Point-of-Care Viral Load Testing to Manage HIV Viremia During the Rollout of Dolutegravir-Based ART in South Africa: A Randomized Feasibility Study (POwER).

BACKGROUND: Data are required regarding the feasibility of conducting a randomized trial of point-of-care viral load (VL) testing to guide management of HIV viremia and to provide estimates of effect to guide potential future trial design. SETTING: Two public South African clinics during the dolutegravir-based antiretroviral therapy (ART) rollout. METHODS: We randomized adults receiving first-line ART, with recent VL ≥1000 copies/mL, in a 1:1 ratio to receive point-of-care Xpert HIV-1 VL versus standard-of-care laboratory VL testing after 12 weeks. Feasibility outcomes included proportions of eligible patients enrolled and completing follow-up and VL process outcomes. Estimates of effect were assessed using the trial primary outcome of VL <50 copies/mL after 24 weeks. RESULTS: From August 2020 to March 2022, we enrolled 80 eligible participants, an estimated 24% of those eligible. 47 of 80 (58.8%) were women, and the median age was 38.5 years (interquartile range [IQR], 33-45). 44 of 80 (55.0%) were receiving dolutegravir, and 36 of 80 (465.0%) were receiving efavirenz. After 12 weeks, point-of-care participants received VL results after median 3.1 hours (IQR 2.6-3.8), versus 7 days (IQR 6-8, P < 0.001) in standard of care. Twelve-week follow-up VL was ≥1000 copies/mL in 13 of 39 (33.3%) point-of-care participants and in 16 of 41 (39.0%) standard-of-care participants; 11 of 13 (84.6%) and 12 of 16 (75.0%) switched to second-line ART. After 24 weeks, 76 of 80 (95.0%) completed follow-up. 27 of 39 (69.2% [95% CI: 53.4 to 81.4]) point-of-care participants achieved VL <50 copies/mL versus 29 of 40 (72.5% [57.0 to 83.9]) standard-of-care participants. Point-of-care participants had median 3 (IQR, 3-4) clinical visits versus 4 (IQR, 4-5) in standard-of-care participants ( P < 0.001). CONCLUSIONS: It was feasible to conduct a trial of point-of-care VL testing to manage viremia. Point-of-care VL lead to quicker results and fewer clinical visits, but estimates of 24-week VL suppression were similar between arms. TRIAL REGISTRATION: Pan African Clinical Trials Registry: PACTR202001785886049.

Diagnostic Accuracy of the Rapid Xpert HIV-1 Viral Load XC, Xpert HIV-1 Viral Load, & m-PIMA HIV-1/2 Viral Load in South African Clinics.

BACKGROUND: We aimed to evaluate the analytic performance of 3 rapid HIV viral load assays: the novel Xpert HIV-1 VL XC (Xpert XC), Xpert HIV-1 VL (Xpert VL), and m-PIMA HIV-1/2 VL (m-PIMA). SETTING: Two South African clinics. METHODS: We conducted a prospective diagnostic accuracy study. Site-laboratory technicians and nurses used the Xpert XC, Xpert VL, and m-PIMA to test plasma samples from people with HIV receiving antiretroviral therapy. We compared results with the Roche cobas HIV-1 reference assay. We determined accuracy to detect viraemia at the World Health Organization (WHO) failure threshold of 1000 copies/mL on all 3 assays, and 50 and 200 copies/mL on the Xpert assays. We assessed the agreement using Bland-Altman plots. RESULTS: We enrolled 140 participants (98 [70%] women, median age 37 years), who provided 189 paired samples at one or more timepoints. We tested 174 samples with the Xpert XC, 188 with the Xpert VL, and 128 with the m-PIMA. At 1000 copies/mL, sensitivity and specificity (95% confidence intervals) were 97% (82 to 100) and 98% (93 to 99) (Xpert XC), 100% (87 to 100) and 96% (91 to 98) (Xpert VL), and 92% (72 to 99) and 99% (93 to 100) (m-PIMA) respectively. At 50 copies/mL, sensitivity and specificity were 93% (81 to 98) and 96% (91 to 99) (Xpert XC), and 95% (84 to 99) and 95% (90 to 98) (Xpert VL) respectively. Mean bias was -0.10 (-0.54 to 0.34) log10 copies/mL (Xpert XC), 0.07 (-0.37 to 0.52) log10 copies/mL (Xpert VL), and -0.26 (-0.83 to 0.31) log10 copies/mL (m-PIMA). CONCLUSIONS: In these South African clinics, the accuracy of all 3 assays was clinically acceptable to detect viraemia at the WHO failure threshold, whereas both Xpert assays were also accurate at detecting low-level viraemia.

