Early antiretroviral therapy is associated with better viral suppression and less HIV drug resistance after implementation of universal treatment in South Africa

All people living with HIV should receive antiretroviral therapy (ART), but those with CD4 counts >500 cells/mm3 at ART initiation (“early initiators”) may be less motivated to adhere to treatment, compared with those with CD4 counts 1,000 copies/mL. We used Poisson regression models with robust variance to evaluate associations between early ART initiation and viral suppression  500 cells/mm3. In multivariable analysis, early initiators were more likely to be virally suppressed compared with late initiators (adjusted risk ratio: 1.29, 95% confidence interval: 1.13–1.46). All 18 participants with viral load >1,000 copies/mL had successful genotyping, which identified drug resistance in 14/18 (77.8%). Among early initiators, drug resistance was detected in only 1/117 (0.9%), compared with 11/93 (11.8%) among late initiators. In conclusion, among people receiving ART in a South African public clinic, early initiators had better viral suppression after 6 months and less drug resistance than late initiators, which further supports universal treatment. Clinical trials registration: NCT03066128

Low CD4 count and educational status predict abnormal cervical smears amongst HIV-positive women initiating antiretroviral therapy in South Africa

Cervical cancer is common amongst human immunodeficiency virus (HIV)-positive women in low- and middle-income countries. In South Africa, more than 7500 cases are diagnosed annually and over 50% result in death, making cervical cancer the leading cause of cancer mortality.1 South Africa’s high HIV prevalence contributes to this high burden, because HIV-positive women are more likely to have persistent human papilloma virus (HPV) infection and precancerous cervical changes.2 Cervical cancer is preventable either through HPV vaccination of girls before sexual debut, which was rolled out in South Africa from 2014, or screening and treatment of precancerous cervical lesions. South African guidelines recommend cervical screening for all HIV-positive women at HIV diagnosis and then every 3 years.1 Antiretroviral therapy (ART) causes immune reconstitution and may reduce the risk of cervical cancer amongst HIV-positive women by lowering HPV acquisition, increasing HPV clearance and slowing the progression to precancerous lesions.2 However, these effects may be diminished for women who initiate ART at low CD4 counts.3 Since 2016, when universal test and treat (UTT) was introduced in South Africa, women began initiating ART at CD4 counts > 500 cells/mm3 (early initiators) and may therefore be protected against precancerous cervical abnormalities and cancer.3 In this study, we aimed to assess whether early initiators of ART had a lower risk of abnormal cervical smears when compared to late initiators (women with a CD4 ≤ 500 cells/mm3 ), after introduction of UTT in South Africa

Intimate partner violence and HIV outcomes among women living with HIV in Durban, South Africa.

This is the final version. Available from Springer via the DOI in this record. Data Availability: Participant data for the STREAM study will be shared and de-identified (text, tables, figures, and appendices) as requested. Data will be available after the proposed use has been approved by an independent review committee.Code Availability: Associated code for any analyses will be shared, as requested.We examined the impact of past-year intimate partner violence (IPV) on HIV outcomes among women living with HIV (WLHIV) in Durban, South Africa. We assessed past-year IPV using the WHO Violence Against Women Questionnaire. We conducted logistic regression to assess associations between demographic variables and IPV at baseline, and between IPV at baseline and longitudinal HIV outcomes. Among 235 WLHIV, 17% reported past-year emotional, physical, or sexual IPV. At baseline, HIV-disclosure to partner was associated with 4.35-fold odds of past-year IPV (95% CI 1.17-16.10) after controlling for children, education, and harmful alcohol use. In the prospective analysis, IPV was associated with not achieving the co-primary outcome of retention in care and viral suppression in univariate (OR = 2.32, 95% CI 1.04-5.18), but not in the multivariate model. In the context of rapid treatment scale-up, the high burden of IPV among WLHIV needs to be prioritized, with an emphasis on disclosure support.National Institute of Allergy and Infectious DiseasesCenter for AIDS Research at the University of WashingtonSouth African National Health Laboratory Service Research TrustSouth African Medical Research CouncilInfectious Disease Society of Americ

Differentiated service delivery for people using second-line antiretroviral therapy: clinical outcomes from a retrospective cohort study in KwaZulu-Natal, South Africa

