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Introduction: There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART). Methods: Completeness of death recording was estimated using a capture-recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil identity document (ID) numbers and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes. Results: After exclusions, 91,548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3-94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2-35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004-2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50 km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults). Conclusions: South Africa's civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously documented improvements in ART mortality over time may be biased if based only on data from patient records. Keywords: antiretroviral therapy; HIV; vital statistics registration; South Africa. To access the supplementary material to this article please see Supplementary Files under Article Tools online., Introduction Antiretroviral treatment (ART) has had a significant impact on AIDS mortality in developing countries [1-4]. However, most of what is known regarding mortality after ART initiation in developing countries [...]

Introduction: Although antiretroviral therapy (ART) reduces individual tuberculosis (TB) risk by two‐thirds, the population‐level impact remains uncertain. Cape Town reports high TB notification rates associated with endemic HIV. We examined population trends in TB notification rates during a 10‐year period of expanding ART. Methods: Annual Cape Town TB notifications were used as numerators and mid‐year Cape Town populations as denominators. HIV‐stratified population was calculated using overall HIV prevalence estimates from the Actuarial Society of South Africa AIDS and Demographic model. ART provision numbers from Western Cape government reports were used to calculate overall ART coverage. We calculated rates per 100,000 population over time, overall and stratified by HIV status. Rates per 100,000 total population were also calculated by ART use at treatment initiation. Absolute numbers of notifications were compared by age and sub‐district. Changes over time were described related to ART provision in the city as a whole (ART coverage) and by sub‐district (numbers on ART). Results: From 2003 to 2013, Cape Town's population grew from 3.1 to 3.7 million inhabitants, and estimated HIV prevalence increased from 3.6 to 5.2%. ART coverage increased from 0 to 63% in 2013. TB notification rates declined by 16% (95% confidence interval (CI), 14–17%) from a 2008 peak (851/100,000) to a 2013 nadir (713/100,000). Decreases were higher among the HIV‐positive (21% (95% CI, 19–23%)) than the HIV‐negative (9% (95% CI, 7–11%)) population. The number of HIV‐positive TB notifications decreased mainly among 0‐ to 4‐ and 20‐ to 34‐year‐olds. Total population rates on ART at TB treatment initiation increased over time but levelled off in 2013. Overall median CD4 counts increased from 146 cells/µl (interquartile range (IQR), 66, 264) to 178 cells/µl (IQR 75, 330; p Conclusions: HIV‐positive TB notification rates declined during a period of rapid scale‐up of ART. Nevertheless, both HIV‐positive and HIV‐negative TB notification rates remained very high. Decreases among HIV positives were likely blunted by TB remaining a major entry to the ART programme and occurring after delayed ART initiation., Introduction Antiretroviral therapy (ART) reduces the individual tuberculosis (TB) risk by two‐thirds [1]. This reduction is time‐ and CD4+ T‐cell (CD4) count‐dependent, however [2]. The TB risk is highest at [...]

Introduction: Routine viral load (VL) monitoring is utilized to assess antiretroviral therapy (ART) adherence and virologic failure, and it is currently scaled-up in many resource-constrained settings. The first routine VL is recommended as late as six months after ART initiation for early detection of sub-optimal adherence. We aimed to assess the optimal timing of first VL measurement after initiation of ART. Methods: This was a retrospective, cohort analysis of routine monitoring data of adults enrolled at three primary care clinics in Khayelitsha, Cape Town, between January 2002 and March 2009. Primary outcomes were virologic failure and switch to secondline ART comparing patients in whom first VL done was at three months (VL3M) and six months (VL6M) after ART initiation. Adjusted hazard ratios (aHR) were estimated using Cox proportional hazard models. Results: In total, 6264 patients were included for the time to virologic failure and 6269 for the time to switch to second-line ART analysis. Patients in the VL3M group had a 22% risk reduction of virologic failure (aHR 0.78, 95% CI 0.64-0.95; p = 0.016) and a 27% risk reduction of switch to second-line ART (aHR 0.73, 95% CI 0.58-0.92; p = 0.008) when compared to patients in the VL6M group. For each additional month of delay of the first VL measurement (up to nine months), the risk of virologic failure increased by 9% (aHR 1.09, 95% CI 1.02-1.15; p =0.008) and switch to second-line ART by 13% (aHR 1.13, 95% CI 1.05-1.21; p < 0.001). Conclusions: A first VL at three months rather than six months with targeted adherence interventions for patients with high VL may improve long-term virologic suppression and reduce switches to costly second-line ART. ART programmes should consider the first VL measurement at three months after ART initiation. Keywords: viral load; HIV; treatment switching; virologic failure., Introduction An estimated 32.6 million people live with HIV/AIDS worldwide and 11.7 million received antiretroviral treatment (ART) in middle- and low-income countries in 2013 [1]. Antiretroviral treatment is effective [2] [...]

