Search

Background The COVER trial evaluated whether nitazoxanide or sofosbuvir/daclatasvir could lower the risk of SARS-CoV-2 infection. Nitazoxanide was selected given its favourable pharmacokinetics and in vitro antiviral effects against SARS-CoV-2. Sofosbuvir/daclatasvir had shown favourable results in early clinical trials. Methods In this clinical trial in Johannesburg, South Africa, healthcare workers and others at high risk of infection were randomized to 24 weeks of either nitazoxanide or sofosbuvir/daclatasvir as prevention, or standard prevention advice only. Participants were evaluated every 4 weeks for COVID-19 symptoms and had antibody and PCR testing. The primary endpoint was positive SARS-CoV-2 PCR and/or serology ≥7 days after randomization, regardless of symptoms. A Poisson regression model was used to estimate the incidence rate ratios of confirmed SARS-CoV-2 between each experimental arm and control. Results Between December 2020 and January 2022, 828 participants were enrolled. COVID-19 infections were confirmed in 100 participants on nitazoxanide (2234 per 1000 person-years; 95% CI 1837–2718), 87 on sofosbuvir/daclatasvir (2125 per 1000 person-years; 95% CI 1722–2622) and 111 in the control arm (1849 per 1000 person-years; 95% CI 1535–2227). There were no significant differences in the primary endpoint between the treatment arms, and the results met the criteria for futility. In the safety analysis, the frequency of grade 3 or 4 adverse events was low and similar across arms. Conclusions In this randomized trial, nitazoxanide and sofosbuvir/daclatasvir had no significant preventative effect on infection with SARS-CoV-2 among healthcare workers and others at high risk of infection.

Cardiovascular disease (CVD) is the leading cause of death globally. The occupational challenges of bus drivers may increase their risk of CVD, including developing obesity, hypertension, and diabetes. We evaluated the medical records of 266 bus drivers visiting an occupational medical practice between 2007 and 2017 in Johannesburg, South Africa, to determine the health status of bus drivers and investigate risk factors for CVD, and their impact on the ability to work. The participants were in majority male (99.3%) with a median age of 41.2 years (IQR 35.2); 23.7% were smokers, and 27.1% consumed alcohol. The median body mass index (BMI) was 26.8 m/kg2 (IQR 7.1), with 63.1% of participants having above normal BMI. Smoking, BMI, and hypertension findings were in line with national South African data, but diabetes prevalence was far lower. Undiagnosed hypertension was found in 9.4% of participants, uncontrolled hypertension in 5.6%, and diabetes in 3.0%. Analysis by BMI category found that obesity was significantly associated with increased odds of hypertension. Uncontrolled hypertension was the main reason for being deemed ‘unfit to work’ (35.3%). Our research highlights the need for more regular screening for hypertension and interventions to address high BMI.

Objective: Dolutegravir exposure at conception was associated with a preliminary signal of increased infant neural tube defect risk. As low maternal folate levels are linked with neural tube defects, we aimed to assess serum folate concentrations in women starting dolutegravir. Design: We analysed serum folate concentrations from stored plasma among women enrolled in the South African ADVANCE trial. Methods: We compared changes in mean serum folate and occurrence of low serum folate (

ObjectivesCardiovascular disease (CVD) is a major problem globally. Truck drivers have an increased risk of CVD due to a sedentary lifestyle, irregular working hours and behavioural choices. We aimed to get insight into the contribution of night shift work to CVD risk in long-distance truck drivers in South Africa.DesignA cross-sectional study.SettingEnrolment took place at three South African truck stop locations in two provinces; Bloemfontein (Free State), Pomona Road (Gauteng) and Soweto (Gauteng).Participants607 males aged ≥18 years with full-time employment as a long-distance truck driver were included. The criteria for inclusion were willingness and being able to provide informed consent and to complete the study procedures.Primary and secondary outcome measuresInformation was collected on sociodemographics, occupational and health characteristics. Physical measurements, an ECG and carotid intima–media thickness (CIMT) measurements were taken. A night shift was defined as working at least 3 hours between 22:00 and 6:00 hours once a week. CVD risk was defined with the Framingham Risk Score (FRS), the Atherosclerotic Cardiovascular Disease (ASCVD) risk algorithm, left ventricular hypertrophy (LVH) and CIMT.ResultsIn total, 607 truck drivers were included of which 305 (50.2%) worked in day shifts only and 302 (49.8%) worked day and night shifts. There was a high prevalence of CVD risk factors in both groups as 33% were hypertensive, 28% obese and 37% had abnormal lipid levels. Working day and night shifts compared with working only day shifts did not result in differences in FRS, ASCVD risk or LVH. No difference was found in CIMT measurements, except for the maximum bulb thickness which was higher in day shift workers.ConclusionsCVD risk factors are considerably present in male truck drivers in South Africa. CVD risk does not differ between dayshift and day–night shift workers in this cross-sectional analysis.

Background Dolutegravir is a component of preferred antiretroviral therapy (ART) regimens. We characterized the pharmacogenetics of dolutegravir exposure after ART initiation in the ADVANCE trial in South Africa. Methods Genome-wide genotyping followed by imputation was performed. We developed a population pharmacokinetic model for dolutegravir using nonlinear mixed-effects modeling. Linear regression models examined associations with unexplained variability in dolutegravir area under the concentration-time curve (AUCVAR). Results Genetic associations were evaluable in 284 individuals. Of 9 polymorphisms previously associated with dolutegravir pharmacokinetics, the lowest P value with AUCVAR was UGT1A1 rs887829 (P = 1.8 × 10−4), which was also associated with log10 bilirubin (P = 8.6 × 10−13). After adjusting for rs887829, AUCVAR was independently associated with rs28899168 in the UGT1A locus (P = .02), as were bilirubin concentrations (P = 7.7 × 10−8). In the population pharmacokinetic model, rs887829 T/T and C/T were associated with 25.9% and 10.8% decreases in dolutegravir clearance, respectively, compared with C/C. The lowest P value for AUCVAR genome-wide was CAMKMT rs343942 (P = 2.4 × 10−7). Conclusions In South Africa, rs887829 and rs28899168 in the UGT1A locus were independently associated with dolutegravir AUCVAR. The novel rs28899168 association warrants replication. This study enhances understanding of dolutegravir pharmacogenetics in Africa.

Host genetic factors are known to modify the susceptibility, severity, and outcomes of COVID-19 and vary across populations. However, continental Africans are yet to be adequately represented in such studies despite the importance of genetic factors in understanding Africa’s response to the pandemic. We describe the development of a research resource for coronavirus host genomics studies in South Africa known as COVIGen-SA—a multicollaborator strategic partnership designed to provide harmonised demographic, clinical, and genetic information specific to Black South Africans with COVID-19. Over 2,000 participants have been recruited to date. Preliminary results on 1,354 SARS-CoV-2 positive participants from four participating studies showed that 64.7% were female, 333 had severe disease, and 329 were people living with HIV. Through this resource, we aim to provide insights into host genetic factors relevant to African-ancestry populations, using both genome-wide association testing and targeted sequencing of important genomic loci. This project will promote and enhance partnerships, build skills, and develop resources needed to address the COVID-19 burden and associated risk factors in South African communities.

