The importance of the "how": the case for differentiated service delivery of long-acting and extended delivery regimens for HIV prevention and treatment.

INTRODUCTION: Long-acting and extended delivery (LAED) regimens for HIV treatment and prevention offer unique benefits to expand uptake, effective use and adherence. To date, research has focused on basic and clinical science around the safety and efficacy of these products. This commentary outlines opportunities in HIV prevention and treatment programmes, both for the health system and clients, that could be addressed through the inclusion of LAED regimens and the vital role of differentiated service delivery (DSD) in ensuring efficient and equitable access. DISCUSSION: The realities and challenges within HIV treatment and prevention programmes are different. Globally, more than 28 million people are accessing HIV treatment-the vast majority on a daily fixed-dose combination oral pill that is largely available, affordable and well-tolerated. Many people collect extended refills outside of health facilities with clinical consultations once or twice a year. Conversely, uptake of daily oral pre-exposure prophylaxis (PrEP) has consistently missed global targets due to limited access with high individual cost and lack of choice contributing to substantial unmet PrEP need. Recent trends in demedicalization, simplification, additional method options and DSD for PrEP have led to accelerated uptake as its availability has become more aligned with user preferences. How people currently receive HIV treatment and prevention services and their barriers to adherence must be considered for the introduction of LAED regimens to achieve the expected improvements in access and outcomes. Important considerations include the building blocks of DSD: who (provider), where (location), when (frequency) and what (package of services). Ideally, all LAED regimens will leverage DSD models that emphasize access at the community level and self-management. For treatment, LAED regimens may address challenges with adherence but their delivery should provide clear advantages over existing oral products to be scaled. For prevention, LAED regimens expand a potential PrEP user's choice of methods, but like other methods, need to be delivered in a manner that can facilitate frequent re-initiation. CONCLUSIONS: To ensure that innovative LAED HIV treatment and prevention products reach those who most stand to benefit, service delivery and client considerations during development, trial and early implementation are critical.

The future of HIV testing in eastern and southern Africa: Broader scope, targeted services.

In this Policy Forum, Anna Grimsrud and colleagues discuss the future of HIV testing in eastern and southern Africa, using insights gleaned from a 2021 expert consultation.

Outcomes of a model integrating tuberculosis testing into COVID-19 services in South Africa.

The coronavirus disease 2019 (COVID-19) pandemic led to a reordering of healthcare priorities. Health resources were turned to the screening and diagnosis of COVID-19, leading to a reduction in tuberculosis (TB) testing and treatment initiation. An innovative model that integrated TB and COVID-19 services was adopted at primary care facilities in Johannesburg Health District, Gauteng. This short report illustrates results from this model's implementation in two facilities. Patients were screened for COVID-19 at a single point of entry and separated according to screening result. Self-reported human immunodeficiency virus (HIV) status, symptom, and symptom duration were then used to determine TB risk amongst those screening positive for COVID-19. Data from clinical records were extracted. Approximately 9% of patients with a positive symptom screen (n = 76) were sent for a TB test and 84% were sent for a COVID-19 test. Amongst those sent for a TB test, 8% (n = 6) had TB detected, and amongst those sent for a COVID-19 test, 18% (n = 128) were positive. Amongst those with COVID-19-related symptoms, 15% (n = 130) presented with a cough or fever and were known HIV positive and 121 (93%) of these were sent for a COVID-19 test and 31 (24%) were sent for a TB test. Given the HIV prevalence and symptoms in our study, our results show lower-than-expected TB tests conducted.Contribution: Our study documents the outcomes of an innovative way to combine operational workflows for TB and COVID-19. This provides a starting point for countries seeking to integrate TB and COVID-19 screening and testing.

Acceleration of differentiated service delivery for HIV treatment in sub-Saharan Africa during COVID-19.

