Search

Background:Linkage between health databases typically requires identifiers such as patient names and personal identification numbers. We developed and validated a record linkage strategy to combine administrative health databases without the use of patient identifiers, with application to South Africa’s public sector HIV treatment program. Methods: We linked CD4 counts and HIV viral loads from South Africa’s HIV clinical monitoring database (TIER.Net) and the National Health Laboratory Service (NHLS) for patients receiving care between 2015-2019 in Ekurhuleni District (Gauteng Province). We used a combination of variables related to lab results contained in both databases (result value; specimen collection date; facility of collection; patient year and month of birth; and sex). Exact matching linked on exact linking variable values while caliper matching applied exact matching with linkage on approximate test dates (± 5 days). We then developed a sequential linkage approach utilising specimen barcode matching, then exact matching, and lastly caliper matching. Performance measures were sensitivity and positive predictive value (PPV); share of patients linked across databases; and percent increase in data points for each linkage approach. Results: We attempted to link 2,017,290 lab results from TIER.Net (representing 523,558 unique patients) and 2,414,059 lab results from the NHLS database. Linkage performance was evaluated using specimen barcodes (available for a minority of records in TIER.net) as a “gold standard”. Exact matching achieved a sensitivity of 69.0% and PPV of 95.1%. Caliper-matching achieved a sensitivity of 75.7% and PPV of 94.5%. In sequential linkage, we matched 41.9% of TIER.Net labs by specimen barcodes, 51.3% by exact matching, and 6.8% by caliper matching, for a total of 71.9% of labs matched, with PPV=96.8% and Sensitivity= 85.9%. The sequential approach linked 86.0% of TIER.Net patients with at least one lab result to the NHLS database (N=1,450,087). Linkage to the NHLS Cohort increased the number of laboratory results associated with TIER.Net patients by 62.6%. Conclusions: Linkage of TIER.Net and NHLS without patient identifiers attained high accuracy and yield without compromising patient privacy. The integrated cohort provides a more complete view of patients’ lab history and could yield more accurate estimates of HIV program indicators.

We describe coverage of maternal syphilis screening, syphilis positivity, coverage of treatment and their association with maternal HIV infection and antiretroviral treatment (ART) status among pregnant women attending South African antenatal clinics. The 2019 antenatal care sentinel survey was a cross-sectional survey conducted from 1 October to 15 November 2019 at 1589 sentinel sites in all nine provinces of the country and aimed to enrol 36,000 pregnant women ages 15–49 years regardless of HIV, ART or syphilis status. Data collection procedures included obtaining written informed consent, a brief interview, medical record review and blood specimen collection. Completed data collection forms and specimens were sent to designated regional laboratories for data capture and HIV serology testing. Data analysis determined four outcomes i) syphilis screening coverage ii) syphilis positivity iii) coverage of any treatment and iv) with Benzathine penicillin G (BPG). Multivariable logistic regression models with or without interaction between HIV infection and ART status with province were used to determine factors associated with syphilis positivity. Of the 41 598 women enrolled, 35 900 were included in the analysis for syphilis screening coverage. The weighted syphilis screening coverage was 96.4% [95% Confidence Interval (CI) 95.9–96.7%] nationally and was lowest among HIV positive women not on ART at 93.5% (95% CI 92.2–94.5%). Syphilis positivity was 2.6% (95% CI 2.4–2.9%) nationally. Among those who were syphilis positive, 91.9% (95% CI 89.8–93.7%) had documentation of syphilis treatment status, of whom 92.0% (95% CI 89.8–93.9%) were treated, with the majority treated with one or more doses of BPG [92.2% (95% CI 89.8–94.3%)]. HIV-positive women, not on ART [adjusted odd ratio (aOR) 2.24 (95% 1.71–2.93)] and those on ART [aOR 2.25 (95% CI 1.91–2.64)] were more likely to be syphilis positive compared to those who were HIV negative. The national syphilis screening coverage met the global screening target of 95%. Syphilis positivity was higher among HIV positive women compared to negative women. Introduction of rapid syphilis testing and ensuring a universal supply of appropriate treatment for syphilis will reduce the likelihood of mother-to-child transmission of syphilis.

Recent studies have shown HIV incidence declines at a population level in several African countries. However, these studies have not directly quantified the extent to which incidence declines are attributable to different HIV programs.We calibrated a mathematical model of the South African HIV epidemic to age- and sex-specific data from antenatal surveys, household surveys, and death registration, using a Bayesian approach. The model was also parameterized using data on self-reported condom use, voluntary medical male circumcision (VMMC), HIV testing, and antiretroviral treatment (ART). Model estimates of HIV incidence were compared against the incidence rates that would have been expected had each program not been implemented.The model estimated incidence in 15-49 year olds of 0.84% (95% CI: 0.75% to 0.96%) at the start of 2019. This represents a 62% reduction (95% CI: 55% to 66%) relative to 2000, a 47% reduction (95% CI: 42% to 51%) relative to 2010, and a 73% reduction (95% CI: 68% to 77%) relative to the incidence that would have been expected in 2019 in the absence of any interventions. The reduction in incidence in 2019 because of interventions was greatest for ART and condom promotion, with VMMC and behavior change after HIV testing having relatively modest impacts. HIV program impacts differed significantly by age and sex, with condoms and VMMC having greatest impact in youth, and overall incidence reductions being greater in men than in women.HIV incidence in South Africa has declined substantially since 2000, with ART and condom promotion contributing most significantly to this decline.

OBJECTIVES South Africa has made remarkable progress in increasing the coverage of antiretroviral therapy (ART) among pregnant women; however, viral suppression among pregnant women receiving ART is reported to be low. Access to routine viral load testing is crucial to identify women with unsuppressed viral load early in pregnancy and to provide timely intervention to improve viral suppression. This study aimed to determine the coverage of maternal viral load monitoring nationally, focusing on viral load testing, documentation of viral load test results, and viral suppression (viral load

Although flucytosine is a key component of WHO-recommended induction treatment for HIV-associated cryptococcal meningitis, this antifungal agent is not widely available in low-income and middle-income countries due to limited production and cost. In 2018, a national flucytosine access programme was initiated in South Africa. We aimed to determine the effectiveness of flucytosine-containing induction regimens in routine care to motivate for the urgent registration of flucytosine and its inclusion in treatment guidelines.In this cross-sectional study, we compared outcomes of adults aged 18 years and older with incident laboratory-confirmed cryptococcal meningitis treated with or without flucytosine-containing regimens at 19 sentinel hospitals in South Africa. A case of cryptococcosis was defined as illness in an adult with: (1) positive cerebrospinal fluid (CSF) India ink microscopy; (2) a positive CSF cryptococcal antigen test; or (3) culture of Cryptococcus neoformans or Cryptococcus gattii from CSF or any other specimen. We excluded patients without a case report form, those with an unknown or negative HIV serology result, those with a recurrent episode, and those who did not receive antifungal treatment in hospital. We assessed cumulative in-hospital mortality at 14 days and 30 days and calculated the overall crude in-hospital case-fatality ratio. We used random-effects logistic regression to examine the association between treatment group and in-hospital mortality.From July 1, 2018, to March 31, 2020, 10 668 individuals were diagnosed with laboratory-confirmed cryptococcal meningitis, 7787 cases diagnosed at non-enhanced surveillance sites and 567 cases from eight enhanced surveillance sites with no access to flucytosine were excluded. Of 2314 adults with a first episode of cryptococcosis diagnosed at 19 facilities with access to flucytosine, 1996 had a case report form and of these, 1539 received induction antifungal treatment and were confirmed HIV-seropositive first-episode cases. Of 1539 patients who received antifungal therapy, 596 (38·7%) individuals received a flucytosine-containing regimen and 943 (61·3%) received another regimen. The median age was 36 years (IQR 32-43) and 906 (58·9%) participants were male and 633 (41·1%) were female. The crude in-hospital case-fatality ratio was 23·9% (95% CI 20·0-27·0; 143 of 596) in those treated with flucytosine-containing regimens and 37·2% (95% CI 34·0-40·0; 351 of 943) in those treated with other regimens. Patients admitted to non-academic hospitals (adjusted odds ratio [aOR] 1·95 [95% CI 1·53-2·48]; p0·0001) and those who were antiretroviral treatment-experienced (aOR 1·30 [1·02-1·67]; p=0·033) were more likely to receive flucytosine. After adjusting for relevant confounders, flucytosine treatment was associated with a 53% reduction in mortality (aOR 0·47 [95% CI 0·35-0·64]; p0·0001). Among survivors, the median length of hospital admission in the flucytosine group was 11 days (IQR 8-15) versus 17 days (13-21) in the comparison group (p=0·0010).In-hospital mortality among patients treated with a flucytosine-containing regimen was comparable to reduced mortality reported in patients receiving a flucytosine-containing regimen in a recent multicentre African clinical trial. Flucytosine-based treatment can be delivered in routine care in a middle-income country with a substantial survival benefit.National Institute for Communicable Diseases, a Division of the National Health Laboratory Service.For the Zulu translation of the abstract see Supplementary Materials section.

