Assessment of weight gain in adult patients living with HIV receiving first-line dolutegravir-based or efavirenz-based ART regimens in routine care clinics in Tshwane district, South Africa: An observational study.

INTRODUCTION: Although dolutegravir (DTG) is deemed stable, safe, cost-effective, and clinically beneficial, it also carries the risk of side effects, including observed weight gain among patients on DTG-based antiretroviral therapy (ART) regimens. We compared weight changes among adults (≥18 years) initiating tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) or tenofovir disoproxil fumarate, emtricitabine, and efavirenz (TEE) regimens and those switching from TEE to TLD (TEE-to-TLD switchers) in three large primary care facilities in South Africa METHODS: We conducted a retrospective longitudinal record review using patient medical records, extracting relevant demographic and clinical data from October 2018 to June 2021 from randomly selected adults who initiated TLD or TEE (initiators) and adult TEE-to-TLD switchers. We assessed weight, body mass index (BMI), and percentage weight changes for both groups and fitted linear regression and generalized linear models to determine factors associated with weight and BMI change and percentage weight change ≥10%, respectively, among treatment initiators. We fitted linear mixed-effect models among TEE-to-TLD switchers to consider repeated measures. RESULTS: Of 860 initiators, 450 (52.3%) initiated on TEE and 410 (47.7%) on TLD, with median follow-up of 1.4 years and 1.0 year, respectively. At initiation, 43.3% on TEE and 40.8% on TLD were overweight or obese. TLD initiators had an adjusted higher mean weight gain of 1.6 kg (p < 0.001) and mean BMI gain of 0.51 kg/m2 (p < 0.001) than TEE initiators. Independent risk factors for higher mean weight and BMI included age ≥50 years, male, on ART for >12 months, initial BMI of <18.5 kg/m2, and CD4 counts <200 cells/µL. Of 298 TEE-to-TLD switchers, 36.6% were overweight or obese at TEE initiation. Comparing before and after TLD switch, TEE-to-TLD switchers had an adjusted mean weight of 1.2 kg less while on TLD (p = 0.026). Being overweight and CD4 counts >350 cells/µL were independent risk factors for lower weight gain after TLD switch. CONCLUSIONS: We report more weight gain among TLD than among TEE initiators, although to a lesser extent than previously reported. TEE-to-TLD switchers experienced less weight gain after TLD switch; return to health before receiving TLD may be a contributory factor. The current findings are reassuring for those switching to a DTG-based regimen.

Assessment of the performance of the plasma separation card for HIV-1 viral load monitoring in South Africa.

Scaling up of newer innovations that address the limitations of the dried blood spot and the logistics of plasma monitoring is needed. We employed a multi-site, cross-sectional assessment of the plasma separation card (PSC) on blood specimens collected from all consenting adults, assenting young and pediatric patients living with HIV from 10 primary healthcare clinics in South Africa. Venous blood for EDTA-plasma samples was collected and analyzed according to the standard of care assay, while collected capillary blood for the PSC samples was analyzed using the Roche COBAS AmpliPrep/Cobas TaqMan (CAP/CTM) HIV-1 Test at the National Reference laboratories. McNemar tests assessed the differences in concordance between the centrifuged plasma and dried plasma spots. The usability of PSC by blood spotting, PSC preparation, and pre-analytical work was assessed by collecting seven-point Likert-scale data from healthcare and laboratory workers. We enrolled 538 patients, mostly adults [n = 515, 95.7% (95% CI: 93.7%-97.1%)] and females [n = 322, 64.2% (95% CI: 60.0%-68.1%)]. Overall, 536 paired samples were collected using both PSC- and EDTA-plasma diagnostics, and 502 paired PSC- and EDTA-plasma samples assessed. Concordance between the paired samples was obtained for 446 samples. Analysis of these 446 paired samples at 1,000 copies per milliliter threshold yielded an overall sensitivity of 87.5% [95% CI: 73.2%-95.8%] and specificity of 99.3% [95% CI: 97.9%-99.8%]. Laboratory staff reported technical difficulties in most tasks. The usability of the PSC by healthcare workers was favorable. For policymakers to consider PSC scale-up for viral load monitoring, technical challenges around using PSC at the clinic and laboratory level need to be addressed. IMPORTANCE: Findings from this manuscript emphasize the reliability of the plasma separation card (PSC), a novel diagnostic method that can be implemented in healthcare facilities in resource-constrained settings. The agreement of the PSC with the standard of care EDTA plasma for viral load monitoring is high. Since the findings showed that these tests were highly specific, we recommend a scale-up of PSC in South Africa for diagnosis of treatment failure.

