Introduction:Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), a measure of cumulative antiretroviral therapy (ART) adherence, is associated with viral suppression and predicts future viremia in persons with HIV (PWH). However, its utility to identify those at risk for virologic failure (VF) and drug resistance is unknown. To address this, we aimed to establish the association between this adherence biomarker and VF with drug resistance in a cohort of PWH initiating first-line ART in KwaZulu-Natal, South Africa. Methods: PWH initiating TFV disoproxil fumarate (TDF)-based ART within a parent prospective cohort were evaluated. Using a nested design, DBS for TFV-DP were collected from cases who developed VF (HIV-1 RNA ≥1000 copies/ml) after ≥5 months on ART versus controls, matched 1:2 by site, age, gender, race and ART duration. Cases were categorized as having VF with or without resistance using genotyping. One-way analysis of variance (ANOVA) was used to compare TFV-DP for controls, cases with VF and resistance, and cases with VF without resistance. Data are presented as mean (standard deviation, SD) or geometric mean [95% confidence interval, 95% CI]. Results and discussion: One thousand participants were enrolled in the parent study between 2014 and 2016, of which 288 (29%) had DBS available. Of these, 94 (33%) were cases and 194 (67%) were controls; 59% were women. Mean age of our population was 33 (SD 8) years. Genotyping was available in 50 (53%) of the 94 cases. Geometric mean TFV-DP in DBS from controls was 708 [95% CI; 647-773] fmol/punch, which was higher compared to participants having VF with resistance (n = 36), 386 [95% CI; 241-617] fmol/punch and VF without resistance (n = 14), 61 [95% CI; 22-164] fmol/punch; p<0.001. Genotype could not be obtained in 44 (47%) cases. Conclusions: TFV-DP in DBS showed a stepwise association with VF and drug resistance in South African PWH. Participants having VF with resistance had mid-range concentrations of TFV-DP, which were higher than those for PWH without resistance. Future research on the clinical utility of TFV-DP concentrations in DBS to predict and prevent the development of VF and drug resistance is needed.

Background In sub-Saharan Africa, rates of sustained HIV virologic suppression remain below international goals. HIV resistance testing, while common in resource-rich settings, has not gained traction due to concerns about cost and sustainability. Objective We designed a randomized clinical trial (REVAMP) to determine the feasibility, effectiveness, and cost-effectiveness of routine HIV resistance testing in sub-Saharan Africa. Approach We describe challenges common to intervention studies in resource-limited settings, and strategies used to address them, including: 1) optimizing generalizability and cost-effectiveness estimates to promote transition from study results to policy; 2) minimizing bias due to patient attrition; and 3) addressing ethical issues related to enrollment of pregnant women. Methods The REVAMP study randomizes people in Uganda and South Africa with virologic failure on first-line therapy to standard of care virologic monitoring or immediate resistance testing. To strengthen external validity study procedures are conducted within publicly-supported laboratory and clinical facilities using local staff. To optimize cost estimates, we collect primary data on quality of life and medical resource utilization. To minimize losses from observation, we collect locally-relevant contact information, including Whatsapp account details, for field-based tracking of missing participants. Finally, pregnant women are followed with increase visit frequency to minimize risk to them and their fetuses. Conclusions REVAMP is a pragammatic randomized clinical trial designed to test the effectiveness and cost-effectiveness of HIV resistance testing versus standard of care in sub-Saharan Africa. We anticipate the results will directly inform HIV polity in sub-Saharan to optimize care for HIV-infected patients.

Background The KwaZulu-Natal (KZN) province of South Africa has the highest prevalence of HIV infection in the world. Viral load (VL) testing is a crucial tool for clinical and programmatic monitoring. Within uMkhanyakude district, VL suppression rates were 91% among patients with VL data; however, VL performance rates averaged only 38·7%. The objective of this study was to determine if enhanced clinic processes and community outreach could improve VL monitoring within this district. Methods A packaged intervention was implemented at three rural clinics in the setting of the KZN HIV AIDS Drug Resistance Surveillance Study. This included file hygiene, outreach, a VL register and documentation revisions. Chart audits were used to assess fidelity. Outcome measures included percentage VL performed and suppressed. Each rural clinic was matched with a peri-urban clinic for comparison before and after the start of each phase of the intervention. Monthly sample proportions were modelled using quasi-likelihood regression methods for over-dispersed binomial data. Results Mkuze and Jozini clinics increased VL performance overall from 33·9% and 35·3% to 75·8% and 72·4%, respectively which was significantly greater than the increases in the comparison clinics (RR 1·86 and 1·68, p < 0·01). VL suppression rates similarly increased overall by 39·3% and 36·2% (RR 1·84 and 1·70, p < 0·01). The Chart Intervention phase showed significant increases in fidelity 16 months after implementation. Conclusions The packaged intervention improved VL performance and suppression rates overall but was significant in Mkuze and Jozini. Larger sustained efforts will be needed to have a similar impact throughout the province.

No abstract

Background: The KwaZulu-Natal (KZN) province of South Africa has the highest prevalence of HIV infection in the world. Viral load (VL) testing is a crucial tool for clinical and programmatic monitoring. Within uMkhanyakude district, VL suppression rates were 91% among patients with VL data; however, VL performance rates averaged only 38•7%. The objective of this study was to determine if enhanced clinic processes and community outreach could improve VL monitoring within this district. Methods: A packaged intervention was implemented at three rural clinics in the setting of the KZN HIV AIDS Drug Resistance Surveillance Study. This included le hygiene, outreach, a VL register and documentation revisions. Chart audits were used to assess delity. Outcome measures included percentage VL performed and suppressed. Each rural clinic was matched with a peri-urban clinic for comparison before and after the start of each phase of the intervention. Monthly sample proportions were modelled using quasi-likelihood regression methods for over-dispersed binomial data. Results: Mkuze and Jozini clinics increased VL performance overall from 33•9% and 35•3% to 75•8% and 72•4%, respectively which was signi cantly greater than the increases in the comparison clinics (RR 1•86 and 1•68, p<0•01). VL suppression rates similarly increased overall by 39•3% and 36•2% (RR 1•84 and 1•70, p<0•01). The Chart Intervention phase showed signi cant increases in delity 16 months after implementation. Conclusions: The packaged intervention improved VL performance and suppression rates overall but was signi cant in Mkuze and Jozini. Larger sustained efforts will be needed to have a similar impact throughout the province.