Introduction Evidence is needed to guide the inclusion of broader groups of people living with HIV (PLHIV) in differentiated service delivery (DSD) programmes. We assessed treatment outcomes among PLHIV on second-line regimens in a community antiretroviral therapy (ART) delivery programme, compared to those who remained at clinics. Methods Using data from 61 public clinics, we did a retrospective cohort study among PLHIV receiving second-line ART following rollout of the Centralized Chronic Medicines Dispensing and Distribution (CCMDD) programme in KwaZulu-Natal, South Africa. We included PLHIV from the timepoint when they were first eligible, though not necessarily referred, for community ART within CCMDD and followed them for 18 months. We used multivariable logistic regression to compare 12-month attrition and viraemia between clients referred for community ART and those remaining in clinic care. Results Among 209,744 PLHIV aged ≥ 18 years who collected ART between October 2016 and December 2018, 7511 (3.6%) received second-line ART. Of these, 2575 (34.3%) were eligible for community ART. The median age was 39.0 years (interquartile range 34.0–45.0) and 1670 (64.9%) were women. Five hundred and eighty-four (22.7%) were referred for community ART within 6 months of meeting eligibility criteria. Overall, 4.5% [95% confidence interval (CI) 3.0–6.6%] in community ART and 4.4% (95% CI 3.5–5.4%) in clinic care experienced attrition at 12 months post eligibility for community ART. Two thousand one hundred and thirty-eight (83.0%) had a viral load recorded 6–18 months after becoming eligible, and of these, 10.3% (95% CI 7.7–13.3%) in community ART and 11.3% (95% CI 9.8–12.9%) in clinic care had viraemia > 200 copies/ml. In separate regressions adjusted for age, gender, district, time on second-line ART, nucleoside reverse transcriptase inhibitor backbone and year of eligibility, no differences in the odds of attrition [adjusted odds ratio (aOR) 1.02, 95% CI 0.71–1.47] or viraemia (aOR 0.91, 95% CI 0.64–1.29) were observed between those in community ART and those remaining in clinic care. Conclusions We found good outcomes among PLHIV who were stable on second-line regimens and referred for community ART. Efforts to expand DSD access among this group should be prioritized

HIV treatment outcomes among people with initiation CD4 counts >500 cells/µL after implementation of Treat All in South African public clinics: a retrospective cohort study

Introduction:&nbsp;The World Health Organisation recommends to&nbsp;Treat All&nbsp;people with HIV, irrespective of CD4 count. However, people with CD4 counts &gt;500&nbsp;cells/&micro;L may be asymptomatic and therefore less motivated to adhere to antiretroviral therapy (ART). We aimed to assess whether people initiated with CD4 counts &gt;500&nbsp;cells/&micro;L had worse treatment outcomes compared to those initiated at lower CD4 counts. Methods:&nbsp;We performed a retrospective cohort study among non‐pregnant adults initiating ART at eight public clinics in South Africa between September 2016, when&nbsp;Treat All&nbsp;was implemented, and August 2017. We assessed whether initiation CD4 count &gt;500&nbsp;cells/&micro;L was associated with the outcomes of attrition (death, lost to follow‐up or treatment interruption &gt;180&nbsp;days), and viraemia &gt;1000&nbsp;copies/mL, by twelve months using Cox proportional hazards and Poisson regression models. Results and discussion:&nbsp;Among 4952 patients initiating ART, the median age was 32.4&nbsp;years (interquartile range (IQR) 27.2 to 39.7), 58.9% were women and 30.3% had an initiation CD4 count &gt;500&nbsp;cells/&micro;L. After twelve months, 3382 (68.3%) were retained in care, 303 (6.1%) had transferred to another clinic, 1010 (20.4%) were lost to follow‐up, 232 (4.7%) had a treatment interruption &gt;180&nbsp;days and 25 (0.5%) were known to have died. Overall, 1267 experienced attrition at a median time of 91&nbsp;days (IQR 23 to 213), with 302 of these (23.8%) experiencing attrition immediately after their ART initiation visit. Among those in care at twelve months with viral load results, 4.6% had viraemia. In multivariable analysis, the hazard of attrition was similar between patients newly eligible for ART with CD4 counts &gt;500&nbsp;cells/&micro;L compared to those with CD4 &le;500&nbsp;cells/&micro;L (adjusted hazard ratio 1.03, 95% confidence interval (CI) 0.90 to 1.17). The risk of viraemia was lower among patients with CD4 counts &gt;500&nbsp;cells/&micro;L compared to those with CD4 &le;500&nbsp;cells/&micro;L (adjusted risk ratio 0.58, 95% CI 0.37 to 0.92). Conclusions:&nbsp;After implementation of&nbsp;Treat All&nbsp;in South African public clinics, we found that patients newly eligible for ART with initiation CD4 counts &gt;500&nbsp;cells/&micro;L had comparable or better outcomes compared to those with lower CD4 counts. These finding support ongoing implementation of&nbsp;Treat All&nbsp;in our setting.</p

