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Background: Although South Africa has an overall mother-to-child transmission (MTCT) of HIV rate <5%, case rates remain high., Objectives: To identify population-level predictors of MTCT to inform targeted interventions to further reduce paediatric HIV incidence., Methods: The study was an ecological analysis of routine laboratory HIV-related test data from a synthetic cohort of women of reproductive age living with HIV (WRLHIV), identified from the National Health Laboratory Service's Corporate Data Warehouse between 2016 and 2017. Criteria based on syphilis screening and timing of HIV-related tests were used to identify pregnant and non-pregnant WRLHIV. Pregnant WRLHIV were followed from cohort entry at the first antenatal care (fANC) visit, through delivery to exit at the latest viral load (VL) or 15 months post delivery. Follow-up for non-pregnant WRLHIV started at cohort entry on 1 January 2016 to exit at the latest VL or 31 December 2018. HIV VL tests performed at cohort entry, delivery and cohort exit described viraemia (VL ≥50 copies/mL) at subdistrict level. A negative binomial regression model determined the association between MTCT cases and the number of viraemic WRLHIV at different time points, controlling for number of WRLHIV aged <25 years at cohort entry and other routine HIV-related indicators at subdistrict level., Results: Of 3 386 507 WRLHIV identified, 178 319 (5.3%) met criteria for pregnancy. Median (interquartile range (IQR)) proportions of women with fANC booking <20 weeks' gestation, maternal HIV seroprevalence during antenatal care (ANC) and antiretroviral therapy (ART) coverage during ANC were 68.2% (62.9 - 72.8), 31.5% (23.4 - 35.7) and 94.8% (89.7 - 97.8), respectively. Viraemia was consistently higher in pregnant v. non-pregnant WRLHIV at median proportions of 42.9% (38.3 - 59.3) v. 35.0% (25.9 - 49.0) at cohort entry (p<0.001) and 36.3% (25.0 - 48.4) v. 29.6% (21.0 - 42.6) at cohort exit (p<0.001). In total, 4 535 children aged <24 months tested HIV polymerase chain reaction-positive, representing a median subdistrict-level case rate of 1 372 (914 - 2 077) per 100 000 live births. Maternal viraemia postpartum, maternal HIV seroprevalence and ART coverage during ANC positively correlated with cases of MTCT, while higher proportions of women with fANC booking <20 weeks' gestation were associated with a decline in MTCT cases., Conclusions: Findings suggest that maternal viraemia postpartum, geographical areas with a higher burden of maternal HIV, women initiating ART late in pregnancy and/or incident maternal HIV during pregnancy are significant population-level predictors of MTCT in the national prevention of MTCT programme. Scale-up of HIV prevention services is required to lower maternal HIV prevalence, while expanded access to HIV testing will fast-track ART initiation among WRLHIV. Increased VL monitoring is critical to improve VL suppression rates for elimination of MTCT.

Background: Retention in care is associated with improved virological control and survival among HIV-infected children. However, retention of children in HIV care remains a challenge., Objectives: To describe, using routine laboratory HIV test data, the retention-in-care and virological outcomes of HIV-infected children aged <18 months in two districts in South Africa., Methods: HIV polymerase chain reaction (PCR)-positive results of children from uMkhanyakude and Tshwane districts in KwaZulu-Natal and Gauteng provinces, respectively, tested between April 2015 and May 2016, were extracted from the National Health Laboratory Service's Corporate Data Warehouse (CDW). HIV-related tests (PCR, viral load (VL), CD4+) were documented longitudinally for each child for ≥13 months after the first positive PCR result by manually searching demographics within the CDW, supplemented by an automated patient-linking algorithm. Test sets were linked if two or more demographics (surname, name, date of birth, folder number) matched exactly. Programmatic indicators assessed included age at first positive PCR test, presumed confirmatory test rates, retention in care, and VL suppression at 6 and 12 months., Results: Ninety-four and 304 children tested HIV PCR-positive in uMkhanyakude and Tshwane, respectively. The median age at diagnosis was 3.6 months (interquartile range (IQR) 1.4 - 7.1) for uMkhanyakude and 2.3 months (IQR 0.1 - 6.7) for Tshwane. In uMkhanyakude, confirmed in utero infections accounted for 18.1% of transmissions (n=17), compared with 29.6% (n=90) in Tshwane. Presumed confirmatory test rates following an initial positive PCR result were 77.7% and 71.7% for uMkhanyakude and Tshwane, respectively. Within 6 months of starting antiretroviral therapy, 43 children (58.9%) were lost to follow-up in uMkhanyakude compared with 160 (73.4%) in Tshwane. Of those retained in care at 6 months with a VL measurement, 15 (60.0%) from uMkhanyakude had a VL <1 000 copies/mL, compared with 24 (48.0%) in Tshwane. For both districts, a third of all HIV PCR-positive children were retained in care at the end of follow-up, with 29 (30.9%) in uMkhanyakude and 99 (32.5%) in Tshwane. Of these, 12 (41.4%) had a VL <1 000 copies/mL in uMkhanyakude compared with 28 (28.3%) in Tshwane., Conclusions: We demonstrate the value of routine laboratory data in monitoring diagnosis, retention and VL suppression in HIV-infected children. This approach is scalable, can be reported near real-time, is relatively inexpensive to implement, and provides a tool for improving paediatric HIV services until clinical databases can assume this role.

