Cognition and Other Non-Motor Symptoms in an At-Risk Cohort for Parkinson's Disease Defined by REM-Sleep Behavior Disorder and Hyposmia.

Background: REM-sleep behavior disorder (RBD) and other non-motor symptoms such as hyposmia were proposed by the Movement Disorder Society as research criteria for prodromal Parkinson's disease (P-PD). Global cognitive deficit was later added. Objective: To compare non-motor symptoms, focusing on cognition, between a P-PD group and a matched control group. Methods: In this cross-sectional, case-control study, in a first set of analyses, we performed extensive cognitive testing on people with (n = 76) and a control group without (n = 195) probable RBD and hyposmia. Furthermore, we assessed motor and non-motor symptoms related to Parkinson's Disease (PD). After propensity score matching, we compared 62 P-PD with 62 age- and sex-matched controls. In addition, we performed regression analyses on the total sample (n = 271). In a second set of analyses, we used, a.o., the CUPRO to evaluate retrograde procedural memory and visuo-constructive functions. Results: People with P-PD showed significantly poorer performances in global cognition, visuo-constructive and executive functions, mainly in mental flexibility (p < 0.001; p = 0.004; p = 0.003), despite similar educational levels (p = 0.415). We observed significantly more motor and non-motor symptoms (p < 0.001; p = 0.004), higher scores for depression (p = 0.004) and apathy (p < 0.001) as well as lower quality of life (p < 0.001) in P-PD. CONCLUSIONS: Our findings confirm that global cognitive, executive, and visuo-constructive deficits define the P-PD group. In addition, depression, apathy, and lower quality of life were more prevalent in P-PD. If replicated in other samples, executive and visuo-constructive deficits should be considered in non-motor P-PD. Determining specific patterns will support early recognition of PD, secondary prevention of complications and the development of neuroprotective treatments.

Correction: Retention on ART and viral suppression among patients in alternative models of differentiated HIV service delivery in KwaZulu-Natal, South Africa.

[This corrects the article DOI: 10.1371/journal.pgph.0000336.].

Correction: Acceptability of unsupervised peer-based distribution of HIV oral self-testing for the hard-to-reach in rural KwaZulu Natal, South Africa: Results from a demonstration study.

[This corrects the article DOI: 10.1371/journal.pone.0264442.].

Adolescents and young adults are the most undiagnosed of HIV and virally unsuppressed in Eastern and Southern Africa: Pooled analyses from five population-based surveys.

Age and gender disparities within the HIV cascade of care are critical to focus interventions efficiently. We assessed gender-age groups at the highest probability of unfavorable outcomes in the HIV cascade in five HIV prevalent settings. We performed pooled data analyses from population-based surveys conducted in Kenya, South Africa, Malawi and Zimbabwe between 2012 and 2016. Individuals aged 15-59 years were eligible. Participants were tested for HIV and viral load was measured. The HIV cascade outcomes and the probability of being undiagnosed, untreated among those diagnosed, and virally unsuppressed (≥1,000 copies/mL) among those treated were assessed for several age-gender groups. Among 26,743 participants, 5,221 (19.5%) were HIV-positive (69.9% women, median age 36 years). Of them, 72.8% were previously diagnosed and 56.7% virally suppressed (88.5% among those treated). Among individuals 15-24 years, 51.5% were diagnosed vs 83.0% among 45-59 years, p<0.001. Among 15-24 years diagnosed, 60.6% were treated vs 86.5% among 45-59 years, p<0.001. Among 15-24 years treated, 77.9% were virally suppressed vs 92.0% among 45-59 years, p<0.001. Among all HIV-positive, viral suppression was 32.9% in 15-24 years, 47.9% in 25-34 years, 64.9% in 35-44 years, 70.6% in 45-59 years. Men were less diagnosed than women (65.2% vs 76.0%, p <0.001). Treatment among diagnosed and viral suppression among treated was not different by gender. Compared to women 45-59 years, young people had a higher probability of being undiagnosed (men 15-24 years OR: 37.9, women 15-24 years OR: 12.2), untreated (men 15-24 years OR:2.2, women 15-24 years OR: 5.7) and virally unsuppressed (men 15-24 years OR: 1.6, women 15-24 years OR: 6.6). In these five Eastern and Southern Africa settings, adolescents and young adults had the largest gaps in the HIV cascade. They were less diagnosed, treated, and virally suppressed, than older counterparts. Targeted preventive, testing and treating interventions should be scaled-up.