Monitoring HIV prevalence using antenatal HIV sentinel surveillance is important for efficient epidemic tracking, programme planning and resource allocation. HIV sentinel surveillance usually employs unlinked anonymous HIV testing which raises ethical, epidemiological and public health challenges in the current era of universal test and treat. The World Health Organization (WHO) recommends that countries should consider using routine prevention of mother-to-child transmission of HIV (PMTCT) data for surveillance. We audited antenatal care clinics to assess the quality of HIV rapid testing practices as the first step to assess whether South Africa is ready to utilize PMTCT programme data for antenatal HIV surveillance. In 2017, we conducted a cross-sectional survey in 360 randomly sampled antenatal care clinics using the adapted WHO Stepwise-Process-for-Improving-the-Quality-of-HIV-Rapid-Testing (SPI-RT) checklist. We calculated median percentage scores within a domain (domain-specific median score), and across all domains (overall median percentage scores). The latter was used to classify sites according to five implementation levels; (from 0

Medical male circumcision (MMC) is a proven intervention for preventing HIV acquisition among males. We describe the circumcision status, eligibility for MMC referral and associations with HIV positivity among symptomatic males attending sexually transmitted infections (STI) services. This study was a secondary analysis of cross-sectional data collected during sentinel surveillance for STI aetiologies. In the sentinel surveillance conducted at primary care facilities located in six South African provinces, an anonymous questionnaire was administered followed by collection of appropriate genital and blood specimens for laboratory testing including HIV, rapid plasma reagin (RPR) and HSV-2 serological testing. During analysis, multivariable logistic regression was used to determine association between prevalent HIV infection and male circumcision among males who were HSV-2 AND/OR RPR serology positive and among those who were negative. A total of 847 males were included the analysis, among whom the median age was 28 years (IQR 24–32 years) with 26.3% aged

Objectives The UNAIDS 95-95-95 global targets for epidemic control aim to ensure by 2030 that 95% of HIV-positive people know their HIV status, 95% of people diagnosed with HIV receive sustained antiretroviral therapy (ART), and 95% of people on ART have viral suppression. While data on the first and second 95 targets are routinely reported nationally, data on the third 95 target are not available for pregnant women in South Africa. The lack of data on the third 95 target limits the inclusion of low viral suppression as one of the contributing factors in MTCT root cause analyses. This study assessed progress towards the 95-95-95 targets among pregnant women between the ages of 15–49 years attending public health facilities in South Africa. Method Data were obtained from two consecutive national cross-sectional antenatal HIV sentinel surveys conducted between 1 October and 15 November in both 2017 and 2019. In each survey, data on age, knowledge of HIV status, ART initiation, and geographical location (province) were extracted from medical records. A blood specimen was collected from each woman and tested for HIV. Viral load tests were performed on HIV-positive specimens. Descriptive and multiple logistic regression analyses were performed to examine association between province and viral suppression (defined as viral load Results Of 10 065 and 11 321 HIV-positive women included in the 2017 and 2019 surveys, respectively, 96.0% (95% confidence interval (CI): 95.6–96.4%) and 97.6% (95% CI: 97.3–97.8%) knew their HIV-positive status; 86.6% (95% CI: 85.9–87.3%) and 96.0% (95% CI: 95.6–96.4%) of those who knew their HIV status were receiving ART; while 64.2% (95% CI: 63.2–65.2%) and 66.0% (95% CI: 65.1–66.8%) of those receiving ART were virally suppressed. Achievement of the third 95 target significantly varied by province ranging from 33.9–72.6% in 2017 and 43.4–77.3% in 2019. Knowledge of HIV-positive status, ART initiation, and viral suppression increased in both 15–24 and 25–49 year age groups between 2017 and 2019. In a multivariable analysis adjusting for survey year, gravidity, and education, the odds of viral suppression significantly varied by province (except KwaZulu-Natal and Western Cape, other provinces were less likely to attain viral suppression compared to Gauteng), age (adjusted odds ratio (AOR) for 15–24 years vs 25–49 years: 0.7, 95% CI: 0.6–0.8), and timing of ART initiation (AOR for ART initiation during pregnancy vs before pregnancy: 0.4, 95% CI: 0.5–0.6). Conclusion Although in 2019 the first and second 95 targets were achieved among pregnant women, meeting the third 95 target remains a challenge. This study highlighted the importance of promoting early ART initiation and the need to target young women in efforts to improve progress towards the third 95 target. Additionally, the provincial variation in viral suppression could be further investigated in future studies to identify and address the root causes underlying these differences.

Background Measurements of HIV exposure could help identify subpopulations at highest risk of acquisition and improve the design of HIV prevention efficacy trials and public health interventions. The HVTN 915 study evaluated the feasibility of self-administered vaginal swabs for detection of HIV virions to assess exposure. Methods Fifty 18- to 25-year-old sexually active HIV-seronegative women using contraception were enrolled in Soweto, South Africa. Participants self-administered daily vaginal swabs and answered sexual behavior questions through mobile phone for 90 days. Clinician-administered vaginal swabs, behavioral questionnaires, HIV diagnostic testing, and counseling were performed at 8 clinic visits. Glycogen concentrations assessed adherence to swabbing. Y-chromosome DNA (Yc-DNA) assessed the accuracy of reported condom use. HIV exposure was measured by virion polymerase chain reaction in swabs from 41 women who reported unprotected vaginal sex during follow-up. Results Glycogen was detected in 315/336 (93.8%) participant-collected and in all clinician-collected swabs. Approximately 20/39 daily swabs (51.3%) linked to mobile reports of unprotected sex tested positive for Yc-DNA, whereas 10/187 swabs collected after 3 days of abstinence or protected sex (5.3%) had detectable Yc-DNA. No participant became HIV infected during the study; yet, exposure to HIV was detected by nucleic acids in 2 vaginal swabs from 1 participant, collected less than 1 hour after coitus. Conclusion There was high adherence to daily vaginal swabbing. Daily mobile surveys had accurate reporting of unprotected sex. Detection of HIV in self-collected vaginal swabs from an uninfected participant demonstrated it was possible to measure HIV exposure, but the detection rate was lower than expected.

In South Africa, adolescent girls and young women aged 15 to 24 years are among the most high-risk groups for acquiring HIV. Progress in reducing HIV incidence in this population has been slow.To describe HIV prevalence and HIV risk behaviors among a sample of adolescent girls and young women and to model the association between exposure to multiple or layered interventions and key HIV biological and behavioral outcomes.This cross-sectional survey was conducted between March 13, 2017, and June 22, 2018, in 2 districts in Gauteng province and in 2 districts in KwaZulu-Natal province in South Africa. A stratified cluster random sampling method was used. Participants included adolescent girls and young women aged 12 to 24 years who lived in each sampled household. Overall, 10 384 participants were enrolled in Gauteng province and 7912 in KwaZulu-Natal province. One parent or caregiver was interviewed in each household. Data analysis was performed from March 12, 2021, to March 1, 2022.DREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe)-like interventions.The primary outcome was HIV prevalence. HIV status was obtained from laboratory-based testing of peripheral blood samples. Secondary outcomes included HIV testing and antiretroviral therapy uptake as well as numerous HIV risk variables that the DREAMS program sought to improve, such as pregnancy, sexually transmitted infection, intimate partner violence, and age-disparate sex.The final sample included 18 296 adolescent girls and young women (median [IQR] age, 19 [15-21] years) in 10 642 households. Approximately half of participants (49.9%; n = 8414) reported engaging in sexual activity, and 48.1% (n = 3946) reported condom use at the most recent sexual encounter. KwaZulu-Natal province had a higher HIV prevalence than Gauteng province (15.1% vs 7.8%; P .001). Approximately one-fifth of participants (17.6%; n = 3291) were not exposed to any interventions, whereas 43.7% (n = 8144) were exposed to 3 or more interventions. There was no association between exposure to DREAMS-like interventions and HIV status. Adolescent girls and young women who accessed 3 or more interventions were more likely to have undergone HIV testing (adjusted odds ratio, 2.39; 95% CI, 2.11-2.71; P .001) and to have used condoms consistently in the previous 12 months (adjusted odds ratio, 1.68; 95% CI, 1.33-2.12; P .001) than those who were not exposed to any interventions.Results of this study suggest that self-reported exposures to multiple or layered DREAMS-like interventions were associated with favorable behavioral outcomes. The beneficial aspects of layering HIV interventions warrant further research to support the sexual and reproductive health of adolescent girls and young women.

Background A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox-protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1-2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. Methods In this phase 2b-3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections of ALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gp120-MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. Results In January 2020, prespecified criteria for nonefficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month follow-up, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P = 0.84). Conclusions The ALVAC-gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity. (HVTN 702 ClinicalTrials.gov number, NCT02968849.).

A positive rapid plasma reagin (RPR) result in children under the age of 2 years indicates either passive transplacental transfer of maternal antibodies or active infection with syphilis (possible congenital syphilis). We describe trends in RPR seropositivity in this population using centralized laboratory data. A secondary analysis of laboratory data collected through the National Health Laboratory Service, Corporate Data Warehouse from 2010 to 2019 was conducted. Of the 127 150 children

Background In South Africa, female sex workers (FSWs) are perceived to play a pivotal role in the country’s HIV epidemic. Understanding their health status and risk factors for adverse health outcomes is foundational for developing evidence-based health care for this population. Objective Describe the methodology used to successfully implement a community-led study of social and employment circumstances, HIV and associated factors amongst FSWs in South Africa. Method A community-centric, cross-sectional, survey of 3,005 adult FSWs was conducted (January–July 2019) on 12 Sex Work (SW) programme sites across nine provinces of South Africa. Sites had existing SW networks and support programmes providing peer education and HIV services. FSWs were involved in the study design, questionnaire development, and data collection. Questions included: demographic, sexual behaviour, HIV testing and treatment/PrEP history, and violence exposure. HIV rapid testing, viral load, CD4 count, HIV recency, and HIV drug resistance genotypic testing were undertaken. Partner organisations provided follow-up services. Results HIV Prevalence was 61.96%, the median length of selling sex was 6 years, and inconsistent condom use was reported by 81.6% of participants, 88.4% reported childhood trauma, 46.2% reported physical or sexual abuse by an intimate partner and 57.4% by a client. More than half of participants had depression and post-traumatic stress disorder (52.7% and 54.1%, respectively). Conclusion This is the first national survey of HIV prevalence amongst FSWs in programmes in South Africa. The data highlight the vulnerability of this population to HIV, violence and mental ill health, suggesting the need for urgent law reform. Based on the unique methodology and the successful implementation alongside study partners, the outcomes will inform tailored interventions. Our rapid rate of enrolment, low rate of screening failure and low proportion of missing data showed the feasibility and importance of community-centric research with marginalised, highly vulnerable populations.

