Costs of distributing HIV self-testing kits in Eswatini through community and workplace models.

BACKGROUND: This study evaluates the implementation and running costs of an HIV self-testing (HIVST) distribution program in Eswatini. HIVST kits were delivered through community-based and workplace models using primary and secondary distribution. Primary clients could self-test onsite or offsite. This study presents total running economic costs of kit distribution per model between April 2019 and March 2020, and estimates average cost per HIVST kit distributed, per client self-tested, per client self-tested reactive, per client confirmed positive, and per client initiating antiretroviral therapy (ART). METHODS: Distribution data and follow-up phone interviews were analysed to estimate implementation outcomes. Results were presented for each step of the care cascade using best-case and worst-case scenarios. A top-down incremental cost-analysis was conducted from the provider perspective using project expenditures. Sensitivity and scenario analyses explored effects of economic and epidemiological parameters on average costs. RESULTS: Nineteen thousand one hundred fifty-five HIVST kits were distributed to 13,031 individuals over a 12-month period, averaging 1.5 kits per recipient. 83% and 17% of kits were distributed via the community and workplace models, respectively. Clients reached via the workplace model were less likely to opt for onsite testing than clients in the community model (8% vs 29%). 6% of onsite workplace testers tested reactive compared to 2% of onsite community testers. Best-case scenario estimated 17,458 (91%) clients self-tested, 633 (4%) received reactive-test results, 606 (96%) linked to confirmatory testing, and 505 (83%) initiated ART. Personnel and HIVST kits represented 60% and 32% of total costs, respectively. Average costs were: per kit distributed US$17.23, per client tested US$18.91, per client with a reactive test US$521.54, per client confirmed positive US$550.83, and per client initiating ART US$708.60. Lower rates for testing, reactivity, and linkage to care in the worst-case scenario resulted in higher average costs along the treatment cascade. CONCLUSION: This study fills a significant evidence gap regarding costs of HIVST provision along the client care cascade in Eswatini. Workplace and community-based distribution of HIVST accompanied with effective linkage to care strategies can support countries to reach cascade objectives.

Secondary distribution of HIV self-test kits by HIV index and antenatal care clients: implementation and costing results from the STAR Initiative in South Africa.

BACKGROUND: Partner-delivered HIV self-testing kits has previously been highlighted as a safe, acceptable and effective approach to reach men. However, less is known about its real-world implementation in reaching partners of people living with HIV. We evaluated programmatic implementation of partner-delivered self-testing through antenatal care (ANC) attendees and people newly diagnosed with HIV by assessing use, positivity, linkage and cost per kit distributed. METHODS: Between April 2018 and December 2019, antenatal care (ANC) clinic attendees and people or those newly diagnosed with HIV clients across twelve clinics in three cities in South Africa were given HIVST kits (OraQuick Rapid HIV-1/2 Antibody Test, OraSure Technologies) to distribute to their sexual partners. A follow-up telephonic survey was administered to all prior consenting clients who were successfully reached by telephone to assess primary outcomes. Incremental economic costs of the implementation were estimated from the provider's perspective. RESULTS: Fourteen thousand four hundred seventy-three HIVST kits were distributed - 10,319 (71%) to ANC clients for their male partner and 29% to people newly diagnosed with HIV for their partners. Of the 4,235 ANC clients successfully followed-up, 82.1% (3,475) reportedly offered HIVST kits to their male partner with 98.1% (3,409) accepting and 97.6% (3,328) using the kit. Among ANC partners self-testing, 159 (4.8%) reported reactive HIVST results, of which 127 (79.9%) received further testing; 116 (91.3%) were diagnosed with HIV and 114 (98.3%) initiated antiretroviral therapy (ART). Of the 1,649 people newly diagnosed with HIV successfully followed-up; 1,312 (79.6%) reportedly offered HIVST kits to their partners with 95.8% (1,257) of the partners accepting and 95.9% (1,206) reported that their partners used the kit. Among these index partners, 297 (24.6%) reported reactive HIVST results of which 261 (87.9%) received further testing; 260 (99.6%) were diagnosed with HIV and 258 (99.2%) initiated ART. The average cost per HIVST distributed in the three cities was US$7.90, US$11.98, and US$14.81, respectively. CONCLUSIONS: Partner-delivered HIVST in real world implementation was able to affordably reach many male partners of ANC attendees and index partners of people newly diagnosed with HIV in South Africa. Given recent COVID-19 related restrictions, partner-delivered HIVST provides an important strategy to maintain essential testing services.