Evidence of HIV incidence reduction in young women, but not in adolescent girls, in KwaZulu-Natal, South Africa.

Objectives: We estimated changes in the HIV incidence from 2013-2018 in Eshowe/Mbongolwane, KwaZulu-Natal, South Africa where Médecins Sans Frontières is engaged in providing HIV testing and care since 2011. Methods: Using data from two cross-sectional household-based surveys conducted in 2013 and 2018, with consenting participants aged 15-59 years, we applied the incidence estimation frameworks of Mahiane et al and Kassanjee et al. Results: In total, 5599 (62.4% women) and 3276 (65.9% women) individuals were included in 2013 and 2018, respectively. We found a mean incidence in women aged 20-29 years of 2.71 cases per 100 person-years (95% confidence interval [CI]: 1.23;4.19) in 2013 and 0.4 cases per 100 person-years (95% CI: 0.0;1.5) in 2018. The incidence in men aged 20-29 years was 1.91 cases per 100 person-years (95% CI: 0.87; 2.93) in 2013 and 0.53 cases per 100 person-years (95% CI: 0.0; 1.4) in 2018. The incidence decline among women aged 15-19 was -0.34 cases per 100 person-years (95% CI: -1.31;0.64). Conclusions: The lack of evidence of incidence decline among adolescent girls is noteworthy and disconcerting. Our findings suggest that large-scale surveys should seriously consider focusing their resources on the core group of women aged 15-19 years.

Mortality among persons with epilepsy in onchocerciasis-endemic and non-endemic areas of sub-Saharan Africa: A systematic review and meta-analysis.

PURPOSE: To document epilepsy-related mortality in sub-Saharan Africa (SSA) and investigate possible associations with onchocerciasis endemicity. METHODS: Systematic review with meta-analysis. Searches were performed in PubMed and Google Scholar (search terms: 'epilepsy'; 'mortality/death'; 'sub-Saharan Africa'). Included studies were classified as high-risk or low-risk for onchocerciasis based on documented endemicity data. Pooled mortality rates and annual case fatality rates (CFR) were calculated, and risk factors for mortality among persons with epilepsy (PWE) were investigated using meta-regression analysis. RESULTS: The 28 eligible studies reported 30 epilepsy surveys, of which 9 (30.0%) were conducted in onchocerciasis high-risk sites. The pooled epilepsy mortality rate was 20.9 (95% CI: 5.9-74.4) per 100,000 person-years, and the pooled CFR was 36.2 (95% CI: 23.9-54.4) per 1,000 PWE per year, albeit with substantial between-study heterogeneity. Compared to onchocerciasis low-risk sites, high-risk sites had higher pooled mortality (342.9 versus 10.0 per 100,000 PY; p<0.001) and CFR (57.0 versus 26.6 per 1,000 PWE per year; p = 0.001). Mortality of PWE was almost five-fold that of people without epilepsy (mortality risk ratio: 4.9; 95% CI: 3.5-6.8). Studies in onchocerciasis high-risk sites and the study which recruited only PWE with nodding syndrome were associated with higher CFR (p = 0.044 and p = 0.002, respectively). The leading causes of epilepsy-related death were status epilepticus (58.5%), drowning (15.7%), and sudden unexpected death in epilepsy (10.1%). CONCLUSION: Epilepsy mortality remains high in SSA. Most reported causes of death among PWE might be averted by improving seizure control. Better epilepsy prevention and care are urgently needed, particularly in onchocerciasis-endemic settings.

Onchocerciasis-associated epilepsy: an update and future perspectives.