Syphilis screening coverage and positivity by HIV treatment status among South African pregnant women enrolled in the 2019 antenatal HIV sentinel survey.

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.

Resistance is common in paediatric patients failing ART in South Africa.

BACKGROUND: Minimal data exist on HIV drug resistance patterns and prevalence among paediatric patients failing ART in resource-limited settings. We assessed levels of HIV drug resistance in children with virological failure. METHODS: This cross-sectional study, performed from March 2017 to March 2019 in South Africa, enrolled HIV-positive children aged ≤19 years, receiving ART through public health facilities with recent evidence suggestive of virological failure (at least one viral load ≥1000 copies/mL), across 45 randomly selected high-volume clinics from all nine provinces. Resistance genotyping was performed using next-generation sequencing technologies. Descriptive analysis taking into account survey design was used to determine outcomes. RESULTS: Among 899 participants enrolled, the adjusted proportion of HIV drug resistance among children with virological failure was 87.5% (95% CI 83.0%-90.9%). Resistance to NNRTIs was detected in 77.4% (95% CI 72.5%-81.7%) of participants, and resistance to NRTIs in 69.5% (95% CI 62.9%-75.4%) of participants. Overall, resistance to PIs was detected in 7.7% (95% CI 4.4%-13.0%) of children. CONCLUSIONS: HIV drug resistance was highly prevalent in paediatric patients failing ART in South Africa, with 9 in 10 patients harbouring resistance to NNRTIs and/or NRTIs. PI-based regimens are predicted to be highly efficacious in achieving virological suppression amongst patients failing NNRTI-based regimens. Scaling up resistance testing amongst patients would facilitate access to second- and third-line regimens in South Africa.

Progress towards the UNAIDS 95-95-95 targets among pregnant women in South Africa: Results from the 2017 and 2019 national Antenatal HIV Sentinel Surveys.

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 <50 copies/mL) using the combined dataset (i.e., both 2017 and 2019 data combined). All analyses considered the survey design. 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.

Is There Risk Compensation among HIV Infected Youth and Adults 15 Years and Older on Antiretroviral Treatment in South Africa? Findings from the 2017 National HIV Prevalence, Incidence, Behaviour and Communication Survey.

In this paper, risk compensation among individuals on antiretroviral therapy (ART), using the 2017 South African national survey on HIV, is explored. A multi-stage stratified cluster random sampling approach was used to realize 11,130 participants 15 years and older. Logistic regression analysis assessed the association between multiple sexual partners, condom use at last sexual encounter, consistency of condom usage and potential explanatory variables using HIV status and ART exposure as a mediator variable. HIV positive participants who were aware and on ART were less likely to have multiple sexual partners, and less likely not to use a condom at last sex compared to HIV positive participants who were aware but not on ART. The odds of reporting multiple sexual partners were significantly lower among older age groups, females, non-Black Africans, and rural settings, and higher among those with tertiary level education, and risky alcohol users. The odds of no condom use at last sexual encounter were more likely among older age groups, females, other race groups, and less likely among those with secondary level education. The odds of inconsistent condom use were more likely among older age groups, females, and other race groups, and less likely among those with tertiary level education, high risk and hazardous alcohol users. Risk compensation is not apparent among HIV infected adults who are on ART. Risk groups that should receive tailored interventions to reduced risky sexual behaviours were identified.