IntroductionInsight into inflammation patterns is needed to understand the pathophysiology of HIV and related cardiovascular disease (CVD). We assessed patterns of inflammation related to HIV infection and CVD risk assessed with carotid intima media thickness (CIMT).MethodsA cross-sectional study was performed in Johannesburg, South Africa, including participants with HIV who were virally suppressed on anti-retroviral therapy (ART) as well as HIV-negative participants who were family members or friends to the HIV-positive participants. Information was collected on CVD risk factors and CIMT. Inflammation was measured with the Olink panel ‘inflammation’, allowing to simultaneously assess 92 inflammation markers. Differences in inflammation patterns between HIV-positive and HIV-negative participants were explored using a principal component analysis (PCA) and ANCOVA. The impact of differentiating immune markers, as identified by ANCOVA, on CIMT was assessed using linear regression while adjusting for classic CVD risk factors.ResultsIn total, 185 HIV-positive and 104 HIV negative participants, 63% females, median age 40.7 years (IQR 35.4 – 47.7) were included. HIV-positive individuals were older (+6 years, p ConclusionHIV positive patients on stable ART and HIV negative controls had similar immune activation patterns. CVD risk in HIV-positive participants was mediated by inflammation markers included in this study.

Africa’s readiness to the respond to the SARS-COV-2 pandemic was tested due to reliance on rapid turn-around-time of polymerase chain reaction results for clinical management, isolation and quarantine decisions. The HIV Molecular Laboratory in Johannesburg, South Africa is one of the largest automated HIV molecular laboratories worldwide, performing 1.2 million tests annually. Despite its extensive molecular capacity and experience in managing high volumes acquired from a large HIV program, significant challenges were encountered during its rapid transition to largescale SARS-CoV-2 testing. Here, we describe the strategies employed to manage challenges related to policy, staff, introduction of new assays and workflow efficiencies, and to mitigate the risks of reprioritization of resources on routine HIV tests, that resulted in a 50% improvement in SARS-COV-2 turn-around-time during the first wave peak during which approximately 25 000 samples were tested per month, and further improvement during the second wave, with 91% within targeted turn-around-time.

Introduction With over 500 000 infections and nearly 12 000 deaths, South Africa (SA) is the African epicenter of the current Coronavirus (COVID-19) pandemic. SA has implemented a 5-stage Risk-Adjusted Strategy which includes a phased national lockdown, requiring social distancing, frequent hand washing and wearing face masks. Strict adherence to this strategy is crucial to reducing COVID-19 transmission, flattening the curve, and preventing resurgence. As part of the 22-country International Citizens Project COVID-19 (ICPcovid), this study aimed to describe the SA adherence to the Risk-Adjusted Strategy and identify determinants of adherence. Method During 24 April-15 May 2020, people were electronically invited, through social media platforms and a text blast, to complete an online survey, accessible via www.icpcovid.com. The survey investigated COVID-19 testing and preventative adherence measures, then used logistic regression analysis to identify predictors of adherence. Results There were 951 participants, with 731(76.9%) 25 to 54 years. Most (672;70.7%) were female, and 705(74.1%) had a university degree. Since the epidemic started, 529(55.6%) and 436(45.9%) participants stated they were eating healthier and taking more vitamins, respectively. Only 82(8.6%) had been COVID-19 tested, and 1(1.2%) tested positive. In public, 905(95.2%) socially distanced, however 99(10.4%) participants had recently attended meetings with over ten people. Regular hand washing was practiced by 907(95.4%) participants, 774(81.4%) wore face masks and 854(89.8%) stayed home when they experienced flu-like symptoms. The odds of adhering to the guidelines were lower among men versus women (AOR 0.72, 95% confidence interval [CI] = 0.528, 0.971) and those who had flu-like symptoms (AOR 0.42, 95% CI = 0.277, 0.628). In contrast, increased odds were reported for those who reported increased vitamin intake (AOR 1.37, 95% CI = 1.044,1.798), and were either cohabiting or married (AOR 1.39, 95% CI = 1.042,1.847). Conclusion Despite high reported adherence, face mask use and symptomatic individuals not self-isolating, were areas for improvement. However, these factors cannot solely account for SA’s increasing COVID-19 cases. Larger general population studies are needed to identify other adherence predictors for a strengthened SA COVID-19 response. While the government must continue to educate the entire population on preventative measures, provide personal protective equipment and stress the importance of adherence, there also needs to be implementation of prioritised prevention strategies for men and single individuals to address their demonstrated lower adherence.

Persistence of symptoms or development of new symptoms relating to SARS-CoV-2 infection late in the course of COVID-19 is an increasingly recognised problem facing the globally infected population and its health systems. ‘Long-COVID’ or ‘COVID long-haulers’ generally describes those persons with COVID-19 who experience symptoms for >28 days after diagnosis, whether laboratory confirmed or clinical. Symptoms are as markedly heterogeneous as seen in acute COVID-19 and may be constant, fluctuate, or appear and be replaced by symptoms relating to other systems with varying frequency. Such multisystem involvement requires a holistic approach to management of long-COVID, and descriptions of cohorts from low- and middle-income countries are eagerly awaited. Although many persons with long-COVID will be managed in primary care, others will require greater input from rehabilitation medicine experts. For both eventualities, planning is urgently required to ensure that the South African public health service is ready and able to respond.

BACKGROUND: Excessive weight gain affects some HIV-positive individuals prescribed dolutegravir- containing regimens. Mechanisms underlying such weight gain are unknown. SETTING: Data and DNA from antiretroviral therapy-naïve participants who were randomized to initiate dolutegravir with emtricitabine plus either tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) in the ADVANCE study (NCT03122262) were used to characterize associations between human genetic polymorphisms and magnitude of weight gain. METHODS: Associations with percent weight gain from baseline to week 48 were assessed using multivariable linear regression models. Primary analyses a priori considered 59 polymorphisms and 10 genes of potential relevance to dolutegravir, TAF or TDF pharmacokinetics. We also explored genome-wide associations. RESULTS: Among the 314 (92%) of 340 dolutegravir recipients who were successfully genotyped, 160 (47%) and 154 (45%) were randomized to TAF/emtricitabine and TDF/emtricitabine, respectively. In target gene analyses, the lowest P-values for the dolutegravir and tenofovir groups were ABCG2 rs4148149 (P = 7.0×10(−4)) and ABCC10 rs67861980 (P = 1.0×10(−2)), respectively, which were not significant after correction for multiple testing. In genome-wide analyses the lowest P-values for dolutegravir, was rs7590091 in TMEM163 (P = 3.7×10(−8)), rs17137701 in LOC105379130 (P = 6.4×10(− 8)) for TAF, and rs76771105 in LOC105371716 (P = 9.7×10(−8)) for TDF. CONCLUSION: Among South African participants in a randomized clinical trial of dolutegravir plus either TAF/emtricitabine or TDF/emtricitabine, we identified several potential genetic associations with weight gain. Only TMEM163 rs7590091 withstood correction for multiple testing. These associations warrant replication in other cohorts.