Onchocerciasis-associated epilepsy (OAE) is an important neglected public health problem in areas with high ongoing onchocerciasis transmission. The risk that children in such areas develop epilepsy is related to their Onchocerca volvulus microfilarial (mf) load. Before the implementation of mass treatment with ivermectin, microfilariae were detected in cerebrospinal fluid (CSF). More recently, neither O. volvulus microfilariae nor DNA were detected in CSF or brain tissue; however, these samples were obtained years after seizure onset. It is possible that during fever-induced increased blood-brain barrier permeability, microfilariae enter the brain and, upon dying, cause an inflammatory reaction inducing seizures. Including OAE in the onchocerciasis disease burden estimation may mobilise extra resources for onchocerciasis disease elimination and treatment/care of OAE-affected persons/families.

Acceptability of unsupervised peer-based distribution of HIV oral self-testing for the hard-to-reach in rural KwaZulu Natal, South Africa: Results from a demonstration study.

BACKGROUND: Innovative models to distribute oral HIV self-tests (HIVST) provide an opportunity to increase access to HIV testing, especially for hard-to-reach populations. This study aimed to describe the acceptability of unsupervised peer-distribution of HIVST as a method to scale-up HIV testing. METHODS: In this study, lay counsellors or community health workers provided HIVST kits to primary recipients (PRs) for distribution to their sexual partners, anyone in their social network (termed secondary recipients) or for self-testing, from September 2018 to March 2020. The study was conducted in Eshowe and Mbongolwane areas in KwaZulu-Natal, South Africa. A structured questionnaire was administered during the recruitment and passive follow-up, when people came for confirmatory HIV testing. Electronic records were retrospectively examined to determine initiation of antiretroviral treatment (ART) for all HIVST users and non-users. RESULTS: Among 36,708 people approached to be primary recipients, 9,891 (26.9%) accepted; 31,341 HIVST kits were distributed with a median of three (IQR: 2-4) per peer. PRs were predominately recruited at primary health clinics (PHCs). However, acceptability of HIVST was thrice as high at community-based testing sites compared to PHCs (64.5% vs. 21.0%; p<0.001). During the study period, 34,715 adults were tested for HIV at both PHCs and community-based testing sites; of these, 1,089 individuals reported HIVST use. Among HIVST users, 893 (82.0%) returned to the clinic for confirmatory testing after testing negative on HIVST; 196 (17.9%) were confirmed HIV positive following a positive HIVST. After excluding 36/196 (18.4%) participants for whom clinical records could not be found in electronic register and 25/160 (15.6%) who were already on ART before receiving HIVST, 129/135 (95.5%) initiated ART, whereas 2,362/2685 (88%) of HIV positive HIVST non-users-initiated ART. CONCLUSION: Unsupervised peer-distribution of HIVST was feasible and acceptable, with more than 25% accepting to be peer-distributors. Acceptability of HIVST was thrice as high in community sites compared to clinics.

Retention on ART and viral suppression among patients in alternative models of differentiated HIV service delivery in KwaZulu-Natal, South Africa.

Differentiated models of HIV care (DMOC) aim to improve health care efficiency. We describe outcomes of five DMOC in KwaZulu-Natal, South Africa: facility adherence clubs (facility AC) and community adherence clubs (community AC), community antiretroviral treatment (ART) groups (CAG), spaced fast lane appointments (SFLA), and community pick up points (PuP). This retrospective cohort study included 8241 eligible patients enrolled into DMOC between 1/1/2012 and 31/12/2018. We assessed retention in DMOC and on ART, and viral load suppression (<1000 copies/mL). Kaplan-Meier techniques were applied to describe crude retention. Mixed effects parametric survival models with Weibull distribution and clustering on health center and individual levels were used to assess predictors for ART and DMOC attrition, and VL rebound (≥1000 copies/mL). Overall DMOC retention was 85%, 80%, and 76% at 12, 24 and 36 months. ART retention at 12, 24 and 36 months was 96%, 93%, 90%. Overall incidence rate of VL rebound was 1.9 episodes per 100 person-years. VL rebound rate was 4.9 episodes per 100 person-years among those enrolled in 2012-2015, and 0.8 episodes per 100 person-years among those enrolled in 2016-2018 (RR 0.12; 95% CI, 0.09-0.15, p<0.001). Prevalence of confirmed virological failure was 0.6% (38/6113). Predictors of attrition from DMOC and from ART were male gender, younger age, shorter duration on ART before enrollment. Low level viremia (>200-399 copies/mL) was associated with higher hazards of VL rebound and attrition from ART. Concurrent implementation of several DMOC in a large ART program is feasible and can achieve sustained retention on ART and VL suppression.