Integration of point-of-care screening for type 2 diabetes mellitus and hypertension into the COVID-19 vaccine programme in Johannesburg, South Africa.

BACKGROUND: South Africa grapples with a substantial burden of non-communicable diseases (NCDs), particularly type 2 diabetes (diabetes) and hypertension. However, these conditions are often underdiagnosed and poorly managed, further exacerbated by the strained primary healthcare (PHC) system and the disruptive impact of the COVID-19 pandemic. Integrating NCD screening with large-scale healthcare initiatives, such as COVID-19 vaccination campaigns, offers a potential solution, especially in low- and middle-income countries (LMICs). We investigated the feasibility and effectiveness of this integration. METHODS: A prospective cohort study was conducted at four government health facilities in Johannesburg, South Africa. NCD screening was incorporated into the COVID-19 vaccination campaign. Participants underwent COVID-19 rapid tests, blood glucose checks, blood pressure assessments, and anthropometric measurements. Those with elevated blood glucose or blood pressure values received referrals for diagnostic confirmation at local PHC centers. RESULTS: Among 1,376 participants screened, the overall diabetes prevalence was 4.1%, combining previously diagnosed cases and newly identified elevated blood glucose levels. Similarly, the hypertension prevalence was 19.4%, comprising pre-existing diagnoses and newly detected elevated blood pressure cases. Notably, 46.1% of participants displayed waist circumferences indicative of metabolic syndrome, more prevalent among females. Impressively, 7.8% of all participants screened were potentially newly diagnosed with diabetes or hypertension. Approximately 50% of individuals with elevated blood glucose or blood pressure successfully linked to follow-up care within four weeks. CONCLUSION: Our study underscores the value of utilizing even brief healthcare interactions as opportunities for screening additional health conditions, thereby aiding the identification of previously undiagnosed cases. Integrating NCD screenings into routine healthcare visits holds promise, especially in resource-constrained settings. Nonetheless, concerted efforts to strengthen care linkage are crucial for holistic NCD management and control. These findings provide actionable insights for addressing the NCD challenge and improving healthcare delivery in LMICs.

A quantitative assessment of the consistency of projections from five mathematical models of the HIV epidemic in South Africa: a model comparison study.

BACKGROUND: Mathematical models are increasingly used to inform HIV policy and planning. Comparing estimates obtained using different mathematical models can test the robustness of estimates and highlight research gaps. As part of a larger project aiming to determine the optimal allocation of funding for HIV services, in this study we compare projections from five mathematical models of the HIV epidemic in South Africa: EMOD-HIV, Goals, HIV-Synthesis, Optima, and Thembisa. METHODS: The five modelling groups produced estimates of the total population, HIV incidence, HIV prevalence, proportion of people living with HIV who are diagnosed, ART coverage, proportion of those on ART who are virally suppressed, AIDS-related deaths, total deaths, and the proportion of adult males who are circumcised. Estimates were made under a "status quo" scenario for the period 1990 to 2040. For each output variable we assessed the consistency of model estimates by calculating the coefficient of variation and examining the trend over time. RESULTS: For most outputs there was significant inter-model variability between 1990 and 2005, when limited data was available for calibration, good consistency from 2005 to 2025, and increasing variability towards the end of the projection period. Estimates of HIV incidence, deaths in people living with HIV, and total deaths displayed the largest long-term variability, with standard deviations between 35 and 65% of the cross-model means. Despite this variability, all models predicted a gradual decline in HIV incidence in the long-term. Projections related to the UNAIDS 95-95-95 targets were more consistent, with the coefficients of variation below 0.1 for all groups except children. CONCLUSIONS: While models produced consistent estimates for several outputs, there are areas of variability that should be investigated. This is important if projections are to be used in subsequent cost-effectiveness studies.