INTRODUCTION: In response to COVID-19, national ministries of health adapted HIV service delivery guidelines to ensure uninterrupted access to antiretroviral therapy (ART) and limit the frequency of contact with health facilities. In this commentary, we summarize four ways in which differentiated service delivery (DSD) for HIV treatment has been accelerated during COVID-19 in policy and implementation in sub-Saharan Africa (SSA) - (i) expanding eligibility for DSD for HIV treatment, (ii) extending multi-month dispensing (MMD) and reducing the frequency of clinical consultations, (iii) emphasizing community-based models and (iv) integrating/aligning with TB preventative therapy (TPT), non-communicable disease (NCD) treatments and family planning commodities. DISCUSSION: Across SSA in 2020, countries both adapted and emphasized policies supporting DSD for HIV treatment in response to COVID-19. Access to DSD for HIV treatment was expanded by reducing the time required on ART before eligibility and being more inclusive of specific populations including children and adolescents, pregnant and breastfeeding women and those on second- and third-line regimens. Access to extended ART refills, or MMD, was accelerated across many countries. A renewed focus was given to out-of-facility community-based models of ART distribution. In some settings, there was acknowledgement of the need to integrate or align other chronic medications with ART. CONCLUSIONS: Adaptations to DSD for HIV treatment in response to COVID-19 have resulted in rapid policy change and in some cases, acceleration of implementation in SSA. As the COVID-19 pandemic evolves, there is a critical need to assess the impact of these adaptations and, where beneficial, ensure that policies implemented in response to COVID-19 become the new normal.

Twenty-four-month outcomes from a cluster-randomized controlled trial of extending antiretroviral therapy refills in ART adherence clubs.

INTRODUCTION: The antiretroviral therapy (ART) adherence club (AC) model has supported clinically stable HIV patients' retention with group ART refills and psychosocial support. Reducing visit frequency by increasing ART refills to six months could further benefit patients and unburden health systems. We conducted a pragmatic non-inferiority cluster randomized trial comparing standard of care (SoC) ACs and six-month refill intervention ACs in a primary care facility in Khayelitsha, South Africa. METHODS: Existing community-based and facility-based ACs were randomized to either SoC or intervention ACs. SoC ACs met five times annually, receiving two-month refills with a four-month refill over year-end. Blood was drawn at one AC visit with a clinical assessment at the next. Intervention ACs met twice annually receiving six-month refills, with an individual blood collection visit before the annual clinical assessment AC visit. The first study visits were in October and November 2017 and participants followed for 27 months. We report retention in care, viral load completion and viral suppression (<400 copies/mL) 24 months after enrolment and calculated intention-to-treat risk differences for the primary outcomes using generalized estimating equations specifying for clustering by AC. RESULTS: Of 2150 participants included in the trial, 977 were assigned to the intervention arm (40 ACs) and 1173 to the SoC (48 ACs). Patient characteristics at enrolment were similar across groups. Retention in care at 24 months was similarly high in both arms: 93.6% (1098/1173) in SoC and 92.6% (905/977) in the intervention arm, with a risk difference of -1.0% (95% CI: -3.2 to 1.3). The intervention arm had higher viral load completion (90.8% (999/1173) versus 85.1% (887/977)) and suppression (87.3% (969 /1173) versus 82.6% (853/977)) at 24 months, with a risk difference for completion of 5.5% (95% CI: 1.5 to 9.5) and suppression of 4.6% (95% CI: 0.2 to 9.0). CONCLUSIONS: Intervention AC patients receiving six-month ART refills showed non-inferior retention in care, viral load completion and viral load suppression to those in SoC ACs, adding to a growing literature showing good outcomes with extended ART dispensing intervals.

Understanding Engagement in HIV Programmes: How Health Services Can Adapt to Ensure No One Is Left Behind.

PURPOSE OF REVIEW: Despite the significant progress in the HIV response, gaps remain in ensuring engagement in care to support life-long medication adherence and viral suppression. This review sought to describe the different points in the HIV care cascade where people living with HIV were not engaging and highlight promising interventions. RECENT FINDINGS: There are opportunities to improve engagement both between testing and treatment and to support re-engagement in care for those in a treatment interruption. The gap between testing and treatment includes people who know their HIV status and people who do not know their status. People in a treatment interruption include those who interrupt immediately following initiation, early on in their treatment (first 6 months) and late (after 6 months or more on ART). For each of these groups, specific interventions are required to support improved engagement. There are diverse needs and specific populations of people living with HIV who are not engaged in care, and differentiated service delivery interventions are required to meet their needs and expectations. For the HIV response to realise the 2030 targets, engagement will need to be supported by quality care and patient choice combined with empowered patients who are treatment literate and have been supported to improve self-management.

'Only twice a year': a qualitative exploration of 6-month antiretroviral treatment refills in adherence clubs for people living with HIV in Khayelitsha, South Africa.

