Point-of-care testing, new antiretroviral regimens and community-based treatment to enhance primary care HIV services in South Africa

Background: The global rollout of antiretroviral therapy has significantly reduced HIV/AIDS related morbidity and mortality. However, there are new challenges in a) providing HIV viral load testing to monitor the effectiveness of ART, b) combating HIV drug resistance, and c) efficiently providing treatment to the 39 million people living with HIV globally. In low- and middle-income countries such as South Africa, most ART is provided in primary care, where there is limited laboratory capacity and where available, viral load testing typically takes several days to turn around, resulting in additional clinic visits for review of results and treatment adjustment. New point-of-care assays have been developed which could be used in primary care clinics to provide same-day viral load results. Patients with viraemia and uncontrolled HIV infection could receive immediate adherence counselling, and ART optimization for those likely to have HIV drug resistance. However, we do not know the clinical effectiveness of these point-of-care assays HIV in primary care settings. Furthermore, the new antiretroviral dolutegravir, which has a higher genetic barrier to HIV drug resistance, has been introduced and will require new monitoring strategies. Lastly, the impacts of dolutegravir, and new models of efficient community ART provision, are not known. Aims: To determine whether point-of-care viral load testing is a promising strategy to improve management of viraemia in primary care in South Africa, and whether its clinical effectiveness can be tested in a large, randomised trial. To assess changes in the ART programme, including the introduction of dolutegravir and community ART delivery programmes, which may necessitate new monitoring strategies. Methods: First, I evaluated the diagnostic accuracy of three point-of-care viral load assays, and conducted the Point-Of-care HIV viral load testing to Enhance Re-suppression (POwER) trial, a randomised pilot/feasibility study. I assessed trial feasibility outcomes (enrolment and retention), 12-week point-of care viral load process outcomes, and the future trial primary outcome of viral suppression at <50 copies/mL after 24 weeks, in the point-of-care and laboratory viral load arms. Second, to explore the impact of a new, likely more effective antiretroviral, dolutegravir, I conducted a post-hoc analysis within POwER, evaluating viral load outcomes and HIV drug resistance by baseline ART regimen. I then evaluated the analytic performance of a novel point-of-care test that measures urine concentrations of tenofovir, a key component of most ART regimens. Third, I evaluated the healthcare context in which these assays may be implemented. I assessed the rollout of dolutegravir, and its impact on viral load outcomes, in a retrospective cohort study using data from 59 South African primary care clinics. Then, using interviews and focus group discussions with patients and healthcare workers, I explored the impact of a community ART programme, that includes over 1 million patients, on the ‘social practice’ of engagement in HIV care. Lastly, I used interrupted time series analysis of routine data from 60 clinics to quantify the impact of COVID-19 on primary care HIV services in South Africa. Results: First, in 189 paired samples, sensitivity and specificity of three different point-of-care viral load assays to detect viraemia was >90%. Enrolment into POwER was disrupted by the COVID-19 pandemic, with 80 eligible participants enrolled between August 2020 to March 2022, versus an initial target of 100 in six months. The 12-week point-of-care viral load result was delivered to participants a median of 3.1 hours (IQR 2.6-3.8) after blood draw, versus 7 days (IQR 6-8, p<0.001) for standard laboratory viral load results. Point-of-care participants had median 3 (IQR 3-4) clinic visits versus 4 (IQR 4-5) in the standard-of-care arm (p<0.001). Retention was high at 95.0% at 24 weeks, and the exploratory primary outcome of 24-week viral suppression was achieved by 27/39 (69.2% [95%CI 53.4-81.4]) point-of-care participants versus 29/40 (72.5% [57.0-83.9]) standard-of-care participants (p=0.808). Second, at enrolment into POwER, 43 participants were receiving dolutegravir, and 37 were receiving the older drug efavirenz as part of their ART regimen. People receiving dolutegravir had no major HIV drug resistance, and therefore achieved rapid viral resuppression after enhanced adherence counselling, meaning there was little opportunity for the point-of-care viral load to exert an effect. The point-of-care urine test had good analytic performance, with >90% sensitivity and specificity to detect tenofovir. Third, in over 220,000 people in 59 South African primary care clinics, over 75% of people were receiving dolutegravir by February 2022. Viral suppression was slightly higher in people receiving dolutegravir compared to those receiving efavirenz (adjusted risk ratio 1·04 [1·01,1·06], adjusted risk difference 3·1% [1·2,5·1]). In a qualitative study, the South African community-based ART programme was found to be acceptable to both patients and healthcare workers and was perceived to overcome several barriers to clinic-based ART collection, resulting in quicker and more convenient care for people living with HIV. Lastly, the COVID-19 lockdown led to a 47.6% drop in HIV testing (incidence rate ratio [IRR] 0.52, 95% CI 0.45-0.62) and a 46.2% decrease in ART initiations (IRR 0.54, 95% CI 0.46-0.63), while there was no marked change in ART collection visits (IRR 0.93, 95% CI 0.79-1.09). Conclusion: Point-of-care viral load assays have acceptable clinical performance in primary care, and it would be feasible to assess their clinical effectiveness in a larger randomised trial. However, the widespread rollout of dolutegravir means that there may be less HIV drug resistance and a potential smaller role for point-of-care viral load tests to improve HIV viraemia. Instead, combination interventions including novel point-of-care adherence assays should be investigated to manage viraemia. Whether point-of-care viral load tests may have more of a role in improving efficiency of community ART delivery programmes should also be evaluated

