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Background: In economic analyses of HIV interventions, South Africa is often used as a case in point, due to the availability of good epidemiological and programme data and the global relevance of its epidemic. Few analyses however use locally relevant cost data. We reviewed available cost data as part of the South African HIV Investment Case, a modelling exercise to inform the optimal use of financial resources for the country’s HIV programme. Methods: We systematically reviewed publication databases for published cost data covering a large range of HIV interventions and summarised relevant unit costs (cost per person receiving a service) for each. Where no data was found in the literature, we constructed unit costs either based on available information regarding ingredients and relevant public-sector prices, or based on expenditure records. Results: Only 42 (5%) of 1,047 records included in our full-text review reported primary cost data on HIV interventions in South Africa, with 71% of included papers covering ART. Other papers detailed the costs of HCT, MMC, palliative and inpatient care; no papers were found on the costs of PrEP, social and behaviour change communication, and PMTCT. The results informed unit costs for 5 of 11 intervention categories included in the Investment Case, with the remainder costed based on ingredients (35%) and expenditure data (10%). Conclusions: A large number of modelled economic analyses of HIV interventions in South Africa use as inputs the same, often outdated, cost analyses, without reference to additional literature review. More primary cost analyses of non-ART interventions are needed. [ABSTRACT FROM AUTHOR]

Voluntary medical male circumcision is an integral part of the South African government’s response to the HIV and AIDS epidemic. Following circumcision, it is recommended that patients abstain from sexual activity for six weeks, as sex may increase the risk of female-to-male HIV transmission and prolong the healing period. This paper investigates the resumption of sexual activity during the healing period among a cohort of school-going males in the KwaZulu-Natal province of South Africa. The analysis for this paper compares two groups of sexually active school-going males: the first group reported having sex during the healing period (n = 40) and the second group (n = 98) reported no sex during the healing period (mean age: 17.7, SD: 1.7).The results show that 29% (n = 40) of young males (mean age: 17.9, SD: 1.8) who were previously sexually active, resumed sexual activity during the healing period, had on average two partners and used condoms inconsistently. In addition, those males that engage in sexual activity during the healing period were less inclined to practice safe sex in the future (AOR = 0.055, p = 0.002) than the group of males who reported no sex during the healing period. These findings suggest that a significant proportion of young males may currently and in the future, subject themselves to high levels of risk for contracting HIV post circumcision. Education, as part of a VMMC campaign, must emphasize the high risk of HIV transmission for both the males their partners during the healing period. [ABSTRACT FROM AUTHOR]

Introduction: HIV self-testing (HIVST) offers a useful addition to HIV testing services and enables individuals to test privately. Despite recommendations to the contrary, repeat HIV testing is frequent among people already on anti-retroviral treatment (ART) and there are concerns that oral self-testing might lead to false negative results. A study was conducted in Khayelitsha, South Africa, to assess feasibility and uptake of HIVST and linkage-to-care following HIVST. Methods: Participants were recruited at two health facilities from 1 March 2016 to 31 March 2017. People under 18 years, or with self-reported previously-diagnosed HIV infection, were excluded. Participants received an OraQuick Rapid HIV-1/2 Antibody kit, and reported their HIVST results by pre-paid text message (SMS) or by returning to the facility. Those not reporting within 7 days were contacted by phone. Electronic and paper-based clinical and laboratory records were retrospectively examined for all participants to identify known HIV outcomes, after matching for name, date of birth, and sex. These findings were compared with self-reported HIVST results where available. Results: Of 639 participants, 401 (62.8%) self-reported a negative HIVST result, 27 (4.2%) a positive result, and 211 (33.0%) did not report. The record search identified that of the 401 participants self-reporting a negative HIVST result, 19 (4.7%) were already known to be HIV positive; of the 27 self-reporting positive, 12 (44%) were known HIV positive. Overall, records showed 57/639 (8.9%) were HIV positive of whom 39/57 (68.4%) had previously-diagnosed infection and 18/57 (31.6%) newly-diagnosed infection. Of the 428 participants who self-reported a result, 366 (85.5%) reported by SMS. Conclusions: HIVST can improve HIV testing uptake and linkage to care. SMS is acceptable for reporting HIVST results but negative self-reports by participants may be unreliable. Use of HIVST by individuals on ART is frequent despite recommendations to the contrary and its implications need further consideration. [ABSTRACT FROM AUTHOR]

Women remain highly vulnerable to HIV infection in sub-Saharan Africa, with female sex workers (FSWs) facing some of the highest rates of HIV. Oral pre-exposure prophylaxis (PrEP) has the potential to reduce new infections among populations at highest risk and end-user perspectives of actual use in ‘real-world’ settings are critical to informing PrEP implementation. This paper presents findings from serial in-depth interviews (IDIs) conducted with FSW participants during the course of the Treatment And Prevention for Sex workers (TAPS) Demonstration Project in South Africa, exploring the lived experiences and perceptions of taking up and using PrEP. This research provides insight into risks and responsibilities facing FSWs perceived as prominent drivers in taking up and using PrEP, how PrEP was adopted to mitigate risk or ameliorate realities, and the characteristics of PrEP most valued, all of which are critical to consider in scale-up. Overall, distrust in the existence and/or efficacy of PrEP affected the motivation of women to come to the clinic and to maintain use. As one of the first reports of PrEP use among FSWs outside of a clinical trial setting, this research shows that it will be important to ensure accurate, relevant, and widespread messaging in communities to generate demand and support for PrEP. [ABSTRACT FROM AUTHOR]

