminders and facility escort), counselling and/or peer support, and conditional incentives. Across all intervention types, ART initiation rates ranged from 27% to 97% and early retention from 47% to 95%. CONCLUSIONS: Despite years of data of men's suboptimal ART outcomes, there is little high-quality evidence on interventions to increase men's ART initiation or early retention in SSA. Additional randomised or quasi-experimental studies are urgently needed.

Understanding school-going adolescent's preferences for accessing HIV and contraceptive care: findings from a discrete choice experiment among learners in Gauteng, South Africa.

BACKGROUND: Many Adolescents in Sub-Saharan Africa do not access HIV and reproductive health services optimally. To improve uptake of these services, it is important to understand the Learners' preferences for how services are delivered so that implementation strategies can reflect this. METHODS: A discrete choice experiment (DCE) was used to elicit preferences. The DCE was completed between 07/2018 and 09/2019 and conducted in 10 high schools situated in neighbourhoods of varying socio-economic status (SES) in Gauteng (South Africa). Learners aged ≥ 15 years (Grades 9-12) were consented and enrolled in the DCE. Parental consent and assent were required if < 18 years old. Conditional logistic regression was used to determine preferred attributes for HIV and contraceptive service delivery. Results were stratified by gender and neighbourhood SES quintile (1 = Lowest SES; 5 = Highest SES). RESULTS: 805 Learners were enrolled (67% female; 66% 15-17 years; 51% in grades 9-10). 54% of Learners in quintile 1 schools had no monthly income (family support, grants, part-time jobs etc.); 38% in quintile 5 schools had access to R100 ($7.55) per month. Preferences for accessing HIV and contraceptive services were similar for male and female Learners. Learners strongly preferred services provided by friendly, non-judgmental staff (Odds ratio 1.63; 95% Confidence Interval: 1.55-1.72) where confidentiality was ensured (1.33; 1.26-1.40). They preferred services offered after school (1.14; 1.04-1.25) with value-added services like free Wi-Fi (1.19; 1.07-1.32), food (1.23; 1.11-1.37) and youth-only waiting areas (1.18; 1.07-1.32). Learners did not have a specific location preference, but preferred not to receive services within the community (0.82; 0.74-0.91) or school (0.88; 0.80-0.96). Costs to access services were a deterrent for most Learners irrespective of school neighbourhood; female Learners were deterred by costs ≥$3.85 (0.79; 0.70-0.91); males by costs ≥ R100 ($7.55) (0.86; 0.74-1.00). CONCLUSIONS: Preferences that encourage utilisation of services do not significantly differ by gender or school neighbourhood SES. Staff attitude and confidentiality are key issues affecting Learners' decisions to access HIV and contraceptive services. Addressing how healthcare providers respond to young people seeking sexual and reproductive health services is critical for improving adolescents' uptake of these services.

One Pill, Once a Day: Simplified Treatment Regimens and Retention in HIV Care.

Simplified drug regimens may improve retention in care for persons with chronic diseases. In April 2013, South Africa adopted a once-daily single-pill human immunodeficiency virus (HIV) treatment regimen as the standard of care, replacing a multiple-pill regimen. Because the regimens had similar biological efficacy, the shift to single-pill therapy offered a real-world test of the impact of simplified drug-delivery mechanisms on patient behavior. Using a quasi-experimental regression discontinuity design, we assessed retention in care among patients starting HIV treatment just before and just after the guideline change. The study included 4,484 patients starting treatment at a large public sector clinic in Johannesburg, South Africa. The share of patients prescribed a single-pill regimen increased by over 40 percentage points between March and April 2013. Initiating treatment after the policy change was associated with 11.7-percentage-points' higher retention at 12 months (95% confidence interval: -2.2, 29.4). Findings were robust to different measures of retention, different bandwidths, and different statistical models. Patients starting treatment early in HIV infection-a key population in the test-and-treat era-experienced the greatest improvements in retention from single-pill regimens.

Reduction in initiations of HIV treatment in South Africa during the COVID pandemic.

