• HIV programmatic outcomes following implementation of the 'Treat-All' policy in a public sector setting in Eswatini: a prospective cohort study

      Kerschberger, B; Schomaker, M; Jobanputra, K; Kabore, SM; Teck, R; Mabhena, E; Mthethwa-Hleza, S; Rusch, B; Ciglenecki, I; Boulle, A (Wiley, 2020-03-03)
      INTRODUCTION: The Treat-All policy - antiretroviral therapy (ART) initiation irrespective of CD4 cell criteria - increases access to treatment. Many ART programmes, however, reported increasing attrition and viral failure during treatment expansion, questioning the programmatic feasibility of Treat-All in resource-limited settings. We aimed to describe and compare programmatic outcomes between Treat-All and standard of care (SOC) in the public sectors of Eswatini. METHODS: This is a prospective cohort study of ≥16-year-old HIV-positive patients initiated on first-line ART under Treat-All and SOC in 18 health facilities of the Shiselweni region, from October 2014 to March 2016. SOC followed the CD4 350 and 500 cells/mm3 treatment eligibility thresholds. Kaplan-Meier estimates were used to describe crude programmatic outcomes. Multivariate flexible parametric survival models were built to assess associations of time from ART initiation with the composite unfavourable outcome of all-cause attrition and viral failure. RESULTS: Of the 3170 patients, 1888 (59.6%) initiated ART under Treat-All at a median CD4 cell count of 329 (IQR 168 to 488) cells/mm3 compared with 292 (IQR 161 to 430) (p < 0.001) under SOC. Although crude programme retention at 36 months tended to be lower under Treat-All (71%) than SOC (75%) (p = 0.002), it was similar in covariate-adjusted analysis (adjusted hazard ratio [aHR] 1.06, 95% CI 0.91 to 1.23). The hazard of viral suppression was higher for Treat-All (aHR 1.12, 95% CI 1.01 to 1.23), while the hazard of viral failure was comparable (Treat-All: aHR 0.89, 95% CI 0.53 to 1.49). Among patients with advanced HIV disease (n = 1080), those under Treat-All (aHR 1.13, 95% CI 0.88 to 1.44) had a similar risk of an composite unfavourable outcome to SOC. Factors increasing the risk of the composite unfavourable outcome under both interventions were aged 16 to 24 years, being unmarried, anaemia, ART initiation on the same day as HIV care enrolment and CD4 ≤ 100 cells/mm3 . Under Treat-All only, the risk of the unfavourable outcome was higher for pregnant women, WHO III/IV clinical stage and elevated creatinine. CONCLUSIONS: Compared to SOC, Treat-All resulted in comparable retention, improved viral suppression and comparable composite outcomes of retention without viral failure.
    • Implementation and operational feasibility of SAMBA I HIV‐1 semi‐quantitative viral load testing at the point‐of‐care in rural settings in Malawi and Uganda

      Gueguen, M; Nicholas, S; Poulet, E; Schramm, B; Szumilin, E; Wolters, L; Wapling, J; Ajule, E; Rakesh, A; Mwenda, R; et al. (Wiley, 2020-11-07)
      Objective We monitored a large‐scale implementation of the Simple Amplification‐Based Assay semi‐quantitative viral load test for HIV‐1 version I (SAMBA I Viral Load = SAMBA I VL) within Médecins Sans Frontières’ HIV programmes in Malawi and Uganda, to assess its performance and operational feasibility. Methods Descriptive analysis of routine programme data between August 2013 and December 2016. The dataset included samples collected for VL monitoring and tested using SAMBA I VL in five HIV clinics in Malawi (four peripheral health centres and one district hospital), and one HIV clinic in a regional referral hospital in Uganda. SAMBA I VL was used for VL testing in patients who had been receiving ART for between 6 months and ten years, to determine whether plasma VL was above or below 1000 copies/mL of HIV‐1, reflecting ART failure or efficacy. Randomly selected samples were quantified with commercial VL assays. SAMBA I instruments and test performance, site throughput, and delays in communicating results to clinicians and patients were monitored. Results Between August 2013 and December 2016 a total of 60 889 patient samples were analysed with SAMBA I VL. Overall, 0.23% of initial SAMBA I VL results were invalid; this was reduced to 0.04% after repeating the test once. Global test failure, including instrument failure, was 1.34%. Concordance with reference quantitative testing of VL was 2620/2727, 96.0% (1338/1382, 96.8% in Malawi; 1282/1345, 95.3% in Uganda). For Chiradzulu peripheral health centres and Arua Hospital HIV clinic, where testing was performed on‐site, same‐day results were communicated to clinicians for between 91% and 97% of samples. Same‐day clinical review was obtained for 84.7% across the whole set of samples tested. Conclusions SAMBA I VL testing is feasible for monitoring cohorts of 1000 to 5000 ART‐experienced patients. Same‐day results can be used to inform rapid clinical decision‐making at rural and remote health facilities, potentially reducing time available for development of resistance and conceivably helping to reduce morbidity and mortality.
    • Implementation of community and facility-based HIV self-testing under routine conditions in southern Eswatini