The costs of interventions for type 2 diabetes mellitus, hypertension and cardiovascular disease in South Africa - a systematic literature review.

BACKGROUND: In the context of a move to universal health coverage, three separate systematic reviews were conducted to summarise available evidence on the direct costs of interventions for type 2 diabetes mellitus, hypertension, and cardiovascular disease in South Africa. METHODS: PubMed® and Web of Science was searched for literature published between 01 and 1995 and 27 October 2022. Additionally, reference and citations lists of retrieved articles and experts were consulted. We also tracked reference lists of previous, related systematic reviews. Eligible publications were cost analyses of clinical interventions targeted at adults age 15 + reporting primary estimates of in- and out-of-hospital costs from a provider perspective. Costs were extracted and converted to 2021 US dollars, and article methodological and reporting quality was appraised using the 2013 CHEERS checklist. RESULTS: Of the 600, 1,172 and 1,466 identified publications for type 2 diabetes mellitus, hypertension, and cardiovascular disease, respectively, 10, 12, and 17 met full inclusion criteria. 60% of articles reported cardiovascular disease costs, 52% were of good reporting quality, and 10%, 50%, and 39% of type 2 diabetes mellitus, hypertension and cardiovascular disease papers reported private-sector costs only. Hypertension drug costs ranged from $2 to $85 per person-month, while type 2 diabetes mellitus drug costs ranged between $57 and $630 per person-year (ppy). Diabetes-related complication treatment costs ranged from $55 for retinopathy treatment to $25,193 ppy for haemodialysis, while cardiovascular disease treatment costs were between $160 and $37,491 ppy. Drugs and treatment of complications were major cost drivers for hypertension and type 2 diabetes mellitus, while hospitalisation drove cardiovascular disease costs. CONCLUSION: The intervention costs of type 2 diabetes mellitus, hypertension and cardiovascular disease care have received more attention recently, particularly diabetes-related complications and cardiovascular disease. However, 39% of identified cardiovascular disease treatment costs used a private sector perspective, leaving significant research gaps in the public sector and the cheaper to treat hypertension and type 2 diabetes mellitus. This review fills an information gap regarding the intervention costs of these diseases in South Africa.

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.

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.

The Role of Remdesivir in South Africa: Preventing COVID-19 Deaths Through Increasing Intensive Care Unit Capacity.

Countries such as South Africa have limited intensive care unit (ICU) capacity to handle the expected number of patients with COVID-19 requiring ICU care. Remdesivir can prevent deaths in countries such as South Africa by decreasing the number of days people spend in ICU, therefore freeing up ICU bed capacity.

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.

Evidence for scaling up HIV treatment in sub-Saharan Africa: A call for incorporating health system constraints.

Jan Hontelez and colleagues argue that the cost-effectiveness studies of HIV treatment scale-up need to include health system constraints to be more informative.

Designing an optimal HIV programme for South Africa: Does the optimal package change when diminishing returns are considered?