Objectives About half of the pregnancies among women living with HIV (WLWH) receiving antiretroviral therapy (ART) in sub-Saharan African countries are reported to be unintended. Unintended pregnancy is associated with late initiation of antenatal care (ANC), and may delay provision of viral load monitoring services, antenatal adherence counselling and support, and other services that promote sustained viral suppression throughout pregnancy. This study examines the association between unsuppressed viral load during the third trimester of pregnancy and unintended pregnancy among women who initiated ART before pregnancy. Methods This was an analysis of data from a national antenatal survey conducted at 1 589 public health facilities in South Africa between 1 October and 15 November 2019. Consenting pregnant women aged 15–49 years attending ANC during the survey period were enrolled. Demographic and clinical data were collected through interview and medical record review. Pregnancy intention was assessed using two questions from the London Measure of Unplanned Pregnancy, and responses were categorized as “unintended,” “undecided,” and “intended.” Blood specimens were collected from all women and tested for HIV; and if positive, a viral load test was performed. A survey domain-based poisson regression model examined the association between unsuppressed viral load during the third trimester of pregnancy and unintended pregnancy among women who initiated ART before pregnancy. Viral suppression was defined as viral load Results Of 10 901 WLWH with viral load data available, 63.3% (95% confidence interval (CI): 62.4%-64.1%) were virally suppressed. Among the 2 681 women (representing 24.1% of all WLWH with viral load data) who initiated ART before pregnancy and were in their third trimester at the time of enrolment, 74.4% (95% CI: 73.0%-75.8%) were virally suppressed. In the same population, the proportion virally suppressed was lower among women whose current pregnancies were unintended (72.1%, 95% CI: 70.1%-74.1%) compared to women whose pregnancies were intended (78.3%, 95% CI: 75.9%-80.5%). In multivariable analyses adjusted for age, gravity, marital status, education, location of facility and syphilis status, unintended pregnancy was associated with unsuppressed viral load during the third trimester (adjusted relative risk: 1.3, 95% CI: 1.1–1.4) among women who initiated ART before pregnancy. Conclusion The identified association between unsuppressed viral load and unintended pregnancy among pregnant women who initiated ART before pregnancy highlights the need to strengthen routine assessment of fertility preferences and provision of contraceptive services to reproductive age WLWH receiving ART.

Background: Human enteroviruses (EV) consist of 106 serotypes and four species: EV-A, EV-B, EV-C and EV-D. Enteroviruses cause clinical symptoms varying from severe to mild. Knowledge of EV burden in South Africa is limited, and as non-polio EV are important causes of acute flaccid paralysis (AFP) and meningitis, information on the circulating serotypes is vital. Methods: Between 2010 and 2012, a total of 832 stool and viral isolate specimens were obtained from two national surveillance programmes at the National Institute for Communicable Diseases: the Rotavirus Sentinel Surveillance Programme (RSSP) and the AFP surveillance programme. Real-time polymerase chain reaction and Sanger sequencing were performed to detect and serotype EV. Results: Non-polio EV were detected in 446 specimens, of which 308 were sequenced. Stool specimens yielded a greater variety of serotypes than viral cultures. EV-B viruses were predominant (58.44%), whilst EV-C viruses were detected in 31% of the specimens tested. South African prevalence for these viruses was higher than other countries, such as France with less than 2%, and Spain and the United States with less than 10%. The most common serotype detected was Enterovirus 99 (EV-C, 8.63%), which has not been reported in other regions. Conclusion: Direct sequencing from stool specimens yields a broader, more comprehensive description of EV infections compared to sequencing from viral cultures. Disease-associated serotypes were detected, but only in small numbers. This study provides a baseline for EV strain circulation; however, surveillance needs to be expanded to improve EV knowledge in South Africa.

BackgroundWe analysed the impact of breastfeeding, antiretroviral drugs and health service factors on cumulative (6 weeks to 18 months) vertical transmission of HIV (MTCT) and ‘MTCT-or-death’, in South Africa, and compared estimates with global impact criteria to validate MTCT elimination: (1) Methods9120 infants aged 6 weeks were enrolled in a nationally representative survey. Of 2811 HIV-exposed uninfected infants (HEU), 2644 enrolled into follow-up (at 3, 6, 9, 12, 15 and 18 months). Using Kaplan-Meier analysis and weighted survey domain-based Cox proportional hazards models, we estimated cumulative risk of MTCT and ‘MTCT or death’ and risk factors for time-to-event outcomes, adjusting for study design and loss-to-follow-up.ResultsCumulative (final) MTCT was 4.3% (95% CI 3.7% to 5.0%); case rate was 1290. Postnatal MTCT (>6 weeks to 18 months) was 1.7% (95% CI 1.2% to 2.4%). Cumulative ‘MTCT-or-death’ was 6.3% (95% CI 5.5% to 7.3%); 81% and 62% of cumulative MTCT and ‘MTCT-or-death’, respectively, occurred by 6 months. Postnatal MTCT increased with unknown maternal CD4-cell-count (adjusted HR (aHR 2.66 (1.5–5.6)), undocumented maternal HIV status (aHR 2.21 (1.0–4.7)) and exclusive (aHR 2.3 (1.0–5.2)) or mixed (aHR 3.7 (1.2–11.4)) breastfeeding. Cumulative ‘MTCT-or death’ increased in households with ‘no refrigerator’ (aHR 1.7 (1.1–2.9)) and decreased if infants used nevirapine at 6 weeks (aHR 0.4 (0.2–0.9)).ConclusionsWhile the

Supplemental Digital Content is available in the text, Objective: To describe viral load levels among pregnant women and factors associated with failure to achieve viral suppression (viral load ≤50 copies/ml) during pregnancy. Design: Between 1 October and 15 November 2017, a cross-sectional survey was conducted among 15–49-year-old pregnant women attending antenatal care (ANC) at 1595 nationally representative public facilities. Methods: Blood specimens were taken from each pregnant woman and tested for HIV. Viral load testing was done on all HIV-positive specimens. Demographic and clinical data were extracted from medical records or self-reported. Survey logistic regression examined factors associated with failure to achieve viral suppression. Result: Of 10 052 HIV-positive participants with viral load data, 56.2% were virally suppressed. Participants initiating antiretroviral therapy (ART) prior to pregnancy had higher viral suppression (71.0%) by their third trimester compared with participants initiating ART during pregnancy (59.3%). Booking for ANC during the third trimester vs. earlier: [adjusted odds ratio (AOR) 1.8, 95% confidence interval (CI):1.4–2.3], low frequency of ANC visits (AOR for 2 ANC visits vs. ≥4 ANC visits: 2.0, 95% CI:1.7–2.4), delayed initiation of ART (AOR for ART initiated at the second trimester vs. before pregnancy:2.2, 95% CI:1.8–2.7), and younger age (AOR for 15–24 vs. 35–49 years: 1.4, 95% CI:1.2–1.8) were associated with failure to achieve viral suppression during the third trimester. Conclusion: Failure to achieve viral suppression was primarily associated with late ANC booking and late initiation of ART. Efforts to improve early ANC booking and early ART initiation in the general population would help improve viral suppression rates among pregnant women. In addition, the study found, despite initiating ART prior to pregnancy, more than one quarter of participants did not achieve viral suppression in their third trimester. This highlights the need to closely monitor viral load and strengthen counselling and support services for ART adherence.

In high HIV burden settings, maximising the coverage of prevention strategies is crucial to achieving epidemic control. However, little is known about the reach and effect of these strategies in some communities.We did a cross-sectional community survey in the adjacent Greater Edendale and Vulindlela areas in the uMgungundlovu district, KwaZulu-Natal, South Africa. Using a multistage cluster sampling method, we randomly selected enumeration areas, households, and individuals. One household member (aged 15-49 years) selected at random was invited for survey participation. After obtaining consent, questionnaires were administered to obtain sociodemographic, psychosocial, and behavioural information, and exposure to HIV prevention and treatment programmes. Clinical samples were collected for laboratory measurements. Statistical analyses were done accounting for multilevel sampling and weighted to represent the population. A multivariable logistic regression model assessed factors associated with HIV infection.Between June 11, 2014, and June 22, 2015, we enrolled 9812 individuals. The population-weighted HIV prevalence was 36·3% (95% CI 34·8-37·8, 3969 of 9812); 44·1% (42·3-45·9, 2955 of 6265) in women and 28·0% (25·9-30·1, 1014 of 3547) in men (p0·0001). HIV prevalence in women aged 15-24 years was 22·3% (20·2-24·4, 567 of 2224) compared with 7·6% (6·0-9·3, 124 of 1472; p0·0001) in men of the same age. Prevalence peaked at 66·4% (61·7-71·2, 517 of 760) in women aged 35-39 years and 59·6% (53·0-66·3, 183 of 320) in men aged 40-44 years. Consistent condom use in the last 12 months was 26·5% (24·1-28·8, 593 of 2356) in men and 22·7% (20·9-24·4, 994 of 4350) in women (p=0·0033); 35·7% (33·4-37·9, 1695 of 5447) of women's male partners and 31·9% (29·5-34·3, 1102 of 3547) of men were medically circumcised (p0·0001), and 45·6% (42·9-48·2, 1251 of 2955) of women and 36·7% (32·3-41·2, 341 of 1014) of men reported antiretroviral therapy (ART) use (p=0·0003). HIV viral suppression was achieved in 54·8% (52·0-57·5, 1574 of 2955) of women and 41·9% (37·1-46·7, 401 of 1014) of men (p0·0001), and 87·2% (84·6-89·8, 1086 of 1251) of women and 83·9% (78·5-89·3, 284 of 341; p=0·3670) of men on ART. Age, incomplete secondary schooling, being single, having more than one lifetime sex partner (women), sexually transmitted infections, and not being medically circumcised were associated with HIV-positive status.The HIV burden in specific age groups, the suboptimal differential coverage, and uptake of HIV prevention strategies justifies a location-based approach to surveillance with finer disaggregation by age and sex. Intensified and customised approaches to seek, identify, and link individuals to HIV services are crucial to achieving epidemic control in this community.The President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.

South Africa has a population of 58.78 million, of which 80.7% are Black African individuals, representing 9 predominant ethnic/linguistic groups (Zulu, Xhosa, Pedi, Tswana, South Sotho, Tsonga, Swati, Venda and Ndebele). HIV-1 and Mycobacterium tuberculosis infection are the leading causes of death (7.8% and 5.9%, respectively) in this population group. To provide reference HLA allele and haplotype data for studies of gene-associations with infectious/non-infectious diseases or vaccine development, we have updated previously published HLA class I (A, B, C) and class II DRB1 genotypes and determined high-resolution class II (DPB1, DQB1) genotypes for n = 142 healthy, unrelated Black South African individuals.