Background Retreatment tuberculosis (TB) disease is common in high-prevalence settings. The risk of repeated episodes of recurrent TB is unknown. We calculated the rate of recurrent TB per subsequent episode by matching individual treatment episodes over a period of 13 years. Methods All recorded TB episodes in Cape Town between 2003 and 2016 were matched by probabilistic linkage of personal identifiers. Among individuals with a first episode notified in Cape Town and who completed their prior treatment successfully we estimated the recurrence rate stratified by subsequent episode and HIV status. We adjusted person-time to background mortality by age, sex, and HIV status. Results A total of 292 915 TB episodes among 263 848 individuals were included. The rate of recurrent TB was 16.4 per 1000 person-years (95% CI, 16.2–16.6), and increased per subsequent episode (8.4-fold increase, from 14.6 to 122.7 per 1000 from episode 2 to 6, respectively). These increases were similar stratified by HIV status. Rates among HIV positives were higher than among HIV negatives for episodes 2 and 3 (2- and 1.5-fold higher, respectively), and the same thereafter. Conclusions TB recurrence rates were high and increased per subsequent episode, independent of HIV status. This suggests that HIV infection is insufficient to explain the high burden of recurrence; it is more likely due to a high annual risk of infection combined with an increased risk of infection or progression to disease associated with a previous TB episode. The very high recurrence rates would justify increased TB surveillance of patients with >1 episode. [ABSTRACT FROM AUTHOR]

Abstract Background In most of the world, microbiologic diagnosis of tuberculosis (TB) is limited to microscopy. Recent guidelines recommend culture-based diagnosis where feasible. Methods In order to evaluate the relative and absolute incremental diagnostic yield of culture-based diagnosis in a high-incidence community in Cape Town, South Africa, subjects evaluated for suspected TB had their samples processed for microscopy and culture over a 21 month period. Results For 2537 suspect episodes with 2 smears and 2 cultures done, 20.0% (508) had at least one positive smear and 29.9% (760) had at least one positive culture. One culture yielded 1.8 times more cases as 1 smear (relative yield), or an increase of 12.0% (absolute yield). Based on the latter value, the number of cultures needed to diagnose (NND) one extra case of TB was 8, compared to 19 if second specimens were submitted for microscopy. Conclusion In a high-burden setting, the introduction of culture can markedly increase TB diagnosis over microscopy. The concept of number needed to diagnose can help in comparing incremental yield of diagnosis methods. Although new promising diagnostic molecular methods are being implemented, TB culture is still the gold standard.

Abstract Background In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009. Methods We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs. Results This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%. Conclusion This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic.

Abstract Background Changes in CD4 cell counts are poorly documented in individuals with low or moderate-level viremia while on antiretroviral treatment (ART) in resource-limited settings. We assessed the impact of on-going HIV-RNA replication on CD4 cell count slopes in patients treated with a first-line combination ART. Method Naïve patients on a first-line ART regimen with at least two measures of HIV-RNA available after ART initiation were included in the study. The relationships between mean CD4 cell count change and HIV-RNA at 6 and 12 months after ART initiation (M6 and M12) were assessed by linear mixed models adjusted for gender, age, clinical stage and year of starting ART. Results 3,338 patients were included (14 cohorts, 64% female) and the group had the following characteristics: a median follow-up time of 1.6 years, a median age of 34 years, and a median CD4 cell count at ART initiation of 107 cells/μL. All patients with suppressed HIV-RNA at M12 had a continuous increase in CD4 cell count up to 18 months after treatment initiation. By contrast, any degree of HIV-RNA replication both at M6 and M12 was associated with a flat or a decreasing CD4 cell count slope. Multivariable analysis using HIV-RNA thresholds of 10,000 and 5,000 copies confirmed the significant effect of HIV-RNA on CD4 cell counts both at M6 and M12. Conclusion In routinely monitored patients on an NNRTI-based first-line ART, on-going low-level HIV-RNA replication was associated with a poor immune outcome in patients who had detectable levels of the virus after one year of ART.

