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Introduction: The best method to measure adherence to antiretroviral therapy (ART) in resource-limited settings has not yet been established, particularly among adolescents and young adults (AYAs). The use of mobile technology may address the need for standardized tools in measuring adherence in this often marginalized population. Methods: We conducted a cross-sectional validation study among AYAs (18– 35 years) attending a South African HIV clinic between 07/2015-09/2017. We determine the diagnostic accuracy of two modes of delivering an adherence questionnaire (self-administered electronic vs interviewer-administered paper-adherence questionnaire) comprising two self-reported adherence tools (South African National Department of Health (NDoH) adherence questionnaire and the Simplified Medication Adherence Questionnaire (SMAQ)) to identify poor adherence compared to; 1) a detectable viral load (≥ 1000 copies/mL) and 2) a sub-optimal concentration of efavirenz (EFV) (EFV ≤ 1.00 μg/mL) measured by therapeutic drug monitoring (TDM). Results: Of 278 included participants, 7.1% and 7.3% completing the electronic- and paper-questionnaires had a detectable viral load, while 14.7% and 16.5% had a sub-optimal concentration of EFV, respectively. According to viral load monitoring, the electronic-adherence questionnaire had a higher sensitivity (Se) in detecting poor adherence than the paper-based version across the NDoH adherence questionnaire (Se: 63.6% vs 33.3%) and SMAQ (Se: 90.9% vs 66.7%). In contrast, when using blood drug concentration (EFV ≤ 1.00 μg/mL), the paper-adherence questionnaire produced a higher sensitivity across both adherence tools; namely the NDoH adherence questionnaire (Se: 50.0% vs 38.1%) and SMAQ (Se: 75.0% vs 57.1%). Conclusion: When using more accurate real-time measures of poor adherence such as TDM in this young adult population, we observe a higher sensitivity of an interviewer-administered paper-adherence questionnaire than an identical set of self-administered adherence questions on an electronic tablet. An interviewer-administered questionnaire may elicit more accurate responses from participants through a sense of increased accountability when engaging with health care workers. [ABSTRACT FROM AUTHOR]

Background: In South Africa, roughly half of the drug-resistant TB cases diagnosed are reported to have been started on treatment. We determined the proportion of persons diagnosed with rifampicin resistant (RR-) TB who initiated treatment in Johannesburg after the introduction of decentralized RR-TB care in 2011. Methods: We retrospectively matched adult patients diagnosed with laboratory-confirmed RR-TB in Johannesburg from 07/2011-06/2012 with records of patients initiating RR-TB treatment at one of the city’s four public sector treatment sites (one centralized, three decentralized). Patients were followed from date of diagnosis until the earliest of RR-TB treatment initiation, death, or 6 months’ follow-up. We report diagnostic methods and outcomes, proportions initiating treatment, and median time from diagnosis to treatment initiation. Results: 594 patients were enrolled (median age 34 (IQR 29–42), 287 (48.3%) female). Diagnosis was by GenoType MTBDRplus (Hain-Life-Science) line probe assay (LPA) (281, 47.3%), Xpert MTB/RIF (Cepheid) (258, 43.4%), or phenotypic drug susceptibility testing (DST) (30, 5.1%) with 25 (4.2%) missing a diagnosis method. 320 patients (53.8%) had multi-drug resistant TB, 158 (26.6%) rifampicin resistant TB by Xpert MTB/RIF, 102 (17.2%) rifampicin mono-resistance, and 14 (2.4%) extensively drug-resistant TB. 256/594 (43.0%) patients initiated treatment, representing 70.7% of those who were referred for treatment (362/594). 338/594 patients (57.0%) did not initiate treatment, including 104 (17.5%) who died before treatment was started. The median time from sputum collection to treatment initiation was 33 days (IQR 12–52). Conclusion: Despite decentralized RR-TB treatment, fewer than half the patients diagnosed in Johannesburg initiated appropriate treatment. Offering treatment at decentralized sites alone is not sufficient; improvements in linking patients diagnosed with RR-TB to effective treatment is essential. [ABSTRACT FROM AUTHOR]