Association between viral suppression during the third trimester of pregnancy and unintended pregnancy among women on antiretroviral therapy: Results from the 2019 antenatal HIV Sentinel Survey, South Africa.

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 <50 copies/mL. 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.

The prevalence of unintended pregnancy and its association with HIV status among pregnant women in South Africa, a national antenatal survey, 2019.

To describe the prevalence of unintended pregnancy and its association with HIV status among pregnant women in South Africa. A cross-sectional survey was conducted between October and mid-November 2019 among pregnant women aged 15-49 years in 1589 selected public antenatal care facilities. Pregnancy intention was assessed using two questions from the London Measure of Unplanned Pregnancy. Survey logistic regression examined factors associated with unintended pregnancy. Among 34,946 participants, 51.6% had an unintended pregnancy. On multivariable analysis, the odds of unintended pregnancy was higher among women who knew their HIV-positive status before pregnancy but initiated treatment after the first antenatal visit (adjusted odds ratio [aOR], 1.5 [95% confidence interval (CI):1.2-1.8]), women who initiated treatment before pregnancy (aOR, 1.3 [95% CI:1.2-1.3]), and women with a new HIV diagnosis during pregnancy (aOR, 1.2 [95% CI:1.1-1.3]) compared to HIV-negative women. Women who were single, in a non-cohabiting or a cohabiting relationship, and young women (15-24 years) had significantly higher risk of unintended pregnancy compared to married women and women aged 30-49 years, respectively. A comprehensive approach, including regular assessment of HIV clients' pregnancy intention, and adolescent and youth-friendly reproductive health services could help prevent unintended pregnancy.

A Comparison of Bayesian Spatial Models for HIV Mapping in South Africa.

Despite making significant progress in tackling its HIV epidemic, South Africa, with 7.7 million people living with HIV, still has the biggest HIV epidemic in the world. The Government, in collaboration with developmental partners and agencies, has been strengthening its responses to the HIV epidemic to better target the delivery of HIV care, treatment strategies and prevention services. Population-based household HIV surveys have, over time, contributed to the country's efforts in monitoring and understanding the magnitude and heterogeneity of the HIV epidemic. Local-level monitoring of progress made against HIV and AIDS is increasingly needed for decision making. Previous studies have provided evidence of substantial subnational variation in the HIV epidemic. Using HIV prevalence data from the 2016 South African Demographic and Health Survey, we compare three spatial smoothing models, namely, the intrinsically conditionally autoregressive normal, Laplace and skew-t (ICAR-normal, ICAR-Laplace and ICAR-skew-t) in the estimation of the HIV prevalence across 52 districts in South Africa. The parameters of the resulting models are estimated using Bayesian approaches. The skewness parameter for the ICAR-skew-t model was not statistically significant, suggesting the absence of skewness in the HIV prevalence data. Based on the deviance information criterion (DIC) model selection, the ICAR-normal and ICAR-Laplace had DIC values of 291.3 and 315, respectively, which were lower than that of the ICAR-skewed t (348.1). However, based on the model adequacy criterion using the conditional predictive ordinates (CPO), the ICAR-skew-t distribution had the lowest CPO value. Thus, the ICAR-skew-t was the best spatial smoothing model for the estimation of HIV prevalence in our study.

Coverage of maternal viral load monitoring during pregnancy in South Africa: Results from the 2019 national Antenatal HIV Sentinel Survey.

