Variation in HIV care and treatment outcomes by facility in South Africa, 2011-2015: A cohort study.

BACKGROUND: Despite widespread availability of HIV treatment, patient outcomes differ across facilities. We propose and evaluate an approach to measure quality of HIV care at health facilities in South Africa's national HIV program using routine laboratory data. METHODS AND FINDINGS: Data were extracted from South Africa's National Health Laboratory Service (NHLS) Corporate Data Warehouse. All CD4 counts, viral loads (VLs), and other laboratory tests used in HIV monitoring were linked, creating a validated patient identifier. We constructed longitudinal HIV care cascades for all patients in the national HIV program, excluding data from the Western Cape and very small facilities. We then estimated for each facility in each year (2011 to 2015) the following cascade measures identified a priori as reflecting quality of HIV care: median CD4 count among new patients; retention 12 months after presentation; 12-month retention among patients established in care; viral suppression; CD4 recovery; monitoring after an elevated VL. We used factor analysis to identify an underlying measure of quality of care, and we assessed the persistence of this quality measure over time. We then assessed spatiotemporal variation and facility and population predictors in a multivariable regression context. We analyzed data on 3,265 facilities with a median (IQR) annual size of 441 (189 to 988) lab-monitored HIV patients. Retention 12 months after presentation increased from 42% to 47% during the study period, and viral suppression increased from 66% to 79%, although there was substantial variability across facilities. We identified an underlying measure of quality of HIV care that correlated with all cascade measures except median CD4 count at presentation. Averaging across the 5 years of data, this quality score attained a reliability of 0.84. Quality was higher for clinics (versus hospitals), in rural (versus urban) areas, and for larger facilities. Quality was lower in high-poverty areas but was not independently associated with percent Black. Quality increased by 0.49 (95% CI 0.46 to 0.53) standard deviations from 2011 to 2015, and there was evidence of geospatial autocorrelation (p < 0.001). The study's limitations include an inability to fully adjust for underlying patient risk, reliance on laboratory data which do not capture all relevant domains of quality, potential for errors in record linkage, and the omission of Western Cape. CONCLUSIONS: We observed persistent differences in HIV care and treatment outcomes across South African facilities. Targeting low-performing facilities for additional support could reduce overall burden of disease.

Evaluating DREAMS HIV prevention interventions targeting adolescent girls and young women in high HIV prevalence districts in South Africa: protocol for a cross-sectional study.

BACKGROUND: Young women in sub-Saharan Africa remain at the epicentre of the HIV epidemic, with surveillance data indicating persistent high levels of HIV incidence. In South Africa, adolescent girls and young women (AGYW) account for a quarter of all new HIV infections. Determined, Resilient, Empowered, AIDS-free, Mentored and Safe (DREAMS) is a strategy introduced by the United States President's Emergency Plan for AIDS Relief (PEPFAR) aimed at reducing HIV incidence among AGYW in 10 countries in sub-Saharan Africa by 25% in the programme's first year, and by 40% in the second year. This study will assess the change in HIV incidence and reduction in risk associated behaviours that can be attributed to the DREAMS initiative in South Africa, using a population-based cross-sectional survey. METHODS: Data will be collected from a household-based representative sample of AGYW (between the ages 12-24 years) in four high prevalence districts (more than 10% of the population have HIV in these districts) in South Africa in which DREAMS has been implemented. A stratified cluster-based sampling approach will be used to select eligible participants for a cross-sectional survey with 18,500, to be conducted over 2017/2018. A questionnaire will be administered containing questions on sexual risk behaviour, selected academic and developmental milestones, prevalence of gender based violence, whilst examining exposure to DREAMS programmes. Biological samples, including two micro-containers of blood and self-collected vulvovaginal swab samples, are collected in each survey to test for HIV infection, HIV incidence, sexually transmitted infections (STIs) and pregnancy. This study will measure trends in population level HIV incidence using the Limiting antigen (LAg) Avidity Enzyme Immuno-Assay (EIA) and monitor changes in HIV incidence. DISCUSSION: Ending the HIV/AIDS pandemic by 2030 requires the continual monitoring and evaluation of prevention programmes, with the aim of optimising efforts and ensuring the achievement of epidemic control. This study will determine the impact DREAMS interventions have had on HIV incidence among AGYW in a 'real world, non-trial setting'.