Objectives: To report predictors of outcomes of second-line ART for HIV treatment in a resource-limited setting.Methods: All adult ART-naïve patients who initiated standard first-line treatment between April 2004 and February 2012 at four public-sector health facilities in Johannesburg, South Africa, experienced virologic failure and initiated standard second-line therapy were included. We assessed predictors of attrition (death and loss to follow-up [≥3 months late for a scheduled visit]) using Cox proportional hazards regression and predictors of virologic suppression (viral load <400 copies/ml ≥3 months after switch) using modified Poisson regression with robust error estimation at 1 year and ever after second-line ART initiation.Results: A total of 1236 patients switched to second-line treatment in a median (IQR) of 1.9 (0.9-4.6) months after first-line virologic failure. Approximately 13% and 45% of patients were no longer in care at 1 year and at the end of follow-up, respectively. Patients with low CD4 counts (<50 vs. ≥200, aHR: 1.85; 95% CI: 1.03-3.32) at second-line switch were at greater risk for attrition by the end of follow-up. About 75% of patients suppressed by 1 year, and 85% had ever suppressed by the end of follow-up.Conclusions: Patients with poor immune status at switch to second-line ART were at greater risk of attrition and were less likely to suppress. Additional adherence support after switch may improve outcomes. [ABSTRACT FROM AUTHOR]

Peripheral neuropathy (PN) is associated with advanced HIV disease and may be a complication of antiretroviral therapy (ART) or anti-tuberculosis (TB) drugs, specifically isoniazid (INH). The effect of non-ART-drug-related PN on treatment outcomes is yet to be determined. We analysed prospectively collected cohort data for HIV-infected ART-naive adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa from June 2004 to June 2009. Patients who presented with signs and symptoms of numbness or dysesthesia prior to initiation of ART were defined as having PN. Cox proportional hazard models were used to estimate the effect of PN alone (HIV-related PN) or PN with a history of INH use (TB-related PN) on mortality, lost to follow-up (LTFU), persistent and recurrent PN by 12 months of follow-up. Of the 9,399 patients initiating ART, 3.9 % had HIV-related PN while a further 1.8 % had TB-related PN. Patients with PN did not have a significantly higher risk of mortality compared to those without PN (hazard ratio (HR) 1.17 95 % CI 0.92-1.49). Patients with TB-related PN were less likely to be LTFU by 12 months (HR 0.65 95 % CI 0.44-0.97) compared to those without PN. Patients with HIV-related PN were at increased risk of persistent PN at 3 months post-ART initiation. Patients with HIV-related PN had a similar risk of recurrent PN compared to those with TB-related PN (HR 1.28 95 % CI 0.72-2.27). We demonstrate that patients with PN at initiation of ART present with advanced HIV disease. Completion of TB treatment may reduce the risk of persistent PN in patients with TB-related PN. Use of HIV drugs, even neurotoxic ones, may overall limit neuropathy. [ABSTRACT FROM AUTHOR]

Background: To assess the quality and completeness of treatment and outcome data in the electronic tuberculosis (TB) and antiretroviral treatment (ART) registers in drug-resistant (DR-) TB patients at three treatment facilities in South Africa.Methods: We did a retrospective cohort study using routinely-collected data from DR-TB registers of rifampicin resistant adults (≥18 years old), on ART, initiating DR-TB treatment between January 2012 and December 2013. We linked patient information from the DR-TB register to the ART register using patient identifiers and an algorithm based on string edit distance and date of birth. We describe data gaps and discrepancies found.Results: Overall, 2852 DR-TB patients met our inclusion criteria based on the DR-TB register data, and of these, 1685 (59%) could be matched to the ART registers. An additional 253 patients from the DR-TB registers were found in the ART registers, having initiated ART, despite the DR-TB register indicating that they were not on ART (or this data was missing). 11% of matched patients did not have TB treatment status recorded in the ART register despite being recorded as being on TB treatment in the DR-TB register, and 78% did not have an ART start date recorded in DR-TB register despite being on ART treatment as per the ART register. 11% of matched patients had a death recorded in one register but not the other, and of those with death recorded in both, 15% of dates differed by > 1 month.Conclusions: The underreporting of death and the lack of ART or TB status in the electronic DR-TB and ART registers could negatively impact monitoring efforts by downplaying the state of the TB/HIV epidemic. Improved recording of these data sources, and data integration across systems, could improve the accuracy of reporting for the national HIV/ART and TB programs. [ABSTRACT FROM AUTHOR]