BACKGROUND: South Africa has a large domestically funded HIV programme with highly saturated coverage levels for most prevention and treatment interventions. To further optimise its allocative efficiency, we designed a novel optimisation method and examined whether the optimal package of interventions changes when interaction and non-linear scale-up effects are incorporated into cost-effectiveness analysis. METHODS: The conventional league table method in cost-effectiveness analysis relies on the assumption of independence between interventions. We added methodology that allowed the simultaneous consideration of a large number of HIV interventions and their potentially diminishing marginal returns to scale. We analysed the incremental cost effectiveness ratio (ICER) of 16 HIV interventions based on a well-calibrated epidemiological model that accounted for interaction and non-linear scale-up effects, a custom cost model, and an optimisation routine that iteratively added the most cost-effective intervention onto a rolling baseline before evaluating all remaining options. We compared our results with those based on a league table. RESULTS: The rank order of interventions did not differ substantially between the two methods- in each, increasing condom availability and male medical circumcision were found to be most cost-effective, followed by anti-retroviral therapy at current guidelines. However, interventions were less cost-effective throughout when evaluated under the optimisation method, indicating substantial diminishing marginal returns, with ICERs being on average 437% higher under our optimisation routine. CONCLUSIONS: Conventional league tables may exaggerate the cost-effectiveness of interventions when programmes are implemented at scale. Accounting for interaction and non-linear scale-up effects provides more realistic estimates in highly saturated real-world settings.

The Impact of Company-Level ART Provision to a Mining Workforce in South Africa: A Cost-Benefit Analysis.

BACKGROUND: HIV impacts heavily on the operating costs of companies in sub-Saharan Africa, with many companies now providing antiretroviral therapy (ART) programmes in the workplace. A full cost-benefit analysis of workplace ART provision has not been conducted using primary data. We developed a dynamic health-state transition model to estimate the economic impact of HIV and the cost-benefit of ART provision in a mining company in South Africa between 2003 and 2022. METHODS AND FINDINGS: A dynamic health-state transition model, called the Workplace Impact Model (WIM), was parameterised with workplace data on workforce size, composition, turnover, HIV incidence, and CD4 cell count development. Bottom-up cost analyses from the employer perspective supplied data on inpatient and outpatient resource utilisation and the costs of absenteeism and replacement of sick workers. The model was fitted to workforce HIV prevalence and separation data while incorporating parameter uncertainty; univariate sensitivity analyses were used to assess the robustness of the model findings. As ART coverage increases from 10% to 97% of eligible employees, increases in survival and retention of HIV-positive employees and associated reductions in absenteeism and benefit payments lead to cost savings compared to a scenario of no treatment provision, with the annual cost of HIV to the company decreasing by 5% (90% credibility interval [CrI] 2%-8%) and the mean cost per HIV-positive employee decreasing by 14% (90% CrI 7%-19%) by 2022. This translates into an average saving of US$950,215 (90% CrI US$220,879-US$1.6 million) per year; 80% of these cost savings are due to reductions in benefit payments and inpatient care costs. Although findings are sensitive to assumptions regarding incidence and absenteeism, ART is cost-saving under considerable parameter uncertainty and in all tested scenarios, including when prevalence is reduced to 1%-except when no benefits were paid out to employees leaving the workforce and when absenteeism rates were half of what data suggested. Scaling up ART further through a universal test and treat strategy doubles savings; incorporating ART for family members reduces savings but is still marginally cost-saving compared to no treatment. Our analysis was limited to the direct cost of HIV to companies and did not examine the impact of HIV prevention policies on the miners or their families, and a few model inputs were based on limited data, though in sensitivity analysis our results were found to be robust to changes to these inputs along plausible ranges. CONCLUSIONS: Workplace ART provision can be cost-saving for companies in high HIV prevalence settings due to reductions in healthcare costs, absenteeism, and staff turnover. Company-sponsored HIV counselling and voluntary testing with ensuing treatment of all HIV-positive employees and family members should be implemented universally at workplaces in countries with high HIV prevalence.

Cost-effectiveness of tenofovir gel in urban South Africa: model projections of HIV impact and threshold product prices.