      Pasipamire, L; Nesbitt, R; Dube, L; Mabena, E; Nzima, M; Dlamini, M; Rugongo, N; Maphalala, N; Obulutsa, TA; Ciglenecki, I; et al. (Wiley, 2020-03-27)
      OBJECTIVES: WHO recommends HIV self-testing (HIVST) as an additional approach to HIV testing services. The study describes the strategies used during phase-in of HIVST under routine conditions in Eswatini (formerly Swaziland). METHODS: Between May 2017 and January 2018, assisted and unassisted oral HIVST was offered at HIV testing services (HTS) sites to people aged ≥ 16 years. Additional support tools were available, including a telephone hotline answered 24/7, HIVST demonstration videos and printed educational information about HIV prevention and care services. Demographic characteristics of HIVST users were described and compared with standard blood-based HTS in the community. HIVST results were monitored with follow-up phone calls and the hotline. RESULTS: During the 9-month period, 1895 people accessed HIVST and 2415 HIVST kits were distributed. More people accessed HIVST kits in the community (n = 1365, 72.0%) than at health facilities (n = 530, 28.0%). The proportion of males and median age among those accessing HIVST and standard HTS in the community were similar (49.3%, 29 years HIVST vs. 48.7%, 27 years standard HTS). In total, 34 (3.9%) reactive results were reported from 938 people with known HIVST results; 32.4% were males, and median age was 30 years (interquartile range 25-36). Twenty-one (62%) patients were known to have received confirmatory blood-based HTS; of these, 20 (95%) had concordant reactive results and 19 (95%) were linked to HIV care at a clinic. CONCLUSION: Integration of HIVST into existing HIV facility- and community-based testing strategies in Eswatini was found to be feasible, and HIVST has been adopted by national testing bodies in Eswatini.
    • Long-term virologic responses to antiretroviral therapy among HIV-positive patients entering adherence clubs in Khayelitsha, Cape Town, South Africa: a longitudinal analysis

      Kehoe, K; Boulle, A; Tsondai, PR; Euvrard, J; Davies, MA; Cornell, M (Wiley, 2020-05-14)
      Introduction In South Africa, an estimated 4.6 million people were accessing antiretroviral therapy (ART) in 2018. As universal Test and Treat is implemented, these numbers will continue to increase. Given the need for lifelong care for millions of individuals, differentiated service delivery models for ART services such as adherence clubs (ACs) for stable patients are required. In this study, we describe long‐term virologic outcomes of patients who have ever entered ACs in Khayelitsha, Cape Town. Methods We included adult patients enrolled in ACs in Khayelitsha between January 2011 and December 2016 with a recorded viral load (VL) before enrolment. Risk factors for an elevated VL (VL >1000 copies/mL) and confirmed virologic failure (two consecutive VLs >1000 copies/mL one year apart) were estimated using Cox proportional hazards models. VL completeness over time was assessed. Results Overall, 8058 patients were included in the analysis, contributing 16,047 person‐years of follow‐up from AC entry (median follow‐up time 1.7 years, interquartile range [IQR]:0.9 to 2.9). At AC entry, 74% were female, 46% were aged between 35 and 44 years, and the median duration on ART was 4.8 years (IQR: 3.0 to 7.2). Among patients virologically suppressed at AC entry (n = 8058), 7136 (89%) had a subsequent VL test, of which 441 (6%) experienced an elevated VL (median time from AC entry 363 days, IQR: 170 to 728). Older age (adjusted hazard ratio [aHR] 0.64, 95% confidence interval [CI] 0.46 to 0.88), more recent year of AC entry (aHR 0.76, 95% CI 0.68 to 0.84) and higher CD4 count (aHR 0.67, 95% CI 0.54 to 0.84) were protective against experiencing an elevated VL. Among patients with an elevated VL, 52% (150/291) with a repeat VL test subsequently experienced confirmed virologic failure in a median time of 112 days (IQR: 56 to 168). Frequency of VL testing was constant over time (82 to 85%), with over 90% of patients remaining virologically suppressed. Conclusions This study demonstrates low prevalence of elevated VLs and confirmed virologic failure among patients who entered ACs. Although ACs were expanded rapidly, most patients were well monitored and remained stable, supporting the continued rollout of this model.
    • Measuring linkage to HIV treatment services following HIV self-testing in low-income settings