Irregular work times promote inconsistent completion of the Pittsburgh Sleep Quality Index (PSQI) among shift workers. We aimed to demonstrate the importance of testing the internal consistency and construct validity of the PSQI and of the Epworth Sleepiness Scale (ESS) by presenting the methodology in a sample of long-haul truckers in South Africa. Internal consistency of the questionnaires was assessed by Cronbach's alpha (defined as raw alpha≥0.70), and construct validity by factor analysis. 302 participants (49.3%) reported at least one night shift/week. Overall, the PSQI and ESS's alpha were 0.42 and 0.85, respectively. The factors explained 19.6% of 57.0% of the variance. The PSQI's alpha was 0.46 in night shift workers and 0.38 in non-night shift workers. In this occupational group, the PSQI must be used with caution. Testing the internal consistency and construct validity among the assessed population seems necessary. Sleep questionnaires adapted to shift workers should be preferred.

Background Long-distance truck drivers are occupationally susceptible to poor health outcomes. Their patterns of healthcare utilisation and the suitability of healthcare services available to them are not well documented. We report on truck driver healthcare utilisation across South Africa and characterise the client population of the clinics serving them for future service development. Methods We analysed anonymised data routinely collected over a two-year period at nine Roadside Wellness Centres. Associations between services accessed and socio-demographic characteristics were assessed using univariable and multivariable logistic regression models. Results We recorded 16,688 visits by 13,252 individual truck drivers (average of 1.26 visits/person) who accessed 17,885 services for an average of 1.07 services/visit and 1.35 services/person. The mean age of truck drivers was 39 years. Sixty-seven percent reported being in stable relationships. The most accessed services were primary healthcare (PHC)(62%) followed by HIV (32%). Low proportions (≤6%) accessed STI,TB and malaria services. Most visits were characterised by only one service being accessed (93%, n = 15,523/16,688). Of the remaining 7% of visits, up to five services were accessed per visit and the combination of TB /HIV services in one visit remained extremely low (

Background In South Africa, the trucking industry employs over 70,000 people and the prevalence of chronic pain in this occupational group was reported at 10%. We investigated factors associated with chronic pain in truck drivers including mental health, physical activity, and sleep, as no study has done so. Methods Southern African male, long-distance truck drivers were recruited at truck stops in Gauteng and Free State Provinces, South Africa (n = 614). Chronic pain was defined as pain present for at least the last three months. Depressive symptoms were assessed with the Patient Health Questionnaire-9, post-traumatic stress disorder with the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), exposure to traumatic events with the Life Events Checklist-5 (LEC-5) and daytime sleepiness with the Epworth Sleepiness Scale. Sleep quality was measured on a four-point Likert scale. Leisure-time physical activity was measured using the Godin-Shephard leisure-time physical activity questionnaire. Associations between these factors, demographic factors and chronic pain were investigated. Results Multivariate analysis showed that working ≥ 2 nights/week (OR = 2.68, 95% CI = 1.55–4.68) was associated with chronic pain and physical activity was protective (OR = 0.97, 95% CI 0.95–0.98). In an exploratory analysis, greater depressive symptoms (p = 0.004), daytime sleepiness (p = 0.01) and worse sleep quality (p = 0.001) was associated with working ≥ 2 nights/week. Lower leisure-time physical activity was associated with worse sleep quality (p = 0.006), but not daytime sleepiness or depressive symptoms (p>0.05). Conclusions There is a clear relationship between working nights and activity levels, and chronic pain, sleep quality, and depression in truck drivers.

Author(s): Lippman, Sheri A; El Ayadi, Alison M; Grignon, Jessica S; Puren, Adrian; Liegler, Teri; Venter, WD Francois; Ratlhagana, Mary J; Morris, Jessica L; Naidoo, Evasen; Agnew, Emily; Barnhart, Scott; Shade, Starley B | Abstract: IntroductionTo achieve epidemic control of HIV by 2030, countries aim to meet 90-90-90 targets to increase knowledge of HIV-positive status, initiation of antiretroviral therapy (ART) and viral suppression by 2020. We assessed the progress towards these targets from 2014 to 2016 in South Africa as expanded treatment policies were introduced using population-representative surveys.MethodsData were collected in January to March 2014 and August to November 2016 in Dr. Ruth Segomotsi Mompati District, North West Province. Each multi-stage cluster sample included 46 enumeration areas (EA), a target of 36 dwelling units (DU) per EA, and a single resident aged 18 to 49 per DU. Data collection included behavioural surveys, rapid HIV antibody testing and dried blood spot collection. We used weighted general linear regression to evaluate differences in the HIV care continuum over time.ResultsOverall, 1044 and 971 participants enrolled in 2014 and 2016 respectively with approximately 77% undergoing HIV testing. Despite increases in reported testing, known status among people living with HIV (PLHIV) remained similar at 68.7% (95% Confidence Interval (CI)n=n60.9-75.6) in 2014 and 72.8% (95% CIn=n63.6-80.4) in 2016. Men were consistently less likely than women to know their status. Among those with known status, PLHIV on ART increased significantly from 80.9% (95% CIn=n71.9-87.4) to 91.5% (95% CIn=n84.4-95.5). Viral suppression (l5000 copies/mL using DBS) among those on ART increased significantly from 55.0% (95% CIn=n39.6-70.4) in 2014 to 81.4% (95% CIn=n72.0-90.8) in 2016. Among all PLHIV an estimated 72.0% (95% CIn=n63.8-80.1) of women and 45.8% (95% CIn=n27.0-64.7) of men achieved viral suppression by 2016.ConclusionsOver a period during which fixed-dose combination was introduced, ART eligibility expanded, and efforts to streamline treatment were implemented, major improvements in the second and third 90-90-90 targets were achieved. Achieving the first 90 target will require targeted and improved testing models for men.