BACKGROUND: There is urgent need for effective HIV prevention methods that women can initiate. The CAPRISA 004 trial showed that a tenofovir-based vaginal microbicide had significant impact on HIV incidence among women. This study uses the trial findings to estimate the population-level impact of the gel on HIV and HSV-2 transmission, and price thresholds at which widespread product introduction would be as cost-effective as male circumcision in urban South Africa. METHODS: The estimated 'per sex-act' HIV and HSV-2 efficacies were imputed from CAPRISA 004. A dynamic HIV/STI transmission model, parameterised and fitted to Gauteng (HIV prevalence of 16.9% in 2008), South Africa, was used to estimate the impact of gel use over 15 years. Uptake was assumed to increase linearly to 30% over 10 years, with gel use in 72% of sex-acts. Full economic programme and averted HIV treatment costs were modelled. Cost per DALY averted is estimated and a microbicide price that equalises its cost-effectiveness to that of male circumcision is estimated. RESULTS: Using plausible assumptions about product introduction, we predict that tenofovir gel use could lead to a 12.5% and 4.9% reduction in HIV and HSV-2 incidence respectively, by year 15. Microbicide introduction is predicted to be highly cost-effective (under $300 per DALY averted), though the dose price would need to be just $0.12 to be equally cost-effective as male circumcision. A single dose or highly effective (83% HIV efficacy per sex-act) regimen would allow for more realistic threshold prices ($0.25 and $0.33 per dose, respectively). CONCLUSIONS: These findings show that an effective coitally-dependent microbicide could reduce HIV incidence by 12.5% in this setting, if current condom use is maintained. For microbicides to be in the range of the most cost-effective HIV prevention interventions, product costs will need to decrease substantially.

A cost-effectiveness analysis of South Africa's COVID-19 vaccination programme.

BACKGROUND: COVID-19 vaccines were rolled out in South Africa beginning in February 2021. In this study we retrospectively assessed the cost-effectiveness of the vaccination programme in its first two years of implementation. METHOD: We modelled the costs, expressed in 2021 US$, and health outcomes of the COVID-19 vaccination programme compared to a no vaccination programme scenario. The study was conducted from a public payer's perspective over two time-horizons - nine months (February to November 2021) and twenty-four months (February 2021 to January 2023). Health outcomes were estimated from a disease transmission model parameterised with data on COVID-19-related hospitalisations and deaths and were converted to disability adjusted life years (DALYs). Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted to assess parameter uncertainty. RESULTS: Incremental cost-effectiveness ratio (ICER) was estimated at US$1600 per DALY averted during the first study time horizon. The corresponding ICER for the second study period was estimated at US$1300 per DALY averted. When 85% of all excess deaths during these periods were included in the analysis, ICERs in the first and second study periods were estimated at US$1070 and US$660 per DALY averted, respectively. In the PSA, almost 100% of simulations fell below the estimated opportunity cost-based cost-effectiveness threshold for South Africa (US$2300 DALYs averted). COVID-19 vaccination programme cost per dose had the greatest impact on the ICERs. CONCLUSION: Our findings suggest that South Africa's COVID-19 vaccination programme represented good value for money in the first two years of rollout.

The potential benefits of long-acting injectable cabotegravir in pregnant and breastfeeding women and their infants.

BACKGROUND: Pregnant and breastfeeding women (PBW) in sub-Saharan Africa have high HIV incidence rates and associated risk of vertical transmission to their infants. Oral preexposure prophylaxis (PrEP) and injectable PrEP (long-acting cabotegravir, or CAB-LA) can potentially reduce this HIV transmission, but population-level impacts are uncertain. METHODS: We extended a previously developed model of HIV and PrEP in South Africa to allow for variable PrEP duration and preference in PBW. We considered three potential scenarios for PrEP provision to PBW: oral PrEP only, CAB-LA only, and allowing oral/CAB-LA choice, with uptake and retention assumptions informed by South African data, each compared with a 'base' scenario without PrEP for PBW. RESULTS: Without PrEP for PBW, the model estimates 1.31 million new infections will occur between 2025 and 2035 in South African adults and children, including 100 000 in PBW, 16 800 in infants at/before birth, and 35 200 in children through breastmilk. In the oral PrEP-only scenario, these numbers would reduce by 1.2% (95% CI: 0.7-1.7%), 8.6% (4.8-12.9%), 4.0% (2.1-5.8%), and 5.3% (3.0-8.2%) respectively. In the CAB-LA-only scenario, the corresponding reductions would be 6.1% (2.9-9.6%), 41.2% (19.8-65.0%), 12.6% (6.0-19.4%), and 29.5% (13.9-46.8%), respectively, and in the oral/CAB-LA choice scenario, similar reductions would be achieved [5.6% (3.4-8.0%), 39% (23.4-55.9%), 12.4% (7.4-16.8%) and 27.6% (16.5-39.9%) respectively]. CONCLUSION: CAB-LA has the potential to be substantially more effective than oral PrEP in preventing HIV acquisition in PBW and vertical transmission, and can also modestly reduce HIV incidence at a population level.