Combining general practice with international work: online survey of experiences of UK GPs

Objectives: To conduct an exploratory study to learn about the experiences of GPs who have undertaken international work. Design: Cross-sectional survey. Setting: Online survey of UK-based GPs. Members of all UK RCGP faculties were invited to participate by email and the survey was publicised on the RCGP website. Participants: All UK-based GPs. Main outcome measures: Types of UK and international work undertaken, barriers, competencies gained, influence on career and future plans. Results: The study identified 439 respondents, in a variety of GP roles at all career stages, who had undertaken international work in their role as a doctor. GPs are undertaking international work in both high and low/middle-income countries, engaging in a wide range of clinical and non-clinical activities. Respondents reported gaining a range of competencies from international work, which could be transferred back to the UK setting to a variable degree. Commonly cited barriers to international work were having to leave friends and family, and concerns regarding future employment and pension. Most reported that engaging in international work had influenced the direction of their career, with the largest proportion stating that they wish to work predominantly in the UK, with some international work in the future. Conclusion: The study highlights the variety of ways in which UK GPs are combining UK general practice and international work, competencies gained with such work, and ability to transfer these back to the UK setting. Historical barriers to international work still exist and future research could further examine the value of such work

Changes in the medical admissions and mortality amongst children in four South African hospitals following the COVID-19 pandemic: A five-year review

Vulnerable children from poor communities with high HIV and Tuberculosis(TB) burdens were impacted by COVID-19 lockdowns. Concern was raised about the extent of this impact and anticipated post-pandemic surges in mortality. Interrupted time series segmented regression analyses were done using routinely collected facility-level data of children admitted for medical conditions at four South African referral hospitals. Monthly admission and mortality data over 60 months from 01 April 2018 to 31 January 2023 was analysed using models which included dummy lockdown level variables, a dummy post-COVID period variable, Fourier terms to account for seasonality, and excess mortality as a proxy for healthcare burden. Of the 45 015 admissions analysed, 1237(2·75%) demised with significant decreases in admissions during all the lockdown levels, with the most significant mean monthly decrease of 450(95%, CI = 657·3, -244·3) p<0·001 in level 5 (the most severe) lockdown. There was evidence of loss of seasonality on a six-month scale during the COVID periods for all admissions (p = 0·002), including under-one-year-olds (p = 0·034) and under-five-year-olds (p = 0·004). No decreases in mortality accompanied decreased admissions. Post-pandemic surges in admissions or mortality were not identified in children with acute gastroenteritis, acute pneumonia and severe acute malnutrition.During the COVID-19 pandemic, paediatric admissions in 4 hospitals serving communities with high levels of HIV, TB and poverty decreased, similar to global experiences; however, there was no change in in-hospital mortality. No post-pandemic surge in admissions or mortality was documented. Differences in the impact of pandemic control measures on the transmission of childhood infections and access to health care may account for differing outcomes seen in our setting compared to the global experiences. Further studies are needed to understand the impact of pandemic control measures on healthcare provision and transmission dynamics and to better inform future responses amongst vulnerable child populations

Healthcare worker perspectives on adaptations to differentiated anti-retroviral therapy delivery during COVID-19 in South Africa: A qualitative inquiry