IntroductionHIV self-testing (HIVST) presents a convenient, private approach that removes barriers to providing HIV testing services. The Self-Testing Africa (STAR) Initiative aims to scale up HIVST among priority and undertested populations. HIVST has the potential to help maintain testing services during the social distancing restrictions implemented to prevent the spread of COVID-19. This project evaluates linkage to confirmatory testing and treatment for HIV-positive clients for the STAR South Africa site.Methods and analysisThis secondary data analysis protocol aims to evaluate different HIVST distribution models from a prospective study implemented during November 2017 and December 2020 by Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute. Routinely collected distribution and self-reported HIVST outcomes data will be deidentified and analysed. The main outcomes of interest are linkage to care and treatment among HIVST users who report a reactive HIVST result. Additionally, we plan to determine sociodemographic factors associated with linkage to care and treatment among HIVST users. Descriptive statistics will be used to describe the variables of interest, and modified Poisson regression with robust variance estimation will be performed to identify factors associated with linkage to care and treatment among HIVST users who report a reactive HIVST result. Risk ratios and 95% CIs for the risk ratios will be reported.Ethics and disseminationThe study protocol has been approved by the University of Witwatersrand Human Research Ethics Committee. The dissemination plan for the study findings will include presentations to local and international health authorities, international conferences and publications in open access journals.

Supplemental Digital Content is Available in the Text., Background: Reducing doses of antiretroviral drugs, including stavudine (d4T), may lower toxicity, while preserving efficacy. There are substantial concerns about renal and bone toxicities of tenofovir disoproxil fumarate (TDF). Setting: HIV-1–infected treatment-naive adults in India, South Africa, and Uganda. Methods: A phase-4, 96-week, randomized, double-blind, noninferiority trial compared d4T 20 mg twice daily and TDF, taken in combination with lamivudine (3TC) and efavirenz (EFV). The primary endpoint was the proportion of participants with HIV-1 RNA

ObjectivesLifestyle and working conditions of truck drivers predisposes them to risk-factors associated with communicable and non-communicable diseases, but little is known about the health status of African truck driver. This study aims to assess a cross-section of truckers in South Africa to describe their health information.SettingThe study took place across three truck-stop rest areas in the South African provinces of Free State and Gauteng.ParticipantsEligibility criteria included being males aged 18 years and older, full-time employment as a long-distance truck driver. A total of 614 male truck drivers participated; 384 (63%) were Zimbabwean and 325 (55%) completed high-school.Primary and secondary outcome measuresThe trucker survey explored demographics; working conditions; sexual, eating and sleeping behaviours; mental health status, medical history and cardiac risk-factors. Medical assessments included physical measurements, glucose and lipid measurements, ECG, carotid intima-media thickness (CIMT) and cardiac ultrasound.ResultsIn the previous month, 554 (91%) participants were sexually active; 522 (86%) had sex with a regular partner; 174 (27%) with a casual partner; 87 (14%) with a sex worker. Average time driving was 10 hours/day, 20 days/month, 302 (50%) never worked night shifts and 74 (12%) worked nights approximately four times per week. 112 (18%) experienced daytime sleepiness and 59 (10%) were ever hospitalised from an accident. Forty-seven (8%, 95% CI 5.3 to 9.5) were HIV-positive, with half taking antiretrovirals. Forty-eight (8%) truckers had some moderate depression, while 21 (4%) suffered from post-traumatic stress disorder. Reported tuberculosis, myocardial infarction, and diabetes were 15 drinks/week) (n=54, 9%), overweight/obesity (n=417, 69%), and hypertension (n=220, 36%,95% CI 32.1 to 39.7). ECG results showed 23 (4.9%) and 29 (5.3%) drivers had left ventricular hypertrophy using the Cornell criterion and product, respectively. CIMT measurements indicated nine (4.2%) drivers had a carotid atherosclerotic plaque.ConclusionThis first holistic assessment of health among southern African male truck drivers demonstrates substantial addressable cardiovascular risk factors, mental health issues and sexual risk behaviours.

Given its associated burden of disease, climate change in South Africa could be reframed as predominately a health issue, one necessitating an urgent health-sector response. The growing impact of climate change has major implications for South Africa, especially for the numerous vulnerable groups in the country. We systematically reviewed the literature by searching PubMed and Web of Science. Of the 820 papers screened, 34 were identified that assessed the impacts of climate change on health in the country. Most papers covered effects of heat on health or on infectious diseases (20/34; 59%). We found that extreme weather events are the most noticeable effects to date, especially droughts in the Western Cape, but rises in vector-borne diseases are gaining prominence. Climate aberration is also linked in myriad ways with outbreaks of food and waterborne diseases, and possibly with the recent Listeria epidemic. The potential impacts of climate change on mental health may compound the multiple social stressors that already beset the populace. Climate change heightens the pre-existing vulnerabilities of women, fishing communities, rural subsistence farmers and those living in informal settlements. Further gender disparities, eco-migration and social disruptions may undermine the prevention—but also treatment—of HIV. Our findings suggest that focused research and effective use of surveillance data are required to monitor climate change’s impacts; traditional strengths of the country’s health sector. The health sector, hitherto a fringe player, should assume a greater leadership role in promoting policies that protect the public’s health, address inequities and advance the country’s commitments to climate change accords.

Background For the prevention and control of chronic diseases, two strategies are frequently highlighted: that public health should be evidence based, and that it should develop a multisectoral approach. At the end of a natural experimental study of the health impacts of new transport infrastructure, we took the opportunity of a knowledge exchange forum to explore how stakeholders assessed, negotiated and intended to apply multisectoral evidence in policy and practice at the intersection of transport and health. We aimed to better understand the challenges they faced in knowledge exchange, as well as their everyday experiences with working in multisectoral remits. Methods In 2015, we conducted participant observation during an interactive event with 41 stakeholders from national and local government, the third sector and academia in Cambridge, UK. Formal and informal interactions between stakeholders were recorded in observational field notes. We also conducted 18 semistructured interviews reflecting on the event and on knowledge exchange in general. Results We found that stakeholders negotiated a variety of challenges. First, stakeholders had to negotiate relatively new formal and informal multisectoral remits; and how to reconcile the differing expectations of transport specialists, who tended to emphasise the importance of precedence in guiding action, and health specialists’ concern for the rigour and synthesis of research evidence. Second, research in this field involved complex study designs, and often produced evidence with uncertain transferability to other settings. Third, health outcomes of transport schemes had political traction and were used strategically but not easily translated into cost-benefit ratios. Finally, knowledge exchange meant multiple directions of influence. Stakeholders were concerned that researchers did not always have skills to translate their findings into understandable evidence, and some stakeholders would welcome opportunities to influence research agendas. Conclusions This case study of stakeholders’ experiences indicates that multisectoral research, practice and policymaking requires the ability and capacity to locate, understand and communicate complex evidence from a variety of disciplines, and integrate different types of evidence into clear business cases beyond sectoral boundaries. Electronic supplementary material The online version of this article (doi:10.1186/s12889-016-3940-x) contains supplementary material, which is available to authorized users.