BACKGROUND: In response to the global pandemic of COVID-19, countries around the world began imposing stay-at-home orders, restrictions on transport, and closures of businesses in early 2020. South Africa implemented a strict lockdown in March 2020 before its first COVID-19 wave started, gradually lifted restrictions between May and September 2020, and then re-imposed restrictions in December 2020 in response to its second wave. There is concern that COVID-19-related morbidity and mortality, fear of transmission, and government responses may have led to a reduction in antiretroviral treatment (ART) initiations for HIV-infected individuals in countries like South Africa. METHODS: We analyzed national, public sector, facility-level data from South Africa's District Health Information System (DHIS) from January 2019 to March 2021 to quantify changes in ART initiation rates stratified by province, setting, facility size and type and compared the timing of these changes to COVID-19 case numbers and government lockdown levels. We excluded facilities with missing data, mobile clinics, and correctional facilities. We estimated the total number of ART initiations per study month for each stratum and compared monthly totals, by year. RESULTS: At the 2471 facilities in the final data set (59% of all ART sites in the DHIS), 28% fewer initiations occurred in 2020 than in 2019. Numbers of ART initiations declined sharply in all provinces in April-June 2020, compared to the same months in 2019, and remained low for the rest of 2020, with some recovery between COVID-19 waves in October 2020 and possible improvement beginning in March 2021. Percentage reductions were largest in district hospitals, larger facilities, and urban areas. After the initial decline in April-June 2020, most provinces experienced a clear inverse relationship between COVID-19 cases and ART initiations but little relationship between ART initiations and lockdown level. CONCLUSIONS: The COVID-19 pandemic and responses to it resulted in substantial declines in the number of HIV-infected individuals starting treatment in South Africa, with no recovery of numbers during 2020. These delays may lead to worse treatment outcomes for those with HIV and potentially higher HIV transmission. Exceptional effort will be needed to sustain gains in combatting HIV.

Similar costs and outcomes for differentiated service delivery models for HIV treatment in Uganda.

This cost-outcome study estimated, from the perspective of the service provider, the total annual cost per client on antiretroviral therapy (ART) and total annual cost per client virally suppressed (defined as < 1000 copies/ml at the time of the study) in Uganda in five ART differentiated service delivery models (DSDMs). These included both facility- and community-based models and the standard of care (SOC), known as the facility-based individual management (FBIM) model. The Ministry of Health (MOH) adopted guidelines for DSDMs in 2017 and sought to measure their costs and outcomes, in order to effectively plan for their resourcing, implementation, and scale-up. In Uganda, the standard of care (FBIM) is considered as a DSDM option for clients requiring specialized treatment and support, or for those who select not to join an alternative DSDM. Note that clients on second-line regimes and considered as "established on treatment" can join a suitable DSDM.Using retrospective client record review of a cohort of clients over a two-year period, with bottom-up collection of clients' resource utilization data, top-down collection of above-delivery level and delivery-level providers' fixed operational costs, and local unit costs. Forty-seven DSDMs located at facilities or community-based points in the four regions of Uganda were included in the study, with 653 adults on ART (> 18 years old) enrolled in a DSDM. The study found that retention in care was 98% for the sample as a whole [96-100%], and viral suppression, 91% [86-93%]. The mean cost to the provider (MOH or NGO implementers) was $152 per annum per client treated, ranging from $141 to $166. Differences among the models' costs were largely due to clients' ARV regimens and the proportions of clients on second line regimens. Service delivery costs, excluding ARVs, other medicines and laboratory tests, were modest, ranging from $9.66-16.43 per client per year. We conclude that differentiated ART service delivery in Uganda achieved excellent treatment outcomes at a cost similar to the standard of care. While large budgetary savings might not be immediately realized, the reallocation of "saved" staff time could improve health system efficiency and with their equivalent or better outcomes and large benefits to clients, client-centred differentiated models would nevertheless add great societal value.

Treatment and pregnancy outcomes of pregnant women exposed to second-line anti-tuberculosis drugs in South Africa.