High Prevalence of NRTI and NNRTI Drug Resistance Among ART-Experienced, Hospitalized Inpatients.

BACKGROUND: Patients hospitalized with advanced HIV have a high mortality risk. We assessed viremia and drug resistance among differentiated care services and explored whether expediting the switching of failing treatments may be justified. SETTING: Hospitals in the Democratic Republic of (DRC) Congo (HIV hospital) and Kenya (general hospital including HIV care). METHODS: Viral load (VL) testing and drug resistance (DR) genotyping were conducted for HIV inpatients ≥15 years, on first-line antiretroviral therapy (ART) for ≥6 months, and CD4 ≤350 cells/µL. Dual-class DR was defined as low-, intermediate-, or high-level DR to at least 1 nucleoside reverse transcriptase inhibitor and 1 non-nucleoside reverse transcriptase inhibitor. ART regimens were considered ineffective if dual-class DR was detected at viral failure (VL ≥1000 copies/mL). RESULTS: Among 305 inpatients, 36.7% (Kenya) and 71.2% (DRC) had VL ≥1000 copies/mL, of which 72.9% and 73.7% had dual-class DR. Among viral failures on tenofovir disoproxil fumarate (TDF)-based regimens, 56.1% had TDF-DR and 29.8% zidovudine (AZT)-DR; on AZT regimens, 71.4% had AZT-DR and 61.9% TDF-DR, respectively. Treatment interruptions (≥48 hours during past 6 months) were reported by 41.7% (Kenya) and 56.7% (DRC). Approximately 56.2% (Kenya) and 47.4% (DRC) on TDF regimens had tenofovir diphosphate concentrations <1250 fmol/punch (suboptimal adherence). Among viral failures with CD4 <100 cells/µL, 76.0% (Kenya) and 84.6% (DRC) were on ineffective regimens. CONCLUSIONS: Many hospitalized, ART-experienced patients with advanced HIV were on an ineffective first-line regimen. Addressing ART failure promptly should be integrated into advanced disease care packages for this group. Switching to effective second-line medications should be considered after a single high VL on non-nucleoside reverse transcriptase inhibitor-based first-line if CD4 ≤350 cells/µL or, when VL is unavailable, among patients with CD4 ≤100 cells/µL.

"It's a secret between us": a qualitative study on children and care-giver experiences of HIV disclosure in Kinshasa, Democratic Republic of Congo.

BACKGROUND: It is estimated that 64,000 children under 15 years of age are living with HIV in the Democratic Republic of Congo (DRC). Non-disclosure - in which the child is not informed about their HIV status - is likely to be associated with poor outcomes during adolescence including increased risk of poor adherence and retention, and treatment failure. Disclosing a child's HIV status to them can be a difficult process for care-givers and children, and in this qualitative study we explored child and care-giver experiences of the process of disclosing, including reasons for delay. METHODS: A total of 22 in-depth interviews with care-givers and 11 in-depth interviews with HIV positive children whom they were caring for were conducted in one health-care facility in the capital city of Kinshasa. Care-givers were purposively sampled to include those who had disclosed to their children and those who had not. Care-givers included biological parents, grandmothers, siblings and community members and 86% of them were female. Interviews were conducted in French and Lingala. All interviews were translated and/or transcribed into French before being manually coded. Thematic analysis was conducted. Verbal informed consent/assent was taken from all interviewees. RESULTS: At the time of interview, the mean age of children and care-givers was 17 (15-19) and 47 (21-70) years old, respectively. Many care-givers had lost family members due to HIV and several were HIV positive themselves. Reasons for non-disclosure included fear of stigmatisation; wanting to protect the child and not having enough knowledge about HIV or the status of the child to disclose. Several children had multiple care-givers, which also delayed disclosure, as responsibility for the child was shared. In addition, some care-givers were struggling to accept their own HIV status and did not want their child to blame them for their own positive status by disclosing to them. CONCLUSIONS: Child disclosure is a complex process for care-givers, health-care workers and the children themselves. Care-givers may require additional psycho-social support to manage disclosure. Involving multiple care-givers in the care of HIV positive children could offer additional support for disclosure.