Assessment of readiness to transition from antenatal HIV surveillance surveys to PMTCT programme data-based HIV surveillance in South Africa: The 2017 Antenatal Sentinel HIV Survey.

OBJECTIVE: South Africa has used antenatal HIV surveys for HIV surveillance in pregnant women since 1990. We assessed South Africa's readiness to transition to programme data based antenatal HIV surveillance with respect to PMTCT uptake, accuracy of point-of-care rapid testing (RT) and selection bias with using programme data in the context of the 2017 antenatal HIV survey. METHODS: Between 1 October and 15 November 2017, the national survey was conducted in 1,595 public antenatal facilities selected using stratified multistage cluster sampling method. Results of point-of-care RT were obtained from medical records. Blood samples were taken from eligible pregnant women and tested for HIV using immunoassays (IA) in the laboratory. Descriptive statistics were used to report on: PMTCT uptake; agreement between HIV point-of-care RT and laboratory-based HIV-1 IA; and selection bias associated with using programme data for surveillance. RESULTS: PMTCT HIV testing uptake was high (99.8%). The positive percent agreement (PPA) between RT and IA was lower than the World Health Organization (WHO) benchmark (97.6%) at 96.3% (95% confidence interval (CI): 95.9%-96.6%). The negative percent agreement was above the WHO benchmark (99.5%), at 99.7% (95% CI: 99.6%-99.7%) nationally. PPA markedly varied by province (92.9%-98.3%). Selection bias due to exclusion of participants with no RT results was within the recommended threshold at 0.3%. CONCLUSION: For the three components assessed, South Africa was close to meeting the WHO standard for transitioning to routine RT data for antenatal HIV surveillance. The wide variations in PPA across provinces should be addressed.

Progress of UNAIDS 90-90-90 targets in a district in KwaZulu-Natal, South Africa, with high HIV burden, in the HIPSS study: a household-based complex multilevel community survey.

BACKGROUND: With the goal of eliminating new HIV infections, UNAIDS set the ambitious 90-90-90 targets to be achieved by 2020. We assessed whether these targets are being met among participants of the HIV Incidence Provincial Surveillance System (HIPSS) in a high-burden district of South Africa. METHODS: We used data from a HIPSS household-based, cross-sectional survey of HIV prevalence and incidence done in the uMgungundlovu district, KwaZulu-Natal, in 2014 and 2015. In randomly selected enumeration areas, 50 households were drawn systematically along a serpentine pattern from a random start point. One eligible individual in each household was asked to provide blood for HIV testing and to complete a questionnaire. If a household refused to participate, the house next to it was approached. Eligible participants were aged 15-49 years, lived in the household, were not planning to move away, and spoke English or Zulu. Viral load was measured in samples positive for HIV. We also assessed participants' HIV linkage to care and treatment. Data were population weighted to allow for multilevel sampling and non-response. FINDINGS: 9812 participants were enrolled, 3547 men (36%) and 6265 women (64%). Overall, 504 of 1014 men (estimate 52%, 95% CI 47-56) and 1833 of 2955 women (65%, 62-67) who were HIV positive knew their HIV status. Of those who knew, 344 of 522 men (69%, 63-75) and 1254 of 1845 women (70%, 68-73) were taking ART. Among recipients of ART, 294 of 341 men (85%, 80-90) and 1117 of 1249 women (90%, 87-92) had viral loads less than 1000 copies per mL. Among all HIV-positive participants, 427 of 1014 men (44%, 39-49) and 1680 of 2955 women (58%, 55-61) had viral loads lower than 1000 copies per mL. INTERPRETATION: No UNAIDS 90-90-90 targets had been met in our study population. Major campaigns are needed to increase HIV testing, especially among men, and to ensure all HIV-positive patients are taking ART. FUNDING: Centers for Disease Control and Prevention and the US Presidents Emergency Plan for AIDS Relief (PEPFAR).

Obtaining a male circumcision prevalence rate of 80% among adults in a short time: An observational prospective intervention study in the Orange Farm township of South Africa.