BACKGROUND: Multi-drug resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) in pregnant women is a cause for concern globally; few data have described the safety of second-line anti-TB medications during pregnancy. We aim to describe TB treatment and pregnancy outcomes among pregnant women receiving second-line anti-tuberculosis treatment for MDR/RR-TB in Johannesburg, South Africa. METHODS: We conducted a retrospective record review of pregnant women (≥ 18 years) who received treatment for MDR/RR-TB between 01/2010-08/2016 at three outpatient treatment sites in Johannesburg, South Africa. Demographic, treatment and pregnancy outcome data were collected from available medical records. Preterm birth (< 37 weeks), and miscarriage were categorized as adverse pregnancy outcomes. RESULTS: Out of 720 women of child-bearing age who received MDR/RR-TB treatment at the three study sites, 35 (4.4%) pregnancies were identified. Overall, 68.7% (24/35) were HIV infected, 83.3% (20/24) were on antiretroviral therapy (ART). Most women, 88.6% (31/35), were pregnant at the time of MDR/RR-TB diagnosis and four women became pregnant during treatment. Pregnancy outcomes were available for 20/35 (57.1%) women, which included 15 live births (11 occurred prior to 37 weeks), 1 neonatal death, 1 miscarriage and 3 pregnancy terminations. Overall, 13/20 (65.0%) women with known pregnancy outcomes had an adverse pregnancy outcome. Of the 28 women with known TB treatment outcomes 17 (60.7%) completed treatment successfully (4 were cured and 13 completed treatment), 3 (10.7%) died and 8 (28.6%) were lost-to-follow-up. CONCLUSIONS: Pregnant women with MDR/RR-TB suffer from high rates of adverse pregnancy outcomes and about 60% achieve a successful TB treatment outcome. These vulnerable patients require close monitoring and coordinated obstetric, HIV and TB care.

Primary healthcare seeking behaviour of low-income patients across the public and private health sectors in South Africa.

BACKGROUND: The proposed National Health Insurance (NHI) system aims to re-engineer primary healthcare (PHC) in South Africa, envisioning both private sector providers and public sector clinics as independent contracting units to the NHI Fund. In 2017, 16% of the South African population had private medical insurance and predominately utilised private providers. However, it is estimated that up to 28% of the population access private PHC services, with a meaningful segment of the low-income, uninsured population paying for these services out-of-pocket. The study objective was to characterise the health seeking behaviour of low-income, patients accessing PHC services in both the public and private sectors, patient movement between sectors, and factors influencing their facility choice. METHODS: We conducted once-off patient interviews on a random sample of 153 patients at 7 private PHC providers (primarily providing services to the low-income mostly uninsured patient population) and their matched public PHC clinic (7 facilities). RESULTS: The majority of participants were economically active (96/153, 63%), 139/153 (91%) did not have health insurance, and 104/153 (68%) earned up to $621/month. A multiple response question found affordability (67%) and convenience (60%) were ranked as the most important reasons for choosing to usually access care at public clinics (48%); whilst convenience (71%) and quality of care (59%) were key reasons for choosing the private sector (32%). There is movement between sectors: 23/76 (30%) of those interviewed at a private facility and 8/77 (10%) of those interviewed at a public facility indicated usually accessing PHC services at a mix of private and public facilities. Results indicate cycling between the private and public sectors with different factors influencing facility choice. CONCLUSIONS: It is imperative to understand the potential impact on where PHC services are accessed once affordability is mitigated through the NHI as this has implications on planning and contracting of services under the NHI.

Understanding the costs and the cost structure of a community-based HIV and gender-based violence (GBV) prevention program: the Woza Asibonisane Community Responses Program in South Africa.