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 three rapid HIV viral load assays: the novel Xpert HIV-1 VL XC (Xpert XC), the Xpert HIV-1 VL (Xpert VL), and the m-PIMA HIV52 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 three assays, and 50 and 200 copies/mL on the Xpert assays. We assessed 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% (82-100) and 98% (93-99) (Xpert XC), 100% (87-100) and 96% (91-98) (Xpert VL), and 92% (72-99) and 99% (93-100) (m-PIMA) respectively. At 50 copies/mL, sensitivity and specificity were 93% (81-98) and 96% (91-99) (Xpert XC), and 95% (84-99) and 95% (90-98) (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 three assays was clinically acceptable to detect viraemia at the WHO failure threshold, while both Xpert assays were also accurate at detecting low level viraemia.</p

Protocol for a randomised feasibility study of Point-Of-care HIV viral load testing to Enhance Re-suppression in South Africa: the POwER study

Introduction Access to HIV viral load testing remains difficult for many people on antiretroviral therapy (ART) in low-income and middle-income countries. Weak laboratory and clinic systems often delay the detection and management of viraemia, which can lead to morbidity, drug resistance and HIV transmission. Point-of-care testing could overcome these challenges. We aim to assess whether it is feasible to conduct a randomised trial of point-of-care viral load testing to manage viraemia. Methods and analysis We will conduct an open-label, single-site, individually randomised, feasibility study of Point-Of-care HIV viral load testing to Enhance Re-suppression, in Durban, South Africa. We will enrol approximately 100 people living with HIV who are aged ≥18 years, receiving first-line ART but with recent viraemia ≥1000 copies/mL, and randomise them 1:1 to receive point-of-care viral load or standard laboratory viral load monitoring, after 12 weeks. All participants will continue to receive care from public sector healthcare workers following South African HIV management guidelines. Participants with persistent viraemia ≥1000 copies/mL will be considered for switching to second-line ART. We will compare the proportion in each study arm who achieve the primary outcome of viral suppression <50 copies/mL at 24 weeks after enrolment. Additional outcomes include proportions retained in the study, proportions with HIV drug resistance, time to viral load results and time to switching to second-line ART. We will assess implementation of point-of-care viral load testing using process evaluation data, and through interviews and focus groups with healthcare workers. Ethics and dissemination University of Oxford Tropical Research Ethics Committee and the Biomedical Research Ethics Committee of the University of KwaZulu-Natal have approved the study. We will present results to stakeholders, and through conferences and open-access, peer-reviewed journals. Trial registration number PACTR202001785886049

Simplifying TREAtment and Monitoring for HIV (STREAM HIV): protocol for a randomised controlled trial of point-of-care urine tenofovir and viral load testing to improve HIV outcomes

Introduction: Substantial improvements in viral suppression among people living with HIV (PLHIV) are needed to end the HIV epidemic, requiring extensive scale-up of low-cost HIV monitoring services. Point-of-care (POC) tests for monitoring antiretroviral therapy (ART) adherence and viral load (VL) may be efficient and effective tools for real-time clinical decision making. We aim to evaluate the effects of a combined intervention of POC ART adherence and VL testing compared with standard-of-care on ART adherence, viral suppression and retention at 6 and 18 months post-ART initiation among PLHIV. Methods and analysis: Simplifying TREAtment and Monitoring for HIV (STREAM HIV) is a two-arm, open-label, randomised controlled superiority trial of POC urine tenofovir (POC TFV) and VL monitoring in PLHIV. We aim to enrol 540 PLHIV initiating a first-line ART regimen at a public HIV clinic in South Africa. Participants will be randomised 1:1 to the intervention or control arm. Intervention arm participants will receive monthly POC TFV testing for the first 5 months and POC VL testing at months 6 and 12. Intervention arm participants will also receive reflex POC TFV testing if viraemic and reflex HIV drug resistance testing for those with viraemia and detectable TFV. Control arm participants will receive standard-of-care, including laboratory-based VL testing at months 6 and 12. Primary outcomes include ART adherence (TFV-diphosphate concentration) at 6 months and viral suppression and retention at 18 months. Secondary outcomes include viral suppression and retention at 6 months, TFV-diphosphate concentration at 18 months, cost and cost-effectiveness of the intervention and acceptability of the intervention among PLHIV and healthcare workers. Ethics and dissemination: STREAM HIV has received ethical approval from the University of Washington Institutional Review Board (STUDY00007544), University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC/00000833/2019) and Division of AIDS Regulatory Support Center (38509). Findings will be disseminated at international conferences and in peer-reviewed journals.</p