Background Operational research is required to design delivery of pre-exposure prophylaxis (PrEP) and early antiretroviral treatment (ART). This paper presents the primary analysis of programmatic data, as well as demographic, behavioural, and clinical data, from the TAPS Demonstration Project, which offered both interventions to female sex workers (FSWs) at 2 urban clinic sites in South Africa. Methods and findings The TAPS study was conducted between 30 March 2015 and 30 June 2017, with the enrolment period ending on 31 July 2016. TAPS was a prospective observational cohort study with 2 groups receiving interventions delivered in existing service settings: (1) PrEP as part of combination prevention for HIV-negative FSWs and (2) early ART for HIV-positive FSWs. The main outcome was programme retention at 12 months of follow-up. Of the 947 FSWs initially seen in clinic, 692 were HIV tested. HIV prevalence was 49%. Among those returning to clinic after HIV testing and clinical screening, 93% of the women who were HIV-negative were confirmed as clinically eligible for PrEP (n = 224/241), and 41% (n = 110/270) of the women who were HIV-positive had CD4 counts within National Department of Health ART initiation guidelines at assessment. Of the remaining women who were HIV-positive, 93% were eligible for early ART (n = 148/160). From those eligible, 98% (n = 219/224) and 94% (n = 139/148) took up PrEP and early ART, respectively. At baseline, a substantial fraction of women had a steady partner, worked in brothels, and were born in Zimbabwe. Of those enrolled, 22% on PrEP (n = 49/219) and 60% on early ART (n = 83/139) were seen at 12 months; we observed high rates of loss to follow-up: 71% (n = 156/219) and 30% (n = 42/139) in the PrEP and early ART groups, respectively. Little change over time was reported in consistent condom use or the number of sexual partners in the last 7 days, with high levels of consistent condom use with clients and low use with steady partners in both study groups. There were no seroconversions on PrEP and 7 virological failures on early ART among women remaining in the study. Reported adherence to PrEP varied over time between 70% and 85%, whereas over 90% of participants reported taking pills daily while on early ART. Data on provider-side costs were also collected and analysed. The total cost of service delivery was approximately US$126 for PrEP and US$406 for early ART per person-year. The main limitations of this study include the lack of a control group, which was not included due to ethical considerations; clinical study requirements imposed when PrEP was not approved through the regulatory system, which could have affected uptake; and the timing of the implementation of a national sex worker HIV programme, which could have also affected uptake and retention. Conclusions PrEP and early ART services can be implemented within FSW routine services in high prevalence, urban settings. We observed good uptake for both PrEP and early ART; however, retention rates for PrEP were low. Retention rates for early ART were similar to retention rates for the current standard of care. While the cost of the interventions was higher than previously published, there is potential for cost reduction at scale. The TAPS Demonstration Project results provided the basis for the first government PrEP and early ART guidelines and the rollout of the national sex worker HIV programme in South Africa., In an observational study, Gabriela Gomez and colleagues report on provision of pre-exposure prophylaxis and antiretroviral treatment for female sex workers in South Africa., Author summary Why was this study done? Female sex workers are a vulnerable population at risk of HIV, and, in some areas of South Africa, nearly 3 out of 4 sex workers are already infected. Pre-exposure prophylaxis (PrEP) and early antiretroviral treatment (ART) are interventions being piloted by national programmes to test whether (and how) they can be successfully delivered in clinics and the public sector. We conducted a study in existing sex-worker-specific clinics to see if female sex workers would take up and use PrEP and early ART if these interventions were offered. We partnered with the South African government to align and incorporate our results into national HIV programming. What did the researchers do and find? We offered PrEP to HIV-negative female sex workers and early ART to HIV-positive female sex workers in 2 clinics located in Johannesburg and Pretoria in South Africa. Over time, we assessed how many women were contacted for the intervention, how many came to the clinic for HIV testing, how many were HIV-negative and -positive, and how many took up the interventions. We then monitored those who participated for at least 12 months to see whether they stayed in the programme and used PrEP or early ART. We found an HIV prevalence of 49% among the 692 women tested. Among those returning to clinic after HIV testing and clinical screening, 93% were confirmed eligible for PrEP, and 94% for early ART. From those eligible, 98% and 94% took up PrEP and early ART, respectively. At the end of the 12-month assessment, 22% remained on PrEP, while 60% remained on early ART, at our clinic sites. It is possible that some women moved to other sites without our knowledge, as other sites started offering PrEP and early ART. The drugs were safe to use with few side effects. We also found that women who stayed in the study reported taking their pills regularly. None of the women who remained in the study in the PrEP group got HIV, and very few women taking early ART had issues supressing the virus. The overall cost of the programme came to approximately US$126 for PrEP and $406 for early ART per person-year. What do these findings mean? These findings suggest that female sex workers may be interested in both PrEP and early ART and that the interventions work well when taken, but longer term commitment may be a challenge. These interventions have already been introduced by the South African government into sex worker programmes, including those for male, female, and transgender people.

BackgroundThe largest proportion of people living with HIV resides in sub-Saharan Africa (SSA). Evidence from developed countries suggests that HIV infection increases the relative risk of cardiovascular disease (CVD) by up to 50%. Differences in lifestyle, gender distribution, routes of HIV transmission and HIV subtype preclude generalisation of data from Western countries to the SSA situation. The Ndlovu Cohort Study aims to provide insight into the burden of cardiovascular risk factors and disease, the mechanisms driving CVD risk and the contribution of HIV infection and its treatment to the development of CVD in a rural area of SSA.DesignThe Ndlovu Cohort Study is a prospective study in the Moutse area, Limpopo Province, South Africa.MethodsA total of 1000 HIV-positive and 1000 HIV-negative participants aged 18 years and older with a male to female ratio of 1:1 will be recruited. Measurements of CVD risk factors and HIV-related characteristics will be performed at baseline, and participants will be followed-up over time at 6–month intervals. The burden of CVD will be assessed with repeated carotid intima–media thickness and pulse wave velocity measurements, as well as by recording clinical cardiovascular events that occur during the follow-up period.ConclusionThis project will contribute to the understanding of the epidemiology and pathogenesis of CVD in the context of HIV infection in a rural area of SSA. The ultimate goal is to improve cardiovascular risk prediction and to indicate preventive approaches in the HIV-infected population and, potentially, for non-infected high-risk populations in a low-resource setting.