BACKGROUND: The Woza Asibonisane Community Responses (CR) Programme was developed to prevent HIV infections and gender-based violence (GBV) within four provinces in South Africa. The Centre for Communication Impact (CCI) in collaboration with six partner non-governmental organizations (NGOs) implemented the programme, which was comprised of multiple types of group discussion and education activities organized and facilitated by each NGO. To date, little information exists on the cost of implementing such multi-objective, multi-activity, community-based programmes. To address this information gap, we estimated the annual cost of implementing the CR Programme for each NGO. METHODS: We used standard methods to estimate the costs for each NGO, which involved a package of multiple activities targeted to distinct subpopulations in specific locations. The primary sources of information came from the implementing organizations. Costs (US dollars, 2017) are reported for each partner for one implementation year (the U.S. Government fiscal year (10/2016-09/2017). In addition to total costs disaggregated by main input categories, a common metric--cost per participant intervention hour--is used to summarize costs across partners. RESULTS: Each activity included in the CR program involve organizing and bringing together a group of people from the target population to a location and then completing the curriculum for that activity. Activities were held in community settings (meeting hall, community center, sports grounds, schools, etc.). The annual cost per NGO varied substantially, from $260,302 to $740,413, as did scale based on estimated total participant hours, from 101,703 to 187,792 participant hours. The cost per participant hour varied from $2.8-$4.6, with NGO labor disaggregated into salaries for management and salaries for service delivery (providing the activity curriculum) contributing to the largest share of costs per participant hour. CONCLUSIONS: The cost of implementing any community-based program depends on: (1) what the program implements; (2) the resources used; and (3) unit costs for such resources. Reporting on costs alone, however, does not provide enough information to evaluate if the costs are 'too high' or 'too low' without a clearer understanding of the benefits produced by the program, and if the benefits would change if resources (and therefore costs) were changed.

When donor funding leaves: an interrupted time-series analysis of the impact of integrating direct HIV care and treatment into public health services in a region of Johannesburg.

BACKGROUND: Early in South Africa's HIV response, donor-funded organizations directly provided HIV treatment through Comprehensive HIV Care, Management and Treatment sites (CCMTs), using their own and government staff. From 2012 to 2014 the donor-funded CCMT model was phased out, leaving nurses in South Africa's public clinics responsible for delivery of antiretroviral treatment (ART) services. We aimed to examine the impact on resources, staff workloads, and service delivery throughout this period of integration of HIV treatment into primary health clinics. METHODS: We conducted an Interrupted Time-Series Analysis (ITSA) using data from three public clinics, including one former CCMT site, in one administrative region of Johannesburg. The ITSA was complemented by visual inspection of the data in Excel. We compared trends in expenditure, clinical staffing levels, patient headcounts, and services rendered at the clinics during four periods: pre-CCMT (2004-2007), CCMT operational (2007-2012), CCMT closure (2012-2014), and post-CCMT (2014-2016). Data were drawn from the country's District Health Information System, a national HIV treatment database, local budget and expenditure reports, National Health Laboratory Service charge records, and staff records. RESULTS: Closure of the CCMT differentially impacted the study clinics. As expected, ART services decreased at Clinic 1, where the CCMT was co-located, and increased at Clinics 2 and 3 possibly reflecting redistribution of patients. Despite a reduction in patient headcounts post-CCMT, Clinic 1 experienced a decrease in staff and a large increase in patients seen per clinical staff member per month. In contrast, Clinics 2 and 3 increased or maintained stable workforces, and staff workloads post closure were similar to pre-closure levels. Other primary care services-contraception and immunisations-seemed largely unaffected at Clinics 1 and 2. At Clinic 3, service delivery reduced, but this was accompanied by lowered patient headcounts generally, likely due to clinic renovations. CONCLUSIONS: In this study, integration of HIV treatment into primary healthcare services did not result in large-scale reductions in overall service delivery. One facility did experience increased staff workloads, but we were unable to assess service quality. To mitigate potential problems, monitoring systems should be introduced in advance and acknowledge the disparate and decentralised management of various data sources.

The impact of adverse events on health-related quality of life among patients receiving treatment for drug-resistant tuberculosis in Johannesburg, South Africa.

