Patterns of engagement in care during clients' first 12 months after HIV treatment initiation in South Africa: A retrospective cohort analysis using routinely collected data.

Retention on antiretroviral therapy (ART) during the early treatment period is one of the most serious challenges facing HIV programs, but the timing and patterns of early disengagement from care remain poorly understood. We describe patterns of engagement in HIV care during the first year after treatment initiation. We analysed retrospective datasets of routinely collected electronic medical register (EMR) data for ≥18-year-old clients who initiated ART at public sector clinics in South Africa after 01/01/2018 and had ≥14 months of potential follow-up. Using scheduled visit dates, we characterized engagement in care as continuous (no treatment interruption), cyclical (at least one visit >28 days late with a return visit observed) or disengaged (visit not attended and no evidence of return). We report 6- and 12-month patterns of retention in care and viral suppression. Among 35,830 participants (65% female, median age 33), in months 0-6, 59% were continuously in care, 14% had engaged cyclically, 11% had transferred to another facility, 1% had died, and 16% had disengaged from care at the initiating facility. Among disengagers in the first 6 months, 58% did not return after their initiation visit. By 12 months after initiation, the overall proportion disengaged was 23%, 45% were classified as continuously engaged in months 7-12, and only 38% of the cohort had maintained continuous engagement at both the 6- and 12-month endpoints. Participants who were cyclically engaged in months 0-6 were nearly twice as likely to disengage in months 7-12 as were continuous engagers in months 0-6 (relative risk 1.76, 95% CI:1.61-1.91) and were more likely to have an unsuppressed viral load by 12 months on ART (RR = 1.28; 95% CI1.13-1.44). The needs of continuous and cyclical engagers and those disengaging at different timepoints may vary and require different interventions or models of care.

Prior exposure to antiretroviral therapy among adult patients presenting for HIV treatment initiation or reinitiation in sub-Saharan Africa: a systematic review.

OBJECTIVES: As countries have scaled up access to antiretroviral therapy (ART) for HIV, attrition rates of up to 30% annually have created a large pool of individuals who initiate treatment with prior ART experience. Little is known about the proportion of non-naïve reinitiators within the population presenting for treatment initiation. DESIGN: Systematic review of published articles and abstracts reporting proportions of non-naïve adult patients initiating ART in sub-Saharan Africa. DATA SOURCES: PubMed, Embase Elsevier, Web of Science Core Collection, International AIDS Society conferences, Conference on Retroviruses and Opportunistic Infections conferences. ELIGIBILITY CRITERIA: Clinical trials and observational studies; reporting on adults in sub-Saharan Africa who initiated lifelong ART; published in English between 1 January 2018 and 11 July 2023 and with data collected after January 2016. Initiator self-report, laboratory discernment of antiretroviral metabolites, and viral suppression at initiation or in the medical record were accepted as evidence of prior exposure. DATA EXTRACTION AND SYNTHESIS: We captured study and sample characteristics, proportions with previous ART exposure and the indicator of previous exposure reported. We report results of each eligible study, estimate the risk of bias and identify gaps in the literature. RESULTS: Of 2740 articles, 11 articles describing 12 cohorts contained sufficient information for the review. Proportions of initiators with evidence of prior ART use ranged from 5% (self-report only) to 53% (presence of ART metabolites in hair or blood sample). The vast majority of screened studies did not report naïve/non-naïve status. Metrics used to determine and report non-naïve proportions were inconsistent and difficult to interpret. CONCLUSIONS: The proportion of patients initiating HIV treatment who are truly ART naïve is not well documented. It is likely that 20%-50% of ART patients who present for ART are reinitiators. Standard reporting metrics and diligence in reporting are needed, as is research to understand the reluctance of patients to report prior ART exposure. PROSPERO REGISTRATION NUMBER: CRD42022324136.

Health systems performance for hypertension control using a cascade of care approach in South Africa, 2011-2017.