Introduction African countries are rapidly adopting guidelines to offer antiretroviral therapy (ART) to all HIV-infected individuals, regardless of CD4 count. For this policy of ‘treat all’ to succeed, millions of new patients must be initiated on ART as efficiently as possible. Studies have documented high losses of treatment-eligible patients from care before they receive their first dose of antiretrovirals (ARVs), due in part to a cumbersome, resource-intensive process for treatment initiation, requiring multiple clinic visits over a several-week period. Methods and analysis The Simplified Algorithm for Treatment Eligibility (SLATE) study is an individually randomised evaluation of a simplified clinical algorithm for clinicians to reliably determine a patient’s eligibility for immediate ART initiation without waiting for laboratory results or additional clinic visits. SLATE will enrol and randomise (1:1) 960 adult, HIV-positive patients who present for HIV testing or care and are not yet on ART in South Africa and Kenya. Patients randomised to the standard arm will receive routine, standard of care ART initiation from clinic staff. Patients randomised to the intervention arm will be administered a symptom report, medical history, brief physical exam and readiness assessment. Patients who have positive (satisfactory) results for all four components of SLATE will be dispensed ARVs immediately, at the same clinic visit. Patients who have any negative results will be referred for further clinical investigation, counselling, tests or other services prior to being dispensed ARVs. After the initial visit, follow-up will be by passive medical record review. The primary outcomes will be ART initiation ≤28 days and retention in care 8 months after study enrolment. Ethics and dissemination Ethics approval has been provided by the Boston University Institutional Review Board, the University of the Witwatersrand Human Research Ethics Committee (Medical) and the KEMRI Scientific and Ethics Review Unit. Results will be published in peer-reviewed journals and made widely available through presentations and briefing documents. Trial registration NCT02891135

There is concern that the expansion of antiretroviral roll-out may impact future drug resistance levels and hence compromise the benefits of antiretroviral therapy (ART) at an individual and population level. We aimed to predict future drug resistance in South Africa and its long-term effects.The previously validated HIV Synthesis model was calibrated to South Africa. Resistance was modeled at the level of single mutations, transmission potential, persistence, and effect on drug activity.We estimate 652 000 people (90% uncertainty range: 543 000-744 000) are living with nonnucleoside reverse transcriptase inhibitor (NNRTIs)-resistant virus in South Africa, 275 000 in majority virus [Non-nucleoside reverse transcriptase inhibitor resistant virus present in majority virus (NRMV)] with an unsuppressed viral load. If current diagnosis and retention in care and eligibility criteria are maintained, in 20 years' time HIV incidence is projected to have declined by 22% (95% confidence interval, CI -23 to -21%), and the number of people carrying NNRTI resistance to be 2.9-fold higher. If enhancements in diagnosis and retention in care occur, and ART is initiated at CD4 cell count less than 500 cells/μl, HIV incidence is projected to decline by 36% (95% CI: -37 to -36%) and the number of people with NNRTI resistance to be 4.1-fold higher than currently. Prevalence of people with viral load more than 500 copies/ml carrying NRMV is not projected to differ markedly according to future ART initiation policy, given the current level of diagnosis and retention are maintained.Prevalence of resistance is projected to increase substantially. However, introduction of policies to increase ART coverage is not expected to lead to appreciably higher prevalence of HIV-positive people with resistance and viral load more than 500 copies/ml. Concern over resistance should not stop expansion of treatment availability.

South Africa is a country with a high incidence of tuberculosis (TB), complicated by coinfection with human immunodeficiency virus (HIV). The Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is used in South Africa as the test for the initial diagnosis of TB, and other molecular platforms such as the m2000 (Abbott Molecular, Des Plaines, IL, USA) are widely used for molecular monitoring of HIV load. The latter platform is now also equipped with the RealTime (RT) MTB and RealTime MTB RIF/INH assays for TB and first-line drug resistance screening but has not been evaluated in settings of HIV and TB coinfection. A prospective clinical validation study was conducted at a community health center in Johannesburg, South Africa, and consenting individuals with presumptive pulmonary TB were enrolled. The performance of the Abbott assays was compared with those of the Xpert MTB/RIF, liquid culture, drug susceptibility testing, and clinical case definitions. A statistical analysis was performed on 206 individuals (73% were HIV positive). The sensitivity and specificity of the RT MTB were 82.5% (confidence interval [CI], 67.2 to 92.7) and 93.1% (CI, 86.2 to 97.2) on raw sputum and 77.5% (CI, 61.5 to 89.2) and 95.1% (CI, 88.9 to 98.4) on concentrated sputum, respectively, compared with those from liquid culture. The RT MTB correctly identified 17/35 more smear-negative culture-positive specimens than the Xpert MTB/RIF. Both the RT MTB and the Xpert MTB/RIF displayed sensitivities >70% and specificities >90% in HIV-positive individuals. The available drug resistance results concurred with MTBDRplus and drug susceptibility profiles. The RT MTB assay has similar diagnostic performance to the Xpert MTB/RIF and is suited to testing presumptive TB patients coinfected with HIV. The existing laboratory information system connectivity, training, and technical support make this a viable polyvalent option to scale up TB alongside HIV laboratory testing services in South Africa.

Introduction The authors report on a health systems strengthening intervention using quality improvement (QI) methods at the subdistrict level to accelerate highly active antiretroviral treatment (HAART) initiation in South Africa. Methods Using a phased scale-up design between August 2006 and November 2009, 14 primary healthcare clinics, one community health centre, one district hospital and one tertiary hospital in a subdistrict were recruited into a ‘learning network’ using QI methods to facilitate cross-facility learning/mentorship/support. Clinic teams consisting of nurses, counsellors, clerks and/or doctors set collective and individual performance targets, analysed their care systems using ‘real-time’ data feedback, and designed/implemented a set of simple changes to improve HIV testing and HAART initiation rates across the region. Data analysis Primary clinic data were used to measure HAART initiation rates (primary outcome) and HIV testing (secondary outcome). We analysed data variation/trends using an interrupted time series design. Logistic regression analysis was applied to examine trends in HAART initiation during the intervention phases. Results Clinics in the learning network increased HIV testing by 301.8% from 891/month (SD=94.2) to 3580/month (SD=327.7) (p

The emergence of HIV drug resistance is a major obstacle to effective antiretroviral (ARV) treatments. This study examined the drug resistance profiles among South African patients virologically failing ARV therapies between 2000 and 2003, prior to the introduction of a national treatment program. Samples were obtained from 65 HIV-1 subtype C-infected patients (39 children and 26 adults) who had received at least two nucleoside reverse transcriptase inhibitors (NRTIs) and either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). Resistance assays were performed using the HIV-1 ViroSeq Genotyping System and mutations were defined according to the Stanford Sequence Resistance Database. Ninety-one percent of patients harbored resistance mutations; the most frequent NRTI mutations were M184V/I (37%), D67N (32%), T215Y/F (25%), K70R (21%), M41L (20%), K219Q/E (14%), and K65R (14%), reflecting the frequent use of lamuvidine and zidovudine. K103N (25%), V106M (20%), and G190A (17%) were found among patients failing nevirapine- or efavirenz-containing regimens. Of the patients who received PIs, the most common mutations were V82A/T (12%), M46I (11%), and L90M (8%). Mutations were similar among adults and children. These data indicate that HIV-1 drug resistance develops in South African subtype C-infected patients failing ARV therapy with mutations comparable to those found among patients infected with subtype B viruses.