BACKGROUND: Adverse events (AEs) are common during treatment of drug-resistant tuberculosis (DR-TB). Little is known about the health-related quality of life (HRQoL) of patients receiving treatment for DR-TB or the effect of AEs on HRQoL. METHODS: We conducted a cross-sectional study among adult patients with laboratory-confirmed rifampicin resistant tuberculosis (TB) on DR-TB treatment at a public-sector outpatient DR-TB clinic in Johannesburg, South Africa between 02/2015-01/2018. Data on HRQoL using the Medical Outcomes Short Form-36 (SF-36) questionnaire and self-reported AEs were collected by trained interviewers through face-to-face interviews. We report averages for the eight major domains and mental (MCS) and physical health (PCS) component summary scores, stratified by whether AEs were reported in the last four weeks. For comparative purposes, we enrolled two other patient groups and included data on a separate group of healthy adults. RESULTS: We enrolled 149 DR-TB patients (median age 36 years IQR 29-43, 55% male, 77.9% HIV-positive, 81% on ART, 61.8% on a standard long-course regimen and 44.3% on DR-TB treatment for less than 6 months). 58/149 (38.9%) patients reported a total of 122 AEs in the preceding 4 weeks, of these the most common were joint pain (n = 22), peripheral neuropathy (n = 16), hearing loss (n = 15), nausea and vomiting (n = 12) and dizziness or vertigo (n = 11). SF-36 domains and summary scores (MCS and PCS) were lower in those who reported an AE compared to those who did not, and both were lower than healthy adults. Compared to those who did not report an AE, patients who reported AEs were more likely to have a low MCS (aRR 2.24 95% CI 1.53-3.27) and PCS (aRR 1.52 95% CI 1.07-2.18) summary score. HRQoL was lower among those on DR-TB treatment for 6 months or less. CONCLUSION: Results show that DR-TB had a substantial impact on patients' quality of life, but that AEs during the early months on treatment may be responsible for reducing HRQoL even further. Our findings highlight the negative effects of injectable agents on HRQoL. Patients require an integrative patient-centered approach to deal with DR-TB and HIV and the potential overlapping toxicities which may be worsened by concurrent treatment.

Data quality of drug-resistant tuberculosis and antiretroviral therapy electronic registers in South Africa.

BACKGROUND: To assess the quality and completeness of treatment and outcome data in the electronic tuberculosis (TB) and antiretroviral treatment (ART) registers in drug-resistant (DR-) TB patients at three treatment facilities in South Africa. METHODS: We did a retrospective cohort study using routinely-collected data from DR-TB registers of rifampicin resistant adults (≥18 years old), on ART, initiating DR-TB treatment between January 2012 and December 2013. We linked patient information from the DR-TB register to the ART register using patient identifiers and an algorithm based on string edit distance and date of birth. We describe data gaps and discrepancies found. RESULTS: Overall, 2852 DR-TB patients met our inclusion criteria based on the DR-TB register data, and of these, 1685 (59%) could be matched to the ART registers. An additional 253 patients from the DR-TB registers were found in the ART registers, having initiated ART, despite the DR-TB register indicating that they were not on ART (or this data was missing). 11% of matched patients did not have TB treatment status recorded in the ART register despite being recorded as being on TB treatment in the DR-TB register, and 78% did not have an ART start date recorded in DR-TB register despite being on ART treatment as per the ART register. 11% of matched patients had a death recorded in one register but not the other, and of those with death recorded in both, 15% of dates differed by > 1 month. CONCLUSIONS: The underreporting of death and the lack of ART or TB status in the electronic DR-TB and ART registers could negatively impact monitoring efforts by downplaying the state of the TB/HIV epidemic. Improved recording of these data sources, and data integration across systems, could improve the accuracy of reporting for the national HIV/ART and TB programs.

Effective public-private partnerships for sustainable antiretroviral therapy: outcomes of the Right to Care health services GP down-referral program.

BACKGROUND: The recently increased access to antiretroviral therapy (ART) in South Africa has placed additional strain on human and infrastructure resources of the public health sector. Capacity from private-sector General Practitioners (GPs) could be leveraged to ease the current burden on the public health sector. METHODS: We conducted a retrospective record review of routine electronic medical record data on a systematic sample of HIV-infected adults (≥18 years old) initiated on ART at a tertiary hospital outpatient HIV clinic in Johannesburg, South Africa and down-referred to private-GPs for continued care after stabilization on ART. We compared these patients ("GP down-referred") to a control-cohort who remained at the referring site ("Clinic A") and patients from a regional hospital outpatient HIV clinic not offering down-referral to GPs ("Clinic B"). Study outcomes assessed are viral load suppression (VL < 50 copies/ml) and attrition from care (all-cause-mortality or > 90-days late for a last-scheduled visit) by 12 months of follow-up following down-referral or eligibility. RESULTS: A total of 3685 patients, comprising 373 (10.1%) GP down-referred, 2599 (70.5%) clinic A controls, and 713 (19.4%) clinic B controls were included in the analysis. Overall, 1535 patients (53.3%) had a suppressed viral load. A higher portion of GP down-referred patients had a suppressed viral load compared to clinic A and B patients (65.7% vs 49.1% vs 58.9%). After adjusting for demographic and baseline clinical covariates, we found no difference in viral load suppression between GP down-referred and control patients (adjusted relative risk [aRR] for clinic A vs GP down-referred 1.0; 95% CI: 0.9-1.1), (aRR for clinic B vs GP down-referred 1.0; 95% CI: 0.9-1.2). Clinic B controls experienced the highest attrition compared to GP down-referred and clinic A controls (33.2% vs 11.3% vs 5.9%) and had a higher risk of attrition compared to GP down-referred patients (adjusted hazard ratio [aHR] 4.2; 95% CI: 2.8-6.5), whereas clinic B controls had a lower risk of attrition (aHR 0.5; 95% CI: 0.3-0.7). CONCLUSIONS AND RECOMMENDATIONS: Our results show that private-GPs can contribute to caring for stabilized public sector HIV patients on life-long ART. However, they require special efforts to improve retention in care.