BackgroundSentinel surveillance of transmitted HIV drug resistance (TDR) among recently infected populations within a country was recommended by the World Health Organization from 2004 to 2015.MethodsSerum specimens collected as part of the 2010, 2011 and 2012 National Antenatal Sentinel HIV Prevalence Surveys were used to estimate provincial and national TDR prevalence in South Africa.ResultsModerate (5–15%) levels of transmitted non-nucleoside reverse transcriptase inhibitor (NNRTI) drug class resistance were detected in three of five provinces surveyed in 2010 and 2011 (Eastern Cape, Free State and KwaZulu-Natal). Inclusion of all nine of South Africa's provinces in the 2012 survey enabled calculation of a national TDR point prevalence estimate: TDR to the NNRTI drug class was 5.4% (95% CI 3.7, 7.8%), with K103N and V106M being the most frequently detected mutations. TDR estimates for the nucleoside reverse transcriptase inhibitor (NRTI) drug class were 1.1% (95% CI 0.5, 2.4%) and 0.6% (95% CI 0.1, 1.6%) for protease inhibitors (PI).ConclusionsThese data provide national TDR estimates for South Africa in 2012 and indicate that levels of TDR were low to moderate for the NNRTI drug class and low for NRTIs and PIs in the population surveyed.

Purpose Adolescent females aged 15–19 account for 62% of new HIV infections and give birth to 16 million infants annually. We quantify the risk of early mother-to-child transmission (MTCT) of HIV among adolescents enrolled in nationally representative MTCT surveillance studies in South Africa. Methods Data from 4,814 adolescent (≤19 years) and 25,453 adult (≥20 years) mothers and their infants aged 4–8 weeks were analyzed. These data were gathered during three nationally representative, cross-sectional, facility-based surveys, conducted in 2010, 2011–2012, and 2012–2013. All infants were tested for HIV antibody (enzyme immunoassay), to determine HIV exposure. Enzyme immunoassay-positive infants or those born to self-reported HIV-positive mothers were tested for HIV infection (total nucleic acid polymerase chain reaction). Maternal HIV positivity was inferred from infant HIV antibody positivity. All analyses were weighted for sample realization and population live births. Results Adolescent mothers, compared with adult mothers, have almost three times less planned pregnancies 14.4% (95% confidence interval [CI]: 12.5–16.5) versus 43.9% (95% CI: 42.0–45.9) in 2010 and 15.2% (95% CI: 13.0–17.9) versus 42.8% (95% CI: 40.9–44.6) in 2012–2013 (p < .0001), less prevention of MTCT uptake (odds ratio [OR] in favor of adult mothers = 3.36, 95% CI: 2.95–3.83), and higher early MTCT (adjusted OR = 3.0, 95% CI: 1.1–8.0), respectively. Gestational age at first antenatal care booking was the only significant predictor of early MTCT among adolescents. Conclusions Interventions that appeal to adolescents and initiate sexual and reproductive health care early should be tested in low- and middle-income settings to reduce differential service uptake and infant outcomes between adolescent and adult mothers.

A single nucleotide polymorphism (SNP), 251 bases upstream from the IL-8 transcription start (−251A>T, rs4073), has been extensively investigated in cancers and inflammatory and infectious diseases in predominantly European and Asian populations. We sequenced the IL-8 gene of 109 black and 32 white South African (SA) individuals and conducted detailed characterization of gene variation and haplotype structure. IL-8 production in phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) of a subset (black: N = 22; white: N = 32) of these individuals was measured using ELISA. Select variants were genotyped for additional black individuals (N = 141), and data from the 1000 Genomes Project were used for haplotype analysis and comparative purposes. In white individuals, the −251A>T SNP formed part of a prevalent six-variant haplotype [haplotype frequency (HF): 61%], Hap-1C, involving the following variants: −251A>T; +394T>G (rs2227307); +780C>T (rs2227306); +1240->A (rs2227541); +1635C>T (rs2227543) and +2770A>T (rs2227543). Hap-1C (−251T+394T+780C+1240+A+1635C+2770A) was composed of two three-variant sub-haplotypes [Hap-1Ca: −251T+394T+1240+A; Hap-1Cb: +780C+1635C+2770A) sharing similarities with haplotypes identified in the black population. Hap-1C was found to be present in European, East and South Asian populations. Four haplotypes were identified in the black population with the two prevalent haplotypes each comprised of two variants: Hap-1B [−251A>T and +1240->A; −251T+1240+A; HF: 14%] and Hap-2B [−743T>C (rs2227532) and +2452A>C (rs2227545); −743C+2452C; HF: 13%]. Populations did not differ in unstimulated PBMC IL-8 production. Upon PHA stimulation, PBMCs from white individuals produced more IL-8 (P = 0.04), suggesting the −251T allele is responsible for higher production, however further analysis revealed that Hap-1C (and constituent sub-haplotypes), did not associate with IL-8 production. Populations did however differ in monocyte number with the white population having significantly more monocytes compared to the black population (P = 0.025), and furthermore monocyte number strongly correlated with IL-8 production in both population groups (black: p = 0.0002, r = 0.71; white: P = 0.0005, r = 0.59). Hap-1B, Hap-2B, and a SNP located one base pair upstream of the IL-8 ATG start codon, +100C>T SNP (rs2227538), all associated with higher IL-8 production in the black population - individuals harbouring at least one of these haplotypes/variant associated with higher IL-8 production (P = 0.003) compared to individuals without. The black population was enriched for individuals harbouring Hap-1B and/or Hap-2B compared to the 1000 Genomes project sub-Saharan African population (P = 0.006), suggesting that SA black individuals may be high IL-8 producers. Given the paucity of IL-8-related studies that have been conducted in populations from sub-Saharan Africa, this study has significantly increased our understanding of this important chemokine in the South African population.

Killer-cell Immunoglobulin-like Receptor (KIR) and Human Leukocyte Antigen (HLA) genotypes vary considerably between individuals and populations due to KIR/HLA allelic variation and variable haplotype configurations of KIR. HLA mediate natural killer cell activity by serving as KIR ligands. KIR/HLA polymorphisms associate with both disease susceptibility and severity. We determined the frequencies of KIR, KIR genotypes and KIR-HLA combinations in 364 healthy individuals from four South African populations. Study participants included black African (n = 167), Caucasian (n = 97), Mixed ancestry (n = 50) and Indian (n = 50) individuals. We identified 48 KIR genotypes that included two genotypes not previously reported. Based on KIR gene content, Indian individuals represented the most distinct group, showing the highest frequencies of KIR2DL2, KIR2DL5, KIR2DS1, KIR2DS2, KIR2DS3 and KIR3DS1, the lowest frequencies of KIR2DL3, KIR2DS4 and KIR3DL1; and a KIR2DL4-negative individual. KIR2DS1 and KIR3DS1 were infrequent in black African populations. HLA-C2 was more common in black African individuals, while HLA-C1 predominated in the other populations. Indian individuals were more likely to possess KIR2DL2 paired with HLA-C1, while Caucasian individuals exhibited the highest frequencies of KIR2DL3 paired with HLA-C1. This report provides comprehensive reference data for further study of the roles of KIR/HLA in non-communicable and infectious diseases in South African populations.

The incidence of HIV infection in young women in Africa is very high. We did a large-scale community-wide phylogenetic study to examine the underlying HIV transmission dynamics and the source and consequences of high rates of HIV infection in young women in South Africa.We did a cross-sectional household survey of randomly selected individuals aged 15-49 years in two neighbouring subdistricts (one urban and one rural) with a high burden of HIV infection in KwaZulu-Natal, South Africa. Participants completed structured questionnaires that captured general demographic, socioeconomic, psychosocial, and behavioural data. Peripheral blood samples were obtained for HIV antibody testing. Samples with HIV RNA viral load greater than 1000 copies per mL were selected for genotyping. We constructed a phylogenetic tree to identify clusters of linked infections (defined as two or more sequences with bootstrap or posterior support ≥90% and genetic distance ≤4·5%).From June 11, 2014, to June 22, 2015, we enrolled 9812 participants, 3969 of whom tested HIV positive. HIV prevalence (weighted) was 59·8% in 2835 women aged 25-40 years, 40·3% in 1548 men aged 25-40 years, 22·3% in 2224 women younger than 25 years, and 7·6% in 1472 men younger than 25 years. HIV genotyping was done in 1589 individuals with a viral load of more than 1000 copies per mL. In 90 transmission clusters, 123 women were linked to 103 men. Of 60 possible phylogenetically linked pairings with the 43 women younger than 25 years, 18 (30·0%) probable male partners were younger than 25 years, 37 (61·7%) were aged 25-40 years, and five (8·3%) were aged 41-49 years: mean age difference 8·7 years (95% CI 6·8-10·6; p0·0001). For the 92 possible phylogenetically linked pairings with the 56 women aged 25-40 years, the age difference dropped to 1·1 years (95% CI -0·6 to 2·8; p=0·111). 16 (39·0%) of 41 probable male partners linked to women younger than 25 years were also linked to women aged 25-40 years. Of 79 men (mean age 31·5 years) linked to women younger than 40 years, 62 (78·5%) were unaware of their HIV-positive status, 76 (96·2%) were not on antiretroviral therapy, and 29 (36·7%) had viral loads of more than 50 000 copies per mL.Sexual partnering between young women and older men, who might have acquired HIV from women of similar age, is a key feature of the sexual networks driving transmission. Expansion of treatment and combination prevention strategies that include interventions to address age-disparate sexual partnering is crucial to reducing HIV incidence and enabling Africa to reach the goal of ending AIDS as a public health threat.President's Emergency Program for AIDS Relief, US Centers for Disease Control and Prevention, South African Medical Research Council, and MAC AIDS Fund.

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. Keywords: Pregnant women, Surveillance, Test agreement, PMTCT, Rapid testing, South Africa

Background South Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT). The first study was conducted in 2010 (under the dual therapy PMTCT policy), the second from 2011 to 12 (PMTCT Option A policy) and the third from 2012 to 13 (PMTCT Option A policy). From 2010 to 2013, infant non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure increased from single dose to daily throughout breastfeeding; maternal nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI exposure increased with initiation of NNRTI-and NRTI- containing triple antiretroviral therapy (ART) earlier in gestation and at higher CD4 cell counts. Methods Three nationally representative surveys were conducted in 2010, 2011–12 and 2012–13. During the surveys, mothers with known, unknown, or no exposure to antiretrovirals for PMTCT and their infants were included, and MTCT was measured. For this paper, infant dried blood spots (iDBS) from HIV PCR positive infants aged 4–8 weeks, with consent for additional iDBS testing, were analysed for HIV drug resistance at the National Institute of Communicable Diseases (NICD), SA, using an in-house assay validated by the Centers for Disease Control and Prevention (CDC). Total viral nucleic acid was extracted from 2 spots and amplified by nested PCR to generate a ~ 1 kb amplicon that was sequenced using Sanger sequencing technologies. Sequence assembly and editing was performed using RECall v3. Results Overall, HIV-1 drug resistance was detected in 51% (95% Confidence interval (CI) [45–58%]) of HIV PCR positive infants, 37% (95% CI [28–47%]) in 2010, 64% (95% CI [53–74%]) in 2011 and 63% (95% CI [47–77%]) in 2012 (p Conclusions These data demonstrate increasing NNRTI resistance amongst newly-diagnosed infants in a high HIV prevalence setting where maternal ART coverage increased across the years, starting earlier in gestation and at higher CD4 cell counts. This is worrying as lifelong maternal ART coverage for HIV positive pregnant and lactating women is increasing. Also of concern is that resistant virus was detected in HIV positive infants whose mothers were not exposed to ARVs, raising questions about circulating resistant virus. Numbers in this group were too small to assess trends over the three years.