Abstract Background Interventions to promote prevention and earlier diagnosis of severe symptomatic hyperlactataemia (SHL) were implemented in the Western Cape provincial antiretroviral programme (South Africa) from 2004. Interventions included clinician education, point-of-care lactate meters, switch from stavudine to zidovudine in high risk patients and stavudine dose reduction. This study assessed trends in referral rate, severity at presentation and case fatality rate for severe SHL. Methods Retrospective study of severe SHL cases diagnosed at a referral facility from 1 January 2003 to 31 December 2008. Severe SHL was defined as patients with compatible symptoms and serum lactate ≥ 5 mmol/l attributable to antiretroviral therapy (ART). Cumulative ART exposure at referring ART clinics was used to calculate referral rates. Results There were 254 severe SHL cases. The referral rate (per thousand patient years [py] ART exposure) peaked in 2005 (20.4/1000py), but fell to 1.3/1000py by 2008 (incidence rate ratio [IRR] = 0.07, 95%CI 0.04-0.11). In 2003, 66.7% of cases presented with a standard bicarbonate (SHCO3) level Conclusions These trends suggest the interventions were associated with reduced referral, less severe metabolic acidosis at presentation and improved survival.

Abstract Background Antiretroviral therapy (ART) dramatically improves outcomes for children in Africa; however excellent adherence is required for treatment success. This study describes the utility of different measures of adherence in detecting lapses in infants and young children in Cape Town, South Africa. Methods In a prospective cohort of 122 HIV-infected children commenced on ART, adherence was measured monthly during the first year of treatment by medication return (MR) for both syrups and tablets/capsules. A questionnaire was administered to caregivers after 3 months of treatment to assess experience with giving medication and self-reported adherence. Viral and immune response to treatment were assessed at the end of one year and associations with measured adherence determined. Results Medication was returned for 115/122 (94%) children with median age (IQR) of 37 (16 – 61) months. Ninety-one (79%) children achieved annual average MR adherence ≥ 90%. This was an important covariate associated with viral suppression after adjustment for disease severity (OR = 5.5 [95%CI: 0.8–35.6], p = 0.075), however was not associated with immunological response to ART. By 3 months on ART, 13 (10%) children had deceased and 11 (10%) were lost to follow-up. Questionnaires were completed by 87/98 (90%) of caregivers of those who remained in care. Sensitivity of poor reported adherence (missing ≥ 1 dose in the previous 3 days) for MR adherence Conclusion Excellent adherence to ART is possible in African infants and young children and the relatively simple low technology measure of adherence by MR strongly predicts viral response. Better socio-economic status and more palatable regimens are associated with better adherence.

Abstract Background A major barrier to accessing free government-provided antiretroviral treatment (ART) in South Africa is the shortage of suitably skilled health professionals. Current South African guidelines recommend that only doctors should prescribe ART, even though most primary care is provided by nurses. We have developed an effective method of educational outreach to primary care nurses in South Africa. Evidence is needed as to whether primary care nurses, with suitable training and managerial support, can initiate and continue to prescribe and monitor ART in the majority of ART-eligible adults. Methods/design This is a protocol for a pragmatic cluster randomised trial to evaluate the effectiveness of a complex intervention based on and supporting nurse-led antiretroviral treatment (ART) for South African patients with HIV/AIDS, compared to current practice in which doctors are responsible for initiating ART and continuing prescribing. We will randomly allocate 31 primary care clinics in the Free State province to nurse-led or doctor-led ART. Two groups of patients aged 16 years and over will be included: a) 7400 registering with the programme with CD4 counts of ≤ 350 cells/mL (mainly to evaluate treatment initiation) and b) 4900 already receiving ART (to evaluate ongoing treatment and monitoring). The primary outcomes will be time to death (in the first group) and viral suppression (in the second group). Patients' survival, viral load and health status indicators will be measured at least 6-monthly for at least one year and up to 2 years, using an existing province-wide clinical database linked to the national death register. Trial registration Controlled Clinical Trials ISRCTN46836853

Background: High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Methods and Findings: Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 20012010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/ml in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count Conclusions: After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary., Introduction Antiretroviral therapy (ART) for HIV-infected patients has been routinely available in some Sub-Saharan African settings for more than a decade. Early analyses of treatment cohorts in this region focussed [...]