Treatment outcomes among children, adolescents, and adults on treatment for tuberculosis in two metropolitan municipalities in Gauteng Province, South Africa.

BACKGROUND: Gauteng Province has the second lowest tuberculosis (TB) incidence rate in South Africa but the greatest proportion of TB/HIV co-infection, with 68% of TB patients estimated to have HIV. TB treatment outcomes are well documented at the national and provincial level; however, knowledge gaps remain on how outcomes differ across detailed age groups. METHODS: Using data from South Africa's National Electronic TB Register (ETR), we assessed all-cause mortality and loss to follow-up (LTFU) among patients initiating treatment for TB between 01/2010 and 12/2015 in the metropolitan municipalities of Ekurhuleni Metropolitan Municipality and the City of Johannesburg in Gauteng Province. We excluded patients who were missing age, had known drug-resistance, or transferred into TB care from sites outside the two metropolitan municipalities. Among patients assigned a treatment outcome, we investigated the association between age group at treatment initiation and mortality or LTFU (treatment interruption of ≥2 months) within 10 months after treatment initiation using Cox proportional hazard models and present hazard ratios and Kaplan-Meier survival curves. RESULTS: We identified 182,890 children (<10 years), young adolescent (10-14), older adolescent (15-19), young adult (20-24), adult (25-49), and older adult (≥50) TB cases without known drug-resistance. ART coverage among HIV co-infected patients was highest for young adolescents (64.3%) and lowest for young adults (54.0%) compared to other age groups (all over 60%). Treatment success exceeded 80% in all age groups (n = 170,017). All-cause mortality increased with age. Compared to adults, young adults had an increased hazard of LTFU (20-24 vs 25-49 years; aHR 1.43 95% CI: 1.33, 1.54) while children, young adolescents, and older adults had lower hazard of LTFU. Patients with HIV on ART had a lower risk of LTFU, but greater risk of death when compared to patients without HIV. CONCLUSIONS: Young adults in urban areas of Gauteng Province experience a disproportionate burden of LTFU and low coverage of ART among co-infected patients. This group should be targeted for interventions aimed at improving clinical outcomes and retention in both TB and HIV care.

Regimen durability in HIV-infected children and adolescents initiating first-line antiretroviral therapy in a large public sector HIV cohort in South Africa.