Background: Adverse events (AEs) are common during treatment of drug-resistant tuberculosis (DR-TB). Little is known about the health-related quality of life (HRQoL) of patients receiving treatment for DR-TB or the effect of AEs on HRQoL.Methods: We conducted a cross-sectional study among adult patients with laboratory-confirmed rifampicin resistant tuberculosis (TB) on DR-TB treatment at a public-sector outpatient DR-TB clinic in Johannesburg, South Africa between 02/2015-01/2018. Data on HRQoL using the Medical Outcomes Short Form-36 (SF-36) questionnaire and self-reported AEs were collected by trained interviewers through face-to-face interviews. We report averages for the eight major domains and mental (MCS) and physical health (PCS) component summary scores, stratified by whether AEs were reported in the last four weeks. For comparative purposes, we enrolled two other patient groups and included data on a separate group of healthy adults.Results: We enrolled 149 DR-TB patients (median age 36 years IQR 29-43, 55% male, 77.9% HIV-positive, 81% on ART, 61.8% on a standard long-course regimen and 44.3% on DR-TB treatment for less than 6 months). 58/149 (38.9%) patients reported a total of 122 AEs in the preceding 4 weeks, of these the most common were joint pain (n = 22), peripheral neuropathy (n = 16), hearing loss (n = 15), nausea and vomiting (n = 12) and dizziness or vertigo (n = 11). SF-36 domains and summary scores (MCS and PCS) were lower in those who reported an AE compared to those who did not, and both were lower than healthy adults. Compared to those who did not report an AE, patients who reported AEs were more likely to have a low MCS (aRR 2.24 95% CI 1.53-3.27) and PCS (aRR 1.52 95% CI 1.07-2.18) summary score. HRQoL was lower among those on DR-TB treatment for 6 months or less.Conclusion: Results show that DR-TB had a substantial impact on patients' quality of life, but that AEs during the early months on treatment may be responsible for reducing HRQoL even further. Our findings highlight the negative effects of injectable agents on HRQoL. Patients require an integrative patient-centered approach to deal with DR-TB and HIV and the potential overlapping toxicities which may be worsened by concurrent treatment. [ABSTRACT FROM AUTHOR]

Background: While efficacy data exist, there are limited data on the outcomes of patients on third-line antiretroviral therapy (ART) in sub-Saharan Africa in actual practice. Being able to identify predictors of switch to third-line ART will be essential for planning for future need. We identify predictors of switch to third-line ART among patients with significant viraemia on a protease inhibitor (PI)-based second-line ART regimen. Additionally, we describe characteristics of all patients on third-line at a large public sector HIV clinic and present their early outcomes. Methods: Retrospective analysis of adults (≥ 18 years) on a PI-based second-line ART regimen at Themba Lethu Clinic, Johannesburg, South Africa as of 01 August 2012, when third-line treatment became available in South Africa, with significant viraemia on second-line ART (defined as at least one viral load ≥ 1000 copies/mL on second-line ART after 01 August 2012) to identify predictors of switch to third-line (determined by genotype resistance testing). Third-line ART was defined as a regimen containing etravirine, raltegravir or ritonavir boosted darunavir, between August 2012 and January 2016. To assess predictors of switch to third-line ART we used Cox proportional hazards regression among those with significant viraemia on second-line ART after 01 August 2012. Then among all patients on third-line ART we describe viral load suppression, defined as a viral load < 400 copies/mL, after starting third-line ART. Results: Among 719 patients in care and on second-line ART as of August 2012 (with at least one viral load ≥ 1000 copies/mL after 01 August 2012), 36 (5.0% over a median time of 54 months) switched to third-line. Time on second-line therapy (≥ 96 vs. < 96 weeks) (adjusted Hazard Ratio (aHR): 2.53 95% CI 1.03–6.22) and never reaching virologic suppression while on second-line ART (aHR: 3.37 95% CI 1.47–7.73) were identified as predictors of switch. In a separate cohort of patients on third-line ART, 78.3% (47/60) and 83.3% (35/42) of those in care and with a viral load suppressed their viral load at 6 and 12 months, respectively. Conclusions: Our results show that the need for third-line is low (5%), but that patients’ who switch to third-line ART have good early treatment outcomes and are able to suppress their viral load. Adherence counselling and resistance testing should be prioritized for patients that are at risk of failure, in particular those who never suppress on second-line and those who have been on PI-based regimen for extended periods. [ABSTRACT FROM AUTHOR]