      Choko, AT; Jamil, MS; MacPherson, P; Corbett, E; Chitembo, L; Ingold, H; Bermudez Aza, E; d'Elbee, M; DiCarlo, M; Majam, M; et al. (Wiley, 2020-06-24)
    • Outcomes of patients on second- and third-line ART enrolled in ART adherence clubs in Maputo, Mozambique.

      Finci, I; Flores, A; Gutierrez Zamudio, A G; Matsinhe, A; de Abreu, E; Issufo, S; Gaspar, I; Ciglenecki, I; Molfino, L (Wiley, 2020-09-22)
      Objectives: Adherence clubs (AC) offer patient-centred access to antiretroviral therapy (ART) while reducing the burden on health facilities. AC were implemented in a health centre in Mozambique specialising in patients with a history of HIV treatment failure. We explored the impact of AC on retention in care and VL suppression of these patients. Methods: We performed a retrospective analysis of patients enrolled in AC receiving second- or third-line ART. The Kaplan-Meier estimates were used to analyse retention in care in health facility, retention in AC and viral load (VL) suppression (VL < 1000 copies/mL). Predictors of attrition and VL rebound (VL ≥ 1000 copies/mL) were assessed using multivariable proportional hazards regression. Results: The analysed cohort contained 699 patients, median age 40 years [IQR: 35-47], 428 (61%) female and 97% second-line ART. Overall, 9 (1.3%) patients died, and 10 (1.4%) were lost to follow-up. Retention in care at months 12 and 24 was 98.9% (95% CI: 98.2-99.7) and 96.4% (95% CI: 94.6-98.2), respectively. Concurrently, 85.8% (95% CI: 83.1-88.2) and 80.9% (95% CI: 77.8-84.1) of patients maintained VL suppression. No association between predictors and all-cause attrition or VL rebound was detected. Among 90 patients attending AC and simultaneously having VL rebound, 64 (71.1%) achieved VL resuppression, 10 (11.1%) did not resuppress, and 14 (15.6%) had no subsequent VL result. Conclusion: Implementation of AC in Mozambique was successful and demonstrated that patients with a history of HIV treatment failure can be successfully retained in care and have high VL suppression rate when enrolled in AC. Expansion of the AC model in Mozambique could improve overall retention in care and VL suppression while reducing workload in health facilities.
    • Population-wide differentials in HIV service access and outcomes in the Western Cape for men as compared to women, South Africa: 2008 to 2018: a cohort analysis

      Osler, M; Cornell, M; Ford, N; Hilderbrand, K; Goemaere, E; Boulle, A (Wiley, 2020-06-26)
      Introduction Few studies have systematically described population‐level differences comparing men and women across the continuum of routine HIV care. This study quantifies differentials in HIV care, treatment and mortality outcomes for men and women over time in South Africa. Methods We analysed population‐wide linked anonymized data, including vital registration linkage, for the Western Cape Province, from the time of first CD4 count. Three antiretroviral therapy guideline eligibility periods were defined: 1 January 2008 to 31 July 2011 (CD4 cell count <200 cells/µL), 1 August 2011 to 31 December 2014 (<350 cells/µL), 1 January 2015 to 31 August 2016 (<500 cells/µL). We estimated care uptake based on service attendance, and modelled associations for men and women with ART initiation and overall, pre‐ART and ART mortality. Separate Cox proportional hazard models were built for each outcome and eligibility period, adjusted for tuberculosis, pregnancy, CD4 count and age. Results Adult men made up 49% of the population and constituted 37% of those living with HIV. In 2009, 46% of men living with HIV attended health services, rising to 67% by 2015 compared to 54% and 77% of women respectively. Men contributed <35% of all CD4 cell counts over 10 years and presented with more advanced disease (39% of all first presentation CD4 cell counts from men were <200 cells/µL compared to 25% in women). ART access was lower in men compared to women (AHR 0.79 (0.77 to 0.80) summarized for Period 2) over the entire study). Mortality was greater in men irrespective of ART (AHR 1.08 (1.01 to 1.16) Period 3) and after ART start (AHR 1.15 (1.05 to 1.20) Period 3) with mortality differences decreasing over time. Conclusions Compared to women, men presented with more advanced disease, were less likely to attend health care services annually, were less likely to initiate ART and had higher mortality overall and while receiving ART care. People living with HIV were more likely to initiate ART if they had acute reasons to access healthcare beyond HIV, such as being pregnant or being co‐infected with tuberculosis. Our findings point to missed opportunities for improving access to and outcomes from interventions for men along the entire HIV cascade.
    • Retention on ART and predictors of disengagement from care in several alternative community-centred ART refill models in rural Swaziland

