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In economic analyses of HIV interventions, South Africa is often used as a case in point, due to the availability of good epidemiological and programme data and the global relevance of its epidemic. Few analyses however use locally relevant cost data. We reviewed available cost data as part of the South African HIV Investment Case, a modelling exercise to inform the optimal use of financial resources for the country's HIV programme. We systematically reviewed publication databases for published cost data covering a large range of HIV interventions and summarised relevant unit costs (cost per person receiving a service) for each. Where no data was found in the literature, we constructed unit costs either based on available information regarding ingredients and relevant public-sector prices, or based on expenditure records. Only 42 (5%) of 1,047 records included in our full-text review reported primary cost data on HIV interventions in South Africa, with 71% of included papers covering ART. Other papers detailed the costs of HCT, MMC, palliative and inpatient care; no papers were found on the costs of PrEP, social and behaviour change communication, and PMTCT. The results informed unit costs for 5 of 11 intervention categories included in the Investment Case, with the remainder costed based on ingredients (35%) and expenditure data (10%). A large number of modelled economic analyses of HIV interventions in South Africa use as inputs the same, often outdated, cost analyses, without reference to additional literature review. More primary cost analyses of non-ART interventions are needed.

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 use of cost-effectiveness thresholds based on a country's income per capita has been criticized for not being relevant to decision making, in particular in middle-income countries such as South Africa. The recent South African HIV Investment Case produced an alternative cost-effectiveness threshold for HIV prevention and treatment interventions based on estimates of life years saved and the country's committed HIV budget. We analysed the optimal mix of HIV interventions over a baseline of the current HIV programme under the committed HIV budget for 2016-2018. We calculated the incremental cost-effectiveness ratio (ICER) as cost per life-year saved (LYS) of 16 HIV prevention and treatment interventions over 20 years (2016-2035). We iteratively evaluated the most cost effective option (defined by an intervention and its coverage) over a rolling baseline to which the more cost effective options had already been added, thereby allowing for diminishing marginal returns to interventions. We constrained the list of interventions to those whose combined cost was affordable under the current HIV budget. Costs are presented from the government perspective, unadjusted for inflation and undiscounted, in 2016 USD. The current HIV budget of about $1.6 billion per year was sufficient to pay for the expansion of condom availability, medical male circumcision, universal treatment, and infant testing at 6 weeks to maximum coverage levels, while also implementing a social and behavior change mass media campaign with a message geared at increasing testing uptake and reducing the number of sexual partners. The combined ICER of this package of services was $547/ LYS. The ICER of the next intervention that was above the affordability threshold was $872/LYS. The results of the South African HIV Investment Case point to an HIV cost-effectiveness threshold based on affordability under the current budget of $547-872 per life year saved, a small fraction of the country's GDP per capita of about $6,000.

One of the key risk factors for cardiovascular disease is hypertension. Hypertension, which leads to heart attacks and strokes, already affects one billion people worldwide, making it a global public health issue. Incidence and prevalence of the condition is on the rise in low- and middle-income countries, with the biggest increase in sub-Saharan Africa and South Africa at the forefront. We examined the prevalence, incidence, predictors, treatment, and control of hypertension among HIV-positive patients on ART in a large South African observational cohort. We conducted a prospective study of ART naïve adults initiating ART at a public sector HIV clinic in South Africa between April 2004-2017. Patients with diagnosed hypertension at ART initiation were excluded from the incidence analysis. Log-binomial regression was used to estimate predictors of hypertension at ART initiation, while competing risks regression was used to evaluate the relationship between predictors of incident hypertension, accounting for death as a competing risk. Among 77,696 eligible patients, 22.0% had prevalent hypertension at ART initiation. Of the remaining patients with no hypertension at ART initiation, 8,125 incident hypertension cases were diagnosed over the period of follow-up, corresponding to an incident rate of 5.4 per 100 person-years (95% confidence interval (CI): 5.3-5.6). We found patients ≥40 years of age and patients with a body mass index (BMI) ≥25kg/m2 were at increased risk of both prevalent and incident hypertension. Male patients and those with pre-hypertension at ART initiation had increased hazards of hypertension over the period of follow-up. When assessing the choice of antiretroviral drug in first-line ART, patients initiated on nevirapine were at 27% increased risk of developing hypertension compared to those initiated on efavirenz, while patients who initiated on either zidovudine or stavudine had a 40% increased risk of developing hypertension compared to patients initiated on tenofovir. Patientswith poorer health status at ART initiation (i.e. WHO III/IV stage, low CD4 count, low hemoglobin levels and low BMI) had a decrease risk of prevalent hypertension. We found an inverse relationship in patients with a CD4 count <50 cells/mm3 at ART initiation who had a 25% increased risk of incident hypertension compared to those with a CD4 count ≥350 cells/mm3. Over 20% of patients in our cohort had hypertension at ART initiation, and 13% of those with normal blood pressure at ART initiation developed hypertension while on ART. Older patients, males, those on nevirapine, zidovudine or stavudine, and those who are overweight/obese should be targeted for frequent blood pressure monitoring and the identification of other cardiovascular risk factors to encourage lifestyle modifications. Additionally, these groups should be offered pharmaceutical therapy to help prevent myocardial infarction, heart failure, stroke, and kidney disease. Further research is needed to determine the level of access and adherence to pharmaceutical treatment for hypertension in this population. Additionally, an HIV-negative comparison population is needed to assess the association of the HIV virus itself with hypertension.