Background: Effective integration of home visit interventions focused on early childhood development into existing service platforms is important for expanding access in low- and middle-income countries (LMICs). We designed and evaluated a home visit intervention integrated into community health worker (CHW) operations in South Africa. Methods and findings: We conducted a cluster-randomized controlled trial in Limpopo Province, South Africa. CHWs operating in ward-based outreach teams (WBOTs; clusters) and caregiver–child dyads they served were randomized to the intervention or control group. Group assignment was masked from all data collectors. Dyads were eligible if they resided within a participating CHW catchment area, the caregiver was at least 18 years old, and the child was born after December 15, 2017. Intervention CHWs were trained on a job aid that included content on child health, nutrition, developmental milestones, and encouragement to engage in developmentally appropriate play-based activities, for use during regular monthly home visits with caregivers of children under 2 years of age. Control CHWs provided the local standard of care. Household surveys were administered to the full study sample at baseline and endline. Data were collected on household demographics and assets; caregiver engagement; and child diet, anthropometry, and development scores. In a subsample of children, electroencephalography (EEG) and eye-tracking measures of neural function were assessed at a lab concurrent with endline and at 2 interim time points. Primary outcomes were as follows: height-for-age z-scores (HAZs) and stunting; child development scores measured using the Malawi Developmental Assessment Tool (MDAT); EEG absolute gamma and total power; relative EEG gamma power; and saccadic reaction time (SRT)—an eye-tracking measure of visual processing speed. In the main analysis, unadjusted and adjusted impacts were estimated using intention-to-treat analysis. Adjusted models included a set of demographic covariates measured at baseline. On September 1, 2017, we randomly assigned 51 clusters to intervention (26 clusters, 607 caregiver–child dyads) or control (25 clusters, 488 caregiver–child dyads). At endline (last assessment June 11, 2021), 432 dyads (71%) in 26 clusters remained in the intervention group, and 332 dyads (68%) in 25 clusters remained in the control group. In total, 316 dyads attended the first lab visit, 316 dyads the second lab visit, and 284 dyads the third lab visit. In adjusted models, the intervention had no significant impact on HAZ (adjusted mean difference (aMD) 0.11 [95% confidence interval (CI): −0.07, 0.30]; p = 0.220) or stunting (adjusted odds ratio (aOR) 0.63 [0.32, 1.25]; p = 0.184), nor did the intervention significantly impact gross motor skills (aMD 0.04 [−0.15, 0.24]; p = 0.656), fine motor skills (aMD −0.04 [−0.19, 0.11]; p = 0.610), language skills (aMD −0.02 [−0.18, 0.14]; p = 0.820), or social–emotional skills (aMD −0.02 [−0.20, 0.16]; p = 0.816). In the lab subsample, the intervention had a significant impact on SRT (aMD −7.13 [−12.69, −1.58]; p = 0.012), absolute EEG gamma power (aMD −0.14 [−0.24, −0.04]; p = 0.005), and total EEG power (aMD −0.15 [−0.23, −0.08]; p < 0.001), and no significant impact on relative gamma power (aMD 0.02 [−0.78, 0.83]; p = 0.959). While the effect on SRT was observed at the first 2 lab visits, it was no longer present at the third visit, which coincided with the overall endline assessment. At the end of the first year of the intervention period, 43% of CHWs adhered to monthly home visits. Due to the COVID-19 pandemic, we were not able to assess outcomes until 1 year after the end of the intervention period. Conclusions: While the home visit intervention did not significantly impact linear growth or skills, we found significant improvement in SRT. This study contributes to a growing literature documenting the positive effects of home visit interventions on child development in LMICs. This study also demonstrates the feasibility of collecting markers of neural function like EEG power and SRT in low-resource settings. Trial registration: PACTR 201710002683810; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=2683; South African Clinical Trials Registry, SANCTR 4407 Peter Rockers and colleagues design and evaluate a home visit intervention integrated into community health worker operations in South Africa. Author summary: Why was this study done?: Prior studies have demonstrated that home visit interventions delivered by community health workers (CHWs) can have a positive impact on child development. We integrated a home visit intervention into existing CHW operations in South Africa to generate evidence useful for local decision-making. A key innovation of this study was the inclusion of 2 markers of neural function as primary outcomes: electroencephalography (EEG) power and saccadic reaction time (SRT), an eye-tracking measure of visual processing speed. What did the researchers do and find?: We conducted a cluster-randomized controlled trial in rural South Africa. Intervention CHWs were trained on a job aid that included content focused on improving child development, for use during regular home visits with caregivers and young children. Control CHWs provided the local standard of care. We enrolled 607 caregiver–child dyads in 26 intervention clusters and 432 dyads in 25 control clusters at the start of the study. At endline, we assessed 432 intervention dyads (71%) and 332 control dyads (68%) to evaluate impact on child development outcomes. The home visit intervention decreased child SRT by 7 milliseconds, indicating improved neural function, but did not significantly impact linear growth or skills. What do these findings mean?: Our findings contribute important new evidence to a growing literature documenting the positive effects of home visit interventions on child development. Collecting markers of neural function in low-resource settings is feasible. [ABSTRACT FROM AUTHOR]