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 < 50 copies/mL). At the time of this study, the first-line regimen for women initiating ART during pregnancy was non-nucleoside reverse transcriptase (NNRTI)-based regimen. METHODS: Between 1 October and 15 November 2019, a cross-sectional survey was conducted among 15- to 49-year-old pregnant women attending antenatal care in 1589 nationally representative public health facilities. Data on ART status, viral load testing and viral load test results were extracted from medical records. Logistic regression was used to examine factors associated with coverage of viral load testing. RESULTS: Of 8112 participants eligible for viral load testing, 81.7% received viral load testing, and 94.1% of the viral load test results were documented in the medical records. Of those who had viral load test results documented, 74.1% were virally suppressed. Women initiated on ART during pregnancy and who received ART for three months had lower coverage of viral load testing (73%) and viral suppression (56.8%) compared with women initiated on ART before pregnancy (82.8% and 76.1%, respectively). Initiating ART during pregnancy rather than before pregnancy was associated with a lower likelihood of receiving a viral load test during pregnancy (adjusted odds ratio = 1.6, 95% confidence interval: 1.4-1.8). CONCLUSIONS: Viral load result documentation was high; viral load testing could be improved especially among women initiating ART during pregnancy. The low viral suppression among women who initiated ART during pregnancy despite receiving ART for three months highlights the importance of enhanced adherence counselling during pregnancy. Our finding supports the WHO recommendation that a Dolutegravir-containing regimen be the preferred regimen for women who are newly initiating ART during pregnancy for more rapid viral suppression.

Recent HIV infection among pregnant women in the 2017 antenatal sentinel cross-sectional survey, South Africa: Assay-based incidence measurement.

INTRODUCTION: New HIV infection during pre-conception and pregnancy is a significant contributor of mother-to-child transmission of HIV in South Africa. This study estimated HIV incidence (defined as new infection within the last one year from the time of the survey which included both new infections occurred during pregnancy or just before pregnancy) among pregnant women and described the characteristics of recently infected pregnant women at national level. METHODS: Between 1 October and 15 November 2017, we conducted a national cross-sectional survey among pregnant women aged 15-49 years old attending antenatal care at 1,595 public facilities. Blood specimens were collected from pregnant women and tested for HIV in a centralised laboratory. Plasma viral load and Limiting Antigen Avidity Enzyme Immunosorbent Assay (LAg) tests were further performed on HIV positive specimens to differentiate between recent and long-term infections. Recent infection was defined as infection that occurred within one year from the date of collection of blood specimen for the survey. Data on age, age of partner, and marital status were collected through interviews. Women whose specimens were classified as recent by LAg assay and with viral loads >1,000 copies/mL were considered as recently infected. The calculated proportion of HIV positive women with recent infection was adjusted for assay-specific parameters to estimate annual incidence. Survey multinomial logistic regression was used to examine factors associated with being recently infected using HIV negative women as a reference group. Age-disparate relationship was defined as having a partner 5 or more years older. RESULTS: Of 10,049 HIV positive participants with LAg and viral load data, 1.4% (136) were identified as recently infected. The annual HIV incidence was 1.5% (95% confidence interval (CI): 1.2-1.7). In multivariable analyses, being single (adjusted odds ratio, aOR: 3.4, 95% CI: 1.8-6.2) or cohabiting (aOR: 3.8, 95% CI: 1.8-7.7), compared to being married as well as being in an age-disparate relationship among young women (aOR: 3.1, 95% CI: 2.0-4.7; reference group: young women (15-24years) whose partners were not 5 years or more older) were associated with higher odds of recent infection. CONCLUSIONS: Compared to previous studies among pregnant women, the incidence estimated in this study was substantially lower. However, the UNAIDS target to reduce incidence by 75% by 2020 (which is equivalent to reducing incidence to <1%) has not been met. The implementation of HIV prevention and treatment interventions should be intensified, targeting young women engaged in age-disparate relationship and unmarried women to fast track progress towards the UNAIDS target.

Population prevalence of sexually transmitted infections in a high HIV burden district in KwaZulu-Natal, South Africa: Implications for HIV epidemic control.