Introduction: In many sub-Saharan African countries, confronting the dual epidemic of HIV and NCDs is a public health priority especially in high HIV burden countries such as South Africa. Evidence shows that poor health as a consequence of NCDs and HIV among the workforce increases absenteeism and leads to decrease in productivity. However, the prevalence of these co-occurring chronic conditions and associated factors is unknown in the educator workforce. Improved understanding has implications for their management and wellbeing of educators. This paper reports the prevalence of selected NCDs and associated factors among HIV positive educators in South Africa using the 2015/6 survey of Educators in Public Schools in South Africa. Methods: This was a second-generation surveillance undertaken among educators in selected public schools in all nine provinces in South Africa. A multi-stage stratified cluster design with probability proportional to size sampling was used to draw a random sample of schools. Factors associated with presence of NCDs were determined using a multivariate backward stepwise logistic regression analysis. Results: A total of 1 365 schools were sampled within which 21 495 (85.5%) educators were interviewed. Out of 2691, HIV Positive educators that responded to the questions on NCDs, 36.9% reported having NCDs. The most commonly reported NCDs were high blood pressure (17.4%), and stomach ulcers (13.5%). The increased odds of reporting the presence of NCDs was significantly associated with being female than male [aOR = 1.5: 95% CI (1.1–1.9), p<0.002], age 45 to 54 years [aOR = 1.8: 95% CI (1.4–2.2), p = p<0.001], and age 55 years and older than those 18 to 24 years [aOR = 2.7: 95% CI (1.8–3.9), p<0.001). The decreased odds of reporting the presence of NCDs was significantly associated with not being absent from school for health reasons [aOR = 0.7: 95% CI (0.6–0.9), p = 0.003]. Conclusion: NCDs care and active screening should be an integral part of HIV programmes including interventions such as prevention, treatment, care and support amongst public school educators in SA. The education department will need to invest in health promotion intervention programmes to prevent and mitigate the negative impact of NCDs and HIV on the sector. [ABSTRACT FROM AUTHOR]

Introduction: The increasing number of people requiring HIV treatment in South Africa calls for efficient use of its human resources for health in order to ensure optimum treatment coverage and outcomes. This paper describes an innovative public-private partnership model which uses private sector doctors to treat public sector patients and ascertains the model’s ability to maintain treatment outcomes over time. Methods: The study used a retrospective design based on the electronic records of patients who were down-referred from government hospitals to selected private general medical practitioners (GPs) between November 2005 and October 2012. In total, 2535 unique patient records from 40 GPs were reviewed. The survival functions for mortality and attrition were calculated. Cumulative incidence of mortality for different time cohorts (defined by year of treatment initiation) was also established. Results: The median number of patients per GP was 143 (IQR: 66–246). At the time of down-referral to private GPs, 13.8% of the patients had CD4 count <200 cell/mm3, this proportion reduced to 6.6% at 12 months and 4.1% at 48 months. Similarly, 88.4% of the patients had suppressed viral load (defined as HIV-1 RNA <400 copies/ml) at 48 months. The patients’ probability of survival at 12 and 48 months was 99.0% (95% CI: 98.4%–99.3%) and 89.0% (95% CI: 87.1%–90.0%) respectively. Patient retention at 48 months remained high at 94.3% (95% CI: 93.0%–95.7%). Conclusions: The study findings demonstrate the ability of the GPs to effectively maintain patient treatment outcomes and potentially contribute to HIV treatment scale-up with the relevant support mechanism. The model demonstrates how an assisted private sector based programme can be effectively and efficiently used to either target specific health concerns, key populations or serve as a stop-gap measure to meet urgent health needs. [ABSTRACT FROM AUTHOR]

Objective: This is the first large-scale assessment of the implementation of HIV Rapid Test Quality Improvement Initiative in South Africa. Methods: We used a quasi-experimental one group post-test only design. The intervention implemented starting April 2014 comprised health-care worker training on quality assurance (QA) of HIV rapid testing and enrolment of the facilities in proficiency testing (PT), targeting 2,077 healthcare facilities in 32 high HIV burden districts. Following the intervention, two consecutive rounds of site assessments were undertaken. The first, conducted after a median of 7.5 months following the training, included 1,915 facilities that participated in the QA training, while the second, conducted after a median of one-year following the first-round assessment included 517 (27.0%) of the 1,915 facilities. In both assessments, the Stepwise-Process-for-Improving-the-quality-of-HIV-Rapid-Testing (SPI-RT) checklist was used to score facilities’ performance in 7 domains: training, physical facility, safety, pre-testing, testing, post-testing and external quality assessment. Facilities’ level of readiness for national certification was assessed. Result: Between 2016 and 2017, there were four PT cycles. PT participation increased from 32.4% (620/1,915) in 2016 to 91.5% (1,753/1,915) in 2017. In each PT cycle, PT results were returned by 76%–87% of facilities and a satisfactory result (>80%) was achieved by ≥95% of facilities. In the SPI-RT assessment, in round-one, 22.3% of facilities were close to or eligible for national certification—this significantly increased to 38.8% in round-two (P-value<0.001). The median SPI-RT score for the domains HIV pre-testing (83.3%) and post-testing (72.2%) remained the same between the two rounds. The median score for the testing domain increased by 5.6% (to 77.8%). Conclusion: Facilities performance on the domains that are critical for accuracy of diagnosis (i.e. pre-testing, testing and post-testing) remained largely unchanged. This study provided several recommendations to improve QA implementation in South Africa, including the need to improve routine use of internal quality control for corrective actions. [ABSTRACT FROM AUTHOR]