Adolescents experience disproportionately high rates of poor ART outcomes compared to adults despite prolonged use of antiretroviral therapy in Southern African treatment programs, presenting a significant challenge to national attempts to meet the UNAIDS 90-90-90 targets for 2020. This cohort study among adolescents aged 12–20 years accessing ART care at two urban public-sector clinics in Johannesburg between September and November 2013 aimed to identify factors potentially associated with poor attendance at clinic visits. Patients were followed up through routine medical records to identify missed visits (failing to attend clinic within 30 days of scheduled visit date) up to 2 years after enrolment. We enrolled 126 adolescents on ART for a median of 6.3 years (IQR: 2.7–8.4). A total of 47 (38%) adolescents missed a scheduled visit within 24 months of enrolment. Older adolescents (18–20 years) were more likely to miss a visit compared to adolescents aged 12–14 years (risk ratio (RR) = 1.72; 95% CI: 1.00–2.95). Those who were identified to have difficulty in taking medication (RR = 1.57; 95% CI: 1.13–2.18) as a barrier to care were more likely to miss a visit compared to adolescents who did not. Awareness of treatment fatigue, challenges to taking ART, and caregiver difficulties is important when considering interventions to improve treatment outcomes among adolescents. [ABSTRACT FROM AUTHOR]

Summary Background The South African Electronic Drug-Resistant Tuberculosis Register (EDRweb) is the national database of registered drug-resistant tuberculosis (DR-TB) cases. Methods This study was a retrospective, de-identified secondary analysis of EDRweb patients initiating treatment for rifampicin-resistant TB (January 2009 to September 2011). The relative risks of death and treatment success were estimated using modified Poisson regression with robust error estimation. Results Seventeen thousand six hundred and ninety-seven cases of DR-TB were registered and met the inclusion criteria; 52.0% ( n = 9207) were male and the median age was 35 years (interquartile range 27–43 years). Of the 9419 cases with HIV infection (53.2%), 7157 (76.0%) were on antiretroviral therapy. Most had undergone previous TB treatment (76.5%, n = 13 531). Multidrug-resistant TB was the most common diagnosis, at 80.6% ( n = 14 272). No treatment outcome was available for 6934 patients (39.2%). For patients with outcomes, 4227 (39.4%) were successfully treated, 2987 (27.8%) died, 2533 (23.7%) were lost to follow-up, and 996 (9.3%) failed. Second-line drug resistance was the strongest predictor of death during DR-TB treatment; extensively drug-resistant TB patients were more likely to have died during treatment (adjusted relative risk 2.63, 95% confidence interval 2.45–2.84). Conclusions Testing for second-line drug resistance at initiation of DR-TB treatment can identify patients most at risk of treatment failure and death and most in need of individualized treatment. [ABSTRACT FROM AUTHOR]