Background: People who use drugs including people who inject drugs (PWUD/ID), sex workers (SWs) and men who have sex with men (MSM) are at increased risk for HIV and viral hepatitis infection. Limited data exists on the epidemiology of these infections among these key population groups (KPs) in South Africa. We aimed to describe the prevalence of hepatitis B (HBV), hepatitis C (HCV) and HIV and related risk factors among these KPs to inform effective responses. Methods: We aimed to recruit 3 500 KPs across Cape Town (SWs, MSM, PWUD/ID), Durban (SWs, PWUD/ID), Pietermaritzburg (SWs), Mthatha (SWs), Port Elizabeth (SWs), Johannesburg (MSM) and Pretoria (MSM and PWUD/ID) for participation in a cross-sectional survey. We used an interviewer administered questionnaire to assess socio-demographic characteristics, drug use and sexual risk practices. We tested for HCV (antibody, viral load and genotype), HBV surface antigen (HBsAg) and HIV antibody. We used descriptive statistics to explore data, which was stratified by KP. Results: Among the 3 439 included in the study (1 528 SWs, 746 MSM, 1 165 PWUD/ID) the median age was 29 years, most participants were black African (60%), and 24% reported homelessness. 82% reported substance use in the last month, including alcohol (46%) and heroin (33%). 75% were sexually active in the previous month, with condom use at last sex at 74%. HIV prevalence was 37% (highest among SWs at 47%), HBsAg prevalence 4% (similar across KPs) and HCV prevalence of 16% (highest among PWUD/ID at 46%). Conclusions: HCV, HBV and HIV are major health threats for KPs in South Africa. While HIV is an important condition for all included KPs, HCV is of particular importance to PWUD/ID. For KPs, HBV vaccination and behaviour change interventions that support consistent condom and lubricant access and use are needed. Coverage of opioid substitution therapy and needle and syringe services and access to HCV treatment for PWUD/ID need to be expanded.

Background People who inject drugs (PWID) are at high risk for hepatitis C (HCV), hepatitis B (HBV) and HIV without accessible harm reduction programmes. Coverage of needle and syringe and opioid substitution therapy (OST) services in South Africa is below global recommendations and no hepatitis services exist for PWID. We assessed HCV, HBV and HIV prevalence and risk factors among PWID accessing harm reduction services in Cape Town, Durban and Pretoria to inform policy and programming. Methods We conducted a cross-sectional survey among PWID in these cities between August 2016 and October 2017. Participants were opportunistically sampled while accessing services. Study team members administered a questionnaire that assessed sociodemographic characteristics, drug use and sexual risk practices. We tested for HCV (antibody, viral load and genotype), HBV surface antigen (HBsAg) and HIV. Bivariate and multivariate analyses assessed associations with HCV serostatus. Results Nine hundred and forty-three PWID were included in the per protocol analysis. The majority (87%, 819/943) were male, the overall median age was 29 and most lived on the street (66%, 626/943). At last injection, 77% (722/943) reported using a new needle and syringe and 17% (163/943) shared equipment. HIV prevalence was 21% (196/926), HBsAg positivity 5% (47/936), HCV seroprevalence 55% (513/937), HCV viraemic prevalence (proportion tested with detectable HCV) 43% (404/937) and HCV viraemic rate (proportion HCV antibody positive with detectable HCV) 79% (404/513). HCV genotype 1a (73%, 270/368) was the most prevalent. In multivariate analysis, HCV infection was positively associated with residing in Pretoria (adjusted odds ratio (aOR) 1.27, 95% CI 1.21–1.34), living on the street (aOR 1.90, 95% CI 1.38–2.60), frequent injecting (aOR 1.58, 95% CI 1.15–2.16) and HIV infection (aOR 1.69, 95% CI 1.15–2.47), and negatively associated with black race (aOR 0.52, 95% CI 0.36–0.74) and sexual activity in the previous month (aOR 0.61, 95% CI 0.42–0.88). Conclusions HCV and HIV are major health threats affecting PWID in these cities. Access to OST and needle and syringe services needs to be increased and integrated with HCV services. Social and structural factors affecting PWID who live on the street need to be addressed.

HIV diagnostics have played a central role in the remarkable progress in identifying, staging, initiating, and monitoring infected individuals on life-saving antiretroviral therapy. They are also useful in surveillance and outbreak responses, allowing for assessment of disease burden and identification of vulnerable populations and transmission "hot spots," thus enabling planning, appropriate interventions, and allocation of appropriate funding. HIV diagnostics are critical in achieving epidemic control and require a hybrid of conventional laboratory-based diagnostic tests and new technologies, including point-of-care (POC) testing, to expand coverage, increase access, and positively impact patient management. In this review, we provide (i) a historical perspective on the evolution of HIV diagnostics (serologic and molecular) and their interplay with WHO normative guidelines, (ii) a description of the role of conventional and POC testing within the tiered laboratory diagnostic network, (iii) information on the evaluations and selection of appropriate diagnostics, (iv) a description of the quality management systems needed to ensure reliability of testing, and (v) strategies to increase access while reducing the time to return results to patients. Maintaining the central role of HIV diagnostics in programs requires periodic monitoring and optimization with quality assurance in order to inform adjustments or alignment to achieve epidemic control.

We describe knowledge of human immunodeficiency virus (HIV) status, correct report of HIV status and antiretroviral therapy (ART) use among sexually transmitted infection (STI) service attendees in South Africa. An anonymous questionnaire was administered and serological HIV testing done. Proportions of attendees reporting knowledge of HIV status and HIV status consistent with laboratory results and ART use (among HIV positives) were determined as were factors associated with knowledge and inconsistent report of HIV status. Of 1054 attendees, 288 (27.3%) were HIV positive and 830 (78.8%) self-reported knowledge of HIV status. Not knowing one's HIV status was associated with male gender [adjusted Odds Ratio (aOR) 2.66 (95% confidence interval (CI) 1.70–4.18] medical circumcision [aOR 0.48 (95% CI 0.24–0.95)] and site [Gauteng Province (GP)-aOR 6.20 (95% CI 3.51–10.95), Eastern Cape (EC)-aOR 17.29 (95% CI 10.08– 29.66) versus Free State (FS)/Western Cape (WC) sites]. Of 219 HIV positive attendees with knowledge of HIV status, 136 (62.1%) self-reported being HIV positive, of whom 80 (58.8%) reported taking ARVs in the preceding 3 days. Inconsistent report of status was associated with males [aOR 2.26 (95%CI 1.05–4.87)], prior STI treatment [aOR 0.33 (95% CI 0.16–0.69)], recent HIV testing (6months) [aOR 3.20 (95% CI 1.62–6.36)] and site [GP-aOR 6.89 (95% 3.21–14.82), EC-aOR 5.08 (95% CI 2.15–11.64) versus FS/WC sites]. Knowledge of HIV status was lower than targeted. HIV testing and linkage to care services are essential in STI-related care and validation of self-reported indicators in this population maybe necessary.

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., Jacob Bor and co-workers use a new measure of care quality to report on facility-level variations in HIV care and outcomes in South Africa., Author summary Why was this study done? Health outcomes have improved as South Africa has expanded access to HIV treatment, yet gaps in the quality of care remain. We develop a measure of quality of HIV care for public sector health facilities in South Africa using harmonized routine data and describe variation in quality over time and space. What did the researchers do and find? We define a measure of quality of HIV care for facilities from 2011 to 2015 using data from the National Health Laboratory Service (NHLS) Corporate Data Warehouse, which have been deduplicated to enable longitudinal patient follow-up. Measures of care outreach, retention, CD4 recovery, viral monitoring, and viral suppression were combined into an index using factor analysis. The quality measure had high reliability across years. Quality improved over the 5 years of the study and was higher in clinics relative to hospitals, in larger facilities, and in rural facilities. High-quality facilities tended to cluster near one another geographically. Quality of care was lower in high-poverty areas, but was not independently correlated with racial composition. What do these findings mean? While quality of HIV care improved in South Africa over the 5 years of the study, there was large variation in quality across facilities. Understanding differences in quality of care over time and across space could guide interventions to achieve better health outcomes.

BackgroundAttrition along the HIV care continuum slows gains in mitigating the South African HIV epidemic. Understanding population-level gaps in HIV identification, linkage, retention in care, and viral suppression is critical to target programming.MethodsWe conducted a population-based household survey, HIV rapid testing, point-of-care CD4 testing, and viral load measurement from dried blood spots using multistage cluster sampling in 2 subdistricts of North West Province from January to March, 2014. We used weighting and multiple imputation of missing data to estimate HIV prevalence, undiagnosed infection, linkage and retention in care, medication adherence, and viral suppression.ResultsWe sampled 1044 respondents aged 18-49. HIV prevalence was 20.0% (95% confidence interval: 13.7 to 26.2) for men and 26.7% (95% confidence interval: 22.1 to 31.4) for women. Among those HIV positive, 48.4% of men and 75.7% of women were aware of their serostatus; 44.0% of men and 74.8% of women reported ever linking to HIV care; 33.1% of men and 58.4% of women were retained in care; and 21.6% of men and 50.0% of women had dried blood spots viral loads

Summary There are limited molecular epidemiological studies of hepatitis C at a national level in South Africa. The introduction of newer treatment modalities for hepatitis C requires knowledge of the genotypes as these may have different prognostic and therapeutic implications. This retrospective study describes genotype distributions of patients attending specialist clinics and a blood donor group studied during the period 2008–2012 in South Africa. Residual samples from diagnostic viral load testing from specialist clinics in South Africa (n=941) and from the South African National Blood Service (n=294) were analysed quantitatively by real-time PCR and genotyped using the Versant line probe assay or sequencing. Genotype 1 was predominant in blood donors (34%), whilst genotype 5a was prevalent in patients (36%). In the blood donor group, genotype 4 was detected for the first time. Genotype 2 was rare in the patient group and not detected in blood donors. Genotype 1 was the predominant genotype in the younger age groups (less than 30 years), whereas genotype 5a was found at higher proportions in the older age groups for both the patient and blood donor groups, comprising more than 60% of genotypes in those older than 50 years. Genotypes 1 and 5 were at highest proportions across all provinces compared to other genotypes. In blood donors, genotype 1 was predominant among Caucasians (43%) and genotype 5a among Blacks (54%). Such information is required for planning the impact on the health sector with regard to newly emerging therapies for hepatitis C and burden of disease.