Future HIV epidemic trajectories in South Africa and projected long-term consequences of reductions in general population HIV testing: a mathematical modelling study.

BACKGROUND: After successful intensive interventions to rapidly increase HIV awareness, coverage of antiretroviral therapy (ART), and viral suppression, HIV programmes in eastern and southern Africa are considering scaling back of some interventions, such as widespread general population HIV testing. We aimed to model whether scaling back of general population HIV testing in South Africa could result in a resurgence of the HIV epidemic or substantial slowing of declines in HIV incidence, resulting in increased long-term ART. METHODS: In this modelling study, we used the Thembisa 4.5 model (a deterministic compartmental model of HIV transmission in South Africa) to project the South African HIV epidemic to 2100 assuming the continuation of 2022 epidemiological conditions and HIV programme implementation. We assessed how implementing reductions in general population HIV testing services in 2025 (while maintaining antenatal, symptom-based, and risk-based testing modalities and other HIV prevention services at 2022 levels) would affect HIV incidence and prevalence among people aged 15-49 years, the year in which incidence would reach one per 1000 people aged 15-49 years (the threshold for virtual elimination of HIV), and associated costs, as well as numbers of additional new HIV infections and AIDS-related deaths. We also modelled the effects of delaying reductions in general population testing services by 5-year increments. Additionally, we modelled the potential effects of reductions in general population testing services in combination with increases or decreases in ART interruption rates (ie, the annual rate at which people who are on ART discontinue ART) and condom usage in 2025-35. FINDINGS: If general population HIV testing services and the HIV risk environment of 2022 were maintained, we projected that HIV incidence would steadily decline from 4·95 (95% CI 4·40-5·34) per 1000 population in 2025 to 0·14 (0·05-0·31) per 1000 in 2100, and that the so-called virtual elimination threshold of less than one new infection per 1000 population per year would be reached in 2055 (95% CI 2051-2060). Scaling back of general population HIV testing services by 25%, 50%, or 75% in 2025 delayed time to reaching the virtual elimination threshold by 5, 13, or 35 years, respectively, whereas complete cessation of general population testing would result in the threshold not being attained by 2100. Although the incidence of HIV continued to fall when general HIV testing services were reduced, our modelling suggested that, with reductions of between 25% and 100%, between 396 000 (95% CI 299 000-474 000) and 2·50 million (1·97 million-2·98 million) additional HIV infections and between 115 000 (94 000-135 000) and 795 000 (670 000-926 000) additional AIDS-related deaths would occur between 2025 and 2075, depending on the extent of reduction in testing. Delaying reductions in general population HIV testing services for 5-25 years mitigated some of these effects. HIV testing accounted for only 5% of total programmatic costs at baseline; reducing testing moderately reduced short-term total annual costs, but increased annual costs after 25 years. Increases in ART interruption and reductions in condom usage were projected to slow the decline in incidence and increase the coverage of general HIV testing services required to control transmission but did not cause rapid resurgence in HIV infections. INTERPRETATION: Our modelling suggests that scaling back of general population HIV testing would not result in a resurgence of HIV infections, but would delay attainment of incidence-reduction targets and result in long-term increases in HIV infections, AIDS-related deaths, and costs (via increased need for ART provision). HIV programmes need to balance short-term potential resource savings with long-term epidemic control objectives. FUNDING: Bill & Melinda Gates Foundation.