Comparative cost analysis of point-of-care versus laboratory-based testing to initiate and monitor HIV treatment in South Africa.

BACKGROUND: The number of people living with HIV (PLHIV) in need of treatment monitoring in low-and-middle-income countries has been rapidly expanding, placing an increasing burden on laboratories. Promising new point-of-care (POC) test have the potential to reduce laboratory workloads, but the implementation cost is uncertain. We sought to estimate the costs of decentralized POC testing compared to centralized laboratory testing for PLHIV initiating treatment in South Africa. METHODS: We conducted a microcosting analyses comparing clinic-based POC testing to centralized laboratory testing for HIV viral load, creatinine, and CD4 count monitoring. We completed time-and-motion studies to assess staff time for sample collection and processing. Instrument costs were estimated assuming five-year lifespans and we applied a 3% annual discount rate. Total costs and cost per patient were estimated over a five-year period: the first year of ART initiation and four years of routine HIV monitoring, following World Health Organization ART monitoring guidelines. RESULTS: We estimated that per-patient costs of POC HIV viral load, CD4, and creatinine tests were USD $25, $11, and $9, respectively, assuming a clinic volume of 50 patients initiated per month. At centralized laboratories, per-patient costs of POC HIV viral load, CD4, and creatinine tests were USD $26, $6, $3. Total monitoring costs of all testing over a 5-year period was $45 higher for POC testing compared to centralized laboratory testing ($210 vs $166). CONCLUSIONS: POC testing for HIV care and treatment can be feasibly implemented within clinics in South Africa, particularly those with larger patient volumes. POC HIV viral load costs are similar to lab-based testing while CD4 count and creatinine testing are more costly as POC tests. Our cost estimates are useful to policymakers in planning resource allocation and can inform cost-effectiveness analyses of POC testing.

Diagnostic accuracy of the Xpert CT/NG and OSOM Trichomonas Rapid assays for point-of-care STI testing among young women in South Africa: a cross-sectional study.

OBJECTIVES: Syndromic management of sexually transmitted infections (STIs) omits asymptomatic infections, particularly among women. Accurate point-of-care assays may improve STI care in low- and middle-income countries (LMICs). We aimed to evaluate the diagnostic performance of the Xpert Chlamydia trachomatis/Neisseria gonorrhoeae (CT/NG) and OSOM Trichomonas vaginalis (TV) Test as part of a STI care model for young women in South Africa. DESIGN: Diagnostic evaluation conducted as part of a prospective cohort study (CAPRISA 083) between May 2016 and January 2017. SETTING: One large public healthcare facility in central Durban, KwaZulu-Natal, South Africa PARTICIPANTS: 247 women, aged 18-40 years, attending for sexual and reproductive services to the clinic. Pregnant and HIV-positive women were excluded. OUTCOMES: Diagnostic performance of the Xpert CT/NG and OSOM TV assays against the laboratory-based Anyplex II STI-7 Detection. All discordant results were further tested on the Fast Track Diagnostics (FTD) STD9 assay. RESULTS: We obtained vaginal swabs from 247 women and found 96.8% (239/247) concordance between Xpert and Anyplex for CT and 100% (247/247) for NG. All eight discrepant CT results were positive on Xpert, but negative on Anyplex. FTD STD9 confirmed three positive and five negative results, giving a confirmed prevalence of CT 15.0% (95% CI 10.5 to 19.4), NG 4.9% (2.2-7.5) and TV 3.2% (1.0-5.4). Sensitivity and specificity of Xpert CT/NG were 100% (100-100) and 97.6% (95.6-99.7) for CT and 100% (100-100) and 100% (100-100) for NG. The sensitivity and specificity of OSOM TV were 75.0% (45.0-100) and 100% (100-100). CONCLUSION: The Xpert CT/NG showed high accuracy among young South African women and combined with the OSOM TV proved a useful tool in this high HIV/STI burden setting. Further implementation and cost-effectiveness studies are needed to assess the potential role of this assay for diagnostic STI testing in LMICs. TRIAL REGISTRATION NUMBER: NCT03407586; Pre-results.