Background: Expanded HIV prevention options are needed to increase uptake of HIV prevention among women, especially in generalized epidemics. As the dapivirine vaginal ring moves forward through regulatory review and open-label extension studies, the potential public health impact and cost-effectiveness of this new prevention method are not fully known. We used mathematical modeling to explore the impact and cost-effectiveness of the ring in different implementation scenarios alongside scale-up of other HIV prevention interventions. Given the knowledge gaps about key factors influencing the ring’s implementation, including potential uptake and delivery costs, we engaged in a stakeholder consultation process to elicit plausible parameter ranges and explored scenarios to identify the possible range of impact, cost, and cost-effectiveness. Methods and findings: We used the Goals model to simulate scenarios of oral and ring pre-exposure prophylaxis (PrEP) implementation among female sex workers and among other women ≤21 years or >21 years with multiple male partners, in Kenya, South Africa, Uganda, and Zimbabwe. In these scenarios, we varied antiretroviral therapy (ART) coverage, dapivirine ring coverage and ring effectiveness (encompassing efficacy and adherence) by risk group. Following discussions with stakeholders, the maximum level of PrEP coverage (oral and/or ring) considered in each country was equal to modern contraception use minus condom use in the two age groups. We assessed results for 18 years, from 2018 to 2035. In South Africa, for example, the HIV infections averted by PrEP (ring plus oral PrEP) ranged from 310,000 under the highest-impact scenario (including ART held constant at 2017 levels, high ring coverage, and 85% ring effectiveness) to 55,000 under the lowest-impact scenario (including ART reaching the UNAIDS 90-90-90 targets by 2020, low ring coverage, and 30% ring effectiveness). This represented a range of 6.4% to 2.2% of new HIV infections averted. Given our assumptions, the addition of the ring results in 11% to 132% more impact than oral PrEP alone. The cost per HIV infection averted for the ring ranged from US$13,000 to US$121,000. Conclusions: This analysis offers a wide range of scenarios given the considerable uncertainty over ring uptake, consistency of use, and effectiveness, as well as HIV testing, prevention, and treatment use over the next two decades. This could help inform donors and implementers as they decide where to allocate resources in order to maximize the impact of the dapivirine ring in light of funding and implementation constraints. Better understanding of the cost and potential uptake of the intervention would improve our ability to estimate its cost-effectiveness and assess where it can have the most impact. [ABSTRACT FROM AUTHOR]

We propose a method for analyzing repeated residential movements based on graphical loglinear models. This method allows an explicit representation of residential presence and absence patterns from several areas without defining mobility measures. We make use of our method to analyze data from one of the most comprehensive demographic surveillance sites in Africa that is characterized by high adult HIV prevalence, high levels of poverty and unemployment and frequent residential changes. Between 2004 and 2016, residential changes were recorded for 8,857 men over 35,500.01 person-years, and for 12,158 women over 57,945.35 person-years. These individuals were HIV negative at baseline. Over the study duration, there were a total of 806 HIV seroconversions in men, and 2,458 HIV seroconversions in women. Our method indicates that establishing a residence outside the rural study area is a strong predictor of HIV seroconversion in men (OR = 2.003, 95% CI = [1.718,2.332]), but not in women. Residing inside the rural study area in a single or in multiple locations is a less significant risk factor for HIV acquisition in both men and women compared to moving outside the rural study area. [ABSTRACT FROM AUTHOR]

Background: We describe CD4 count recovery among HIV positive individuals who initiated antiretroviral therapy (ART) with and without severe immune suppression using complete laboratory data from South Africa’s national HIV treatment programme between 2010 and 2014 and discuss implications for CD4 count monitoring. Methods: Retrospective analysis of routinely collected laboratory data from South Africa’s National Health Laboratory Service (NHLS). A probabilistic record linkage algorithm was used to create a cohort of HIV positive individuals who initiated ART between 2010 and 2014 based on timing of CD4 count and viral load measurements. A CD4 count < 50 copies/μl at ART initiation was considered severe immunosuppression. A multivariable piecewise mixed-effects linear regression model adjusting for age, gender, year of starting ART, viral suppression in follow up and province was used to predict CD4 counts during follow up. Results: 1,070,900 individuals had evidence of starting ART during 2010–2014 and met the criteria for inclusion in the cohort -46.6% starting ART with CD4 < 200 cells/μl and 10.1% with CD4 < 50 cells/ μl. For individuals with CD4 counts < 200 cells/μl, predicted CD4 counts > 200 cells/μl, >350 cells/μl and >500 cells/μl corresponded with mean follow up durations of 1.5 years (standard deviation [s.d] 1.1), 1.9years (s.d 1.2) and 2.1 years (s.d 1.3 years). For those with CD4 counts < 50 cells/μl, predicted CD4 count above these threshold corresponded with mean follow up durations of 2.5 years (s.d 0.9 years), 4.4 years (s.d 0.4 years) and 5.0 years (s.d 0.1years) for recovery to the same thresholds. CD4 count recovery varied mostly with duration on ART, CD4 count at the start of ART and gender. Conclusion: For individuals starting with ART with severe immunosuppression, CD4 recovery to 200cells/μl did not occur or took longer than 12 month for significant proportions. CD4 monitoring and interventions recommended for advanced HIV disease should continue until full recovery. [ABSTRACT FROM AUTHOR]