The provision of antiretroviral therapy (ART) in low and middle‐income countries is a chronic disease intervention of unprecedented magnitude and is the dominant health systems challenge for high‐burden countries, many of which rank among the poorest in the world. Substantial external investment, together with the requirement for service evolution to adapt to changing needs, including the constant shift to earlier ART initiation, makes outcome monitoring and reporting particularly important. However, there is growing concern at the inability of many high‐burden countries to report on the outcomes of patients who have been in care for various durations, or even the number of patients in care at a particular point in time. In many instances, countries can only report on the number of patients ever started on ART. Despite paper register systems coming under increasing strain, the evolution from paper directly to complex electronic medical record solutions is not viable in many contexts. Implementing a bridging solution, such as a simple offline electronic version of the paper register, can be a pragmatic alternative. This paper describes and recommends a three‐tiered monitoring approach in low‐ and middle‐income countries based on the experience implementing such a system in the Western Cape province of South Africa. A three‐tier approach allows Ministries of Health to strategically implement one of the tiers in each facility offering ART services. Each tier produces the same nationally required monthly enrolment and quarterly cohort reports so that outputs from the three tiers can be aggregated into a single database at any level of the health system. The choice of tier is based on context and resources at the time of implementation. As resources and infrastructure improve, more facilities will transition to the next highest and more technologically sophisticated tier. Implementing a three‐tier monitoring system at country level for pre‐antiretroviral wellness, ART, tuberculosis and mother and child health services can be an efficient approach to ensuring system‐wide harmonization and accurate monitoring of services, including long term retention in care, during the scale‐up of electronic monitoring solutions., Introduction The provision of antiretroviral therapy (ART) in low‐ and middle‐income countries is a chronic disease intervention of unprecedented magnitude [1–3] and is the dominant health systems challenge for countries [...]

Abstract Background Given the size of the HIV epidemic in South Africa and other developing countries, scaling up antiretroviral treatment (ART) represents one of the key public health challenges of the next decade. Appropriate priority setting and budgeting can be assisted by economic data on the costs and cost-effectiveness of ART. The objectives of this research were therefore to estimate HIV healthcare utilisation, the unit costs of HIV services and the cost per life year (LY) and quality adjusted life year (QALY) gained of HIV treatment interventions from a provider's perspective. Methods Data on service utilisation, outcomes and costs were collected in the Western Cape Province of South Africa. Utilisation of a full range of HIV healthcare services was estimated from 1,729 patients in the Khayelitsha cohort (1,146 No-ART patient-years, 2,229 ART patient-years) using a before and after study design. Full economic costs of HIV-related services were calculated and were complemented by appropriate secondary data. ART effects (deaths, therapy discontinuation and switching to second-line) were from the same 1,729 patients followed for a maximum of 4 years on ART. No-ART outcomes were estimated from a local natural history cohort. Health-related quality of life was assessed on a sub-sample of 95 patients. Markov modelling was used to calculate lifetime costs, LYs and QALYs and uncertainty was assessed through probabilistic sensitivity analysis on all utilisation and outcome variables. An alternative scenario was constructed to enhance generalizability. Results Discounted lifetime costs for No-ART and ART were US$2,743 and US$9,435 over 2 and 8 QALYs respectively. The incremental cost-effectiveness ratio through the use of ART versus No-ART was US$1,102 (95% CI 1,043-1,210) per QALY and US$984 (95% CI 913-1,078) per life year gained. In an alternative scenario where adjustments were made across cost, outcome and utilisation parameters, costs and outcomes were lower, but the ICER was similar. Conclusion Decisions to scale-up ART across sub-Saharan Africa have been made in the absence of incremental lifetime cost and cost-effectiveness data which seriously limits attempts to secure funds at the global level for HIV treatment or to set priorities at the country level. This article presents baseline cost-effectiveness data from one of the longest running public healthcare antiretroviral treatment programmes in Africa that could assist in enhancing efficient resource allocation and equitable access to HIV treatment.