OBJECTIVE: Longer intervals between routine clinic visits and medication refills are part of patient-centred, differentiated service delivery (DSD). They have been shown to improve patient outcomes as well as optimise health services-vital as 'universal test-and-treat' targets increase numbers of HIV patients on antiretroviral treatment (ART). This qualitative study explored patient, healthcare worker and key informant experiences and perceptions of extending ART refills to 6 months in adherence clubs in Khayelitsha, South Africa. DESIGN AND SETTING: In-depth interviews were conducted in isiXhosa with purposively selected patients and in English with healthcare workers and key informants. All transcripts were audio-recorded, transcribed and translated to English, manually coded and thematically analysed. The participants had been involved in a randomised controlled trial evaluating multi-month ART dispensing in adherence clubs, comparing 6-month and 2-month refills. PARTICIPANTS: Twenty-three patients, seven healthcare workers and six key informants. RESULTS: Patients found that 6-month refills increased convenience and reduced unintended disclosure. Contrary to key informant concerns about patients' responsibility to manage larger quantities of ART, patients receiving 6-month refills were highly motivated and did not face challenges transporting, storing or adhering to treatment. All participant groups suggested that strict eligibility criteria were necessary for patients to realise the benefits of extended dispensing intervals. Six-month refills were felt to increase health system efficiency, but there were concerns about whether the existing drug supply system could adapt to 6-month refills on a larger scale. CONCLUSIONS: Patients, healthcare workers and key informants found 6-month refills within adherence clubs acceptable and beneficial, but concerns were raised about the reliability of the supply chain to manage extended multi-month dispensing. Stepwise, slow expansion could avoid overstressing supply and allow time for the health system to adapt, permitting 6-month ART refills to enhance current DSD options to be more efficient and patient-centred within current health system constraints.

Let's talk chronic disease: can differentiated service delivery address the syndemics of HIV, hypertension and diabetes?

PURPOSE OF REVIEW: Differentiated service delivery (DSD) for HIV provides an approach to scaling services that are client-centred and aims to address client challenges whilst reducing the burden on health systems. With access to antiretroviral therapy, people living with HIV are living longer and increasingly present with comorbid conditions, such as hypertension and diabetes. This review presents the syndemic burden of HIV, hypertension and diabetes and highlights opportunities and challenges to leveraging DSD across diseases. RECENT FINDINGS: Prevalence of hypertension and diabetes in the eight highest HIV prevalence countries ranges between 20-24% (31.9% in those >50 years old) and 4-10%, respectively. Service delivery models addressing the concurrent syndemics focus primarily on integration of services. Two DSD examples were found where people living with HIV and other comorbidities had their care and treatment supported in healthcare worker-led facility-based adherence clubs. SUMMARY: Key enablers that have supported DSD for HIV such as simplified algorithms, optimized formulations, secure drug supply, and strengthened monitoring and evaluation systems are lacking for hypertension and diabetes and thus pose a major challenge to leveraging DSD models for people with syndemic conditions. However, the DSD approach may also catalyse opportunities to provide person-centred care for these syndemics and more implementation research in this area is warranted.

A cluster randomized controlled trial of extending ART refill intervals to six-monthly for anti-retroviral adherence clubs.

BACKGROUND: The antiretroviral therapy (ART) adherence club (AC) differentiated service delivery model, where clinically stable ART patients receive their ART refills and psychosocial support in groups has supported clinically stable patients' retention and viral suppression. Patients and health systems could benefit further by reducing visit frequency and increasing ART refills. We designed a cluster-randomized control trial comparing standard of care (SoC) ACs and six-month ART refill (Intervention) ACs in a large primary care facility in Khayelitsha, South Africa. METHODS: Existing ACs were randomized to either the control (SOC ACs) or intervention (Intervention ACs) arm. SoC ACs meet five times annually, receiving two-month ART refills with a four-month ART refill over year-end. Blood is drawn at the AC visit ahead of the clinical assessment visit. Intervention ACs meet twice annually receiving six-month ART refills, with a third individual visit for routine blood collection anytime two-four weeks before the annual clinical assessment AC visit. Primary outcomes will be retention in care, annual viral load assessment completion and viral load suppression. (<400copies/mL) after 2 years. Ethics approval has been granted by the University of Cape Town (HREC 652/2016) and the Medecins Sans Frontieres (MSF) Ethics Review Board (#1639). Results will be published in peer-reviewed journals and made widely available through presentations and briefing documents. DISCUSSION: Evaluation of an extended ART refill interval in adherence clubs will provide evidence towards novel model adaptions that can be made to further improve convenience for patients and leverage health system efficiencies. TRIAL REGISTRATION: Registered with the Pan African Clinical Trial Registry: PACTR201810631281009. Registered 11 September 2018.