World Health Organization recommends a target for the male circumcision prevalence rate of 80%. This rate will have a substantial impact on the human immunodeficiency virus-acquired immunodeficiency syndrome epidemic in Eastern and Southern Africa. The objective of the study was to assess whether an innovative intervention can lead to an increased voluntary male medical circumcision (VMMC) uptake among adults in a short time. This prospective observational study of a demand generation intervention was conducted in the township of Orange Farm (South Africa) in August to November 2015. In this community male circumcision prevalence rate among adults was stable between 2010 and 2015 at 55% and 57%, despite regular VMMC campaigns at community level and the presence of a VMMC clinic that offered free VMMC. The intervention took place in a random sample of 981 households where 522 men aged 18 to 49 years accepted to participate in the study. Among the 226 uncircumcised men, 212 accepted to be enrolled in the intervention study. A personal male circumcision adviser trained in interpersonal communication skills was assigned to each uncircumcised participant. The male circumcision advisers were trained to explain the risks and benefits of VMMC, and to discuss 24 possible reasons given by men for not being circumcised. Participants were then followed for 9 weeks. Each participant had a maximum of 3 motivational interviews at home. Participants who decided to be circumcised received financial compensation for their time equivalent to 2.5 days of work at the minimum South African salary rate. Among the 212 uncircumcised men enrolled in the intervention, 69.8% (148/212; 95% confidence interval [CI]; 63.4%-75.7%) agreed to be circumcised, which defines the uptake of the intervention. The male circumcision prevalence rate of the sample increased from 56.7% (296/522) to 81.4% (425/522; 77.9%-84.6%), P < 0.001, corresponding to a relative increase of 43.6% (95% CI: 35.4%-53.7%). The reported reasons for accepting circumcision were motivational interviews with the male circumcision adviser (83.1%), and time compensation (39.4%).Increased uptake of VMMC uptake can be obtained in a short time among adult males but requires an intense intervention centered on uncircumcised men at an individual level and time compensation.

Design and implementation of an external quality assessment program for HIV viral load measurements using dried blood spots.

An external quality assurance program was developed for HIV-1 RNA viral load measurements taken from dried blood spots using a reference panel and field-collected specimens. The program demonstrated that accurate and reproducible quantitation can be obtained from field-collected specimens. Residual proviral DNA may confound interpretation in virologically suppressed subjects.

Measles outbreak in South Africa: epidemiology of laboratory-confirmed measles cases and assessment of intervention, 2009-2011.

BACKGROUND: Since 1995, measles vaccination at nine and 18 months has been routine in South Africa; however, coverage seldom reached >95%. We describe the epidemiology of laboratory-confirmed measles case-patients and assess the impact of the nationwide mass vaccination campaign during the 2009 to 2011 measles outbreak in South Africa. METHODS: Serum specimens collected from patients with suspected-measles were tested for measles-specific IgM antibodies using an enzyme-linked immunosorbent assay and genotypes of a subset were determined. To estimate the impact of the nationwide mass vaccination campaign, we compared incidence in the seven months pre- (1 September 2009-11 April 2010) and seven months post-vaccination campaign (24 May 2010-31 December 2010) periods in seven provinces of South Africa. RESULTS: A total of 18,431 laboratory-confirmed measles case-patients were reported from all nine provinces of South Africa (cumulative incidence 37 per 100,000 population). The highest cumulative incidence per 100,000 population was in children aged <1 year (603), distributed as follows: <6 months (302/100,000), 6 to 8 months (1083/100,000) and 9 to 11 months (724/100,000). Forty eight percent of case-patients were ≥ 5 years (cumulative incidence 54/100,000). Cumulative incidence decreased with increasing age to 2/100,000 in persons ≥ 40 years. A single strain of measles virus (genotype B3) circulated throughout the outbreak. Prior to the vaccination campaign, cumulative incidence in the targeted vs. non-targeted age group was 5.9-fold higher, decreasing to 1.7 fold following the campaign (P<0.001) and an estimated 1,380 laboratory-confirmed measles case-patients were prevented. CONCLUSION: We observed a reduction in measles incidence following the nationwide mass vaccination campaign even though it was conducted approximately one year after the outbreak started. A booster dose at school entry may be of value given the high incidence in persons >5 years.

The World Health Organization African region external quality assessment scheme for anti-HIV serology.