Approximately 1 million South Africans are infected with Hepatitis C virus (HCV). The standard of care (SOC) in South Africa is combination therapy (pegylated interferon and ribavirin). HCV genotypes and/or mutations in the core/non-structural regions have been associated with response to therapy and/or disease progression. This study examines mutations in the core (29-280 amino acids, including ∼ 90 E1 amino acids) and NS5B (241-306 amino acids) regions on pre-treatment isolates from patients attending Johannesburg hospitals or asymptomatic South African blood donors. Diversity within known CD4+ and CD8+ T-cell epitopes was also explored. Samples grouped into subtypes 1a(N = 10) 1b(N = 12), 3a(N = 5), 4a(N = 3) and 5a(N = 61). Two mutations, associated with interferon resistance-R70Q and T110N-were present in 29 genotype 5a core sequences. No resistance mutation to NS5B nucleotide inhibitors, sofosbuvir was found. Six putative CD8+ and one CD4+ T-cell epitope sequence in the core region showed binding scores of

This community-based cohort study examines trends in coverage of HIV prevention and treatment programs and HIV incidence among adults in the hyperendemic area of KwaZulu-Natal, South Africa., Key Points Question What are the trends in the coverage of HIV prevention and treatment programs and HIV incidence in a hyperendemic area of KwaZulu-Natal, South Africa? Findings This community-based cohort study of 2 sequential surveys in 9812 and 10 236 respondents showed that HIV incidence in young women (aged 15-19 years) declined significantly from 4.63 to 2.74 per 100 person-years, but declines were marginal or remained unchanged among men and women in other age groups. In parallel, the uptake of medical male circumcision, knowledge of HIV-positive status, antiretroviral therapy, and viral suppression increased. Meaning These findings suggest that, to further reduce HIV incidence, prevention and treatment program coverage must be intensified and scaled up., Importance In Africa, the persistently high HIV incidence rate among young women is the major obstacle to achieving the goal of epidemic control. Objective To determine trends in coverage of HIV prevention and treatment programs and HIV incidence. Design, Setting, and Participants This cohort study consisted of 2 sequential, community-based longitudinal studies performed in the Vulindlela and Greater Edendale area in KwaZulu-Natal, South Africa. Participants enrolled from June 11, 2014, to June 22, 2015 (2014 survey), with a single follow-up visit from June 24, 2016, to April 3, 2017 (2016 cohort), or enrolled from July 8, 2015, to June 7, 2016 (2015 survey), with a single follow-up visit from November 7, 2016, to August 30, 2017 (2017 cohort). Men and women aged 15 to 49 years were enrolled in the 2014 and 2015 surveys, and HIV-seronegative participants aged 15 to 35 years were followed up in the 2016 and 2017 cohorts. Analysis was conducted from January 1 through December 31, 2018. Exposures HIV prevention and treatment programs in a real-world, nontrial setting. Main Outcomes and Measures Trends in sex- and age-specific HIV incidence rates, condom use, voluntary medical male circumcision, knowledge of HIV-seropositive status, uptake of antiretroviral therapy, and viral suppression. Results A total of 9812 participants (6265 women [63.9%]; median age, 27 years [interquartile range, 20-36 years]) from 11 289 households were enrolled in the 2014 survey, and 10 236 participants (6341 women [61.9%]; median age, 27 years [interquartile range, 20-36 years]) from 12 247 households were enrolled in the 2015 survey. Of these, 3536 of 4539 (annual retention rate of 86.7%) completed follow-up in the 2016 cohort, and 3907 of 5307 (annual retention rate of 81.4%) completed follow-up in the 2017 cohort. From 2014 to 2015, condom use with last sex partner decreased by 10% from 24.0% (n = 644 of 3547) to 21.6% (n = 728 of 3895; P = .12) in men and by 17% from 19.6% (n = 1039 of 6265) to 16.2% (n = 871 of 6341; P = .002) in women. Voluntary medical male circumcision increased by 13% from 31.9% (1102 of 3547) to 36.1% (n = 1472 of 3895); P = .007) in men, and the proportion of women reporting that their partner was circumcised increased by 35% from 35.7% (n = 1695 of 4766) to 48.2% (n = 2519 of 5207; P

This mixed-methods study used qualitative interviews to explore discrepancies between self-reported HIV care and treatment-related behaviors and the presence of antiretroviral medications (ARVs) in a population-based survey in South Africa. ARV analytes were identified among 18% of those reporting HIV-negative status and 18% of those reporting not being on ART. Among participants reporting diagnosis over a year prior, 19% reported multiple HIV tests in the past year. Qualitative results indicated that participant misunderstandings about their care and treatment played a substantial role in reporting inaccuracies. Participants conflated the term HIV test with CD4 and viral load testing, and confusion with terminology was compounded by recall difficulties. Data entry errors likely also played a role. Frequent discrepancies between biomarkers and self-reported data were more likely due to poor understanding of care and treatment and biomedical terminology than intentional misreporting. Results indicate a need for improving patient-provider communication, in addition to incorporating objective measures of treatment and care behaviors such as ARV analytes, to reduce inaccuracies.

The gap in HIV testing remains significant and new modalities such as HIV self-testing (HIVST) have been recommended to reach key and under-tested populations. In December 2016, the World Health Organization (WHO) released the Guidelines on HIV Self-Testing and Partner Notification: A Supplement to the Consolidated Guidelines on HIV Testing Services (HTS) and urged member countries to develop HIVST policy and regulatory frameworks. In South Africa, HIVST was included as a supplementary strategy in the National HIV Testing Services Policy in 2016, and recently, guidelines for HIVST were included in the South African National Strategic Plan for HIV, sexually transmitted infections and tuberculosis 2017–2022. This document serves as an additional guidance for the National HIV Testing Services Policy 2016, with specific focus on HIVST. It is intended for policy advocates, clinical and non-clinical HTS providers, health facility managers and healthcare providers in private and public health facilities, non-governmental, community-based and faith-based organisations involved in HTS and outreach, device manufacturers, workplace programmes and institutes of higher education.

Negative results on standard HIV antibody tests have been described among HIV-infected children suppressed on antiretroviral therapy (ART) started early in life. Here, we describe the frequency and predictors of this phenomenon in a well characterized cohort of treated children.We selected samples from 103 HIV-infected children who started ART 14 months of age or less and from 122 children who started 6 months of age or less followed as part of two sequential clinical trials in Johannesburg, South Africa. Children had attained viral suppression on ART and had received ART for between 3 and 6.4 years (mean 4.3 years) when tested for HIV antibody using a standard ELISA (Genescreen HIV1/2 version 2; Bio-rad).Only children 6 months of age or less when ART was started had negative antibody results when tested after suppression on ART several years later. Negative or low-positive antibody results were observed in 40.0, 37.0 and 27.8% of children starting ART less than 2 months of age, or starting during month 2 or 3, respectively. This dropped to 5.9, 3.5 and 5.3% if ART was started during month 4, 5 and 6, respectively. Higher CD4 percentage prior to ART initiation and no recorded intermittent viremia also predicted negative antibody results.Testing negative on standard HIV antibody tests occurs fairly commonly among HIV-infected children who started ART 3 months of age or less and are virally suppressed. It would be prudent in clinical practice to avoid HIV antibody tests among virally suppressed, early-treated children to prevent unnecessary confusion.

Background There is a paucity of data on the national population-level effectiveness of preventing mother-to-child transmission (PMTCT) programmes in high-HIV-prevalence, resource-limited settings. We assessed national PMTCT impact in South Africa (SA), 2010. Methods A facility-based survey was conducted using a stratified multistage, cluster sampling design. A nationally representative sample of 10 178 infants aged 4–8 weeks was recruited from 565 clinics. Data collection included caregiver interviews, record reviews and infant dried blood spots to identify HIV-exposed infants (HEI) and HIV-infected infants. During analysis, self-reported antiretroviral (ARV) use was categorised: 1a: triple ARV treatment; 1b: azidothymidine >10 weeks; 2a: azidothymidine ≤10 weeks; 2b: incomplete ARV prophylaxis; 3a: no antenatal ARV and 3b: missing ARV information. Findings were adjusted for non-response, survey design and weighted for live-birth distributions. Results Nationally, 32% of live infants were HEI; early mother-to-child transmission (MTCT) was 3.5% (95% CI 2.9% to 4.1%). In total 29.4% HEI were born to mothers on triple ARV treatment (category 1a) 55.6% on prophylaxis (1b, 2a, 2b), 9.5% received no antenatal ARV (3a) and 5.5% had missing ARV information (3b). Controlling for other factors groups, 1b and 2a had similar MTCT to 1a (Ref; adjusted OR (AOR) for 1b, 0.98, 0.52 to 1.83; and 2a, 1.31, 0.69 to 2.48). MTCT was higher in group 2b (AOR 3.68, 1.69 to 7.97). Within group 3a, early MTCT was highest among breastfeeding mothers 11.50% (4.67% to 18.33%) for exclusive breast feeding, 11.90% (7.45% to 16.35%) for mixed breast feeding, and 3.45% (0.53% to 6.35%) for no breast feeding). Antiretroviral therapy or >10 weeks prophylaxis negated this difference (MTCT 3.94%, 1.98% to 5.90%; 2.07%, 0.55% to 3.60% and 2.11%, 1.28% to 2.95%, respectively). Conclusions SA, a high-HIV-prevalence middle income country achieved