BACKGROUND: Sexually transmitted infections (STIs) and Human immunodeficiency virus (HIV) share a complex bidirectional relationship, however, population prevalence and the association between the presence of STIs and HIV in a high HIV burden district in KwaZulu-Natal, South Africa is not known. METHODS: A total of 9812 participants aged 15-49 years were enrolled in a cross-sectional population-based household survey. Participants completed a structured questionnaire and provided first-pass urine (males) or self-collected vulvo-vaginal swabs (females) for the detection of STIs. RESULTS: Prevalence of herpes simplex virus type-2 (HSV-2) was 57.8%, syphilis was 1.6%, Neisseria gonorrhoeae was 2.8%, Chlamydia trachomatis was 7.1%, Trichomonas vaginalis was 9.0%, Mycoplasma genitalium was 5.5% and HIV was 36.3%. HIV positive status was associated with an increased probability of having M. genitalium (aPR = 1.49, 95% CI 1.02-2.19) among males and syphilis (aPR = 2.54, 95% CI 1.32-4.86), N. gonorrhoeae (aPR = 2.39, 95% CI 1.62-3.52), T. vaginalis (aPR = 1.70, 95% CI 1.43-2.01) and M. genitalium (aPR = 1.60, 95% CI 1.15-2.22) among females. HIV viral load ≥400 copies per mL was associated with an increased probability of N. gonorrhoeae (aPR = 1.91, 95% CI 1.36-2.70), C. trachomatis (aPR = 1.52, 95% CI 1.12-2.05) and M. genitalium (aPR = 1.83, 95% CI 1.27-2.63). CONCLUSIONS: The high prevalence of STIs and the association between STIs and HIV, and HIV viral load underscores the public health implications of sustained transmission risk of STIs and HIV. These findings highlight the urgent need for expanding STI surveillance and implementing interventions to monitor and reduce the STI burden.

Awareness of HIV-positive status and linkage to treatment prior to pregnancy in the "test and treat" era: A national antenatal sentinel survey, 2017, South Africa.

INTRODUCTION: Knowledge of HIV status in South Africa (SA) is reported to be 90% among people living with HIV. National level estimates could mask population-specific levels, which are critical to monitor program coverage and potential impact. Using data from the 2017 national antenatal sentinel survey, we assessed knowledge of HIV-positive status, initiation of antiretroviral therapy (ART), and socio-demographic characteristics associated with knowledge of HIV-positive status prior to the current pregnancy among women attending antenatal care. METHODS: Between 1 October and 15 November 2017, a nationally representative sample of 32,716 pregnant women were enrolled from 1,595 public health facilities selected from all districts of SA. Data on age, gravidity, knowledge of HIV-positive status and ART initiation prior to pregnancy were extracted from medical records. A blood sample was collected from each woman regardless of prior knowledge of HIV status or ART history, and tested for HIV in the laboratory. All HIV-positive pregnant women enrolled in the survey were eligible for inclusion in the analysis. Multivariable survey logistic regression was used to examine factors associated with knowledge of HIV-positive status prior to the current pregnancy. RESULTS: Of 10,065 eligible HIV-positive women, 60.8% (95% confidence interval (CI):59.9%-61.7%) knew their HIV status prior to the current pregnancy, of whom 91.1% (95% CI: 90.4%-91.7%) initiated ART prior to the current pregnancy. Knowledge of HIV-positive status was lower among adolescent girls and young women (15-24 years) (38.9%) and primigravid women (40.5%) compared with older women (35-49 years) (75.5%) and multigravid women (64.7%). In a multivariable analysis, significant effect modification was found between gravidity and age (P value = 0.047). Being in the age group 15-24 years compared to the age group 35-49 years decreased the odds of knowing HIV-positive status by 80% (adjusted odds ratio (AOR): 0.2, 95% CI:0.1-0.4) among primigravid women and by 60%(AOR: 0.4, 95% CI:0.3-0.4) among multigravid women. CONCLUSION: Knowledge of HIV-positive status prior to the current pregnancy fell short of the target of 90% among pregnant women living with HIV. This was especially low among adolescent girls and young women, highlighting the gap in youth friendly reproductive health and HIV testing services.

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

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

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

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

Viral suppression and factors associated with failure to achieve viral suppression among pregnant women in South Africa.

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.

Trends in HIV Prevention, Treatment, and Incidence in a Hyperendemic Area of KwaZulu-Natal, South Africa.