Simplified drug regimens may improve retention in care for persons with chronic diseases. In April 2013, South Africa adopted a once-daily single-pill human immunodeficiency virus (HIV) treatment regimen as the standard of care, replacing a multiple-pill regimen. Because the regimens had similar biological efficacy, the shift to single-pill therapy offered a real-world test of the impact of simplified drug-delivery mechanisms on patient behavior. Using a quasi-experimental regression discontinuity design, we assessed retention in care among patients starting HIV treatment just before and just after the guideline change. The study included 4,484 patients starting treatment at a large public sector clinic in Johannesburg, South Africa. The share of patients prescribed a single-pill regimen increased by over 40 percentage points between March and April 2013. Initiating treatment after the policy change was associated with 11.7–percentage-points' higher retention at 12 months (95% confidence interval: −2.2, 29.4). Findings were robust to different measures of retention, different bandwidths, and different statistical models. Patients starting treatment early in HIV infection—a key population in the test-and-treat era—experienced the greatest improvements in retention from single-pill regimens. [ABSTRACT FROM AUTHOR]

Background: Multi-drug resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) in pregnant women is a cause for concern globally; few data have described the safety of second-line anti-TB medications during pregnancy. We aim to describe TB treatment and pregnancy outcomes among pregnant women receiving second-line anti-tuberculosis treatment for MDR/RR-TB in Johannesburg, South Africa.Methods: We conducted a retrospective record review of pregnant women (≥ 18 years) who received treatment for MDR/RR-TB between 01/2010-08/2016 at three outpatient treatment sites in Johannesburg, South Africa. Demographic, treatment and pregnancy outcome data were collected from available medical records. Preterm birth (< 37 weeks), and miscarriage were categorized as adverse pregnancy outcomes.Results: Out of 720 women of child-bearing age who received MDR/RR-TB treatment at the three study sites, 35 (4.4%) pregnancies were identified. Overall, 68.7% (24/35) were HIV infected, 83.3% (20/24) were on antiretroviral therapy (ART). Most women, 88.6% (31/35), were pregnant at the time of MDR/RR-TB diagnosis and four women became pregnant during treatment. Pregnancy outcomes were available for 20/35 (57.1%) women, which included 15 live births (11 occurred prior to 37 weeks), 1 neonatal death, 1 miscarriage and 3 pregnancy terminations. Overall, 13/20 (65.0%) women with known pregnancy outcomes had an adverse pregnancy outcome. Of the 28 women with known TB treatment outcomes 17 (60.7%) completed treatment successfully (4 were cured and 13 completed treatment), 3 (10.7%) died and 8 (28.6%) were lost-to-follow-up.Conclusions: Pregnant women with MDR/RR-TB suffer from high rates of adverse pregnancy outcomes and about 60% achieve a successful TB treatment outcome. These vulnerable patients require close monitoring and coordinated obstetric, HIV and TB care. [ABSTRACT FROM AUTHOR]

Background: Young people face many barriers to accessing appropriate health care services including screening for HIV and tuberculosis (TB). The study aimed to identify perceived barriers to the uptake of health services among young adults entering the tertiary education system in South Africa. Methods: We conducted a cross-sectional study among first-year students aged 18–25 years, registered at one of three universities in Johannesburg, South Africa, in 2017. Participants completed a self-administered paper-based questionnaire. We describe perceived barriers to accessing health services, stratified by gender and recent engagement in TB or HIV services, together with sources of information about HIV and TB. Results: Seven hundred and ninety-two (792) students were included in the study of which 54.8% were female. Perceived barriers to accessing services included long waiting time (n = 342,43.2%), attitude of health workers (n = 263,33.2%), lack of sufficient information/poor health literacy (n = 148,18.7%), and inability to leave/stay away from studies (n = 137,17.3%). Among participants who tested for HIV in the past 6 months (n = 400, 50.5%), waiting time and attitude of health care workers were perceived as barriers to accessing services. Compared to males, females were more likely to view attitudes of health workers (40.3% vs. 25.0%; p = 0.001) and inability to leave/stay away from studies (20.5% vs.13.4%; p = 0.025) as potential barriers. While just over half of the students (50.5%; 400/792) in this study had accessed health services in the past 6 months, very few (15.0%) opted to use campus health services, and even less (5%) reported receiving information about HIV and TB from the university itself. Conclusion: Despite perceived barriers to accessing HIV and TB services off campus, fewer than one in five students starting out at university opted to use campus health services. Campus health services could address many of the barriers unique to university students. [ABSTRACT FROM AUTHOR]