Substantial but spatially heterogeneous progress in male circumcision for HIV prevention in South Africa.

BACKGROUND: Voluntary medical male circumcision (VMMC) reduces the risk of male HIV acquisition by 60%. Programmes to provide VMMCs for HIV prevention have been introduced in sub-Saharan African countries with high HIV burden. Traditional circumcision is also a long-standing male coming-of-age ritual, but practices vary considerably across populations. Accurate estimates of circumcision coverage by age, type, and time at subnational levels are required for planning and delivering VMMCs to meet targets and evaluating their impacts on HIV incidence. METHODS: We developed a Bayesian competing risks time-to-event model to produce region-age-time-type specific probabilities and coverage of male circumcision with probabilistic uncertainty. The model jointly synthesises data from household surveys and health system data on the number of VMMCs conducted. We demonstrated the model using data from five household surveys and VMMC programme data to produce estimates of circumcision coverage for 52 districts in South Africa between 2008 and 2019. RESULTS: Nationally, in 2008, 24.1% (95% CI: 23.4-24.8%) of men aged 15-49 were traditionally circumcised and 19.4% (18.9-20.0%) were medically circumcised. Between 2010 and 2019, 4.25 million VMMCs were conducted. Circumcision coverage among men aged 15-49 increased to 64.0% (63.2-64.9%) and medical circumcision coverage to 42% (41.3-43.0%). Circumcision coverage varied widely across districts, ranging from 13.4 to 86.3%. The average age of traditional circumcision ranged between 13 and 19 years, depending on local cultural practices. CONCLUSION: South Africa has made substantial, but heterogeneous, progress towards increasing medical circumcision coverage. Detailed subnational information on coverage and practices can guide programmes to identify unmet need to achieve national and international targets.

Voluntary medical male circumcision reduces the risk of male HIV acquisition. Programmes to provide circumcisions for HIV prevention have been introduced in sub-Saharan African countries with high HIV burden. Estimates of circumcision coverage are needed for planning and delivering circumcisions to meet targets and evaluate their impacts on HIV incidence. We developed a model to integrate date from both household surveys and health systems on the number of circumcisions conducted, and applied it to understand how the practices and coverage of circumcision are changing in South Africa. National circumcision coverage increased considerably between 2008 and 2019, however, there remains a substantial subnational variation across districts and age groups. Further progress is needed to reach national and international targets.

What will it take for an injectable ARV to change the face of the HIV epidemic in high-prevalence countries? Considerations regarding drug costs and operations.

INTRODUCTION: The proven effectiveness of injectable cabotegravir (CAB-LA) is higher than that of any other HIV prevention intervention ever trialled or implemented, surpassing medical male circumcision, condoms and combination antiretroviral treatment. Based on our own analyses and experience with the South African oral pre-exposure prophylaxis (PrEP) programme, we review the supply and demand side factors that would need to be in place for a successful rollout of CAB-LA, and delineate lessons for the launch of other long-acting and extended delivery (LAED) antiretroviral drugs. DISCUSSION: On the supply side, CAB-LA will have to be offered at a price that makes the drug affordable and cost-effective to low- and middle-income countries, especially those with high HIV prevalence. An important factor in lowering prices is a guaranteed market volume, which in turn necessitates the involvement of large funders, such as PEPFAR and the Global Fund, and a fairly rapid scale-up of the drug. Such a scale-up would have to involve speedy regulatory approval and WHO pre-qualification, swift integration of CAB-LA into national guidelines and planning for large enough manufacturing capacity, including the enabling of local manufacture. On the demand side, existing demand for HIV prevention products has to be harnessed and additional demand created, which will be aided by designing CAB-LA programmes at the primary healthcare or community level, and involving non-traditional outlets, such as private pharmacies and doctors' practices. CONCLUSIONS: CAB-LA could be the game changer for HIV prevention that we have been hoping for, and serve as a useful pilot for other LAEDs. A successful rollout would involve building markets of a guaranteed size; lowering the drug's price to a level possibly below the cost of production, while also lowering the cost of production altogether; harnessing, creating and sustaining demand for the product over the long term, wherever possible, in national programmes rather than single demonstration sites; and establishing and maintaining manufacturing capacity and supply chains. For this, all parties have to work together-including originator and generic manufacturers, donor organizations and other large funders, and the governments of low- and middle-income countries, in particular those with high HIV prevalence.