Once again the nation is outraged by the now familiar annual tale of how a number of initiates undergoing traditional male circumcision in several provinces have paid with permanent disability, or the ultimate penalty of death, for taking part in cultural practices that have outlived their value in today's South Africa. While we respect the rights of people to engage in culturally important initiation practices, it is unacceptable that every year during the winter months a large number of initiates continue to die or be maimed for life.

South Africa already has the world’s biggest antiretroviral (ARV) programme. With the introduction of extended criteria for initiating ARVs, the National Department of Health wishes to increase the number of people on ARVs by around two million over the next 2 years. Adoption of a chronic disease management model, with extended task shifting, decentralisation and new approaches to distribution of ARVs, must be embraced if this is to be successfully achieved without huge increases in resources. In this editorial we discuss the need for change, and the current substantial blocks to progress (principally in prescribing and dispensing legislation) that contradict national treatment guidance and should be addressed as a matter of urgency. In addition, we draw attention to threatened regulatory changes that may further worsen the situation.

For the past 25 years, South Africa has had to deal with the inexorable and monumental rise of HIV. From one or two isolated cases, in the late 1980s, South Africa now has an estimated 6.4 million people infected with HIV, with high rates of concomitant tuberculosis, which will profoundly affect the country for decades to come. For nearly 10 years, the South African government's response to the HIV epidemic was described as denialist, which was estimated to have resulted in the deaths of 330,000 people because lifesaving antiretroviral therapy (ART) was not provided (Chigwedere et al. J Acquir Immune Defic Syndr. 49:410-15, 2008; Heywood 2004). However, the story of the HIV and AIDS response in South Africa over the past 5 years is one of great progress after almost a decade of complex and tragic denialism that united civil society in a way not seen since the opposition to apartheid. Today, South Africa can boast of close to 3 million people on ART, by far the largest number in the world. Prevention efforts appear to be yielding results but there continues to be large numbers of new infections, with a profound peak in incidence in young women aged 15 to 24 years. In addition, infections occur across the gender spectrum in older age groups. As a result of the massive increase in access to ART after 2004 and particularly after 2008 as political will towards the HIV ART programme improved, there has been a marked increase in life expectancy, from 56 to 61 years in the period 2009-2012 alone; the aggressive expansion of the prevention of mother to child transmission (PMTCT) to HIV-positive pregnant women has been accompanied by dramatic decrease in HIV transmission to infants; and a 25 % decrease in child and infant mortality rates in the period 2009-2012. This progress in access is significantly due to a civil society movement that was prepared to pose a rights-based challenge to a governing party in denial and to brave health officials, politicians and clinicians working in a hostile system to bring about change.

This prospective non-randomized study of clinic attendees, compares self-reported HIV disclosure patterns in relation to access to antiretroviral access and counselling. It was carried out in public sector hospital HIV clinics in Johannesburg, South Africa, and 144 HIV-positive men and women attending the HIV clinics participated in the study.The results showed that there was no correlation between being on antiretroviral therapy and disclosure of HIV status. There was also no correlation between disclosure of HIV status and with different levels of counselling and access to support groups. Disclosure levels were high (92% told at least one person), however, there was a high level of delayed (15% greater than a year) or non-disclosure (21%) to partners. Family members and partners provided most moral support after disclosure. Having access to antiretroviral therapy and support groups and available counselling did not seem to affect disclosure patterns. It is possible that a patients beliefs about their treatment plays a more important role for disclosure than the actual treatment itself. Other factors are also likely important for disclosure, such as the patient's social network especially with their families, and knowledge of the disease.

Public sector antiretroviral provision had a slow start in South Africa despite a raging epidemic and a World AIDS conference that shed significant public light on the disparities of therapy access globally. This was largely due to political prevarication in the midst of AIDS denialism. There has been an unprecedented expansion in the HIV treatment programme since 2008. As a result, South Africa now has the largest number of patients on antiretroviral drugs in the world, and South African life expectancy has increased by more than a decade. However, this has led to a number of fiscal, logistic and operational challenges that the country must face as the treatment programme continues to expand. Challenges include increasing detection within communities, linkage and retention in care, while strengthening operational support functions such as consistent drug supply, health staffing and infrastructure, diagnostic services, programme monitoring and sustainable financing. As a middle-income country, albeit with marked income inequality, and the heaviest HIV burden in the world, South Africa is a test case of whether a large-scale public health programme can boast of success in the face of numerous other health-system challenges.

SettingSouth Africa has the third highest tuberculosis (TB) burden in the world. Intensified case finding, recommended by WHO, is one way to control TB.ObjectiveTo evaluate the effectiveness and acceptability of a paper slip method for TB contact tracing.MethodTB patients were offered paper slips to give to their contacts, inviting them for TB screening. The number of contacts screened and the proportion diagnosed with TB was calculated. Contacts that returned to the clinic after receiving the slips were interviewed. A focus group discussion (FGD) with TB patients was held to determine their acceptability.ResultsFrom 718 paper slips issued, a 26% TB contact tracing rate was found, with a 12% case detection rate. The majority (68%) of contacts were screened within 2 weeks of receiving the slip. Age and gender were not significantly associated with time to screening. 16% of the contacts screened did not reside with the TB patients. 98% of the contacts said the method was acceptable. FGD findings show that this method is acceptable and may prevent stigma associated with TB/HIV.ConclusionThis simple, inexpensive method yields high contact tracing and case detection rates and potentially would yield additional benefits outside households.

In South Africa, the incidence of HIV-associated cryptococcal meningitis remains high despite the increased coverage of antiretroviral treatment, and in routine care settings, the disease is associated with a case-fatality ratio of more than 50%. Laboratory-based screening and pre-emptive antifungal treatment of cryptococcal disease have been suggested for routine implementation as part of the National Strategic Plan for HIV, STIs and TB, 2012 - 2016. In the first phase of a national screening programme, screening will begin at almost 500 healthcare facilities in the Gauteng and Free State provinces, and NHLS laboratories will reflexively test the remnant specimen of any blood sample with a CD4+ T-lymphocyte count

High fertility intentions amongst HIV-positive women have been reported elsewhere. Less is known about how clinical and HIV treatment characteristics correlate with fertility intentions. We use cross-sectional baseline data from a prospective cohort study to assess pregnancy intentions and patient–provider communication around fertility. Non-pregnant, HIV-positive women aged 18–35 on ART were recruited through convenience sampling at Johannesburg antiretroviral (ART) treatment facilities. Among the 850 women in this analysis, those on efavirenz had similar fertility intentions over the next year as women on nevirapine-based regimens (33% vs. 38%). In multivariate analysis, recent ART initiation was associated with higher current fertility intentions; there was no association with CD4 cell count. Forty-one percent of women had communicated with providers about future pregnancy options. Women on ART may choose to conceive at times that are sub-optimal for maternal, child and partner health outcomes and should be routinely counseled around safer pregnancy options.