Background: HIV diagnosis in South Africa is based on a point-of-care testing (PoCT) algorithm with paper-based record-keeping. Aggregated testing data are reported routinely. To facilitate improved HIV case-based surveillance, the Western Cape Province implemented a unique pilot intervention to digitise PoCT results, at an individual level, and generate an electronic register using the newly developed Provincial Health Data Centre (PHDC). We describe the intervention (phased) and present an evaluation of the operational feasibility of the intervention. We also offer implementation insights into establishing electronic capture of individual level testing data.Methods: Cross-sectional analyses were conducted on records of all patients attending a local Community Health Centre who had an HIV-PoCT during the study period. Data from the intervention were linked to the PHDC using a unique identifier and compared with aggregate data from the paper-based register. Correlation coefficients were calculated to quantify the correlation between the two monthly datasets. To support an understanding of the findings, the Department of Health project management team generated reflections on the implementation process, which were then grouped thematically into implementation lessons.Results: In total, 11,337 PoCT records were digitised (70% (7954) during Phase I; and 30% (3383) during Phase II). Linkage of forms to the PHDC was 96% in Phase I and 98% in Phase II. Comparison with aggregate data showed high correlation during Phase I, but notable divergence during Phase II. Divergence in Phase II was due to stringent data quality requirements and high clinical staff turnover. Factors supporting implementation success in Phase I included direct oversight of data capturing by a manager with clinical and operational insight. Implementation challenges included operational, health system, and high cost-related issues.Conclusions: We demonstrate that rapid digitisation of HIV PoCT data, without compromising currently collected aggregate data, is operationally feasible, and can contribute to person-level longitudinal HIV case-based surveillance. To take to scale, we will need to improve PoCT platforms and clerical and administrative systems. Although we highlight challenges, we demonstrate that electronic HIV testing registers can successfully replace manual registers and improve efforts to monitor and evaluate HIV testing strategies. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest that untreated human immunodeficiency virus (HIV) infection is associated with a reduced incidence of pregnancy, but studies of the effect of antiretroviral treatment (ART) on pregnancy incidence have been inconsistent.Methods: Routine data from health services in the Western Cape province of South Africa were linked to identify pregnancies during 2007-2017 and maternal HIV records. The time from the first (index) pregnancy outcome date to the next pregnancy was modeled using Cox proportional hazards models.Results: During 2007-2017, 1 042 647 pregnancies were recorded. In all age groups, pregnancy incidence rates were highest in women who had started ART, lower in HIV-negative women, and lowest in ART-naive HIV-positive women. In multivariable analysis, after controlling for the most recent CD4+ T-cell count, pregnancy incidence rates in HIV-positive women receiving ART were higher than those in untreated HIV-positive women (adjusted hazard ratio, 1.63; 95% confidence interval, 1.59-1.67) and those in HIV-negative women.Conclusion: Among women who have recently been pregnant, receipt of ART is associated with high rates of second pregnancy. Better integration of family planning into HIV care services is needed. [ABSTRACT FROM AUTHOR]

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

Efavirenz-based first-line regimens have been widely used for children ≥3 years of age starting antiretroviral therapy, despite possible resistance with prior exposure to non-nucleoside reverse transcriptase inhibitors for prevention of mother-to-child transmission (PMTCT). We used logistic regression to examine the association between PMTCT exposure and viral failure (VF) defined as two consecutive viral loads (VL)>1000 copies/ml between 6–18 months on ART. Children with previous nevirapine exposure for PMTCT were not at higher risk of VF compared to unexposed children (adjusted Odds Ratio (aOR): 0.79; 95% CI:0.56, 1.11). [ABSTRACT FROM AUTHOR]