Hypertension is a major contributor to global morbidity and mortality. In South Africa, the government has employed a whole systems approach to address the growing burden of non-communicable diseases. We used a novel incident care cascade approach to measure changes in the South African health system's ability to manage hypertension between 2011 and 2017. We used data from Waves 1-5 of the National Income Dynamics Study (NIDS) to estimate trends in the hypertension care cascade and unmet treatment need across four successive cohorts with incident hypertension. We used a negative binomial regression to identify factors that may predict higher rates of hypertension control, controlling for socio-demographic and healthcare factors. In 2011, 19.6% (95%CI 14.2, 26.2) of individuals with incident hypertension were diagnosed, 15.4% (95%CI 10.8, 21.4) were on treatment and 7.1% had controlled blood pressure. By 2017, the proportion of individuals with diagnosed incident hypertension had increased to 24.4% (95%CI 15.9, 35.4). Increases in treatment (23.3%, 95%CI 15.0, 34.3) and control (22.1%, 95%CI 14.1, 33.0) were also observed, translating to a decrease in unmet need for hypertension care from 92.9% in 2011 to 77.9% in 2017. Multivariable regression showed that participants with incident hypertension in 2017 were 3.01 (95%CI 1.77, 5.13) times more likely to have a controlled blood pressure compared to those in 2011. Our data show that while substantial improvements in the hypertension care cascade occurred between 2011 and 2017, a large burden of unmet need remains. The greatest losses in the incident hypertension care cascades came before diagnosis. Nevertheless, whole system programming will be needed to sufficiently address significant morbidity and mortality related to having an elevated blood pressure.

Costs and outcomes of routine HIV oral pre-exposure prophylaxis implementation across different service delivery models and key populations in South Africa.

Background: Oral pre-exposure prophylaxis (PrEP) is a highly efficacious biomedical HIV prevention tool, yet despite being recommended by the World Health Organization (WHO) since 2015, uptake and persistence remain limited in much of the world, including sub Saharan Africa (SSA). There is a dearth of evidence-based interventions to improve PrEP uptake and persistence in SSA, and the full costs of PrEP programs implemented in routine care settings remain largely unknown. This study aimed to evaluate the cost of delivery of daily oral PrEP, and associated outcomes, to different key and priority populations across different service delivery models (SDMs) in South Africa. Methods: We conducted bottom-up micro-costing of PrEP service delivery from the provider perspective within twelve urban SDMs providing routine PrEP services to various key and propriety populations in Gauteng and KwaZulu-Natal provinces in South Africa. The SDMs included in-facility and outreach models that focused on men who have sex with men (MSM), female sex workers (FSW) and adolescent girls and young women (AGYW). We identified all within- and above-facility activities supporting PrEP delivery, obtained input costs from program budgets, expenditure records and staff interviews, and determined individual resource usage between February 2019 and February 2020 through retrospective medical record review. Our primary outcome was PrEP coverage at six months (defined as having sufficient PrEP drug dispensed at the last visit to be covered at six months post PrEP-initiation). A subset (N=633) of all enrolled subjects had the potential for 12 months of follow-up and were included in a 12-month outcome analysis. We report the cost per client initiated on PrEP in 2021 United States Dollars (USD). Findings: We collected medical record data from 1,281 people who initiated PrEP at 12 SDMs between February and August 2019 and had at least six months of potential follow-up. The average number of visits was 2.3 for in-facility models and 1.5 for outreach models and 3,086 months of PrEP was dispensed. PrEP coverage at six months varied greatly across SDMs, from 41.8% at one MSM-focused fixed clinic to 0% in an MSM-focused outreach model. In general, in-facility programs had higher six-month coverage than outreach programs. Across all SDMs with PrEP clients with potential for 12 months of follow-up (n=633), PrEP coverage at 12 months was 13.6%, with variability between SDMs. The average six-month cost per client initiated on PrEP ranged from $29 to $590, with higher average costs generally observed for the in-facility programs ($152 in-facility versus $84 for outreach). The average monthly cost per PrEP client who had six-month PrEP coverage ranged from $18 to $160 dependent on SDM. Interpretation: This study is an important addition to the PrEP outcome and cost literature in the SSA region. Results show that costs and outcomes vary considerably across different SDMs and populations in real world PrEP programs and provide crucial information for further scale-up of the oral PrEP program in South Africa and the greater SSA region.

Economic evaluation of a cluster randomized, non-inferiority trial of differentiated service delivery models of HIV treatment in Zimbabwe.