Cryptococcal meningitis (CM) is a major cause of death among HIV-infected individuals. It causes an estimated 957 900 cases and 624 700 deaths worldwide annually, the vast majority of them in sub-Saharan Africa.1 In Cape Town, CM is now the most common cause of adult meningitis (63% of all microbiologically confirmed cases2), and acute outcomes are poor.3 Even with optimal treatment in study settings, 10-week mortality rates are between 24% and 37%.4,5 In 2009, in a routine care setting at an urban hospital in Johannesburg, 67% of patients had died or were lost to follow-up at 3 months (N Govender et al., unpublished data). Unfortunately almost half of South African patients still receive sub-optimal initial treatment with oral fluconazole rather than intravenous amphotericin B.3,6 Clearly, given the substantial mortality and morbidity associated with CM, preventive interventions should be prioritised.

Self-tests for HIV in South Africa are currently unregulated. Gaps in law and policy have created a legal loophole where such tests could effectively be sold in supermarkets, but not in pharmacies. At the same time, South Africa lacks an effective regulating mechanism for diagnostic tests, which brings the quality and reliability of all self-tests into question. The authors argue for greater access to, and availability of, quality HIV self-tests. This strategy will encourage regular HIV testing, allay fears about stigma and confidentiality when testing in public facilities, and decrease the costs associated with traditional voluntary counselling and testing, and is likely to lead to earlier diagnosis and treatment of HIV. The South African Medical Association (SAMA) recently warned the public against using HIV self-testing kits. SAMA chairman Norman Mabasa noted that it was ‘risky’ for individuals to test themselves ‘unmonitored’ and that it might lead to devastated patients or suicide. 1-3

The South African HIV National Strategic Plan (NSP) aims to provide access to appropriate treatment, care and support to 80% of the HIV-infected population by 2011. By mid-2008, highly active antiretroviral treatment (HAART) was being dispensed to about half the HIV-infected population in need. Reaching the NSP targets will require full mobilisation of all of South Africa's health facilities. While the NSP has broad political and programmatic support from the Department of Health and civil society, and managers are able to recite the national targets, it has been difficult for these managers to relate the targets to their own geographical areas of responsibility. National, regional and district targets for HIV care have been set from South Africa's relatively good census, modelling and epidemiological data. However, few practical tools are available to help clinicians and managers understand their facility's actual contribution to the district regional and national NSP targets for each step of the HIV care pathway (HIV testing, CD4 testing, HAART referral and initiation). The calculation of HAART initiation targets is complicated by the anticipated additional demand for treatment that will be generated by a change in the recommended CD4-count threshold for initiation of treatment.4 Accordingly, we provide a data-based tool that is readily available, and that district and facility managers can use to calculate their annual steady-state HIV testing, CD4 testing and HAART initiation requirements. These calculated values can be used for local and regional planning and to assess and improve current performance at facility level.

To the Editor: In South Africa, an estimated 30% of the cadaveric donor pool is HIV-infected; in consequence, these organs are discarded. An undersupply of donor organs combined with limited resources tends to exclude HIV-positive patients from renal replacement programmes. We evaluated the acceptance of using HIV-positive donor kidneys for transplantation into HIV-infected recipients, and found that the vast majority (90% of health care workers and 80% of patients, N=20 and 80, respectively) found this approach acceptable for expanding the organ donor pool, which indicates broad patient and health care worker support for using HIV-infected donor kidneys.

Nevirapine used in single doses to prevent mother-to-child transmission has been shown to be associated with the development of transient resistant mutations. Here we describe the presence of V106M in seven out of 141 South African women (5%) 6 weeks after receiving nevirapine. V106M is a novel resistance mutation found in subtype C viruses exposed to efavirenz. This mutation is thus also induced at a low frequency in subtype C viruses exposed to single dose nevirapine.

There are many valuable lessons for HIV and other disease programs to learn from the last ten years. Looking back questions of sustainability have arisen in Africa (with the exception of southern Africa) as the HIV response is largely funded out of the national tax base reflecting the political commitment that is now more important than donor generosity. Funding from the President’s Emergency Fund for AIDS Relief (PEPFAR) and Global Fund technical and resource assistance has meant an sustained annual decrease in overall health costs over the last few years. Monitoring requirements have been eased and the treatment cost per patient has decreased has decreased. There is a lot to celebrate in the past decade and clear heroes – including the Treatment Access Campaign Medicins Sans Frontiers and Sectopm 27 – set the tone for an upcoming decade of even greater success towards building a quality HIV program.

No abstract.

Background Point-of-care CD4 testing can provide immediate CD4 reporting at HIV-testing sites. This study evaluated performance of capillary blood sampling using the point-of-care Pima™ CD4 device in representative primary health care clinics doing HIV testing. Methods Prior to testing, prescribed capillary-sampling and instrument training was undertaken by suppliers across all sites. Matching venous EDTA samples were drawn throughout for comparison to laboratory predicate methodology (PLG/CD4). In Phase I, Pima™ cartridges were pipette-filled with EDTA venous blood in the laboratory (N = 100). In Phase II (N = 77), Pima™ CD4 with capillary sampling was performed by a single operator in a hospital-based antenatal clinic. During subsequent field testing, Pima™ CD4 with capillary sampling was performed in primary health care clinics on HIV-positive patients by multiple attending nursing personnel in a rural clinic (Phase-IIIA, N = 96) and an inner-city clinic (Phase-IIIB, N = 139). Results Pima™ CD4 compared favourably to predicate/CD4 when cartridges were pipette-filled with venous blood (bias -17.3 ± STDev = 36.7 cells/mm3; precision-to-predicate %CV < 6%). Decreased precision of Pima™ CD4 to predicate/CD4 (varying from 17.6 to 28.8%SIM CV; mean bias = 37.9 ± STDev = 179.5 cells/mm3) was noted during field testing in the hospital antenatal clinic. In the rural clinic field-studies, unacceptable precision-to-predicate and positive bias was noted (mean 28.4%SIM CV; mean bias = +105.7 ± STDev = 225.4 cells/mm3). With additional proactive manufacturer support, reliable performance was noted in the subsequent inner-city clinic field study where acceptable precision-to-predicate (11%SIM CV) and less bias of Pima™ to predicate was shown (BA bias ~11 ± STDev = 69 cells/mm3). Conclusions Variable precision of Pima™ to predicate CD4 across study sites was attributable to variable capillary sampling. Poor precision was noted in the outlying primary health care clinic where the system is most likely to be used. Stringent attention to capillary blood collection technique is therefore imperative if technologies like Pima™ are used with capillary sampling at the POC. Pima™ CD4 analysis with venous blood was shown to be reproducible, but testing at the point of care exposes operators to biohazard risk related to uncapping vacutainer samples and pipetting of blood, and is best placed in smaller laboratories using established principles of Good Clinical Laboratory Practice. The development of capillary sampling quality control methods that assure reliable CD4 counts at the point of care are awaited.