Outcomes of patients enrolled in an antiretroviral adherence club with recent viral suppression after experiencing elevated viral loads.

BACKGROUND: Eligibility for differentiated antiretroviral therapy (ART) delivery models has to date been limited to low-risk stable patients. OBJECTIVES: We examined the outcomes of patients who accessed their care and treatment through an ART adherence club (AC), a differentiated ART delivery model, immediately following receiving support to achieve viral suppression after experiencing elevated viral loads (VLs) at a high-burden ART clinic in Khayelitsha, South Africa. METHODS: Beginning in February 2012, patients with VLs above 400 copies/mL either on first- or second-line regimens received a structured intervention developed for patients at risk of treatment failure. Patients who successfully suppressed either on the same regimen or after regimen switch were offered immediate enrolment in an AC facilitated by a lay community health worker. We conducted a retrospective cohort analysis of patients who enrolled in an AC directly after receiving suppression support. We analysed outcomes (retention in care, retention in AC care and viral rebound) using Kaplan-Meier methods with follow-up from October 2012 to June 2015. RESULTS: A total of 165 patients were enrolled in an AC following suppression (81.8% female, median age 36.2 years). At the closure of the study, 119 patients (72.0%) were virally suppressed and 148 patients (89.0%) were retained in care. Six, 12 and 18 months after AC enrolment, retention in care was estimated at 98.0%, 95.0% and 89.0%, respectively. Viral suppression was estimated to be maintained by 90.0%, 84.0% and 75.0% of patients at 6, 12 and 18 months after AC enrolment, respectively. CONCLUSION: Our findings suggest that patients who struggled to achieve or maintain viral suppression in routine clinic care can have good retention and viral suppression outcomes in ACs, a differentiated ART delivery model, following suppression support.

Patient experiences of ART adherence clubs in Khayelitsha and Gugulethu, Cape Town, South Africa: A qualitative study.

BACKGROUND: Globally, 37 million people are in need of lifelong antiretroviral treatment (ART). With the continual increase in the number of people living with HIV starting ART and the need for life-long retention and adherence, increasing attention is being paid to differentiated service delivery (DSD), such as adherence clubs. Adherence clubs are groups of 25-30 stable ART patients who meet five times per year at their clinic or a community location and are facilitated by a lay health-care worker who distributes pre-packed ART. This qualitative study explores patient experiences of clubs in two sites in Cape Town, South Africa. METHODS: A total of 144 participants took part in 11 focus group discussions (FGDs) and 56 in-depth interviews in the informal settlements of Khayelitsha and Gugulethu in Cape Town, South Africa. Participants included current club members, stable patients who had never joined a club and club members referred back to clinician-led facility-based standard care. FGDs and interviews were conducted in isiXhosa, translated and transcribed into English, entered into NVivo, coded and thematically analysed. RESULTS: The main themes were 1) understanding and knowledge of clubs; 2) understanding of and barriers to enrolment; 3) perceived benefits and 4) perceived disadvantages of the clubs. Participants viewed membership as an achievement and considered returning to clinician-led care a 'failure'. Moving between clubs and the clinic created frustration and broke down trust in the health-care system. CONCLUSIONS: Adherence clubs were appreciated by patients, particularly time-saving in relation to flexible ART collection. Improved patient understanding of enrolment processes, eligibility and referral criteria and the role of clinical oversight is essential for building relationships with health-care workers and trust in the health-care system.

The Case For Family-Centered Differentiated Service Delivery for HIV.