Introduction : We describe the overall accuracy and performance of a serial rapid HIV testing algorithm used in community-based HIV testing in the context of a population-based household survey conducted in two sub-districts of uMgungundlovu district, KwaZulu-Natal, South Africa, against reference fourth-generation HIV-1/2 antibody and p24 antigen combination immunoassays. We discuss implications of the findings on rapid HIV testing programmes. Methods : Cross-sectional design: Following enrolment into the survey, questionnaires were administered to eligible and consenting participants in order to obtain demographic and HIV-related data. Peripheral blood samples were collected for HIV-related testing. Participants were offered community-based HIV testing in the home by trained field workers using a serial algorithm with two rapid diagnostic tests (RDTs) in series. In the laboratory, reference HIV testing was conducted using two fourth-generation immunoassays with all positives in the confirmatory test considered true positives. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value and false-positive and false-negative rates were determined. Results : Of 10,236 individuals enrolled in the survey, 3740 were tested in the home (median age 24 years (interquartile range 19–31 years), 42.1% males and HIV positivity on RDT algorithm 8.0%). From those tested, 3729 (99.7%) had a definitive RDT result as well as a laboratory immunoassay result. The overall accuracy of the RDT when compared to the fourth-generation immunoassays was 98.8% (95% confidence interval (CI) 98.5–99.2). The sensitivity, specificity, positive predictive value and negative predictive value were 91.1% (95% CI 87.5–93.7), 99.9% (95% CI 99.8–100), 99.3% (95% CI 97.4–99.8) and 99.1% (95% CI 98.8–99.4) respectively. The false-positive and false-negative rates were 0.06% (95% CI 0.01–0.24) and 8.9% (95% CI 6.3–12.53). Compared to true positives, false negatives were more likely to be recently infected on limited antigen avidity assay and to report antiretroviral therapy (ART) use. Conclusions : The overall accuracy of the RDT algorithm was high. However, there were few false positives, and the sensitivity was lower than expected with high false negatives, despite implementation of quality assurance measures. False negatives were associated with recent (early) infection and ART exposure. The RDT algorithm was able to correctly identify the majority of HIV infections in community-based HIV testing. Messaging on the potential for false positives and false negatives should be included in these programmes. Keywords HIV; antibody testing; sensitivity; specificity; misdiagnosis (Published: 29 August 2017) Kufa T et al. Journal of the International AIDS Society 2017, 20 :21753 http://www.jiasociety.org/index.php/jias/article/view/21753 | http://dx.doi.org/10.7448/IAS.20.7.21753

Background South Africa has utilized three independent data sources to measure the impact of its program for the prevention of mother–to–child transmission (PMTCT) of HIV. These include the South African National Health Laboratory Service (NHLS), the District Health Information System (DHIS), and South African PMTCT Evaluation (SAPMTCTE) surveys. We compare the results of each, outlining advantages and limitations, and make recommendations for monitoring transmission rates as South Africa works toward achieving elimination of mother–to–child transmission (eMTCT). Methods HIV polymerase chain reaction (PCR) test data, collected between 1 January 2010 to 31 December 2014, from the NHLS, DHIS and SAPMTCTE surveys were used to compare early mother–to–child transmission (MTCT) rates in South Africa. Data from the NHLS and DHIS were also used to compare early infant diagnosis (EID) coverage. Results The age–adjusted NHLS early MTCT rates of 4.1% in 2010, 2.6% in 2011 and 2.3% in 2012 consistently fall within the 95% confidence interval as measured by three SAPMTCTE surveys in corresponding time periods. Although DHIS data over–estimated MTCT rates in 2010, the MTCT rate declines thereafter to converge with age–adjusted NHLS MTCT rates by 2012. National EID coverage from NHLS data increases from around 52% in 2010 to 87% in 2014. DHIS data over–estimates EID coverage, but this can be corrected by employing an alternative estimate of the HIV–exposed infant population. Conclusion NHLS and DHIS, two routine data sources, provide very similar early MTCT rate estimates that fall within the SAPMTCTE survey confidence intervals for 2012. This analysis validates the usefulness of routine data sources to track eMTCT in South Africa.

BACKGROUND We characterize engagement with HIV care in South Africa in 2012 to identify areas for improvement towards achieving global 90-90-90 targets. METHODS Over 3.9 million CD4 cell count and 2.7 million viral load measurements reported in 2012 in the public sector were extracted from the national laboratory electronic database. The number of persons living with HIV (PLHIV), number and proportion in HIV care, on antiretroviral therapy (ART) and with viral suppression (viral load

Background Eliminating mother–to–child transmission of HIV (EMTCT), defined as ≤50 infant HIV infections per 100 000 live births, is a global priority. Since 2011 policies to prevent mother–to–child transmission of HIV (PMTCT) shifted from maternal antiretroviral (ARV) treatment or prophylaxis contingent on CD4 cell count to lifelong maternal ARV treatment (cART). We sought to measure progress with early (4–8 weeks postpartum) MTCT prevention and elimination, 2011–2013, at national and sub–national levels in South Africa, a high antenatal HIV prevalence setting ( ≈ 29%), where early MTCT was 3.5% in 2010. Methods Two surveys were conducted (August 2011–March 2012 and October 2012–May 2013), in 580 health facilities, randomly selected after two–stage probability proportional to size sampling of facilities (the primary sampling unit), to provide valid national and sub–national–(provincial)–level estimates. Data collectors interviewed caregivers of eligible infants, reviewed patient–held charts, and collected infant dried blood spots (iDBS). Confirmed positive HIV enzyme immunoassay (EIA) and positive total HIV nucleic acid polymerase chain reaction (PCR) indicated infant HIV exposure or infection, respectively. Weighted survey analysis was conducted for each survey and for the pooled data. Findings National data from 10 106 and 9120 participants were analyzed (2011–12 and 2012–13 surveys respectively). Infant HIV exposure was 32.2% (95% confidence interval (CI) 30.7–33.6%), in 2011–12 and 33.1% (95% CI 31.8–34.4%), provincial range of 22.1–43.6% in 2012–13. MTCT was 2.7% (95% CI 2.1%–3.2%) in 2011–12 and 2.6% (95% CI 2.0–3.2%), provincial range of 1.9–5.4% in 2012–13. HIV–infected ARV–exposed mothers had significantly lower unadjusted early MTCT (2.0% [2011–12: 1.6–2.5%; 2012–13:1.5–2.6%]) compared to HIV–infected ARV–naive mothers [10.2% in 2011–12 (6.5–13.8%); 9.2% in 2012–13 (5.6–12.7%)]. Pooled analyses demonstrated significantly lower early MTCT among exclusive breastfeeding (EBF) mothers receiving >10 weeks ARV prophylaxis or cART compared with EBF and no ARVs: (2.2% [95% CI 1.25–3.09%] vs 12.2% [95% CI 4.7–19.6%], respectively); among HIV–infected ARV–exposed mothers, 24.9% (95% CI 23.5–26.3%) initiated cART during or before the first trimester, and their early MTCT was 1.2% (95% CI 0.6–1.7%). Extrapolating these data, assuming 32% EIA positivity and 2.6% or 1.2% MTCT, 832 and 384 infants per 100 000 live births were HIV infected, respectively. Conclusions Although we demonstrate sustained national–level PMTCT impact in a high HIV prevalence setting, results are far–removed from EMTCT targets. Reducing maternal HIV prevalence and treating all maternal HIV infection early are critical for further progress.

BackgroundWe describe CD4 count recovery among HIV positive individuals who initiated antiretroviral therapy (ART) with and without severe immune suppression using complete laboratory data from South Africa's national HIV treatment programme between 2010 and 2014 and discuss implications for CD4 count monitoring.MethodsRetrospective analysis of routinely collected laboratory data from South Africa's National Health Laboratory Service (NHLS). A probabilistic record linkage algorithm was used to create a cohort of HIV positive individuals who initiated ART between 2010 and 2014 based on timing of CD4 count and viral load measurements. A CD4 count < 50 copies/μl at ART initiation was considered severe immunosuppression. A multivariable piecewise mixed-effects linear regression model adjusting for age, gender, year of starting ART, viral suppression in follow up and province was used to predict CD4 counts during follow up.Results1,070,900 individuals had evidence of starting ART during 2010-2014 and met the criteria for inclusion in the cohort -46.6% starting ART with CD4 < 200 cells/μl and 10.1% with CD4 < 50 cells/ μl. For individuals with CD4 counts < 200 cells/μl, predicted CD4 counts > 200 cells/μl, >350 cells/μl and >500 cells/μl corresponded with mean follow up durations of 1.5 years (standard deviation [s.d] 1.1), 1.9years (s.d 1.2) and 2.1 years (s.d 1.3 years). For those with CD4 counts < 50 cells/μl, predicted CD4 count above these threshold corresponded with mean follow up durations of 2.5 years (s.d 0.9 years), 4.4 years (s.d 0.4 years) and 5.0 years (s.d 0.1years) for recovery to the same thresholds. CD4 count recovery varied mostly with duration on ART, CD4 count at the start of ART and gender.ConclusionFor individuals starting with ART with severe immunosuppression, CD4 recovery to 200cells/μl did not occur or took longer than 12 month for significant proportions. CD4 monitoring and interventions recommended for advanced HIV disease should continue until full recovery.

