Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults.

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.).

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

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

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.

Interleukin-8 genetic diversity, haplotype structure and production differ in two ethnically distinct South African populations.

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.

Trends in RPR Seropositivity among Children Younger than 2 Years in South Africa, 2010-2019.

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 <2 years included in the analysis, 10 969 [8.6%; 95% confidence interval (95% CI) 85-88]) were RPR seropositive. RPR seropositivity increased from 6.5% to 13.0% between 2010 and 2019. Overall, the annual rate of RPR seropositivity was relatively stable between 2010 and 2018 with a range of 89-127/100 000 live births, increasing sharply to 165/100 000 livebirths in 2019. KwaZulu-Natal and North West provinces recorded the largest increases in annual seropositivity rate, while Eastern Cape and Western Cape had the most significant declines. Although this analysis is limited to laboratory results, in the absence of major changes in testing practices, there may be a rise in the burden of antenatal syphilis exposure in utero indicating an increase in maternal syphilis and syphilis transmission in the general population. South Africa needs to intensify Mother-to-Child Transmission of syphilis elimination efforts to reach the WHO target of ≤50 cases per 100 live births by 2030.

Diagnosis of Human Immunodeficiency Virus Infection.

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.

Medical Male Circumcision and Associations Among Sexually Transmitted Infections Service Attendees.

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 < 25 years. Of these, 166 (19.6%) were medically circumcised, 350 (41.4%) traditionally circumcised while 324 (39%) were not circumcised. The yield of assessment for MMC referral was 27.7%. Overall HIV positivity was 23.1%. Compared to no circumcision, MMC had a statistically insignificant 62% lower odds of being HIV positive -among males who were HSV-2 and RPR negative- adjusted odds ratio [aOR] 0.38 [95% confidence interval (CI) 0.12-1.18], p = 0.094. Among those HSV-2 AND/OR RPR positive, MMC had a statistically insignificant 26% lower odds of being HIV positive- aOR 0.74 (95% CI 0.41-1.36), p = 0.334. In both groups HIV positivity increased with age but was positively associated with condom use at last sexual encounter [aOR 3.41 (95% CI 1.43-8.15)] and previous treatment for an STI syndrome [aOR 3.81 (95% CI 1.60-9.05)] among those HSV-2 and RPR negative. High HIV positivity and high yield of eligibility for VMMC referral among males attending STI services points to the need for better integration of HIV prevention and treatment with STI care.

Hepatitis B, hepatitis C and HIV prevalence and related sexual and substance use risk practices among key populations who access HIV prevention, treatment and related services in South Africa: findings from a seven-city cross-sectional survey (2017).

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 of HIV and viral hepatitis infection. Limited epidemiological data on the infections exists in key populations (KPs) in South Africa. We investigated the prevalence of hepatitis B (HBV), hepatitis C (HCV) and HIV and selected risk factors among these KPs to inform effective responses. METHODS: We used convenience sampling to recruit a targeted 3500 KPs accessing HIV-related health services 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) into a cross-sectional survey. An interviewer questionnaire to assess socio-demographic characteristics, drug use and sexual risk practices, was administered. HBV surface antigen (HBsAg); HCV antibody, viral load and genotype, and HIV antibody, was tested. RESULTS: Among the 3439 people included in the study (1528 SWs, 746 MSM, 1165 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 was 16% (highest among PWUD/ID at 46%). CONCLUSIONS: HBV, HCV and HIV pose a health burden for KPs in South Africa. While HIV is key for all included KPs, HCV is of particular importance to PWUD/ID. For KPs, HBV vaccination and behavioural 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.

The role of drug resistance in poor viral suppression in rural South Africa: findings from a population-based study.

BACKGROUND: Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa. METHODS: We conducted HIV drug resistance genotyping and ART analyte testing on dried blood spots (DBS) from HIV-positive adults participating in a 2014 survey in North West Province. Among those with virologic failure (> 5000 copies/mL), we describe frequency of DRM to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI), report association of resistance with antiretroviral therapy (ART) status, and assess resistance to first and second line therapy. Analyses are weighted to account for sampling design. RESULTS: Overall 170 DBS samples were assayed for viral load and ART analytes; 78.4% of men and 50.0% of women had evidence of virologic failure and were assessed for drug resistance, with successful sequencing of 76/107 samples. We found ≥1 DRM in 22% of participants; 47% were from samples with detectable analyte (efavirenz, nevirapine or lopinavir). Of those with DRM and detectable analyte, 60% showed high-level resistance and reduced predicted virologic response to ≥1 NRTI/NNRTI typically used in first and second-line regimens. CONCLUSIONS: DRM and predicted reduced susceptibility to first and second-line regimens were common among adults with ART exposure in a rural South African population-based sample. Results underscore the importance of ongoing virologic monitoring, regimen optimization and adherence counseling to optimize durable virologic suppression.

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'.

Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4-8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011-12 and 2012-13.