Differentiated care, or differentiated service delivery (DSD), is increasingly being promoted as one of the possible ways to address and improve access, quality, and efficiency of HIV prevention, care, and treatment. Family-centered care has long been promoted within the provision of HIV services, but the full benefits have not necessarily been realized. In this article, we bring together these two approaches and make the case for how family-centered DSD can offer benefits to both people affected by HIV and the health system. Family-centered DSD approaches are presented for HIV testing and antiretroviral therapy (ART) delivery, referencing policies, best practice examples, and evidence from the field. With differentiated family-centered ART delivery, the potential efficiencies gained by extending ART refills can both benefit clients by reducing the frequency and intensity of contact with the health service and lead to health system gains by not requiring multiple providers to care for one family. A family-centered DSD approach should also be leveraged along the HIV care cascade in the provision of prevention technologies and mobilizing family members to receive regular HIV testing. Furthermore, a family-centered lens should be applied wherever DSD is implemented to ensure that, for example, adolescents who are pregnant receive an adapted package of quality care.

High rates of retention and viral suppression in the scale-up of antiretroviral therapy adherence clubs in Cape Town, South Africa.

INTRODUCTION: Increasingly, there is a need for health authority scale up of successfully piloted differentiated models of antiretroviral therapy (ART) delivery. However, there is a paucity of evidence on system-wide outcomes after scale-up. In the Cape Town health district, stable adult patients were referred to adherence clubs (ACs) - a group model of ART delivery with five visits per year. By the end of March 2015, over 32,000 ART patients were in an AC. We describe patient outcomes of a representative sample of AC patients during this scale-up. METHODS: Patients enrolled in an AC at non-research supported sites between 2011 and 2014 were eligible for analysis. We sampled 10% of ACs (n = 100) in quintets proportional to the number of ACs at each facility, linking each patient to city-wide laboratory and service access data to validate retention and virologic outcomes. We digitized registers and used competing risks regression and cross-sectional methods to estimate outcomes: mortality, transfers, loss to follow-up (LTFU) and viral load suppression (≤400 copies/mL). Predictors of LTFU and viral rebound were assessed using Cox proportional hazards models. RESULTS: Of the 3216 adults contributing 4019 person years of follow-up (89% in an AC, median 1.1 years), 70% were women. Retention was 95.2% (95% CI, 94.0-96.4) at 12 months and 89.3% (95% CI, 87.1-91.4) at 24 months after AC enrolment. In the 13 months prior to analysis closure, 88.1% of patients had viral load assessments and of those, viral loads ≤400 copies/mL were found in 97.2% (95% CI, 96.5-97.8) of patients. Risk of LTFU was higher in younger patients and in patients accessing ART from facilities with larger ART cohorts. Risk of viral rebound was higher in younger patients, those that had been on ART for longer and patients that had never sent a buddy to collect their medication. CONCLUSIONS: This is the first analysis reporting patient outcomes after health authorities scaled-up a differentiated care model across a high burden district. The findings provide substantial reassurance that stable patients on long-term ART can safely be offered care options, which are more convenient to patients and less burdensome to services.

Adherence clubs for long-term provision of antiretroviral therapy: cost-effectiveness and access analysis from Khayelitsha, South Africa.

OBJECTIVES: As the scale of the South African HIV epidemic calls for innovative models of care that improve accessibility for patients while overcoming chronic human resource shortages, we (i) assess the cost-effectiveness of lay health worker-led group adherence clubs, in comparison with a nurse-driven 'standard of care' and (ii) describe and evaluate the associated patient cost and accessibility differences. METHODS: Our cost-effectiveness analysis compares an 'adherence club' innovation to conventional nurse-driven care within a busy primary healthcare setting in Khayelitsha, South Africa. In each alternative, we calculate provider costs and estimate rates of retention in care and viral suppression as key measures of programme effectiveness. All results are presented on an annual or per patient-year basis. In the same setting, a smaller sample of patients was interviewed to understand the direct and indirect non-healthcare cost and access implications of the alternatives. Access was measured using McIntyre and colleagues' 2009 framework. RESULTS: Adherence clubs were the more cost-effective model of care, with a cost per patient-year of $300 vs. $374 and retention in care at 1 year of 98.03% (95% CI 97.67-98.33) for clubs vs. 95.49% (95% CI 95.01-95.94) for standard of care. Viral suppression in clubs was 99.06% (95% CI 98.82-99.27) for clubs vs. 97.20% (95% CI 96.81-97.56) for standard of care. When interviewed, club patients reported fewer missed visits, shorter waiting times and higher acceptability of services compared to standard of care. CONCLUSIONS: Adherence clubs offer the potential to enhance healthcare efficiency and patient accessibility. Their scale-up should be supported.