Background: HIV self-testing (HIVST) may increase HIV testing uptake, facilitating earlier treatment for key populations like MSM who experience barriers accessing clinic-based HIV testing. HIVST usability among African MSM has not been explored. Methods: We assessed usability of oral fluid (OF) and fingerstick (FS; blood) HIVST kits during three phases among MSM with differing degrees of HIVST familiarity in Mpumalanga, South Africa. In 2015, 24 HIVST-naïve MSM conducted counselor-observed OF and FS HIVST after brief demonstration. In 2016 and 2017, 45 and 64 MSM with experience using HIVST in a pilot study chose one HIVST to conduct with a counselor-observer present. In addition to written, the latter group had access to video instructions. We assessed frequency of user errors and reported test use ease, changes in error frequency by phase, and covariates associated with correct usage using log-Poisson and Gaussian generalized estimating equations. Results: Among OF users (n = 57), 15–30% committed errors in each phase; however, observers consistently rated participants as able to test alone. Among FS users (n = 100), observers noted frequent errors, most commonly related to blood collection and delivery. We found suggestive evidence (not reaching statistical significance) that user errors decreased, with 37.5%, to 28.1%, and 18.2% committing errors in phases I, II, and III, respectively (p-value:0.08), however observer concerns remained constant. Ease and confidence using HIVST increased with HIV testing experience. Participants using three HIVST were more likely (RR:1.92, 95% CI:1.32, 2.80) to report ease compared to those without prior HIVST experience. Never testers (RR:0.66, 95% CI:0.44–0.99) reported less ease performing HIVST compared to participants testing in the past six months. Conclusions: MSM were able to perform the OF test. Fingerstick test performance was less consistent; however preference for fingerstick was strong and performance may improve with exposure and instructional resources. Continued efforts to provide accessible instructions are paramount. [ABSTRACT FROM AUTHOR]

Introduction: WHO recommends antiretroviral treatment (ART) for all HIV-positive individuals. This study evaluated the association between baseline CD4 count and attrition in a cohort of HIV positive adults initiating ART at three department of health (DOH) clinics routinely providing ART at baseline CD4 counts >500cells/μL for the HPTN 071 (PopART) trial. Methods: All clients attending the DOH clinics were managed according to standard care guidelines with the exception that those starting ART outside of pertinent local guidelines signed research informed consent. DOH data on all HIV-positive adult clients recorded as having initiated ART between January 2014 and November 2015 at the three study clinics was analysed. Attrition, included clients lost to follow up or died, and was defined as ‘being three or more months late for an antiretroviral pharmacy pick-up appointment’. All clients were followed until attrition, transfer out or end May 2016. Results: A total of 2423 clients with a median baseline CD4 count of 328 cells/μL (IQR 195–468) were included of whom 631 (26.0%) experienced attrition and 140 (5.8%) were TFO. Attrition was highest during the first six months of ART (IR 38.3/100 PY; 95% CI 34.8–42.1). Higher attrition was found amongst those with baseline CD4 counts > 500 cells/μL compared to those with baseline CD4 counts of 0–500 cells/μL (aHR 1.26, 95%CI 1.05 to 1.52) This finding was confirmed on subset analyses when restricted to individuals non-pregnant at baseline and when restricted to individuals with follow up of > 12months. Conclusions: Attrition in this study was high, particularly during the first six months of treatment. Attrition was highest amongst clients starting ART at baseline CD4 counts > 500 cells/μL. Strategies to improve retention amongst ART clients, particularly those starting ART at baseline CD4 counts >500cells/μL, need strengthening. Improved monitoring of clients moving in and out of ART care and between clinics will assist in better understanding attrition and ART coverage in high burden countries. [ABSTRACT FROM AUTHOR]

Background: We aimed to describe the field experiences and recommendations of clinic-based health care providers (HCP) regarding the implementation of universal antiretroviral therapy (ART) in rural KwaZulu-Natal, South Africa. Methods: In Hlabisa sub-district, the local HIV programme of the Department of Health (DoH) is decentralized in 18 clinics, where ART was offered at a CD4 count ≤500 cells/μL from January 2015 to September 2016. Within the ANRS 12249 TasP trial, implemented in part of the sub-district, universal ART (no eligibility criteria) was offered in 11 mobile clinics between March 2012 and June 2016. A cross-sectional qualitative survey was conducted in April–July 2016 among clinic-based nurses and counsellors providing HIV care in the DoH and TasP trial clinics. In total, 13 individual interviews and two focus groups discussions (including 6 and 7 participants) were conducted, audio-recorded, transcribed, and thematically analyzed. Results: All HCPs reported an overall good experience of delivering ART early in the course of HIV infection, with most patients willing to initiate ART before being symptomatic. Yet, HCPs underlined that not feeling sick could challenge early ART initiation and adherence, and thus highlighted the need to take time for counselling as an important component to achieve universal ART. HCPs also foresaw logistical challenges of universal ART, and were especially concerned about increasing workload and ART shortage. HCPs finally recommended the need to strengthen the existing model of care to facilitate access to ART, e.g., community-based and integrated HIV services. Conclusions: The provision of universal ART is feasible and acceptable according to HCPs in this rural South-African area. However their experiences suggest that universal ART, and more generally the 90-90-90 UNAIDS targets, will be difficult to achieve without the implementation of new models of health service delivery. [ABSTRACT FROM AUTHOR]

Background: In 2010 South Africa revised its HIV treatment guidelines to allow the initiation and management of patients on antiretroviral therapy (ART) by nurses, rather than solely doctors, under a program called NIMART (Nurse Initiated and Managed Antiretroviral Therapy). We compared the outcomes and costs of NIMART between the two major public sector HIV treatment delivery models in use in South Africa today, primary health clinics and hospital-based HIV clinics. Methods and findings: The study was conducted at one hospital-based outpatient HIV clinic and one primary health clinic (PHC) in Gauteng Province. A retrospective cohort of adult patients initiated on ART at the PHC was propensity-score matched to patients initiated at the hospital outpatient clinic. Each patient was assigned a 12-month outcome of alive and in care or died/lost to follow up. Costs were estimated from the provider perspective for the 12 months after ART initiation. The proportion of patients alive and in care at 12 months did not differ between the PHC (76.5%) and the hospital-based site (74.2%). The average annual cost per patient alive and in care at 12 months after ART initiation was significantly lower at the PHC (US$238) than at the hospital outpatient clinic (US$428). Conclusions: Initiating and managing ART patients at PHCs under NIMART is producing equally good outcomes as hospital-based HIV clinic care at much lower cost. Evolution of hospital-based clinics into referral facilities that serve complicated patients, while investing most program expansion resources into PHCs, may be a preferred strategy for achieving treatment coverage targets. [ABSTRACT FROM AUTHOR]