About 85% of Zimbabwe's >1.4 million people living with HIV are on antiretroviral treatment (ART). Further expansion of its treatment program will require more efficient use of existing resources. Two promising strategies for reducing resource utilization per patient are multi-month medication dispensing and community-based service delivery. We evaluated the costs to providers and patients of community-based, multi-month ART delivery models in Zimbabwe. We used resource and outcome data from a cluster-randomized non-inferiority trial of three differentiated service delivery (DSD) models targeted to patients stable on ART: 3-month facility-based care (3MF), community ART refill groups (CAGs) with 3-month dispensing (3MC), and CAGs with 6-month dispensing (6MC). Using local unit costs, we estimated the annual cost in 2020 USD of providing HIV treatment per patient from the provider and patient perspectives. In the trial, retention at 12 months was 93.0% in the 3MF, 94.8% in the 3MC, and 95.5% in the 6MC arms. The total average annual cost of HIV treatment per patient was $187 (standard deviation $39), $178 ($30), and $167 ($39) in each of the three arms, respectively. The annual cost/patient was dominated by ART medications (79% in 3MF, 87% in 3MC; 92% in 6MC), followed by facility visits (12%, 5%, 5%, respectively) and viral load (8%, 8%, 2%, respectively). When costs were stratified by district, DSD models cost slightly less, with 6MC the least expensive in all districts. Savings were driven by differences in the number of facility visits made/year, as expected, and low uptake of annual viral load tests in the 6-month arm. The total annual cost to patients to obtain HIV care was $10.03 ($2) in the 3MF arm, $5.12 ($0.41) in the 3MC arm, and $4.40 ($0.39) in the 6MF arm. For stable ART patients in Zimbabwe, 3- and 6-month community-based multi-month dispensing models cost less for both providers and patients than 3-month facility-based care and had non-inferior outcomes.

The integration of tuberculosis and HIV testing on GeneXpert can substantially improve access and same-day diagnosis and benefit tuberculosis programmes: A diagnostic network optimization analysis in Zambia.

Diagnostic network optimization (DNO), a geospatial optimization technique, can improve access to diagnostics and reduce costs through informing policy-makers' decisions on diagnostic network changes. In Zambia, viral load (VL) testing and early infant diagnosis (EID) for HIV has been performed at centralized laboratories, whilst the TB-programme utilizes a decentralized network of GeneXpert platforms. Recently, the World Health Organization (WHO) has recommended point-of-care (POC) EID/VL to increase timely diagnosis. This analysis modelled the impact of integrating EID/VL testing for children and pregnant/breastfeeding-women (priority-HIV) with TB on GeneXpert in Zambia. Using OptiDx, we established the baseline diagnostic network using inputs for testing demand (October 2019-September 2020), referrals, testing sites, testing platforms, and costs for HIV/TB testing (transport, test, device) respectively in Zambia. Next, we integrated priority-HIV testing on GeneXpert platforms, historically only utilized by the TB-programme. 228,265 TB tests were conducted on GeneXpert devices and 167,458 (99%) of priority-HIV tests on centralized devices at baseline, of which 10% were tested onsite at the site of sample collection. With integration, the average distance travelled by priority-HIV tests decreased 10-fold (98km to 10km) and the proportion tested onsite increased (10% to 48%). 52% of EID tests are likely to be processed within the same-day from a baseline of zero. There were also benefits to the TB-programme: the average distance travelled/specimen decreased (11km to 7km), alongside potential savings in GeneXpert device-operating costs (30%) through cost-sharing with the HIV-programme. The total cost of the combined testing programmes reduced marginally by 1% through integration/optimization. DNO can be used to strategically leverage existing capacity to achieve the WHO's recommendation regarding POC VL/EID testing. Through DNO of the Zambian network, we have shown that TB/HIV testing integration can improve the performance of the diagnostic network and increase the proportion of specimens tested closer to the patient whilst not increasing costs.

Preferences for services in a patient's first six months on antiretroviral therapy for HIV in South Africa and Zambia (PREFER): research protocol for a prospective observational cohort study.

Background: For patients on HIV treatment in sub-Saharan Africa, the highest risk for loss from care remains the first six months after antiretroviral (ART) initiation, when patients are not yet eligible for differentiated service delivery (DSD) models that offer lower-burden, patient-centred care and thus improve treatment outcomes. To reduce early disengagement from care, the PREFER study will use a sequential mixed-methods approach to describe the characteristics, needs, concerns, and preferences of patients in South Africa and Zambia 0-6 months after ART initiation or re-initiation. Protocol: PREFER is an observational, prospective cohort study of adults on ART for ≤6 months at 12 public healthcare facilities in Zambia and 18 in South Africa. Its objective is to describe and understand the needs and preferences of initiating and re-initiating ART clients to inform the design of DSD models for the early HIV treatment period, improve early treatment outcomes, and distinguish the barriers encountered by naïve patients from those facing re-initiators. It has four components: 1) survey of clients 0-6 months after ART initiation (identify characteristics and preferences of clients starting ART); 2) follow up through routinely collected medical records for <24 months after enrollment (describe resource utilization and patterns and predictors of engagement in care); 3) focus group discussions and discrete choice experiment (explore reported barriers to and facilitators of retention); and 4) in South Africa only, collection of blood samples (assess the prevalence of ARV metabolites indicating prior ART use). Conclusions: PREFER aims to understand why the early treatment period is so challenging and how service delivery can be amended to address the obstacles that lead to early disengagement from care. It will generate information about client characteristics and preferences to help respond to patients' needs and design better strategies for service delivery and improve resource allocation going forward.