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 < .001). Knowledge of HIV-seropositive status increased by 21% from 51.8% (n = 504 of 3547) to 62.9% (n = 570 of 3895; P < .001) in men and by 14% from 64.6% (n = 1833 of 6265) to 73.4% (n = 2182 of 6341; P < .001) in women. Use of antiretroviral therapy increased by 32% from 36.7% (n = 341 of 3547) to 48.6% (n = 432 of 3895; P < .001) in men and by 29% from 45.6% (n = 1251 of 6265) to 58.8% (n = 1743 of 6341; P < .001) in women; HIV viral suppression increased by 20% from 41.9% (n = 401 of 3547) to 50.3% (n = 456 of 3895; P = .005) in men and by 13% from 54.8% (n = 1547 of 6265) to 61.9% (n = 1828 of 6341; P < .001) in women. Incidence of HIV declined in women aged 15 to 19 years from 4.63 (95% CI, 3.29-6.52) to 2.74 (95% CI, 1.84-4.09) per 100 person-years (P = .04) but declined marginally or remained unchanged among men and women in other age groups. Conclusions and Relevance: This study showed a significant decline in HIV incidence in young women; however, to further reduce HIV incidence, HIV prevention and treatment program coverage must be intensified and scaled up.

Longitudinal adherence to maternal antiretroviral therapy and infant Nevirapine prophylaxis from 6 weeks to 18 months postpartum amongst a cohort of mothers and infants in South Africa.

BACKGROUND: Despite improved policies to prevent mother-to-child HIV transmission (MTCT), adherence to maternal antiretroviral therapy (ART) and infant Nevirapine prophylaxis (NVP) is low in South Africa. We describe ART adherence amongst a cohort of HIV-positive mothers and HIV-exposed but uninfected infants from 6 weeks until 18 months post-delivery and identify risk factors for nonadherence. METHODS: Data were collected in 2012-2014 through a nationally representative survey of PMTCT effectiveness. Mother-infant pairs were enrolled during the infant's first immunization visit at 6 weeks. Mothers and HIV-exposed infants (2811 pairs) were followed to 18 months at 3-month intervals. Mothers who self-reported being on ART at 6 weeks postpartum (N = 1572 (55.9%)) and infants on NVP at 6 weeks (N = 2370 (84.3%)) were eligible for this analysis and information about their adherence was captured at each interview they attended thereafter. We defined nonadherence within each 3-month interval as self-report of missing > 5% of daily ART/NVP doses, estimated adherence using a Cox survival curve with Andersen & Gill setup for recurring events, and identified risk factors for nonadherence with an extended Cox regression model (separately for mothers and infants) in Stata 13. Results are not nationally representative as this is a subgroup analysis of the follow-up cohort. RESULTS: Amongst mothers on ART at 6 weeks postpartum, cumulative adherence to maternal ART until 18 months was 63.4%. Among infants on NPV at 6 weeks postpartum, adherence to NVP was 74.5%.. Risk factors for nonadherence to maternal ART, controlling for other factors, included mother's age (16-24 years vs. ≥34 years, adjusted Hazard Ratio (aHR): 1.9, 95% CI: 1.4-2.5), nondisclosure of HIV status to anyone (nondisclosure vs. disclosure: aHR: 1.7, 95% CI: 1.3-2.1), and timing of ART initiation (initiated ART after delivery vs. initiated ART before delivery: aHR: 1.6, 95% CI: 1.3-2.0). Provincial variation was seen in nonadherence to infant NVP, controlling for other factors. CONCLUSION: Maintaining ART adherence until 18 months postpartum remains a crucial challenge, with maternal ART adherence among the six week maternal ART cohort below 65% and infant NVP adherence among breastfeeding infants in this cohort below 75%.This is gravely concerning, given the global policy shift to lifelong ART amongst pregnant and lactating women, and the need for extended infant prophylaxis amongst mothers who are not virally suppressed. Our findings suggest that young mothers and mothers who do not disclose their status should be targeted with messages to improve adherence, and that late maternal ART initiation (after delivery) increases the risk of maternal nonadherence.