Given compelling evidence associating voluntary medical male circumcision (VMMC) with men’s reduced HIV acquisition through heterosexual intercourse, South Africa in 2010 began scaling up VMMC. To project the resources needed to complete 4.3 million circumcisions between 2010 and 2016, we (1) estimated the unit cost to provide VMMC; (2) assessed cost drivers and cost variances across eight provinces and VMMC service delivery modes; and (3) evaluated the costs associated with mobilize and motivate men and boys to access VMMC services. Cost data were systematically collected and analyzed using a provider’s perspective from 33 Government and PEPFAR-supported (U.S. President's Emergency Plan for AIDS Relief) urban, rural, and peri-urban VMMC facilities. The cost per circumcision performed in 2014 was US$132 (R1,431): higher in public hospitals (US$158 [R1,710]) than in health centers and clinics (US$121 [R1,309]). There was no substantial difference between the cost at fixed circumcision sites and fixed sites that also offer outreach services. Direct labor costs could be reduced by 17% with task shifting from doctors to professional nurses; this could have saved as much as $15 million (R163.20 million) in 2015, when the goal was 1.6 million circumcisions. About $14.2 million (R154 million) was spent on medical male circumcision demand creation in South Africa in 2014—primarily on personnel, including community mobilizers (36%), and on small and mass media promotions (35%). Calculating the unit cost of VMMC demand creation was daunting, because data on the denominator (number of people reached with demand creation messages or number of people seeking VMMC as a result of demand creation) were not available. Because there are no “dose-response” data on demand creation ($X in demand creation will result in an additional Z% increase in VMMC clients), research is needed to determine the appropriate amount and allocation of demand creation resources. [ABSTRACT FROM AUTHOR]

Background: High BMI and blood pressure are leading chronic disease risk factors in South Africa. Longterm effects of HIV and ART on adiposity and blood pressure are poorly understood, and direct comparisons of risk factor trajectories in HIV- versus HIV+ populations are rare. Methods: In 2003 and 2010, height, weight, and blood pressure were recorded in a study population (n = 505) in KwaZulu-Natal, South Africa (30% adult HIV prevalence). We modeled change in BMI and BP longitudinally in HIV- individuals (n = 315), seroconverters (n = 32), HIV+ patients not on ART (HIV+ART−; n = 52), HIV+ patients on ART for 0–<2 years as of 2010 (HIV+ART0–<2 yrs; n = 18), patients on ART for 2–5 years (HIV+ART2–5yrs; n = 44), and a subgroup with unknown HIV status (n = 44). Difference-in-differences were assessed in reference to the HIV- population. Results: Between 2003 and 2010, BMI increased significantly in the HIV- group, by 0.874 (95% CI 0.339, 1.41; p = 0.001), to 30.4. BMI drop was significantly greater in HIV+ART0-<2yrs than in HIV+ART2–5yrs (p = 0.005). DID in BMI in HIV+ART0-<2yrs versus the reference was -5.21 (95% CI -7.53, -2.90; p = 0.001), and DID in HIV+ART2–5yrs versus reference was -1.35 (95% CI -2.89, 0.189; p = 0.086). DID in SBP in HIV+ART−vs HIV- DID was -7.55 mmHg (95% CI -13.2 to -1.90; p = 0.009). Conclusion: Short-term ART (0–<2 years) was associated with larger weight loss than either no ART or long-term ART. Once on ART for 2+ years, individuals ‘caught up’ on weight gain with the HIV- population. Our results showcase the importance of health system readiness to address the burgeoning double burden of disease in South Africa. [ABSTRACT FROM AUTHOR]

Background: South African HIV treatment guidelines call for patients who fail first-line antiretroviral therapy (ART) to be switched to second-line ART, yet logistical issues, clinician decisions and patient preferences make delay in switching to second-line likely. We explore the impact of delaying second-line ART after first-line treatment failure on rates of death and virologic failure. Methods: We include patients with documented virologic failure on first-line ART from an observational cohort of 9 South African clinics. We explored predictors of delayed second-line switch and used marginal structural models to analyze rates of death following first-line failure by categorical time to switch to second-line. Cox proportional hazards models were used to examine virologic failure on second-line ART among patients who switched to second-line. Results: 5895 patients failed first-line ART, and 63% switched to second-line. Among patients who switched, median time to switch was 3.4 months (IQR: 1.1–8.7 months). Longer time to switch was associated with higher CD4 counts, lower viral loads and more missed visits prior to first-line failure. Worse outcomes were associated with delay in second-line switch among patients with a peak CD4 count on first-line treatment ≤100 cells/mm3. Among these patients, marginal structural models showed increased risk of death (adjusted HR for switch in 6–12 months vs. 0–1.5 months = 1.47 (95% CI: 0.94–2.29), and Cox models showed increased rates of second-line virologic failure despite the presence of survivor bias (adjusted HR for switch in 3–6 months vs. 0–1.5 months = 2.13 (95% CI: 1.01–4.47)). Conclusions: Even small delays in switch to second-line ART were associated with increased death and second-line failure among patients with low CD4 counts on first-line. There is opportunity for healthcare providers to switch patients to second-line more quickly. [ABSTRACT FROM AUTHOR]