Objectives: Antiretroviral therapy (ART) has been associated with unfavourable lipid profile changes and increased risk of cardiovascular disease (CVD). With a growing population on ART in South Africa, there has been concern about the increase in noncommunicable diseases such as CVD. We determined risk factors associated with increased total cholesterol (TC) in a large cohort on ART and describe the clinical management thereof., Methods: We conducted an observational cohort study of ART-naïve adults initiating standard first-line ART in a large urban clinic in Johannesburg, South Africa. TC was measured annually for most patients. A proportional hazards regression model was used to determine risk factors associated with incident high TC (≥ 6 mmol/L)., Results: Significant risk factors included initial regimen non-tenofovir vs. tenofovir [hazard ratio (HR) 1.54; 95% confidence interval (CI) 1.14-2.08], age ≥40 vs. <30 years (HR 3.22; 95% CI 2.07-4.99), body mass index (BMI) ≥ 30 kg/m 2 (HR 1.65; 95% CI 1.18-2.31) and BMI 25-29.9 kg/m 2 (HR 1.70; 95% CI 1.30-2.23) vs. 18-24.9 kg/m 2 , and baseline CD4 count < 50 cells/μL (HR 1.55; 95% CI 1.10-2.20) and 50-99 cells/μL (HR 1.40; 95% CI 1.00-1.97) vs. > 200 cells/μL. Two-thirds of patients with high TC were given cholesterol-lowering drugs, after repeat TC measurements about 12 months apart, while 31.8% were likely to have received dietary counselling only., Conclusions: Older age, higher BMI, lower CD4 count and a non-tenofovir regimen were risk factors for incident elevated TC. Current guidelines do not indicate regular cholesterol testing at ART clinic visits, which are the main exposure to regular clinical monitoring for most HIV-positive individuals. If regular cholesterol monitoring is conducted, improvements can be made to identify and treat patients sooner., (© 2017 British HIV Association.)

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., (© 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

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., Competing Interests: The authors have declared that no competing interests exist.

High levels of adherence are required to achieve the full benefit of ART. We assess the effectiveness of electronic adherence monitoring devices among patients failing second-line ART, as measured by viral load suppression. Cohort study of Wisepill™ real-time adherence monitoring in addition to intensified adherence counselling over 3 months in adults with a viral load ≥400 copies/ml on second-line ART in Johannesburg, South Africa between August 2013 and January 2014. Patients were sent SMS reminders upon missing a scheduled dose. We compared outcomes to earlier historical cohorts receiving either intensified adherence counselling or adherence counselling alone. Overall, 63 % of the participants (31/49) took >80 % of their prescribed medication; this dropped from 76 to 53 and 49 % at 1, 2 and 3 months post-enrolment respectively. Compared to those with good adherence (>80 %), participants with poor adherence (≤80 %) had a higher risk for a subsequently elevated viral load ≥400 copies/ml (relative risk (RR) 1.47 95 % CI 0.97-2.23). Participants found the intervention "acceptable and useful" but by 6 months after eligibility they were only slightly more likely to be alive, in care and virally suppressed compared to those who received intensified adherence counselling (44.9 vs. 38.5 %; RR 1.19; 95 % CI 0.85-1.67) or adherence counselling alone (44.9 vs. 40.9 %; RR 1.12; 95 % CI 0.81-1.56). In patients with an elevated viral load on second-line ART electronic adherence monitoring was associated with a modest, but not significant, improvement in viral suppression., Competing Interests: The authors declare that they have no conflict of interest.