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.

How soon should patients be eligible for differentiated service delivery models for antiretroviral treatment? Evidence from a retrospective cohort study in Zambia.

OBJECTIVES: Patient attrition is high the first 6 months after antiretroviral therapy (ART) initiation. Patients with <6 months of ART are systematically excluded from most differentiated service delivery (DSD) models, which are intended to support retention. Despite DSD eligibility criteria requiring ≥6 months on ART, some patients enrol earlier. We compared loss to follow-up (LTFU) between patients enrolling in DSD models early with those enrolled according to guidelines, assessing whether the ART experience eligibility criterion is necessary. DESIGN: Retrospective cohort study using routinely collected electronic medical record data. SETTING: PARTICIPANTS: Adults (≥15 years) who initiated ART between 1 January 2019 and 31 December 2020. OUTCOMES: LTFU (>30 days late for scheduled visit) at 18 months for 'early enrollers' (DSD enrolment after <6 months on ART) and 'established enrollers' (DSD enrolment after ≥6 months on ART). We used a log-binomial model to compare LTFU risk, adjusting for age, sex, location, ART refill interval and DSD model. RESULTS: For 6340 early enrollers and 25 857 established enrollers, there were no differences in sex (61% female), age (median 37 years) or location (65% urban). ART refill intervals were longer for established versus early enrollers (72% vs 55% were given 4-6 months refills). LTFU at 18 months was 3% (192 of 6340) for early enrollers and 5% (24 646 of 25 857) for established enrollers. Early enrollers were 41% less likely to be LTFU than established patients (adjusted risk ratio 0.59, 95% CI 0.50 to 0.68). CONCLUSIONS: Patients enrolled in DSD after <6 months of ART were more likely to be retained than patients established on ART prior to DSD enrolment. A limitation is that early enrollers may have been selected for DSD due to providers' and patients' expectations about future retention. Offering DSD models to ART patients soon after ART initiation may help address high attrition during the early treatment period. TRIAL REGISTERATION NUMBER: NCT04158882.

Changes in HIV treatment differentiated care uptake during the COVID-19 pandemic in Zambia: interrupted time series analysis.

INTRODUCTION: Differentiated service delivery (DSD) models aim to improve the access of human immunodeficiency virus treatment on clients and reduce requirements for facility visits by extending dispensing intervals. With the advent of the COVID-19 pandemic, minimising client contact with healthcare facilities and other clients, while maintaining treatment continuity and avoiding loss to care, has become more urgent, resulting in efforts to increase DSD uptake. We assessed the extent to which DSD coverage and antiretroviral treatment (ART) dispensing intervals have changed during the COVID-19 pandemic in Zambia. METHODS: We used client data from Zambia's electronic medical record system (SmartCare) for 737 health facilities, representing about three-fourths of all ART clients nationally. We compared the numbers and proportional distributions of clients enrolled in DSD models in the 6 months before and 6 months after the first case of COVID-19 was diagnosed in Zambia in March 2020. Segmented linear regression was used to determine whether the outbreak of COVID-19 in Zambia further accelerated the increase in DSD scale-up. RESULTS AND DISCUSSION: Between September 2019 and August 2020, 181,317 clients aged 15 or older (81,520 and 99,797 from 1 September 2019 to 1 March 2020 and from 1 March to 31 August 2020, respectively) enrolled in DSD models in Zambia. Overall participation in all DSD models increased over the study period, but uptake varied by model. The rate of acceleration increased in the second period for home ART delivery (152%), ≤ 2-month fast-track (143%) and 3-month MMD (139%). There was a significant reduction in the enrolment rates for 4- to 6-month fast-track (-28%) and "other" models (-19%). CONCLUSIONS: Participation in DSD models for stable ART clients in Zambia increased after the advent of COVID-19, but dispensing intervals diminished. Eliminating obstacles to longer dispensing intervals, including those related to supply chain management, should be prioritized to achieve the expected benefits of DSD models and minimize COVID-19 risk.

Incidence rate of Kaposi sarcoma in HIV-infected patients on antiretroviral therapy in Southern Africa: a prospective multicohort study.

BACKGROUND: The risk of Kaposi sarcoma (KS) among HIV-infected persons on antiretroviral therapy (ART) is not well defined in resource-limited settings. We studied KS incidence rates and associated risk factors in children and adults on ART in Southern Africa. METHODS: We included patient data of 6 ART programs in Botswana, South Africa, Zambia, and Zimbabwe. We estimated KS incidence rates in patients on ART measuring time from 30 days after ART initiation to KS diagnosis, last follow-up visit, or death. We assessed risk factors (age, sex, calendar year, WHO stage, tuberculosis, and CD4 counts) using Cox models. FINDINGS: We analyzed data from 173,245 patients (61% female, 8% children aged <16 years) who started ART between 2004 and 2010. Five hundred and sixty-four incident cases were diagnosed during 343,927 person-years (pys). The overall KS incidence rate was 164/100,000 pys [95% confidence interval (CI): 151 to 178]. The incidence rate was highest 30-90 days after ART initiation (413/100,000 pys; 95% CI: 342 to 497) and declined thereafter [86/100,000 pys (95% CI: 71 to 105), >2 years after ART initiation]. Male sex [adjusted hazard ratio (HR): 1.34; 95% CI: 1.12 to 1.61], low current CD4 counts (≥500 versus <50 cells/µL, adjusted HR: 0.36; 95% CI: 0.23 to 0.55), and age (5-9 years versus 30-39 years, adjusted HR: 0.20; 95% CI: 0.05 to 0.79) were relevant risk factors for developing KS. INTERPRETATION: Despite ART, KS risk in HIV-infected persons in Southern Africa remains high. Early HIV testing and maintaining high CD4 counts is needed to further reduce KS-related morbidity and mortality.