Background: Age-disparate partnerships are hypothesized to increase HIV-risk for young women. However, the evidence base remains mixed. Most studies have focused only on unprotected sex among women in the partnership. Consequently, little is known about other risky behaviours, such as transactional sex, alcohol use, and concurrency, as well as the behaviours of the men who partner with young women. We therefore examined differences in various sexual behaviours of both young women and their male partners by partnership age difference. Methods: We used nationally representative data from South Africa (2012) on partnerships reported by 16–24 year old black African women (n = 818) and by black African men in partnerships with 16–24 year old women (n = 985). We compared sexual behaviours in age-disparate partnerships and age-similar partnerships, using multiple logistic regression to control for potential confounders and to assess rural/urban differences. Results: Young women in age-disparate partnerships were more likely to report unprotected sex than young women in similar-aged partnerships (aOR:1.51; p = 0.014; 95%CI:1.09–2.11). Men in partnerships with young women were more likely to report unprotected sex (aOR:1.92; p<0.01; 95%CI:1.31–2.81), transactional sex (aOR:2.73; p<0.01; 95%CI:1.64–4.56), drinking alcohol before sex (aOR:1.60; p = 0.062; 95%CI:0.98–2.61), and concurrency (aOR:1.39; p = 0.097; 95%CI:0.94–2.07) when their partners were five or more years younger. The association between age-disparate partnerships and transactional sex (aOR:4.14; p<0.01; 95%CI: 2.03–8.46) and alcohol use (aOR:2.24; p<0.013; 95%CI:1.20–4.19) was only found in urban areas. Conclusions: Results provide evidence that young women’s age-disparate partnerships involve greater sexual risk, particularly through the risky behaviours of their male partners, with the risk amplified for young women in urban areas. [ABSTRACT FROM AUTHOR]

Background: WHO recommends a male circumcision (MC) prevalence rate higher than 80% to have a substantial impact on the HIV-AIDS epidemic in Eastern and Southern Africa. Orange Farm, a township in South Africa, has a free-for-service voluntary medical male circumcision (VMMC) clinic in operation since 2008. Following an intense campaign from 2008 to 2010, MC prevalence rate increased to 55.4% (ANRS-12126). Ongoing and past VMMC campaigns focused on youths, through school talks, and adults at a community level. The main objective of the study was to assess the change in MC prevalence rate among adults aged 18–19 and 18–49 years in the past 5 years. Methods: A cross-sectional survey (ANRS-12285) was conducted among a random sample of 522 adult men in 2015. MC status and characteristics of participants were collected through a genital examination and a face-to-face questionnaire. Results: MC prevalence rate among young adult men aged 18–19 years increased markedly from 61.2% (95%CI: 57.4% to 65.0%) in 2010 to 87.5% (76.0% to 94.6%) in 2015 (p<0.001). In the same period, among men aged 18–49 years, MC prevalence rate varied slightly from 55.4% (53.6% to 57.1%) to 56.7% (52.4% to 60.9%). In 2015, 84.9% (79.2% to 89.5%) of uncircumcised adult men reported that they were willing to be circumcised. However, we estimated that only 4.6% (11/237; 2.5% to 7.9%) of the uncircumcised men underwent circumcision in 2015, despite 117/185 (63.2%; 95%CI: 56.1% to 69.9%) who reported that they were definitely willing to become circumcised. Conclusions: In Orange Farm, VMMC campaigns were successful among the youth and led to a sufficiently high MC prevalence rate to have a substantial impact in the future on the HIV-AIDS epidemic. However, despite high acceptability and a free VMMC service, VMMC campaigns since 2010 have failed to increase MC prevalence rate among adults to above 80%. These campaigns should be revisited. [ABSTRACT FROM AUTHOR]

Background: In 2012, South Africa set a goal of circumcising 4.3 million men ages 15–49 by 2016. By the end of March 2014, 1.9 million men had received voluntary medical male circumcision (VMMC). In an effort to accelerate progress, South Africa undertook a modeling exercise to determine whether circumcising specific client age groups or geographic locations would be particularly impactful or cost-effective. Results will inform South Africa’s efforts to develop a national strategy and operational plan for VMMC. Methods and Findings: The study team populated the Decision Makers’ Program Planning Tool, Version 2.0 (DMPPT 2.0) with HIV incidence projections from the Spectrum/AIDS Impact Module (AIM), as well as national and provincial population and HIV prevalence estimates. We derived baseline circumcision rates from the 2012 South African National HIV Prevalence, Incidence and Behaviour Survey. The model showed that circumcising men ages 20–34 offers the most immediate impact on HIV incidence and requires the fewest circumcisions per HIV infection averted. The greatest impact over a 15-year period is achieved by circumcising men ages 15–24. When the model assumes a unit cost increase with client age, men ages 15–29 emerge as the most cost-effective group. When we assume a constant cost for all ages, the most cost-effective age range is 15–34 years. Geographically, the program is cost saving in all provinces; differences in the VMMC program’s cost-effectiveness across provinces were obscured by uncertainty in HIV incidence projections. Conclusion: The VMMC program’s impact and cost-effectiveness vary by age-targeting strategy. A strategy focusing on men ages 15–34 will maximize program benefits. However, because clients older than 25 access VMMC services at low rates, South Africa could consider promoting demand among men ages 25–34, without denying services to those in other age groups. Uncertainty in the provincial estimates makes them insufficient to support geographic targeting. [ABSTRACT FROM AUTHOR]