The role of modelling and analytics in South African COVID-19 planning and budgeting.

BACKGROUND: The South African COVID-19 Modelling Consortium (SACMC) was established in late March 2020 to support planning and budgeting for COVID-19 related healthcare in South Africa. We developed several tools in response to the needs of decision makers in the different stages of the epidemic, allowing the South African government to plan several months ahead. METHODS: Our tools included epidemic projection models, several cost and budget impact models, and online dashboards to help government and the public visualise our projections, track case development and forecast hospital admissions. Information on new variants, including Delta and Omicron, were incorporated in real time to allow the shifting of scarce resources when necessary. RESULTS: Given the rapidly changing nature of the outbreak globally and in South Africa, the model projections were updated regularly. The updates reflected 1) the changing policy priorities over the course of the epidemic; 2) the availability of new data from South African data systems; and 3) the evolving response to COVID-19 in South Africa, such as changes in lockdown levels and ensuing mobility and contact rates, testing and contact tracing strategies and hospitalisation criteria. Insights into population behaviour required updates by incorporating notions of behavioural heterogeneity and behavioural responses to observed changes in mortality. We incorporated these aspects into developing scenarios for the third wave and developed additional methodology that allowed us to forecast required inpatient capacity. Finally, real-time analyses of the most important characteristics of the Omicron variant first identified in South Africa in November 2021 allowed us to advise policymakers early in the fourth wave that a relatively lower admission rate was likely. CONCLUSION: The SACMC's models, developed rapidly in an emergency setting and regularly updated with local data, supported national and provincial government to plan several months ahead, expand hospital capacity when needed, allocate budgets and procure additional resources where possible. Across four waves of COVID-19 cases, the SACMC continued to serve the planning needs of the government, tracking waves and supporting the national vaccine rollout.

Integration of point-of-care screening for type 2 diabetes mellitus and hypertension with COVID-19 rapid antigen screening in Johannesburg, South Africa.

AIMS: We sought to evaluate the yield and linkage-to-care for diabetes and hypertension screening alongside a study assessing the use of rapid antigen tests for COVID-19 in taxi ranks in Johannesburg, South Africa. METHODS: Participants were recruited from Germiston taxi rank. We recorded results of blood glucose (BG), blood pressure (BP), waist circumference, smoking status, height, and weight. Participants who had elevated BG (fasting ≥7.0; random ≥11.1mmol/L) and/or BP (diastolic ≥90 and systolic ≥140mmHg) were referred to their clinic and phoned to confirm linkage. RESULTS: 1169 participants were enrolled and screened for elevated BG and elevated BP. Combining participants with a previous diagnosis of diabetes (n = 23, 2.0%; 95% CI:1.3-2.9%) and those that had an elevated BG measurement (n = 60, 5.2%; 95% CI:4.1-6.6%) at study enrollment, we estimated an overall indicative prevalence of diabetes of 7.1% (95% CI:5.7-8.7%). When combining those with known hypertension at study enrollment (n = 124, 10.6%; 95% CI:8.9-12.5%) and those with elevated BP (n = 202; 17.3%; 95% CI:15.2-19.5%), we get an overall prevalence of hypertension of 27.9% (95% CI:25.4-30.1%). Only 30.0% of those with elevated BG and 16.3% of those with elevated BP linked-to-care. CONCLUSION: By opportunistically leveraging existing COVID-19 screening in South Africa to screen for diabetes and hypertension, 22% of participants received a potential new diagnosis. We had poor linkage-to-care following screening. Future research should evaluate options for improving linkage-to-care, and evaluate the large-scale feasibility of this simple screening tool.