Facility-based HIV self-testing strategies may substantially and cost-effectively increase the number of men and youth tested for HIV in Malawi: results from an individual-based mathematical model.

INTRODUCTION: Malawi is rapidly closing the gap in achieving the UNAIDS 95-95-95 targets, with 90% of people living with HIV in Malawi aware of their status. As we approach epidemic control, interventions to improve coverage will become more costly. There is, therefore, an urgent need to identify innovative and low-cost strategies to maintain and increase testing coverage without diverting resources from other HIV services. The objective of this study is to model different combinations of facility-based HIV testing modalities and determine the most cost-effective strategy to increase the proportion of men and youth testing for HIV. METHODS: A data-driven individual-based model was parameterized with data from a community-representative survey (socio-demographic, health service utilization and HIV testing history) of men and youth in Malawi (data collected August 2019). In total, 79 different strategies for the implementation of HIV self-testing (HIVST) and provider-initiated-testing-and-counselling at the outpatient department (OPD) were evaluated. Outcomes included percent of men/youth tested for HIV in a 12-month period, cost-effectiveness and human resource requirements. The testing yield was assumed to be constant across the scenarios. RESULTS: Facility-based HIVST offered year-round resulted in the greatest increase in the proportion of men and youth tested in the OPD (from 45% to 72%-83%), was considered cost-saving for HIVST kit priced at $1.00, and generally reduced required personnel as compared to the status quo. At higher HIVST kit prices, and more relaxed eligibility criteria, all scenarios that considered year-round HIVST in the OPD remained on the cost-effectiveness frontier. CONCLUSIONS: Facility-based HIVST is a cost-effective strategy to increase the proportion of men/youth tested for HIV in Malawi and decreases the human resource requirements for HIV testing in the OPD-providing additional healthcare worker time for other priority healthcare activities.

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.

Reduction in initiations of drug-sensitive tuberculosis treatment in South Africa during the COVID-19 pandemic: Analysis of retrospective, facility-level data.

In response to the global pandemic of COVID-19, 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, the deprioritization of TB activities, fear of transmission, and societal restrictions led to a reduction in tuberculosis (TB) treatment initiations. We analysed monthly public sector, facility-level data from South Africa's District Health Information System (DHIS) from January 2019 to April 2021 to quantify changes in TB treatment initiation numbers stratified by province, setting, and facility type and compared the timing of these changes to COVID-19 case numbers and government lockdown levels. At the 1189 facilities that reported observations for all 28 months of our study period, TB treatment initiations in 2020 were 20.4% lower than in 2019 and 21.9% lower in the first four months of 2021 than in 2019. At the 3669 facilities that reported observations in ≤28 months, numbers of TB treatment initiations declined sharply in all provinces in May-August 2020, compared to the same months in 2019. After recovering somewhat in the last four months of 2020, numbers plummeted again in early 2021. Percentage reductions were somewhat larger in urban and peri-urban areas than in rural areas. Most provinces experienced a clear inverse relationship between COVID-19 cases and TB treatment initiations but little relationship between TB treatment initiations and lockdown level. The COVID-19 pandemic and responses to it resulted in substantial declines in the number of individuals starting treatment for TB in South Africa and risked progress toward achieving TB management goals. Exceptional effort will be needed to sustain gains in combating TB.

Multimonth dispensing of up to 6 months of antiretroviral therapy in Malawi and Zambia (INTERVAL): a cluster-randomised, non-blinded, non-inferiority trial.