INTRODUCTION: In April 2010, tenofovir and abacavir replaced stavudine in public sector first-line antiretroviral therapy (ART) for children under 20 years old in South Africa. The association of both abacavir and tenofovir with fewer side effects and toxicities compared to stavudine could translate to increased durability of tenofovir or abacavir-based regimens. We evaluated changes over time in regimen durability for paediatric patients 3-19 years of age at eight public sector clinics in Johannesburg, South Africa. METHODS: Cohort analysis of treatment-naïve, non-pregnant paediatric patients from 3 to 19 years old initiated on ART between April 2004 and December 2013. First-line ART regimens before April 2010 consisted of stavudine or zidovudine with lamivudine and either efavirenz or nevirapine. Tenofovir and/or abacavir was substituted for stavudine after April 2010 in first-line ART. We evaluated the frequency and type of single-drug substitutions, treatment interruptions and switches to second-line therapy. Fine and Gray competing risk regression models were used to evaluate the association of antiretroviral drug type with single-drug substitutions, treatment interruptions and second-line switches in the first 24 months on treatment. RESULTS: Three hundred and ninety-eight (15.3%) single-drug substitutions, 187 (7.2%) treatment interruptions and 86 (3.3%) switches to second-line therapy occurred among 2602 paediatric patients over 24-months on ART. Overall, the rate of single-drug substitutions started to increase in 2009, peaked in 2011 at 25% and then declined to 10% in 2013, well after the integration of tenofovir into paediatric regimens; no patients over the age of 3 were initiated on abacavir for first-line therapy. Competing risk regression models showed patients on zidovudine or stavudine had upwards of a fivefold increase in single-drug substitution vs. patients initiated on tenofovir in the first 24 months on ART. Older adolescents also had a two- to threefold increase in treatment interruptions and switches to second-line therapy compared to younger patients in the first 24 months on ART. CONCLUSIONS: The decline in single-drug substitutions is associated with the introduction of tenofovir. Tenofovir use could improve regimen durability and treatment outcomes in resource-limited settings.

Acceptability and feasibility of a financial incentive intervention to improve retention in HIV care among pregnant women in Johannesburg, South Africa.

Women initiating antiretroviral therapy during pregnancy are at high risk of dropping out of HIV care after delivery. We assessed the acceptability and feasibility of a financial incentive - a one-time R50 (∼USD4) supermarket voucher for completing one postpartum visit ≤10 weeks of delivery - to improve postpartum retention. We enrolled 100 pregnant, HIV-positive women at a primary health clinic in Johannesburg, South Africa. Participants were interviewed at enrollment and we reviewed files to assess retention ≥14 weeks postpartum. Median (IQR) respondent age was 28 years (24-31) and 31% were employed. Most (86%) said the incentive would motivate them to return and 76% supported clinics offering incentives. Among the 23% who found the intervention unacceptable, the most frequent reason was perceived personal responsibility for health. Feasibility was demonstrated, as 79.7% (51/64) of eligible participants received a voucher. When asked to rank preferred hypothetical incentive interventions, assistance with social services ranked first (29%), followed by infant formula (22%) and cash (21%); assistance with social services was the top-ranked choice by both those who found the voucher incentive intervention acceptable and unacceptable. To encourage HIV-positive women to remain in care, respondents most frequently suggested health education (34%), counseling (29%), financial incentives (25%), home visits (13%), and better service (6%). Our results suggest financial incentives are acceptable, but women frequently expressed preference for integrated services and improved education and counseling to improve retention. Interventions exploring the feasibility and efficacy of education and counseling interventions to improve postpartum HIV care are warranted.

Impact of Xpert MTB/RIF and decentralized care on linkage to care and drug-resistant tuberculosis treatment outcomes in Johannesburg, South Africa.

BACKGROUND: In 2011, South Africa improved its ability to test for rifampicin-resistant TB (RR-TB) by introducing GeneXpert MTB/RIF. At the same time, the South African National TB program adopted a policy decentralized, outpatient treatment for drug resistant (DR-) TB. We aim to analyze the impact of these changes on linkage to care and DR-TB treatment outcomes. METHODS: We retrospectively matched adult patients diagnosed with laboratory-confirmed RR-TB in Johannesburg from 07/2011-06/2012 (early cohort) and 07/2013-06/2014 (late cohort) with records of patients initiating DR-TB treatment at one of the city's four public sector treatment sites. We determine the proportion of persons diagnosed with RR-TB who initiated DR-TB treatment and report time to treatment initiation (TTI) before and after the implementation of Xpert MTB/RIF roll-out in Johannesburg, South Africa. We conducted a sub-analysis among those who initiated DR-TB treatment at the decentralized outpatient DR-TB centers to determine if delays in treatment initiation have a subsequent impact on treatment outcomes. RESULTS: Five hundred ninety four patients were enrolled in the early cohort versus 713 in the late cohort. 53.8 and 36.8% of patients were diagnosed with multi-drug resistant TB in the early and late cohorts, respectively. The proportion of RR-TB confirmed cases diagnosed by Xpert MTB/RIF increased from 43.4 to 60.5% between the early and late cohorts, respectively. The proportion who initiated treatment increased from 43.1% (n = 256) to 60.3% (n = 430) in the late cohort. Pre-treatment mortality during the early and the late cohort reduced significantly from 17.5 to 5.8% while lost to follow-up remained high. Although TTI reduced by a median of 19 days, from 33 days (IQR 12-52) in the early cohort to 14 days (IQR 7-31) in the late cohort, this did not translate to improved treatment outcomes and we found no difference in terms of treatment success or on-treatment mortality for those that initiated without delay vs. those that deferred initiation. CONCLUSION: Pre-treatment mortality reduced significantly during late Xpert MTB/RIF coverage but there was no significant difference after treatment was initiated. Despite improvements there is still a significant diagnosis and treatment gap for patients diagnosed with RR-TB and improving treatment outcomes remains critical.