To develop a model for identifying areas at high risk for sporadic measles outbreaks based on an analysis of factors associated with a national outbreak in South Africa between 2009 and 2011.Data on cases occurring before and during the national outbreak were obtained from the South African measles surveillance programme, and data on measles immunization and population size, from the District Health Information System. A Bayesian hierarchical Poisson model was used to investigate the association between the risk of measles in infants in a district and first-dose vaccination coverage, population density, background prevalence of human immunodeficiency virus (HIV) infection and expected failure of seroconversion. Model projections were used to identify emerging high-risk areas in 2012.A clear spatial pattern of high-risk areas was noted, with many interconnected (i.e. neighbouring) areas. An increased risk of measles outbreak was significantly associated with both the preceding build-up of a susceptible population and population density. The risk was also elevated when more than 20% of infants in a populous area had missed a first vaccine dose. The model was able to identify areas at high risk of experiencing a measles outbreak in 2012 and where additional preventive measures could be undertaken.The South African measles outbreak was associated with the build-up of a susceptible population (owing to poor vaccine coverage), high prevalence of HIV infection and high population density. The predictive model developed could be applied to other settings susceptible to sporadic outbreaks of measles and other vaccine-preventable diseases.Mettre au point un modèle permettant d'identifier les zones à haut risque d'épidémies sporadiques de rougeole, sur la base d'une analyse des facteurs associés à une épidémie nationale en Afrique du Sud, entre 2009 et 2011.Les données sur les cas survenus avant et pendant l'épidémie nationale ont été obtenues auprès du programme sud-africain de surveillance de la rougeole, et les données sur la vaccination contre la rougeole et la taille de la population auprès du système d'informations sanitaires des districts. Un modèle hiérarchique bayésien de Poisson a été utilisé pour étudier l'association entre le risque de rougeole chez les nourrissons dans un district et la couverture vaccinale pour la première dose, la densité de population, la prévalence sous-jacente de l'infection par le virus de l'immunodéficience humaine (VIH) et l'échec attendu de la séroconversion. Les projections du modèle ont été utilisées pour identifier les nouvelles zones à haut risque en 2012.Un schéma spatial clair des zones à haut risque a été observé, avec de nombreuses zones interconnectées (c'est-à-dire voisines). Un risque accru d'épidémie de rougeole a été significativement associé à la constitution préalable d'une population vulnérable ainsi qu'à la densité de population. Le risque était aussi élevé lorsque plus de 20% des nourrissons dans une zone fortement peuplée n'avaient pas reçu une première dose du vaccin. Le modèle a été en mesure d'identifier les zones à haut risque d’épidémie de rougeole en 2012, ainsi que là où des mesures préventives supplémentaires pourraient être prises.L'épidémie de rougeole en Afrique du Sud a été associée à la constitution d'une population vulnérable (en raison d'une couverture vaccinale médiocre), à la prévalence élevée de l'infection par le VIH et à une forte densité de population. Le modèle prédictif développé pourrait être appliqué à d'autres contextes sensibles aux épidémies sporadiques de rougeole et à d'autres maladies qui peuvent être prévenues par la vaccination.Desarrollar un modelo para identificar las áreas con riesgo alto de sufrir brotes esporádicos de sarampión en base a un análisis de los factores asociados a un brote nacional en Sudáfrica entre los años 2009 y 2011.Los datos de los casos ocurridos antes y durante el brote nacional se obtuvieron del programa de vigilancia del sarampión de Sudáfrica, y la información acerca de la vacunación contra el sarampión y el tamaño de la población, del sistema de información sanitaria por distritos. Se empleó un modelo de Poisson jerárquico bayesiano para investigar la relación entre el riesgo de sarampión en niños de un distrito con la cobertura de la primera dosis de la vacuna, la densidad de población, el historial de prevalencia de la infección por el virus de la inmunodeficiencia humana (VIH) y el fracaso previsto de la seroconversión. Las proyecciones del modelo se utilizaron para identificar áreas de alto riesgo nuevas en 2012.Se observó un patrón espacial claro de las áreas de alto riesgo con muchas zonas conectadas (esto es, colindantes). El riesgo superior de sufrir un brote de sarampión se asoció de modo significativo tanto con el crecimiento previo de un grupo de población vulnerable como con la densidad de población, y también fue elevado cuando más del 20% de los niños en un área populosa no había recibido la primera dosis de la vacuna. El modelo fue capaz de identificar las áreas con riesgo alto de sufrir un brote de sarampión en 2012 y donde podrían emprenderse medidas de prevención adicionales.El brote de sarampión en Sudáfrica estuvo asociado con el aumento de un grupo de población vulnerable (debido a una cobertura de vacunación insuficiente), una prevalencia elevada de la infección por VIH y una densidad de población alta. El modelo predictivo desarrollado podría aplicarse a otros lugares susceptibles de sufrir brotes esporádicos de sarampión y otras enfermedades inmunoprevenibles.وضع نموذج لتحديد المناطق شديدة التعرض لمخاطر فاشيات الحصبة الفرادية بالاستناد إلى تحليل للعوامل المرتبطة بفاشية وطنية في جنوب أفريقيا في الفترة من 2009 إلى 2011.تم الحصول على بيانات حول الحالات الواقعة قبل الفاشية الوطنية وأثناءها من برنامج ترصد الحصبة في جنوب أفريقيا، وبيانات حول التمنيع ضد الحصبة وحجم السكان من نظام المعلومات الصحية للمناطق. وتم استخدام نموذج بواسون الهرمي وفق نظرية بايز لتحري الارتباط بين مخاطر الحصبة لدى الرضع في تغطية التطعيم بالجرعة الأولى من لقاح الحصبة على مستوى المقاطعة والكثافة السكانية ومدى الانتشار الأساسي لعدوى فيروس العوز المناعي البشري والفشل المتوقع في انقلاب تفاعلية المصل. وتم استخدام استقراءات النموذج لتحديد المناطق شديدة التعرض للمخاطر المستجدة في عام 2012.لوحظ وجود نمط مكاني واضح للمناطق شديدة التعرض للمخاطر مع وجود العديد من المناطق المتداخلة (أي المتجاورة). وارتبط ازدياد مخاطر فاشية الحصبة إلى حد كبير بكل من التراكم السابق للسكان سريعي التأثر والكثافة السكانية. وازدادت كذلك المخاطر عندما فوت 20 % من الرضع في منطقة مكتظة بالسكان الجرعة الأولى من اللقاح. واستطاع النموذج تحديد المناطق شديدة التعرض لمخاطر الإصابة بفاشية الحصبة في عام 2012 والمناطق التي يمكن اتخاذ تدابير وقائية إضافية فيها.ارتبطت فاشية الحصبة في جنوب أفريقيا بتراكم السكان سريعي التأثر (نظراً لضعف التغطية باللقاح) وارتفاع نسبة انتشار عدوى فيروس العوز المناعي البشري وزيادة الكثافة السكانية. ويمكن تطبيق النموذج التنبؤي الموضوع على البيئات الأخرى الحساسة لفاشيات الحصبة الفرادية وغيرها من الأمراض التي يمكن توقيها باللقاح.基于2009 年和2011 年之间南非全国疫情相关的因素分析，建立一种用以识别麻疹疫情点状爆发高风险地区的模型。从南非麻疹监测项目获取全国疫情之前和期间的病例数据，从区域卫生信息系统获取有关麻疹免疫和人口规模的数据。使用贝叶斯分层泊松模型研究一个地区婴儿麻疹风险和第一剂疫苗接种覆盖率、人口密度、艾滋病毒(HIV)感染背景患病率和预期血清转化失败之间的关系。使用模型预测识别2012 年新出现的高风险地区。指出一个明确的高风险地区空间形态，其具有多个相互关联的(即相邻)地区。麻疹爆发的风险增加与先前易感人群累积和人口密度显著相关。如果一个人口稠密的地区有超过20%的婴儿错过第一剂疫苗接种，则风险还会提高。该模型能够识别2012 年爆发麻疹疫情的高风险地区以及可以采取额外预防措施的地区。南非麻疹爆发与易感人群(由于较差的疫苗覆盖率)累积、HIV感染的高发生率和高人口密度相关。所建立的预测模型可以应用于其他易受麻疹和其他疫苗可预防疾病点状爆发影响的背景。Разработать модель определения районов повышенного риска возникновения спорадических вспышек кори на основе анализа факторов, связанных со вспышкой кори национального масштаба в Южной Африке в период с 2009 по 2011 гг.Были получены данные по случаям заболевания корью Южноафриканской программы эпидемиологического надзора за корью, зафиксированным до и во время национальной вспышки, а также данные по противокоревой иммунизации и численности населения Окружной медицинской информационной системы. Для исследования связи риска возникновения кори у детей в округе с охватом первой дозы вакцины, плотностью населения, сопутствующим преобладанием инфекции вируса иммунодефицита человека (ВИЧ) и ожидаемым отсутствием сероконверсии использовалась байесовская иерархическая модель Пуассона. Проекции модели использовались для определения новых районов повышенного риска в 2012 году.Отмечена четкая пространственная картина районов повышенного риска со многими взаимосвязанными (т.е. соседними) районами. Повышенный риск возникновения вспышек кори в значительной степени был связан как с предшествующим ростом уязвимых слоев населения, так и с его плотностью. Риск возникновения вспышки также повышался, когда более 20% детей в густонаселенном районе пропускали первую дозу вакцины. Данная модель позволила определить районы повышенного риска возникновения вспышки кори в 2012 году, и районы, где могли быть предприняты профилактические меры.Вспышка кори в Южной Африке была связана с ростом уязвимых слоев населения (по причине недостаточного охвата населения прививкой), высоким уровнем заболеваемости ВИЧ-инфекцией и высокой плотностью населения. Разработанная модель прогнозированиямогла бы применяться в других условиях, подверженных спорадическим вспышкам кори и другим инфекциям, контролируемым методами вакцинопрофилактики.

Data about respiratory coinfections with 2009 pandemic influenza A virus subtype H1N1 during the 2009-2010 influenza pandemic in Africa are limited. We used an existing surveillance program for severe acute respiratory illness to evaluate a new multiplex real-time polymerase chain reaction assay and investigate the role of influenza virus and other respiratory viruses in pneumonia hospitalizations during and after the influenza pandemic in South Africa.The multiplex assay was developed to detect 10 respiratory viruses, including influenza A and B viruses, parainfluenza virus types 1-3, respiratory syncytial virus (RSV), enterovirus, human metapneumovirus (hMPV), adenovirus (AdV), and rhinovirus (RV), followed by influenza virus subtyping. Nasopharyngeal and oropharyngeal specimens were collected from patients hospitalized with pneumonia at 6 hospitals during 2009-2010.Validation against external quality controls confirmed the high sensitivity (91%) and specificity (100%) and user-friendliness, compared with other PCR technologies. Of 8173 patients, 40% had single-virus infections, 17% had coinfections, and 43% remained negative. The most common viruses were RV (25%), RSV (14%), AdV (13%), and influenza A virus (5%). Influenza virus, RSV, PIV type 3, and hMPV showed seasonal patterns.The data provide a better understanding of the viral etiology of hospitalized cases of pneumonia and demonstrate the usefulness of this multiplex assay in respiratory disease surveillance in South Africa.

Summary 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).