Replacing conventional, facility-based HIV treatment with less intensive differentiated service delivery (DSD) models could benefit DSD clients and the health system, but its value depends on maintaining or improving clinical outcomes. We compared retention and viral suppression between antiretroviral therapy (ART) clients enrolled in DSD models to those eligible for but not enrolled in DSD models in South Africa. We applied a target trial emulation (TTE) methodology to data from South Africa's electronic medical record system (TIER.Net) for 24 public-sector health facilities across three provinces and estimated retention in care (attended facility visit within 12 months) and viral suppression (<400 copies/ml3) at 12, 24, and 36 months after follow-up start date, defined as DSD enrollment date for the intervention arm and the first trial enrollment period facility visit for the comparison arm. Clients were eligible for DSD models if they were ≥18 years old, on ART ≥12 months, and had two suppressed viral load (VL) measurements, per prevailing national guidelines. For the TTE, we designated eight 6-month target trial enrollment periods between 1 July 2017 and 1 July 2021. For each period, we estimated the risk differences for retention in care and viral suppression by comparing those enrolled in DSD models to those not enrolled, using a Poisson distribution with an identity link function. We report adjusted and unadjusted risk differences for clients enrolled in DSD models and for DSD-eligible clients not enrolled in a DSD model. Estimates were adjusted for age, sex, urban/rural facility setting, province, WHO stage at ART initiation, and years on ART at trial enrollment. 49,595 unique individuals were eligible for DSD enrollment over eight target trials, contributing to a total of 148,943 trial-clients, of whom 17% (25,775) were enrolled in DSD models. The pooled adjusted risk difference for retention in care between clients enrolled in DSD and those not enrolled in DSD was 3.2% (95% confidence interval (CI) [1.6%,4.7%]) at 12 months, 4.2% (95% CI [2.4%,6.0%]) at 24 months, and 4.4% (95% CI [2.0%,6.8%]) at 36 months. For viral suppression, the adjusted risk difference comparing DSD to non-DSD was estimated to be 1.4% (95% CI [-0.5%,3.2%]) at 12 months, 1.7% (95% CI [-0.5%,4.0%]) at 24 months, and 1.4% (95% CI [-0.6%,4.4%]) at 36 months. Results remained consistent across target trials. Clients who were younger, received care from a facility in an urban settings, or had less ART experience at trial enrollment had lower retention. Study limitations include reliance on routinely collected medical records and the likely presence of residual confounding. Clients enrolled in DSD models in South Africa had slightly better retention in care and similar viral suppression to those who were eligible for but not enrolled in DSD. With better or equivalent outcomes, DSD models can be assessed on the basis of non-clinic costs and benefits, such as changes in quality of care and resource utilization. Clinicaltrials.gov NCT04149782.