Objective To investigate cost changes for health systems and participants, resulting from switching to short treatment regimens for multidrug-resistant (MDR) tuberculosis. Methods We compared the costs to health systems and participants of long (20 to 22 months) and short (9 to 11 months) MDR tuberculosis regimens in Ethiopia and South Africa. Cost data were collected from participants in the STREAM phase-III randomized controlled trial and we estimated health-system costs using bottom-up and top-down approaches. A cost--effectiveness analysis was performed by calculating the incremental cost per unfavourable outcome avoided. Findings Health-care costs per participant in South Africa were 8340.7 United States dollars (US$) with the long and US$ 6618.0 with the short regimen; in Ethiopia, they were US$ 6096.6 and US$ 4552.3, respectively. The largest component of the saving was medication costs in South Africa (67%; US$ 1157.0 of total US$ 1722.8) and social support costs in Ethiopia (35%, US$ 545.2 of total US$ 1544.3). In Ethiopia, trial participants on the short regimen reported lower expenditure for supplementary food (mean reduction per participant: US$ 225.5) and increased working hours (i.e. 667 additional hours over 132 weeks). The probability that the short regimen was cost--effective was greater than 95% when the value placed on avoiding an unfavourable outcome was less than US$ 19 000 in Ethiopia and less than US$ 14 500 in South Africa. Conclusion The short MDR tuberculosis treatment regimen was associated with a substantial reduction in health-system costs and a lower financial burden for participants. [ABSTRACT FROM AUTHOR]

Background: Drug resistant-tuberculosis is a growing burden on the South African health care budget. In response the National Department of Health implemented two important strategies in 2011; universal access to drug-sensitivity testing for rifampicin with Xpert MTB/RIF as the first-line diagnostic test for TB; and decentralization of treatment for RR/MDR-TB to improve access and reduce costs of treatment. Objective: Estimate the costs by treatment outcome of decentralized care for rifampicin and multi-drug resistant tuberculosis under routine conditions. The study was set at an outpatient drug resistant-tuberculosis treatment facility at a public academic hospital in Johannesburg, South Africa. During the study period 18–24 month long course treatment was offered for rifampicin-resistant and multi-drug-resistant tuberculosis. Methods: Data are from a prospective observational cohort study. Costs of treatment were estimated from the provider perspective using bottom-up micro-costing. Costs were estimated as patient-level resource use multiplied by the unit cost of the resource. Clinic visits, drugs, laboratory tests, and total days hospitalized were collected from patients' medical records. Staff time was estimated through a time and motion study. A successful treatment outcome was defined as cure or completion of the regimen. Results: We enrolled 124 patients with 52% having a successful outcome. The average total cost/patient for all patients was $3,430 and $4,530 for successfully treated patients. The largest contributors to total cost across all outcomes were drugs (43%) and staff (28%). The average cost to achieve a successful outcome including all patients who started treatment ("production cost") in the cohort is $6,684. Conclusions: Decentralized, outpatient RR/MDR-TB care under South Africa's 2011 strategy costs 74% less per patient than the previous strategy of inpatient care. The treatment cost of RR/MDR-TB is primarily driven by drug and staff costs, which are in turn dependant on treatment length. [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]

Objective: In resource-limited settings, where genotypic drug resistance testing is rarely performed and poor adherence is the most common reason for treatment failure, programmatic approaches to handling treatment failure are essential. This study was performed to describe one such approach to adherence optimisation.Methods: This was a single-arm study of patients on second-line protease inhibitor (PI)-based antiretroviral therapy (ART) with a HIV-1 RNA ≥400 copies/ml in Johannesburg, South Africa, between 1 March 2012 and 1 December 2013. Patients underwent enhanced adherence counselling. Those with improved adherence and a repeat viral load of >1000 copies/ml underwent HIV-1 drug resistance testing. We describe results using simple proportions and 95% confidence intervals.Results: Of the 400 patients who underwent targeted adherence counselling after an elevated viral load on second-line ART, 388 (97%) underwent repeat viral load testing. Most of these (n = 249; 64%, 95% CI 59-69) resuppressed (<400 copies/ml) on second line. By the end of follow-up (1 March 2014), among the 139 (36%, 95% CI: 31-41%), who did not initially resuppress after being targeted, 106 had a viral load >400 copies/ml, 11 switched to third line, 5 were awaiting third line, 4 had died and 13 were lost to follow-up. Among the unsuppressed, 48 successfully underwent resistance testing with some resistance detected in most (41/48).Conclusions: Most (64%) second-line treatment failure in this clinic is related to adherence and can be overcome with careful adherence support. Controlled interventions are needed to determine what the optimal approach is to improving second-line outcomes and reducing the need for third-line ART. [ABSTRACT FROM AUTHOR]