During the COVID-19 pandemic, the South African Centralized Chronic Medicines Dispensing and Distribution (CCMDD) programme, adapted to include extended 12-month antiretroviral therapy (ART) prescriptions, 3-months ART refills and earlier eligibility criteria at 6-months after ART initiation. We aimed to explore the experiences of healthcare workers (HCWs) in implementing these adaptations, and to understand the overall impact of COVID-19 on CCMDD. We conducted semi-structured in-depth interviews with HCWs in eThekwini District clinics, KwaZulu-Natal, South Africa. Interviews were audio-recorded, transcribed, translated, and analysed thematically. Between 18 February and 13 December 2022, we conducted 21 interviews with nurses, doctors, pharmacists, clinic managers and a community pick-up-point staff member. There were mixed perceptions about COVID-19 adaptations to CCMDD. HCWs reported that COVID-19 adaptations to CCMDD helped keep clients away from clinics, reducing exposure to COVID-19, minimizing queues, alleviating client frustration, and easing workload, which enabled more focused attention on clients with greater needs. Clients reportedly preferred 12-month prescriptions as it gave them independence. However, HCWs were concerned about clients’ ART adherence, potential to miss out on clinical input, and difficulties aligning annual viral load results, during the 12 months without clinic attendance. The extended eligibility and multi-month dispensing were acceptable to HCWs, but concerns were expressed about non-adherence and stock shortages. Challenges, including staff shortages due to sickness, increased workload, inadequate training, HCWs’ distrust in clients’ ability to manage their health autonomously, and staff’s limited involvement in decisions about the adaptations, impacted on their implementation. While HCWs reported benefits of 12-month prescribing, extended eligibility and multi-month dispensing in CCMDD, long-term implementation would require addressing concerns about impacts on adherence, alignment of annual viral loads and timely follow up. Prioritizing HCW input in decision-making processes and enhancing provider-client interactions will be pivotal in ensuring the effectiveness of CCMDD adaptations

COVID-19 and HIV viral load suppression in children and adolescents in Durban, South Africa

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic poses challenges to paediatric and adolescent HIV treatment programme. Modelling exercises raised concerns over potential impact of disruptions. OBJECTIVES: To describe the impact of the COVID-19 pandemic on viral load (VL) testing among infants, children and adolescents on antiretroviral treatment (ART) in Durban, South Africa. METHOD: Routinely collected, aggregated data of monthly VL counts done on all those less than 19 years old from January 2018 to January 2022 was analysed. An interrupted time series analysis using a Prais-Winsten linear regression model, including terms for lockdowns and excess mortality determined VL trends. RESULTS: The unadjusted mean VL was 2166 (confidence interval [CI]: 252.2) and 2016 (CI: 241.9), P = 0.039, and percentage VL suppression rates (72.9%, CI: 2.4% vs 73.6%, CI: 1.8%) across COVID and pre-COVID periods, showing no significant difference, P = 0.262. In the interrupted time series analysis, modelled monthly VL counts did not differ significantly by lockdown level (e.g., level 5 lockdown: -210.5 VLs, 95% CI: -483.0 to +62.1, P = 0.138) or excess mortality (-0.1, 95% CI: -6.3 to 6.1, P = 0.969). A significant downward trend in VL testing over time, including during the pre-COVID-19 period (-6.6 VL per month, 95% CI: -10.4 to -2.7, P = 0.002), was identified. CONCLUSION: Viral load suppression for children and adolescents were not negatively affected by COVID-19. A trend of decrease in VL testing predated COVID-19. WHAT THIS STUDY ADDS: Evidence presented that HIV VL testing and suppression rates in children and adolescents in a high burden setting were sustained through the COVID pandemic

Health worker experiences of implementing TB infection prevention and control: a qualitative evidence synthesis to inform implementation recommendations

Implementation of TB infection prevention and control (IPC) measures in health facilities is frequently inadequate, despite nosocomial TB transmission to patients and health workers causing harm. We aimed to review qualitative evidence of the complexity associated with implementing TB IPC, to help guide the development of TB IPC implementation plans. We undertook a qualitative evidence synthesis of studies that used qualitative methods to explore the experiences of health workers implementing TB IPC in health facilities. We searched eight databases in November 2021, complemented by citation tracking. Two reviewers screened titles and abstracts and reviewed full texts of potentially eligible papers. We used the Critical Appraisals Skills Programme checklist for quality appraisal, thematic synthesis to identify key findings and the GRADE-CERQual method to appraise the certainty of review findings. The review protocol was pre-registered on PROSPERO, ID CRD42020165314. We screened 1062 titles and abstracts and reviewed 102 full texts, with 37 studies included in the synthesis. We developed 10 key findings, five of which we had high confidence in. We describe several components of TB IPC as a complex intervention. Health workers were influenced by their personal occupational TB risk perceptions when deciding whether to implement TB IPC and neglected the contribution of TB IPC to patient safety. Health workers and researchers expressed multiple uncertainties (for example the duration of infectiousness of people with TB), assumptions and misconceptions about what constitutes effective TB IPC, including focussing TB IPC on patients known with TB on treatment who pose a small risk of transmission. Instead, TB IPC resources should target high risk areas for transmission (crowded, poorly ventilated spaces). Furthermore, TB IPC implementation plans should support health workers to translate TB IPC guidelines to local contexts, including how to navigate unintended stigma caused by IPC, and using limited IPC resources effectively