Framework for the implementation of advanced HIV disease diagnostics in sub-Saharan Africa: programmatic perspectives.

Patients with advanced HIV disease have a high risk of mortality, mainly from tuberculosis and cryptococcal meningitis. The advanced HIV disease management package recommended by WHO, which includes diagnostics, therapeutics, and patient psychosocial support, is barely implemented in many different countries. Here, we present a framework for the implementation of advanced HIV disease diagnostics. Laboratory and point-of-care-based reflex testing, coupled with provider-initiated requested testing, for cryptococcal antigen and urinary Mycobacterium tuberculosis lipoarabinomannan antigen, should be done for all patients with CD4+ cell counts of 200 cells per µL or less. Implementation of the advanced HIV disease package should be encouraged within primary health-care facilities and task shifting of testing to lay cadres could facilitate access to rapid results. Implementation of differentiated antiretroviral therapy delivery models can allow clinicians enough time to focus on the management of patients with advanced HIV disease. Efficient up-referral and post-discharge systems, including the development of patient-centric advanced HIV disease literacy, are also crucial. Implementation of the advanced HIV disease package is feasible at all health-care levels, and it should be part of the core of the global response towards ending AIDS as a public health threat.

Time to embrace access programmes for medicines: lessons from the South African flucytosine access programme.

BACKGROUND: Cryptococcal meningitis (CM) is estimated to cause 181 000 deaths annually, with the majority occurring in Sub-Saharan Africa. Flucytosine is recommended by the World Health Organization as part of the treatment for CM. Widespread use of flucytosine could reduce mortality in hospital by as much as 40% compared to the standard of care, yet due to market failure, quality-assured flucytosine remains unregistered and largely inaccessible throughout Africa. METHODS: The recently established South African flucytosine clinical access programme is an attempt to address the market failure that led to a lack of public sector access to flucytosine for CM, by making the medicine freely available to tertiary hospitals in South Africa. RESULTS: Between November 2018 and September 2019, 327 CM patients received flucytosine through this programme, with efforts to support sustainable national scale-up presently ongoing. We describe why this programme was needed, its catalytic potential, what is still required to ensure widespread access to flucytosine, and observations from this experience that may have wider relevance. CONCLUSIONS: The South African flucytosine access programme illustrates how access programmes may be one part of the solution to addressing the vicious cycle of perceived low demand, limiting manufacturer interest in specific product markets.

Distribution of advanced HIV disease from three high HIV prevalence settings in Sub-Saharan Africa: a secondary analysis data from three population-based cross-sectional surveys in Eshowe (South Africa), Ndhiwa (Kenya) and Chiradzulu (Malawi).

Background: Despite substantial progress in antiretroviral therapy (ART) scale up, some people living with HIV (PLHIV) continue to present with advanced HIV disease, contributing to ongoing HIV-related morbidity and mortality.Objective: We aimed to quantify population-level estimates of advanced HIV from three high HIV prevalence settings in Sub-Saharan Africa.Methods: Three cross-sectional surveys were conducted in (Ndhiwa (Kenya): September-November 2012), (Chiradzulu (Malawi): February-May 2013) and (Eshowe (South Africa): July-October 2013). Eligible individuals 15-59 years old who consented were interviewed at home followed by rapid HIV test and CD4 count test if tested HIV-positive. Advanced HIV was defined as CD4 < 200 cells/µl. We used logistic regression to identify patient characteristics associated with advanced HIV.Results: Among 18,991 (39.2% male) individuals, 4113 (21.7%) tested HIV-positive; 385/3957 (9.7% (95% Confidence Interval [CI]: 8.8-10.7)) had advanced HIV, ranging from 7.8% (95%CI 6.4-9.5) Chiradzulu (Malawi) to 11.8% (95%CI 9.8-14.2) Ndhiwa (Kenya). The proportion of PLHIV with advanced disease was higher among men 15.3% (95% CI 13.2-17.5) than women 7.5% (95%CI 6.6-8.6) p < 0.001. Overall, 62.7% of all individuals with advanced HIV were aware of their HIV status and 40.3% were currently on ART. Overall, 65.6% of individuals not on ART had not previously been diagnosed with HIV, while only 29.6% of those on ART had been on ART for ≥6 months. Individuals with advanced HIV disease were more likely to be men (adjusted Odds Ratio [aOR]; 2.1 (95%CI 1.7-2.6), and more likely not to be on ART (aOR; 1.7 (95%CI 1.3-2.1).Conclusion: In our study, about 1 in 10 PLHIV had advanced HIV with nearly 40% of them unaware of their HIV status. However, a substantial proportion of patients with advanced HIV were established on ART. Our findings suggest the need for a dual focus on alternative testing strategies to identify PLHIV earlier as well as improving ART retention.