Does voluntary medical male circumcision protect against sexually transmitted infections among men and women in real-world scale-up settings? Findings of a household survey in KwaZulu-Natal, South Africa.

INTRODUCTION: Male circumcision (MC) confers partial protection to men against HIV and, in research settings, some sexually transmitted infections (STIs). It is also associated with protection from some STIs among female partners. However, real-world data on changes in STI transmission associated with large-scale public African medical male circumcision (MMC) conducted for HIV prevention are lacking and would improve estimates of the health impact of MMC. METHODS: The HIV Incidence Provincial Surveillance System is a community-based surveillance platform for HIV prevalence, incidence and intervention coverage trends in KwaZulu-Natal province, South Africa. HIPPS collected cross-sectional self-reported data on circumcision status (from men), partner circumcision status for past three partners (from women) and demographic characteristics and behavioural risk factors; and tested participants for HIV, herpes simplex virus type 2 (HSV-2), syphilis, hepatitis B, N eisseria gonorrhoeae, C hlamydia trachomatis, Trichomonas vaginalis and Mycoplasma genitalium. Bivariable and multivariable analyses were performed on associations between own (men) or partner's (women) circumcision status and each STI. Multivariable analyses adjusted for age, demographic characteristics and behavioural risk factors, and incorporated false discovery rate (FDR) correction. RESULTS: Among men, MMC had a protective association with HSV-2 (OR 0.66, 95% CI 0.50 to 0.86), hepatitis B (OR 0.53, 95% CI 0.30 to 0.95), HIV (OR 0.50, 95% CI 0.38 to 0.65) and M. genitalium (OR 0.53, 95% CI 0.32 to 0.88). Among women, partner circumcision had a protective association with HSV-2 (OR 0.71, 95% CI 0.53 to 0.95) and HIV (OR 0.66, 95% CI 0.49 to 0.90). Associations with HIV and HSV-2 remained significant for men and all women after FDR correction. CONCLUSION: These real-world data, supporting protective associations between MMC conducted for HIV prevention and STIs in men and women, can help clarify the full impact of MMC and support a role in broader sexual health programming.

Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000-2016: A Pooled Sequence Analysis.

BACKGROUND: South Africa has the largest public antiretroviral therapy (ART) programme in the world. We assessed temporal trends in pretreatment HIV-1 drug resistance (PDR) in ART-naïve adults from South Africa. METHODS: We included datasets from studies conducted between 2000 and 2016, with HIV-1 pol sequences from more than ten ART-naïve adults. We analysed sequences for the presence of 101 drug resistance mutations. We pooled sequences by sampling year and performed a sequence-level analysis using a generalized linear mixed model, including the dataset as a random effect. FINDINGS: We identified 38 datasets, and retrieved 6880 HIV-1 pol sequences for analysis. The pooled annual prevalence of PDR remained below 5% until 2009, then increased to a peak of 11·9% (95% confidence interval (CI) 9·2-15·0) in 2015. The pooled annual prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR remained below 5% until 2011, then increased to 10.0% (95% CI 8.4-11.8) by 2014. Between 2000 and 2016, there was a 1.18-fold (95% CI 1.13-1.23) annual increase in NNRTI PDR (p < 0.001), and a 1.10-fold (95% CI 1.05-1.16) annual increase in nucleoside reverse-transcriptase inhibitor PDR (p = 0.001). INTERPRETATION: Increasing PDR in South Africa presents a threat to the efforts to end the HIV/AIDS epidemic. These findings support the recent decision to modify the standard first-line ART regimen, but also highlights the need for broader public health action to prevent the further emergence and transmission of drug-resistant HIV. SOURCE OF FUNDING: This research project was funded by the South African Medical Research Council (MRC) with funds from National Treasury under its Economic Competitiveness and Support Package. DISCLAIMER: The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CDC.