Delivery of community-based antiretroviral therapy to maintain viral suppression and retention in care in South Africa

Background: To determine whether the Centralized Chronic Medication Dispensing and Distribution (CCMDD) program in South Africa's differentiated ART delivery model affects clinical outcomes, we assessed viral load (VL) suppression and retention in care between patients participating in the program and those receiving the clinic-based standard of care. Methods: Clinically stable people living with HIV (PLHIV) eligible for differentiated care were referred to the national CCMDD program and followed up for up to 6 months. In this secondary analysis of trial cohort data, we estimated the association between routine patient participation in the CCMDD program and their clinical outcomes of viral suppression (<200 copies/mL) and retention in care. Results: Among 390 PLHIV, 236 (61%) were assessed for CCMDD eligibility; 144 (37%) were eligible, and 116 (30%) participated in the CCMDD program. Participants obtained their ART in a timely manner at 93% (265/286) of CCMDD visits. VL suppression and retention in care was very similar among CCMDD-eligible patients who participated in the program compared with patients who did not participate in the program (aRR: 1.03; 95% CI: 0.94–1.12). VL suppression alone (aRR: 1.02; 95% CI: 0.97–1.08) and retention in care alone (aRR: 1.03; 95% CI: 0.95–1.12) were also similar between CCMDD-eligible PLHIV who participated in the program and those who did not. Conclusion: The CCMDD program successfully facilitated differentiated care among clinically stable participants. PLHIV participating in the CCMDD program maintained a high proportion of viral suppression and retention in care, indicating that community-based ART delivery model did not negatively affect their HIV care outcomes

Long‐term usage patterns and clinical outcomes in a community‐based differentiated antiretroviral therapy delivery programme in South Africa

Introduction: There is little data on long-term implementation and outcomes for people living with HIV (PLHIV) in differentiated antiretroviral therapy (ART) delivery programmes. We aimed to analyse usage patterns of and associated treatment outcomes in a community ART programme, within the Centralized Chronic Medicines Dispensing and Distribution programme, in South Africa over 3.5 years. Methods: We performed a retrospective cohort study among PLHIV on first-line ART who were eligible for community ART delivery between October 2016 and March 2019, from 56 urban clinics in KwaZulu-Natal, South Africa. Follow-up ended in March 2020. We measured referral rates and, among those referred, we characterized patterns of community ART usage using group-based trajectory modelling following referral. We used survival analysis to measure the association between community ART usage and loss-to-care (no visit for ≥365 days) and logistic regression to measure the association between community ART usage and viraemia (≥50 copies/ml). Results: Among the 80,801 patients eligible for community ART, the median age was 36 years, 69.8% were female and the median (interquartile range [IQR]) follow-up time was 22 (13–31) months. In total, 49,961 (61.8%) were referred after a median of 6 (IQR 2–13) months from first eligibility. After referral, time spent in community ART varied; 42% remained consistently in community ART, 15% returned to consistent clinic-based care and the remaining 43% oscillated between community ART and clinic-based care. Following referral, the incidence of loss-to-care was 3.93 (95% confidence interval [CI]: 3.71–4.15) per 100 person-years during periods of community ART usage compared to 5.75 (95% CI: 5.28–6.25) during clinic-based care. In multivariable models, community ART usage was associated with a 36% reduction in the hazards of loss-to-care (adjusted hazard ratio: 0.64 [95% CI: 0.57–0.72]). The proportion of patients who became viraemic after first community ART referral was 5.2% and a 10% increase in time in community ART was associated with a 3% reduction in odds of viraemia (adjusted odds ratio: 0.97 [95% CI: 0.95–0.99]). Conclusions: Community ART usage patterns vary considerably, while clinical outcomes were good. Promoting consistent community ART usage may reduce clinic burden and the likelihood of patients being lost to care, while sustaining viral suppression