Tenofovir stock shortages have limited impact on clinic- and patient-level HIV treatment outcomes in public sector clinics in South Africa.

OBJECTIVE: Using data from four public sector clinics in South Africa, we sought to investigate provider- and patient-level outcomes, to understand how the 2012 tenofovir stock shortage affected the HIV care and monitoring of ART patients. METHODS: Prospective cohort analysis of ART-naïve, non-pregnant, HIV-infected patients >18 years initiating first-line ART between 1 July 2011-31 March 2013. Linear regression was used for all outcomes (number of ART initiates, days between pharmacy visits, transfers, single-drug substitutions, treatment interruptions, missed pharmacy visits, loss to follow-up and elevated viral load). We fit splines to smooth curves with knots at the beginning (1 February 2012) and end (31 August 2012) of the stock shortage and displayed results graphically by clinic. Difference-in-difference models were used to evaluate the effect of the stock shortage on outcomes. RESULTS: Results suggest a potential shift in the management of patients during the shortage, mainly fewer average days between visits during the shortage vs. before or after at all four clinics, and a significant difference in the proportion of patients missing visits during vs. before (RD: 1.2%; 95% CI: 0.5%, 2.0%). No significant difference was seen in other outcomes. CONCLUSION: While South Africa has made great strides to extend access to ART and increase the quality of the health services provided, patient care can be affected when stock shortages/outs occur. While our results show little effect on treatment outcomes, this most likely reflects the clinics' ability to mitigate the crisis by continuing to keep patient care and treatment as consistent as possible.

Treatment outcomes of over 1000 patients on second-line, protease inhibitor-based antiretroviral therapy from four public-sector HIV treatment facilities across Johannesburg, South Africa.

OBJECTIVES: To report predictors of outcomes of second-line ART for HIV treatment in a resource-limited setting. METHODS: All adult ART-naïve patients who initiated standard first-line treatment between April 2004 and February 2012 at four public-sector health facilities in Johannesburg, South Africa, experienced virologic failure and initiated standard second-line therapy were included. We assessed predictors of attrition (death and loss to follow-up [≥3 months late for a scheduled visit]) using Cox proportional hazards regression and predictors of virologic suppression (viral load <400 copies/ml ≥3 months after switch) using modified Poisson regression with robust error estimation at 1 year and ever after second-line ART initiation. RESULTS: A total of 1236 patients switched to second-line treatment in a median (IQR) of 1.9 (0.9-4.6) months after first-line virologic failure. Approximately 13% and 45% of patients were no longer in care at 1 year and at the end of follow-up, respectively. Patients with low CD4 counts (<50 vs. ≥200, aHR: 1.85; 95% CI: 1.03-3.32) at second-line switch were at greater risk for attrition by the end of follow-up. About 75% of patients suppressed by 1 year, and 85% had ever suppressed by the end of follow-up. CONCLUSIONS: Patients with poor immune status at switch to second-line ART were at greater risk of attrition and were less likely to suppress. Additional adherence support after switch may improve outcomes.

Correction: Initiating Antiretroviral Therapy for HIV at a Patient's First Clinic Visit: The RapIT Randomized Controlled Trial.

[This corrects the article DOI: 10.1371/journal.pmed.1002015.].