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

Background: Achieving the 95-95-95 global targets by 2030, innovative HIV testing models, such as HIV self-testing are needed for people, who are unaware of their HIV status. We aimed to explore key informants, mountain climbing porters, and female bar workers' attitudes, perceived norms, and personal agency related to HIV self-testing.Methods: This was a formative qualitative study to inform the design of an HIV self-testing intervention in Northern Tanzania. Informed by the Integrated Behaviour Model, we conducted four focus group discussions, and 18 in-depth interviews with purposively selected participants. Data were analyzed using the framework method.Results: We recruited 55 participants. Most participants had positive attitudes towards HIVST, in that they anticipated positive consequences related to the introduction and uptake of HIVST. These included privacy and convenience, avoidance of long queues at health facilities, reduced counselor workload, and reduced indirect costs (given that transport to health facilities might not be required). Participants expressed the belief that significant people in their social environment, such as parents and peers, would approve their uptake of HIVST, and that they would accept HIVST. Additionally, features of HIVST that might facilitate its uptake were that it could be performed in private and would obviate visits to health facilities. Most participants were confident in their capacity to use HIVST kits, while a few were less confident about self-testing while alone. Strategies to maximize beliefs about personal agency and facilitate uptake included supplying the self-test kits in a way that was easy to access, and advocacy. Perceived potential constraints to the uptake of HIVST were the cost of buying the self-test kits, poverty, illiteracy, poor eyesight, fear of knowing one's HIV status, lack of policy/ guidelines for HIVST, and the absence of strategies for linkage to HIV care, treatment, and support.Conclusions: The findings suggest that HIVST may be feasible to implement in this study setting, with the majority of participants reporting positive attitudes, supportive perceived norms, and self-efficacy. Hence, future HIVST interventions should address the negative beliefs, and perceived barriers towards HIVST to increase HIV testing among the target population in Northern Tanzania. [ABSTRACT FROM AUTHOR]

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

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Background: More than 40% of adults in Sub-Saharan Africa are unaware of their HIV status. HIV self-testing (HIVST) is a novel approach with a potential to increase uptake of HIV testing and linkage to care for people who test HIV positive. We explored HIV stakeholder's perceptions about factors that enable or deter the uptake of HIV self-testing and experiences of self-testing of adult users in Africa.Methods: This systematic review of qualitative evidence included articles on qualitative studies published or made available between January 1998 to February 2018 on perspectives of key stakeholders, including HIV policymakers, HIV experts, health care providers, and adult men and women (18 years and above) about factors that enable or deter the uptake of HIV self-testing and experiences of self-testing among adult users. We searched CINAHL, MEDLINE in Pubmed, EMBASE, AJOL, PsycINFO, Social Science Citation Index (SSCI), and Web of Science for articles in English on HIVST with qualitative data from different African countries.Results: In total, 258 papers were retrieved, and only nine (9) studies conducted in 5 African countries were eligible and included in this synthesis. Perceived facilitators of the uptake of HIVST were autonomy and self-empowerment, privacy, confidentiality, convenience, opportunity to test, including couples HIV testing, and ease of use. The perceived barriers included the cost of buying self-test kits, perceived unreliability of test results, low literacy, fear and anxiety of a positive test result, and potential psychological and social harms. HIV stakeholder's concerns about HIVST included human right issues, lack of linkage to care, lack of face-to-face counseling, lack of regulatory and quality assurance systems, and quality of self-test kits. Actual HIVST users expressed preference of oral-fluid self-testing because of ease of use, and that it is less invasive and painless compared to finger-stick/whole blood-based HIV tests. Lack of clear instructions on how to use self-test kits, and existing different products of HIVST increases rates of user errors.Conclusions: Overcoming factors that may deter HIV testing, and HIVST, in particular, is complex and challenging, but it has important implications for HIV stakeholders, HIVST users, and public health in general. Research is warranted to explore the actual practices related to HIVST among different populations in Africa. [ABSTRACT FROM AUTHOR]

Background: Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults. Methods and Findings: Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV- positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2-30.2) at age 20 y and 10.1 y (95% CI: 9.3-10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0-39.7) and 14.4 y (95% CI: 13.3-15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1-46.0) if her baseline CD4 count was [greater than or equal to] 200 cells/µl, compared to 29.5 y (95% CI: 26.2-33.0) if her baseline CD4 count was Conclusions: South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well., Introduction Estimates of life expectancies of HIV-infected individuals are important in providing information to patients about their long-term prognosis, in projecting the future costs of HIV-related care, and in forecasting [...]