A regional external quality assessment scheme (REQAS) for anti-HIV serology aimed to objectively assess reliability and quality of HIV testing processes in the African region. This involved the distribution of proficiency testing (PT) panels to participating laboratories from 2002 to 2010. During the survey period, this included 16 distributions of PT panels to 49 laboratories in 30 countries, and the overall average score during the nine-year survey period was 98.9%, with a frequency of accurate detection, of anti-HIV-1 and/or anti-HIV-2 antibodies in the PT panels, ranging from 93% to 100%. Problems highlighted included lack of human resources and frequent stock outs of test kits, reagents and consumables for routine HIV testing. The design of the REQAS allowed appraisal of the reliability of anti-HIV serological testing methods utilised by laboratories for clinical assessment of patients and/or surveillance programmes. The REQAS was able to demonstrate that laboratories participating in the REQAS performed well and sustained their participation in the scheme. This bodes well for clinical diagnosis, surveillance and training activities at these reference laboratories.

Epidemiologic and virologic assessment of the 2009 influenza A (H1N1) pandemic on selected temperate countries in the Southern Hemisphere: Argentina, Australia, Chile, New Zealand and South Africa.

UNLABELLED: INTRODUCTION AND SETTING: Our analysis compares the most comprehensive epidemiologic and virologic surveillance data compiled to date for laboratory-confirmed H1N1pdm patients between 1 April 2009 - 31 January 2010 from five temperate countries in the Southern Hemisphere-Argentina, Australia, Chile, New Zealand, and South Africa. OBJECTIVE: We evaluate transmission dynamics, indicators of severity, and describe the co-circulation of H1N1pdm with seasonal influenza viruses. RESULTS: In the five countries, H1N1pdm became the predominant influenza strain within weeks of initial detection. South Africa was unique, first experiencing a seasonal H3N2 wave, followed by a distinct H1N1pdm wave. Compared with the 2007 and 2008 influenza seasons, the peak of influenza-like illness (ILI) activity in four of the five countries was 3-6 times higher with peak ILI consultation rates ranging from 35/1,000 consultations/week in Australia to 275/100,000 population/week in New Zealand. Transmission was similar in all countries with the reproductive rate ranging from 1.2-1.6. The median age of patients in all countries increased with increasing severity of disease, 4-14% of all hospitalized cases required critical care, and 26-68% of fatal patients were reported to have ≥1 chronic medical condition. Compared with seasonal influenza, there was a notable downward shift in age among severe cases with the highest population-based hospitalization rates among children <5 years old. National population-based mortality rates ranged from 0.8-1.5/100,000. CONCLUSIONS: The difficulty experienced in tracking the progress of the pandemic globally, estimating its severity early on, and comparing information across countries argues for improved routine surveillance and standardization of investigative approaches and data reporting methods.

Polymerase chain reaction for diagnosis of human immunodeficiency virus infection in infancy in low resource settings.

BACKGROUND: Diagnosis of human immunodeficiency virus (HIV) is essential for accessing treatment. Current HIV diagnostic protocols for infants require adaptation and validation before they can be implemented in the developing world. The timing and type of HIV assays will be dictated by country-specific circumstances and experience from similar settings. The performance of an HIV-1 DNA polymerase chain reaction (PCR) test, and in particular a single test at 6 weeks of age, in diagnosing HIV subtype C infection acquired in utero or peripartum was assessed. METHODS: A retrospective review of 1825 Amplicor HIV-1 DNA PCR version 1.5 tests performed between 2000 and 2004 in 2 laboratories in Johannesburg, South Africa on 769 effectively non-breast-fed infants from 3 clinically well characterized cohorts was undertaken. The HIV status of each infant was used as the standard against which the HIV PCR results were compared. RESULTS: The overall sensitivity and specificity of the HIV PCR test were 99.3 and 99.5% respectively. A single test was 98.8% sensitive and 99.4% specific in the 627 infants tested at 6 weeks of age (58 HIV-infected and 569 HIV-uninfected). Repeat testing of all positive HIV PCR tests minimized false positive results. CONCLUSIONS: In resource-poor settings where HIV PCR testing in an environment of good laboratory practice is feasible, a single 6-week HIV DNA PCR test can increase identification of HIV-infected children substantially from current levels. Further operational research on how best to implement and monitor such a diagnostic protocol in specific local settings, especially in breast-fed infants, is necessary.