The epidemiology of rape and sexual violence in the platinum mining district of Rustenburg, South Africa: Prevalence, and factors associated with sexual violence.

BACKGROUND: Estimates for the prevalence of rape and other forms of sexual violence (SV) vary in South Africa. This survey aimed to provide clarity by quantifying the prevalence of SV (forced sex or sexual acts) by 1) sexual partners, and 2) non-partners, and to describe factors associated with these outcomes among women (18-49 years) living in Rustenburg Municipality. MATERIALS AND METHODS: We conducted a cluster-randomized household survey (November-December 2015). Women were asked about their experiences of SV, associated attitudes and behaviours, and access to services. Logistic regression was used to determine factors associated with partner and non-partner SV. RESULTS: Of eligible households, 83·1% (1700/2044) participated. Of 966 women invited, 836 participated (86·5%). Average age of participants was 31.6 years (95%CI: 30·9, 32·4) with 45% having completed at least secondary school, and 60% unemployed or looking for work. Lifetime prevalence of SV was 24.9% (95%CI: 21·7-28·5), reaching 9.0% (95% CI: 6·6-12·1) by age 15. Almost one third told no one of their SV experiences. Factors related to financial dependence were associated with SV by a partner. History of termination of pregnancy increased the likelihood of SV by a non-partner as an adult. Women who experienced SV in childhood or as an adult were more likely to experience SV from a different type of perpetrator than those who did not. CONCLUSIONS: We found a high prevalence of SV, including during childhood, in this setting, with limited access to care. This and the high morbidity attributed to SV calls for increased service provision.

Simplifying switch to second-line antiretroviral therapy in sub Saharan Africa: predicted effect of using a single viral load to define efavirenz-based first-line failure.

BACKGROUND: Many individuals failing first-line antiretroviral therapy (ART) in sub-Saharan Africa never initiate second-line ART or do so after significant delay. For people on ART with a viral load more than 1000 copies/ml, the WHO recommends a second viral load measurement 3 months after the first viral load and enhanced adherence support. Switch to a second-line regimen is contingent upon a persistently elevated viral load more than 1000 copies/ml. Delayed second-line switch places patients at increased risk for opportunistic infections and mortality. METHODS: To assess the potential benefits of a simplified second-line ART switch strategy, we use an individual-based model of HIV transmission, progression and the effect of ART which incorporates consideration of adherence and drug resistance, to compare predicted outcomes of two policies, defining first-line regimen failure for patients on efavirenz-based ART as either two consecutive viral load values more than 1000 copies/ml, with the second after an enhanced adherence intervention (implemented as per current WHO guidelines) or a single viral load value more than 1000 copies/ml. We simulated a range of setting-scenarios reflecting the breadth of the sub-Saharan African HIV epidemic, taking into account potential delays in defining failure and switch to second-line ART. FINDINGS: The use of a single viral load more than 1000 copies/ml to define ART failure would lead to a higher proportion of persons with nonnucleoside reverse-transcriptase inhibitor resistance switched to second-line ART [65 vs. 48%; difference 17% (90% range 14-20%)], resulting in a median 18% reduction in the rate of AIDS-related death over setting scenarios (90% range 6-30%; from a median of 3.1 to 2.5 per 100 person-years) over 3 years. The simplified strategy also is predicted to reduce the rate of AIDS conditions by a median of 31% (90% range 8-49%) among people on first-line ART with a viral load more than 1000 copies/ml in the past 6 months. For a country of 10 million adults (and a median of 880 000 people with HIV), we estimate that this approach would lead to a median of 1322 (90% range 67-3513) AIDS deaths averted per year over 3 years. For South Africa this would represent around 10 215 deaths averted annually. INTERPRETATION: As a step towards reducing unnecessary mortality associated with delayed second-line ART switch, defining failure of first-line efavirenz-based regimens as a single viral load more than 1000 copies/ml should be considered.

