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.

Keywords: primary care
viral load
differentiated care
HIV
point-of-care
community care
South Africa
anti-retroviral therapy
dolutegravir
Advisor: Butler, C
Garrett, N
Hayward, G
Tonkin-Crine, S