Background: The effect of the rapid scale-up of vertical antiretroviral treatment (ART) programs for HIV in sub-Saharan Africa on the overall health system is under intense debate. Some have argued that these programs have reduced access for people suffering from diseases unrelated to HIV because ART programs have drained human and physical resources from other parts of the health system; others have claimed that the investments through ART programs have strengthened the general health system and the population health impacts of ART have freed up health care capacity for the treatment of diseases that are not related to HIV. To establish the population-level impact of ART programs on health care utilization in the public-sector health system, we compared trends in health care utilization among HIV-infected people receiving and not receiving ART with HIV-uninfected people during a period of rapid ART scale-up. Methods and Findings: We used data from the Wellcome Trust Africa Centre for Population Health, which annually elicited information on health care utilization from all surveillance participants over the period 2009–2012 (N = 32,319). We determined trends in hospitalization, and public-sector and private-sector primary health care (PHC) clinic visits for HIV-infected and -uninfected people over a time period of rapid ART scale-up (2009–2012) in this community. We regressed health care utilization on HIV status and ART status in different calendar years, controlling for sex, age, and area of residence. The proportion of people who reported to have visited a public-sector primary health care (PHC) clinic in the last 6 months increased significantly over the period 2009–2012, for both HIV-infected people (from 59% to 67%; p<0.001), and HIV-uninfected people (from 41% to 47%; p<0.001). In contrast, the proportion of HIV-infected people visiting a private-sector PHC clinic declined from 22% to 12% (p<0.001) and hospitalization rates declined from 128 to 82 per 1000 PY (p<0.001). For HIV-uninfected people, the proportion visiting a private-sector PHC clinic declined from 16% to 9%, and hospitalization rates declined from 78 to 44 per 1000 PY (p<0.001). After controlling for potential confounding factors, all trends remained of similar magnitude and significance. Conclusions: Our results indicate that the ART scale-up in this high HIV prevalence community has shifted health care utilization from hospitals and private-sector primary care to public-sector primary care. Remarkably, this shift is observed for both HIV-infected and -uninfected populations, supporting and extending hypotheses of ‘therapeutic citizenship’ whereby HIV-infected patients receiving ART facilitate primary care access for family and community members. One explanation of our findings is that ART has improved the capacity or quality of primary care in this community and, as a consequence, increasingly met overall health care needs at the primary care level rather than at the secondary level. Future research needs to confirm this causal interpretation of our findings using qualitative work to understand causal mechanisms or quasi-experimental quantitative studies to increase the strength of causal inference. [ABSTRACT FROM AUTHOR]

Background: In high HIV prevalence settings, offering HIV testing may be a reasonable part of contact tracing of index tuberculosis (TB) patients. We evaluated the uptake of HIV counselling and testing (HCT) among household contacts of index TB patients and the proportion of newly diagnosed HIV-infected persons linked into care as part of a household TB contact tracing study. Methods: We recruited index TB patients at public health clinics in two South African provinces to obtain consent for household contact tracing. During scheduled household visits we offered TB symptom screening to all household members and HCT to individuals ≥14years of age. Factors associated with HCT uptake were investigated using a random effects logistic regression model. Results & Discussion: Out of 1,887 listed household members ≥14 years old, 984 (52%) were available during a household visit and offered HCT of which 108 (11%) self-reported being HIV infected and did not undergo HCT. Of the remaining 876, a total of 304 agreed to HCT (35%); 26 (8.6%) were newly diagnosed as HIV positive. In multivariable analysis, factors associated with uptake of HCT were prior testing (odds ratio 1.6; 95% confidence interval [CI]: 1.1–2.3) and another member in the household testing (odds ratio 2.4; 95% CI: 1.7–3.4). Within 3 months of testing HIV-positive, 35% reported initiating HIV care. Conclusion: HCT as a component of household TB contact tracing reached individuals without prior HIV testing, however uptake of HIV testing was poor. Strategies to improve HIV testing in household contacts should be evaluated. [ABSTRACT FROM AUTHOR]

Reaching universal HIV-status awareness is crucial to ensure all HIV-infected patients access antiretroviral treatment (ART) and achieve virological suppression. Opportunities for HIV testing could be enhanced by offering self-testing in populations that fear stigma and discrimination when accessing conventional HIV Counselling and Testing (HCT) in health care facilities. This qualitative research aims to examine the feasibility and acceptability of unsupervised oral self-testing for home use in an informal settlement of South Africa. Eleven in-depth interviews, two couple interviews, and two focus group discussions were conducted with seven healthcare workers and thirteen community members. Thematic analysis was done concurrently with data collection. Acceptability to offer home self-testing was demonstrated in this research. Home self-testing might help this population overcome barriers to accepting HCT; this was particularly expressed in the male and youth groups. Nevertheless, pilot interventions must provide evidence of potential harm related to home self-testing, intensify efforts to offer quality counselling, and ensure linkage to HIV/ART-care following a positive self-test result. [ABSTRACT FROM AUTHOR]

Near-perfect adherence to antiretroviral therapy (ART) is required to achieve the best possible prevention and treatment outcomes. Yet, there have been particular concerns about the challenges of adherence among patients living in resource-limited settings in sub-Saharan Africa. The primary objective of this study was to explore adherence in a low-resourced, rural community of high HIV prevalence in South Africa and to identify specific individual and structural factors that can either challenge or support adherence in this context. We applied digital stories as a qualitative research tool to gain insights into personal contexts of HIV and ART adherence. Through an inductive thematic analysis of twenty story texts, soundtracks and drawings, we explored experiences, understandings, and contexts of the participants and identified potential barriers and facilitators for those on lifelong treatment. We found that many of the stories reflected a growing confidence in the effectiveness of ART, which should be viewed as a key facilitator to successful adherence since this attitude can promote disclosure and boost access to social support. Nevertheless, stories also highlighted the complexity of the issues that individuals and households face as they deal with HIV and ART in this setting and it is clear that an overburdened local healthcare system has often struggled to meet the demands of a rapidly expanding epidemic and to provide the necessary medical and emotional support. Our analysis suggests several opportunities for further research and the design of novel health interventions to support optimal adherence. Firstly, future health promotion campaigns should encourage individuals to test together, or at least accompany each other for testing, to encourage social support from the outset. Additionally, home-based testing and ART club interventions might be recommended to make it easier for individuals to adhere to their treatment regimens and to provide a sense of support and solidarity. [ABSTRACT FROM AUTHOR]