BACKGROUND: Facility-based, multimonth dispensing of antiretroviral therapy (ART) for HIV could reduce burdens on patients and providers and improve retention in care. We assessed whether 6-monthly ART dispensing was non-inferior to standard of care and 3-monthly ART dispensing. METHODS: We did a pragmatic, cluster-randomised, unblinded, non-inferiority trial (INTERVAL) at 30 health facilities in Malawi and Zambia. Eligible participants were aged 18 years or older, HIV-positive, and were clinically stable on ART. Before randomisation, health facilities (clusters) were matched on the basis of country, ART cohort size, facility type (ie, hospital vs health centre), and region or province. Matched clusters were randomly allocated (1:1:1) to standard of care, 3-monthly ART dispensing, or 6-monthly ART dispensing using a simple random allocation sequence. The primary outcome was retention in care at 12 months, defined as the proportion of patients with less than 60 consecutive days without ART during study follow-up, analysed by intention to treat. A 2·5% margin was used to assess non-inferiority. This study is registered with ClinicalTrials.gov, NCT03101592. FINDINGS: Between May 15, 2017, and April 30, 2018, 9118 participants were randomly assigned, of whom 8719 participants (n=3012, standard of care group; n=2726, 3-monthly ART dispensing group; n=2981, 6-monthly ART dispensing group) had primary outcome data available at 12 months and were included in the primary analysis. The median age of participants was 42·7 years (IQR 36·1-49·9) and 5774 (66·2%) of 8719 were women. The primary outcome was met by 2478 (82·3%) of 3012 participants in the standard of care group, 2356 (86·4%) of 2726 participants in the 3-monthly ART dispensing group, and 2729 (91·5%) of 2981 participants in the 6-monthly ART dispensing group. After adjusting for clustering, for retention in care at 12 months, the 6-monthly ART dispensing group was non-inferior to the standard of care group (percentage-point increase 9·1 [95% CI 0·9-17·2]) and to the 3-monthly ART dispensing group (5·0% [1·0-9·1]). INTERPRETATION: Clinical visits with ART dispensing every 6 months was non-inferior to standard of care and 3-monthly ART dispensing. 6-monthly ART dispensing is a promising strategy for the expansion of ART provision and achievement of HIV treatment targets in resource-constrained settings. FUNDING: US Agency for International Development.

Do differentiated service delivery models for HIV treatment in sub-Saharan Africa save money? Synthesis of evidence from field studies conducted in sub-Saharan Africa in 2017-2019.

Introduction: "Differentiated service delivery" (DSD) for antiretroviral therapy (ART) for HIV is rapidly being scaled up throughout sub-Saharan Africa, but only recently have data become available on the costs of DSD models to healthcare providers and to patients. We synthesized recent studies of DSD model costs in five African countries. Methods: The studies included cluster randomized trials in Lesotho, Malawi, Zambia, and Zimbabwe and observational studies in Uganda and Zambia. For 3-5 models per country, studies collected patient-level data on clinical outcomes and provider costs for 12 months. We compared costs of differentiated models to those of conventional care, identified drivers of cost differences, and summarized patient costs of seeking care. Results: The studies described 22 models, including conventional care. Of these, 13 were facility-based and 9 community-based models; 15 were individual and 7 group models. Average provider cost/patient/year ranged from $100 for conventional care in Zambia to $187 for conventional care with 3-month dispensing in Zimbabwe. Most DSD models had comparable costs to conventional care, with a difference in mean annual cost per patient ranging from 11.4% less to 9.2% more, though some models in Zambia cost substantially more. Compared to all other models, models incorporating 6-month dispensing were consistently slightly less expensive to the provider per patient treated. Savings to patients were substantial for most models, with patients' costs roughly halved. Conclusion: In five field studies of the costs of DSD models for HIV treatment, most models within each country had relatively similar costs to one another and to conventional care. 6-month dispensing models were slightly less expensive, and most models provided substantial savings to patients. Limitations of our analysis included differences in costs included in each study. Research is needed to understand the effect of DSD models on the costs of ART programmes as a whole.

Bringing Data Analytics to the Design of Optimized Diagnostic Networks in Low- and Middle-Income Countries: Process, Terms and Definitions.

Diagnostics services are an essential component of healthcare systems, advancing universal health coverage and ensuring global health security, but are often unavailable or under-resourced in low- and middle-income (LMIC) countries. Typically, diagnostics are delivered at various tiers of the laboratory network based on population needs, and resource and infrastructure constraints. A diagnostic network additionally incorporates screening and includes point-of-care testing that may occur outside of a laboratory in the community and clinic settings; it also emphasizes the importance of supportive network elements, including specimen referral systems, as being critical for the functioning of the diagnostic network. To date, design and planning of diagnostic networks in LMICs has largely been driven by infectious diseases such as TB and HIV, relying on manual methods and expert consensus, with a limited application of data analytics. Recently, there have been efforts to improve diagnostic network planning, including diagnostic network optimization (DNO). The DNO process involves the collection, mapping, and spatial analysis of baseline data; selection and development of scenarios to model and optimize; and lastly, implementing changes and measuring impact. This review outlines the goals of DNO and steps in the process, and provides clarity on commonly used terms.