Background: Many women undergoing cervical screening as part of a national South African screening programme may be positive for HIV. The performance of liquid-based cytology (LBC) on samples from HIV-positive women needs to be determined. Objectives: The performance of the Cellslide® automated LBC system was evaluated as a possible alternative to conventional cytology in a national cervical cancer screening programme. Methods: Split samples from 348 HIV-positive women attending an HIV treatment clinic in Johannesburg, South Africa were examined by conventional cytology and monolayer LBC methods. All samples were stained, examined and reported in the same manner. Cy to technologists were blinded to the conventional smear diagnosis if the LBC smear was screened and vice versa. Results: The same percentage of inadequate smears (1.4%) was obtained by conventional cytology and LBC. Atypical squamous cells of undetermined significance were observed in 5.2% of conventional smears and 4.0% of LBC smears. Low-grade squamous intraepithelial lesions were found in 35.6% of conventional smears and 32.7% of LBC smears. Only one conventional smear was categorised as atypical squamous cells - cannot exclude a high-grade lesion, whereas five such cases were identified on LBC. High-grade squamous intraepithelial lesions were seen in 21.6% of conventional smears and 23.3% LBC smears. No invasive carcinoma was identified. Conclusion: The performance of the Cellslide® LBC system was similar to that of conventional cytology in this population of high-risk HIV-positive women, indicating that it may be introduced successfully as part of a cervical cancer screening programme. [ABSTRACT FROM AUTHOR]

Background: Gauteng Province has the second lowest tuberculosis (TB) incidence rate in South Africa but the greatest proportion of TB/HIV co-infection, with 68% of TB patients estimated to have HIV. TB treatment outcomes are well documented at the national and provincial level; however, knowledge gaps remain on how outcomes differ across detailed age groups.Methods: Using data from South Africa's National Electronic TB Register (ETR), we assessed all-cause mortality and loss to follow-up (LTFU) among patients initiating treatment for TB between 01/2010 and 12/2015 in the metropolitan municipalities of Ekurhuleni Metropolitan Municipality and the City of Johannesburg in Gauteng Province. We excluded patients who were missing age, had known drug-resistance, or transferred into TB care from sites outside the two metropolitan municipalities. Among patients assigned a treatment outcome, we investigated the association between age group at treatment initiation and mortality or LTFU (treatment interruption of ≥2 months) within 10 months after treatment initiation using Cox proportional hazard models and present hazard ratios and Kaplan-Meier survival curves.Results: We identified 182,890 children (<10 years), young adolescent (10-14), older adolescent (15-19), young adult (20-24), adult (25-49), and older adult (≥50) TB cases without known drug-resistance. ART coverage among HIV co-infected patients was highest for young adolescents (64.3%) and lowest for young adults (54.0%) compared to other age groups (all over 60%). Treatment success exceeded 80% in all age groups (n = 170,017). All-cause mortality increased with age. Compared to adults, young adults had an increased hazard of LTFU (20-24 vs 25-49 years; aHR 1.43 95% CI: 1.33, 1.54) while children, young adolescents, and older adults had lower hazard of LTFU. Patients with HIV on ART had a lower risk of LTFU, but greater risk of death when compared to patients without HIV.Conclusions: Young adults in urban areas of Gauteng Province experience a disproportionate burden of LTFU and low coverage of ART among co-infected patients. This group should be targeted for interventions aimed at improving clinical outcomes and retention in both TB and HIV care. [ABSTRACT FROM AUTHOR]