South African doctors (n = 211) experienced in antiretroviral therapy use were asked via an online questionnaire about the WHO 2013 adult antiretroviral integrated guidelines, as well as clinical and personal issues, in three hypothetical scenarios: directing the Minister of Health, advising a family member requiring therapy amidst unstable antiretroviral supplies, and where doctors themselves were HIV-positive. Doctors (54%) favoured the 500 cells/μl WHO initiation threshold if advising the Minister; a third recommended retaining the 350 cells/μl threshold used at the time of the survey. However, they favoured a higher initiation threshold for their family member. Doctors were 4.9 fold more likely to initiate modern treatment, irrespective of their CD4 cell count, for themselves than for public-sector patients (95%CI odds ratio = 3.33–7.33; P<0.001, although lower if limited to stavudine-containing regimens. Doctors were equally concerned about stavudine-induced lactic acidosis and lipoatrophy. The majority (84%) would use WHO-recommended first-line therapy, with concerns split between tenofovir-induced nephrotoxicity (55%), and efavirenz central nervous system effects (29%). A majority (61%), if HIV-positive, would pay for a pre-initiation resistance test, use influenza-prophylaxis (85%), but not INH-prophylaxis (61%), and treat their cholesterol and blood pressure concerns conventionally (63% and 60%). Over 60% wanted viral loads and creatinine measured six monthly. A third felt CD4 monitoring only necessary if clinically indicated or if virological failure occurred. They would use barrier prevention (83%), but not recommend pre-exposure prophylaxis, if their sexual partner was HIV-negative (68%). A minority would be completely open about their HIV status, but the majority would disclose to their sexual partners, close family and friends. Respondents were overwhelmingly in favour of continued antiretrovirals after breastfeeding. In conclusion, doctors largely supported adult WHO guidelines as public policy, although would initiate treatment at higher CD4 counts for their family and themselves. Resistance to INH-prophylaxis is unexpected and warrants investigation. [ABSTRACT FROM AUTHOR]

Background: Human Immunodeficiency Virus (HIV) status disclosure has been shown to provide several benefits, both at the individual and societal levels. Aim: To determine risk factors associated with disclosing HIV status among antiretroviral therapy (ART) recipients in South Africa. Setting: A cross-sectional study on risk factors for viremia and drug resistance took place at two outpatient HIV clinics in 2008, at a large hospital located in Soweto, South Africa. Methods: We conducted a secondary data analysis on socio-economic characteristics and HIV status disclosure to anyone, focusing on gender differences. Descriptive and multivariable logistic regression analyses were performed to model the associations between risk factors and HIV status disclosure. Additionally, descriptive analysis was conducted to describe gender differences of HIV status disclosure to partner, parents, parents in law, partner, child, family, employer, and other. Patients: A total of 883 patients were interviewed. The majority were women (73%) with median age of 39 years. Results: Employed patients were less likely to disclose than unemployed (odds ratio (OR) 0.36; 95% confidence interval (CI) 0.1–1.0; p = 0.05)). Women with higher income were more likely to disclose (OR 3.25; 95% CI 0.90–11.7; p = 0.07) than women with lower income, while men with higher income were less likely (OR 0.20; 95% CI 0.02–1.99; p = 0.17) than men with lower income. Men were more likely than women to disclose to their partner (p<0.01), and to partner and family (p<0.01), women were more likely than men to disclose to child and family (p<0.01), to child, family and others (p = 0.01). Conclusion: Being employed imposed a risk factor for HIV status disclosure, additionally we found an interaction effect of gender and income on disclosure. Interventions designed to reduce workplace discrimination and gender-sensitive interventions promoting disclosure are strongly recommended. [ABSTRACT FROM AUTHOR]

Objective: To improve the treatment of MDR-TB and HIV co-infected patients, we investigated the relationship between health system performance and patient treatment outcomes at 4 decentralised MDR-TB sites. Methods: In this mixed methods case study which included prospective comparative data, we measured health system performance using a framework of domains comprising key health service components. Using Pearson Product Moment Correlation coefficients we quantified the direction and magnitude of the association between health system performance and MDR-TB treatment outcomes. Qualitative data from participant observation and interviews analysed using systematic text condensation (STC) complemented our quantitative findings. Findings: We found significant differences in treatment outcomes across the sites with successful outcomes varying from 72% at Site 1 to 52% at Site 4 (p<0.01). Health systems performance scores also varied considerably across the sites. Our findings suggest there is a correlation between treatment outcomes and overall health system performance which is significant (r = 0.99, p<0.01), with Site 1 having the highest number of successful treatment outcomes and the highest health system performance. Although the ‘integration’ domain, which measured integration of MDR-TB services into existing services appeared to have the strongest association with successful treatment outcomes (r = 0.99, p<0.01), qualitative data indicated that the ‘context’ domain influenced the other domains. Conclusion: We suggest that there is an association between treatment outcomes and health system performance. The chance of treatment success is greater if decentralised MDR-TB services are integrated into existing services. To optimise successful treatment outcomes, regular monitoring and support are needed at a district, facility and individual level to ensure the local context is supportive of new programmes and implementation is according to guidelines. [ABSTRACT FROM AUTHOR]