      Pasipamire, L; Nesbitt, RC; Ndlovu, S; Sibanda, G; Mamba, S; Lukhele, N; Pasipamire, M; Kabore, SM; Rusch, B; Ciglenecki, I; et al. (Wiley, 2018-09-21)
      A broad range of community-centred care models for patients stable on anti-retroviral therapy (ART) have been proposed by the World Health Organization to better respond to patient needs and alleviate pressure on health systems caused by rapidly growing patient numbers. Where available, often a single alternative care model is offered in addition to routine clinical care. We operationalized several community-centred ART delivery care models in one public sector setting. Here, we compare retention in care and on ART and identify predictors of disengagement with care.
    • "We give them threatening advice…": expectations of adherence to antiretroviral therapy and their consequences among adolescents living with HIV in rural Malawi

      Burns, R; Magalasi, D; Blasco, P; Szumilin, E; Pasquier, E; Schramm, B; Wringe, A (Wiley, 2020-03-02)
      Introduction Many adolescents living with HIV in sub‐Saharan Africa struggle to achieve optimal adherence to antiretroviral therapy (ART), but few studies have investigated how their treatment‐taking decisions are influenced by their social interactions with providers, caregivers and community leaders. This study aims to explore the narratives that define expectations of adherence to ART among adolescents living with HIV in a rural Malawian setting. Methods Overall, 45 in‐depth interviews were conducted in 2016 with adolescents living with HIV, caregivers, health workers and community leaders, and four group sessions using participatory tools were undertaken with adolescents. Interviews and group sessions were audio‐recorded, transcribed and translated into English. Data were coded inductively and analysed thematically. Results Adolescents were given strict behavioural codes around optimal treatment adherence, which were often enforced through encouragement, persuasian and threats. In HIV clinics, some staff supported adolescents with broader concerns relating to living with HIV, but other measures to address sub‐optimal adherence in HIV clinics were perceived by patients as punitive, including pill‐counts and increased frequency of clinic visits. Community leaders felt responsible for young peoples' health, sometimes attempting to influence their treatment‐taking by threatening to withdraw services, or to publically “out” those deemed to be non‐adherent. At home, discussions with adolescents about HIV were often limited to dose reminders, and some caretakers resorted to physical punishment to ensure adherence. While some adolescents complied with strictly‐enforced adherence rules, others demonstrated resistance by hiding missed doses, secretly throwing away drugs, or openly refusing to take them. Conclusions The potential of young people to adhere to their ART may be undermined by restrictive messages and punitive approaches to enforce and control their engagement with treatment at home, in the clinic and in the wider community. Interventions should focus on creating safe spaces for adolescents to speak frankly about the adherence challenges that they face and support for caregivers including home‐based interventions.
    • Where do HIV-infected adolescents go after transfer? - Tracking transition/transfer of HIV-infected adolescents using linkage of cohort data to a health information system platform

      Davies, MA; Tsondai, P; Tiffin, N; Eley, B; Rabie, H; Euvrard, J; Orrell, C; Prozesky, H; Wood, R; Cogill, D; et al. (Wiley, 2017-03-16)
      To evaluate long-term outcomes in HIV-infected adolescents, it is important to identify ways of tracking outcomes after transfer to a different health facility. The Department of Health (DoH) in the Western Cape Province (WCP) of South Africa uses a single unique identifier for all patients across the health service platform. We examined adolescent outcomes after transfer by linking data from four International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) cohorts in the WCP with DoH data.