Many sub-Saharan Africa countries are scaling up differentiated service delivery (DSD) models for HIV treatment to increase access and remove barriers to care. We assessed factors associated with attrition after DSD model enrollment in Zambia, focusing on patient-level characteristics. We conducted a retrospective record review using electronic medical records (EMR) of adults (≥15 years) initiated on antiretroviral (ART) between 01 January 2018 and 30 November 2021. Attrition was defined as lost to follow-up (LTFU) or died by November 30, 2021. We categorized DSD models into eight groups: fast-track, adherence groups, community pick-up points, home ART delivery, extended facility hours, facility multi-month dispensing (MMD, 4-6-month ART dispensing), frequent refill care (facility 1-2 month dispensing), and conventional care (facility 3 month dispensing, reference group). We used Fine and Gray competing risk regression to assess patient-level factors associated with attrition, stratified by sex and rural/urban setting. Of 547,281 eligible patients, 68% (n = 372,409) enrolled in DSD models, most commonly facility MMD (n = 306,430, 82%), frequent refill care (n = 47,142, 13%), and fast track (n = 14,433, 4%), with <2% enrolled in the other DSD groups. Retention was higher in nearly all DSD models for all dispensing intervals, compared to the reference group, except fast track for the ≤2 month dispensing group. Retention benefits were greatest for patients in the extended clinic hours group and least for fast track dispensing. Although retention in HIV treatment differed by DSD type, dispensing interval, and patient characteristics, nearly all DSD models out-performed conventional care. Understanding the factors that influence the retention of patients in DSD models could provide an important step towards improving DSD implementation.

Background: Coronavirus disease 2019 (COVID-19) has had a devastating impact globally, with severe health and economic consequences. To prepare health systems to deal with the pandemic, epidemiological and cost projection models are required to inform budgets and efficient allocation of resources. This study estimates daily inpatient care costs of COVID-19 in South Africa, an important input into cost projection and economic evaluation models. Methods: We adopted a micro-costing approach, which involved the identification, measurement and valuation of resources used in the clinical management of COVID-19. We considered only direct medical costs for an episode of hospitalisation from the South African public health system perspective. Resource quantities and unit costs were obtained from various sources. Inpatient costs per patient day was estimated for consumables, capital equipment and human resources for three levels of inpatient care – general wards, high care wards and intensive care units (ICUs). Results: Average daily costs per patient increased with the level of care. The highest average daily cost was estimated for ICU admissions – 271 USD to 306 USD (financial costs) and ~800 USD to 830 USD (economic costs, excluding facility fee) depending on the need for invasive vs. non-invasive ventilation (NIV). Conversely, the lowest cost was estimated for general ward-based care – 62 USD to 79 USD (financial costs) and 119 USD to 278 USD (economic costs, excluding facility fees) depending on the need for supplemental oxygen. In high care wards, total cost was estimated at 156 USD, financial costs and 277 USD, economic costs (excluding facility fees). Probabilistic sensitivity analyses suggest our costs estimates are robust to uncertainty in cost inputs. Conclusion: Our estimates of inpatient costs are useful for informing budgeting and planning processes and cost-effectiveness analysis in the South African context. However, these estimates can be adapted to inform policy decisions in other context.

Introduction In the current era of universal antiretroviral treatment (ART), health systems have the dual challenge of a growing number of people living with HIV and on ART who are also receiving chronic, life‐long treatment for non‐communicable diseases. Current evidence suggests that 6‐month multi‐month dispensing (6MMD) can maintain at least equivalent clinical outcomes to conventional care and reduce costs, but little is known when integrating 6MMD for multiple conditions. We examined the cost‐effectiveness of integrated multi‐month drug dispensing for people living with HIV and hypertension. Methods Using an age‐ and sex‐specific hybrid decision tree and Markov state‐transition model, we constructed a 100,000‐person simulated population cohort who may develop HIV and hypertension and initiate treatment at clinics in South Africa over a 10‐year time horizon. We assessed the incremental costs and effectiveness of 6MMD versus conventional care from a health system perspective under different conditions of care‐seeking, eligibility and uptake of 6MMD for clinically stable patients. Model inputs were sourced from previously published literature. 6MMD was defined as reducing the frequency of clinic visits by increasing the number of medications dispensed to stable patients at each visit from 3 to 6 months. For the integrated 6MMD, we assumed that comorbid patients receive both HIV and hypertension drugs at the same facility on the same day. Results Our study demonstrates that integrated 6MMD for HIV and hypertension in South Africa can avert between 0.8 and 1 DALYs and increase health systems costs between $24 and $49 per patient per year, compared to the status quo. One‐way sensitivity analysis showed that HTN drug cost and prevalence of HIVHTN and HIV were key drivers in the cost per DALYs averted. Overall, integrated 6MMD with a greater proportion of well‐controlled patients and lower mortality rates led to greater cost savings or better cost‐effectiveness (less than $50 per DALY averted) across a wide range of loss‐to‐follow‐up (LTFU) factor variation. Conclusions By better controlling disease among patients already in care, integrated 6MMD can be more beneficial than the status quo treatment by resulting in fewer cases of LTFU and fewer deaths through high‐quality care.

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.

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.