Clinical outcomes after Viremia among people receiving dolutegravir vs efavirenz-based first-line antiretroviral therapy in South Africa

Background We aimed to compare clinical outcomes after viremia between dolutegravir vs efavirenz-based first-line antiretroviral therapy (ART) as evidence is lacking outside clinical trials in resource-limited settings. Methods We conducted a retrospective cohort analysis with routine data from 59 South African clinics. We included people with HIV aged ≥15 years receiving first-line tenofovir disoproxil fumarate, lamivudine, dolutegravir (TLD) or tenofovir disoproxil fumarate, emtricitabine, efavirenz (TEE) and with first viremia (≥50 copies/mL) between June and November 2020. We used multivariable modified Poisson regression models to compare retention in care and viral suppression (<50 copies/mL) after 12 months between participants on TLD vs TEE. Results At first viremia, among 9657 participants, 6457 (66.9%) were female, and the median age (interquartile range [IQR]) was 37 (31–44) years; 7598 (78.7%) were receiving TEE and 2059 (21.3%) TLD. Retention in care was slightly higher in the TLD group (84.9%) than TEE (80.8%; adjusted risk ratio [aRR], 1.03; 95% CI, 1.00–1.06). Of 6569 participants retained in care with a 12-month viral load, viral suppression was similar between the TLD (78.9%) and TEE (78.8%) groups (aRR, 1.02; 95% CI, 0.98–1.05). However, 3368 participants changed ART during follow-up: the majority from TEE to first-line TLD (89.1%) or second-line (TLD 3.4%, zidovudine/emtricitabine/lopinavir-ritonavir 2.1%). In a sensitivity analysis among the remaining 3980 participants who did not change ART during follow-up and had a 12-month viral load, viral suppression was higher in the TLD (78.9%) than TEE (74.9%) group (aRR, 1.07; 95% CI, 1.03–1.12). Conclusions Among people with viremia on first-line ART, dolutegravir was associated with slightly better retention in care and similar or better viral suppression than efavirenz

Clinical outcomes after extended 12-month antiretroviral therapy prescriptions in a community-based differentiated HIV service delivery programme in South Africa: a retrospective cohort study

Introduction: There is an urgent need for more efficient models of differentiated antiretroviral therapy (ART) delivery for people living with HIV (PLHIV), with the World Health Organization calling for evidence to guide whether annual ART prescriptions and consultations (12M scripts) should be recommended in global guidelines. We assessed the association between 12M scripts (allowed temporarily during the COVID-19 pandemic) versus standard 6-month prescriptions and consultations (6M scripts) and clinical outcomes. Methods: We performed a retrospective cohort study using routine, de-identified data from 59 public clinics in KwaZulu-Natal, South Africa. We included PLHIV aged ≥18 years with a recent suppressed viral load (VL) who had been referred for community ART delivery with 6M or 12M scripts. We used modified Poisson regression to compare 12-month retention-in-care (≤90 days late for all visits) and viral suppression (<50 copies/ml) between prescription groups. Results: Among 27,148 PLHIV referred for community ART during Jun–Dec 2020, 57.4% received 12M scripts. The median age was 39 years and 69.4% were women. Age, sex, prior community ART use and time on ART were similar across groups. However, more of the 12M script group had dolutegravir-based regimens (60.0% vs. 46.3%). The median (interquartile range) number of clinic visits in the year of follow-up was 1(1-1) in the 12M group and 2(2-3) in the 6M group. Retention was 94.6% (95% confidence interval [CI]: 94.2%–94.9%) among those receiving 12M scripts and 91.8% (95% CI: 91.3%–92.3%) among those with 6M scripts. 17.1% and 16.9% of clients in the 12M and 6M groups were missing follow-up VL data, respectively. Among those with VLs, 92.4% (95% CI: 92.0%–92.9%) in the 12M group and 91.4% (95% CI: 90.8%–92.0%) in the 6M group were suppressed. After adjusting for age, sex, ART regimen, time on ART, prior community ART use and calendar month, retention (adjusted risk ratio [aRR]: 1.03, 95% CI: 1.01–1.05) and suppression (aRR: 1.00, 95% CI: 0.99–1.01) were similar across groups. Conclusions: Among PLHIV referred for community ART with a recent suppressed VL, the use of 12M scripts reduced clinic visits without impacting short-term clinical outcomes. 12M scripts should be considered for differentiated service delivery programmes