Outcomes of patients enrolled in an antiretroviral adherence club with recent viral suppression after experiencing elevated viral loads.

BACKGROUND: Eligibility for differentiated antiretroviral therapy (ART) delivery models has to date been limited to low-risk stable patients. OBJECTIVES: We examined the outcomes of patients who accessed their care and treatment through an ART adherence club (AC), a differentiated ART delivery model, immediately following receiving support to achieve viral suppression after experiencing elevated viral loads (VLs) at a high-burden ART clinic in Khayelitsha, South Africa. METHODS: Beginning in February 2012, patients with VLs above 400 copies/mL either on first- or second-line regimens received a structured intervention developed for patients at risk of treatment failure. Patients who successfully suppressed either on the same regimen or after regimen switch were offered immediate enrolment in an AC facilitated by a lay community health worker. We conducted a retrospective cohort analysis of patients who enrolled in an AC directly after receiving suppression support. We analysed outcomes (retention in care, retention in AC care and viral rebound) using Kaplan-Meier methods with follow-up from October 2012 to June 2015. RESULTS: A total of 165 patients were enrolled in an AC following suppression (81.8% female, median age 36.2 years). At the closure of the study, 119 patients (72.0%) were virally suppressed and 148 patients (89.0%) were retained in care. Six, 12 and 18 months after AC enrolment, retention in care was estimated at 98.0%, 95.0% and 89.0%, respectively. Viral suppression was estimated to be maintained by 90.0%, 84.0% and 75.0% of patients at 6, 12 and 18 months after AC enrolment, respectively. CONCLUSION: Our findings suggest that patients who struggled to achieve or maintain viral suppression in routine clinic care can have good retention and viral suppression outcomes in ACs, a differentiated ART delivery model, following suppression support.

Stock-outs of antiretroviral and tuberculosis medicines in South Africa: A national cross-sectional survey.

BACKGROUND: HIV and TB programs have rapidly scaled-up over the past decade in Sub-Saharan Africa and uninterrupted supplies of those medicines are critical to their success. However, estimates of stock-outs are largely unknown. This survey aimed to estimate the extent of stock-outs of antiretroviral and TB medicines in public health facilities across South Africa, which has the world's largest antiretroviral treatment (ART) program and a rising multidrug-resistant TB epidemic. METHODS: We conducted a cross-sectional telephonic survey (October-December 2015) of public health facilities. Facilities were asked about the prevalence of stock-outs on the day of the survey and in the preceding three months, their duration and impact. RESULTS: Nationwide, of 3547 eligible health facilities, 79% (2804) could be reached telephonically. 88% (2463) participated and 4% (93) were excluded as they did not provide ART or TB treatment. Of the 2370 included facilities, 20% (485) reported a stock-out of at least 1 ARV and/or TB-related medicine on the day of contact and 36% (864) during the three months prior to contact, ranging from 74% (163/220) of health facilities in Mpumalanga to 12% (32/261) in the Western Cape province. These 864 facilities reported 1475 individual stock-outs, with one to fourteen different medicines out of stock per facility. Information on impact was provided in 98% (1449/1475) of stock-outs: 25% (366) resulted in a high impact outcome, where patients left the facility without medicine or were provided with an incomplete regimen. Of the 757 stock-outs that were resolved 70% (527) lasted longer than one month. INTERPRETATION: There was a high prevalence of stock-outs nationwide. Large interprovincial differences in stock-out occurrence, duration, and impact suggest differences in provincial ability to prevent, mitigate and cope within the same framework. End-user monitoring of the supply chain by patients and civil society has the potential to increase transparency and complement public sector monitoring systems.