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 < 0.0001), particularly to the NNRTI drug class. Pooled analyses across all three surveys demonstrated that infants whose mothers received ART showed the highest prevalence of resistance (74%); 26% (21/82) of HIV PCR positive infants with no or undocumented antiretroviral drug (ARV) exposure harboured NNRTI resistance. 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.

Feasibility of community-based HIV self-screening in South Africa: a demonstration project.

BACKGROUND: HIV diagnosis is a critical step in linking HIV-infected individuals to care and treatment and linking HIV-uninfected persons to prevention services. However, the uptake of HIV testing remains low in many countries. HIV self-screening (HIVSS) is acceptable to adults, but there is limited data on HIVSS feasibility in community programmes. This study aimed to evaluate the feasibility of HIVSS in South Africa. METHODS: We conducted a prospective study that enrolled participants through mobile site, homebased, workplace and sex worker programmes in two townships from May to November 2017. Following an information session on HIVSS, interested participants were offered one of three methods of HIVSS testing: supervised, semi-supervised, and unsupervised. Participants who opted for unsupervised testing and those who tested HIV positive after semi- or supervised HIVSS were followed up telephonically or with a home visit one week after receipt of the test kit to confirm results and linkages to care. Follow-up visits were concluded when the participant indicated that they had used the kit or had accessed a confirmatory HIV test. RESULTS: Of the 2061 people approached, 88.2% (1818/2061) received HIV testing information. Of this group, 89% (1618/1818) were enrolled in the study and 70.0% (1133/1618) were tested for HIV with the kit. The median age was 28 (IQR:23-33) years with an even gender distribution. Of those enrolled, 43.0% (696/1618) were identified through homebased outreach, 42.5% (687/1618) through mobile sites, 7.3% (118/1618) at their workplace and 7.2% (117/1618) from sex worker programmes. A total of 68.7% (1110/1616) selected unsupervised HIVSS, whereas 6.3% (101/1616) opted for semi-supervised and 25.0% ((405/1616) chose supervised HIVSS. Overall, the HIV prevalence using the HIVSS test was 8.2% (93/1129). Of those newly diagnosed with HIV, 16% (12/75) were initiated on ART. Almost half (48.0%; 543/1131) of those tested were linked to a primary HIV test as follows: supervised (85.2%; 336/394); semi-supervised (93.8%; 91/97) and unsupervised (18.1%; 116/640). CONCLUSION: Unsupervised HIVSS was by far the most selected and utilised HIVSS method. Linkages to primary and confirmatory testing for the unsupervised HIVSS and further care were low, despite home visits and telephonic reminders.

Understanding hepatitis B, hepatitis C and HIV among people who inject drugs in South Africa: findings from a three-city cross-sectional survey.

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.

Beyond Social Desirability Bias: Investigating Inconsistencies in Self-Reported HIV Testing and Treatment Behaviors Among HIV-Positive Adults in North West Province, South Africa.

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.

Progress towards the UNAIDS 90-90-90 goals by age and gender in a rural area of KwaZulu-Natal, South Africa: a household-based community cross-sectional survey.

BACKGROUND: The Joint United Nations Programme on HIV/AIDS (UNAIDS) has developed an ambitious strategy to end the AIDS epidemic. After eight years of antiretroviral therapy (ART) program we assessed progress towards the UNAIDS 90-90-90 targets in Mbongolwane and Eshowe, KwaZulu-Natal, South Africa. METHODS: We conducted a cross-sectional household-based community survey using a two-stage stratified cluster probability sampling strategy. Persons aged 15-59 years were eligible. We used face-to-face interviewer-administered questionnaires to collect information on history of HIV testing and care. Rapid HIV testing was performed on site and venous blood specimens collected from HIV-positive participants for antiretroviral drug presence test, CD4 count and viral load. At the time of the survey the CD4 threshold for ART initiation was 350 cells/µL. We calculated progression towards the 90-90-90 UNAIDS targets by estimating three proportions: HIV positive individuals who knew their status (first 90), those diagnosed who were on ART (second 90), and those on ART who were virally suppressed (third 90). RESULTS: We included 5649/6688 (84.5%) individuals. Median age was 26 years (IQR: 19-40), 62.3% were women. HIV prevalence was 25.2% (95% CI: 23.6-26.9): 30.9% (95% CI: 29.0-32.9) in women; 15.9% (95% CI: 14.0-18.0) in men. Overall progress towards the 90-90-90 targets was as follows: 76.4% (95% CI: 74.1-78.6) knew their status, 69.9% (95% CI: 67.0-72.7) of those who knew their status were on ART and 93.1% (95% CI: 91.0-94.8) of those on ART were virally suppressed. By sex, progress towards the 90-90-90 targets was: 79%-71%-93% among women; and 68%-68%-92% among men (p-values of women and men comparisons were < 0.001, 0.443 and 0.584 respectively). By age, progress was: 83%-75%-95% among individuals aged 30-59 years and 64%-58%-89% among those aged 15-29 years (p-values of age groups comparisons were < 0.001, < 0.001 and 0.011 respectively). CONCLUSIONS: In this context of high HIV prevalence, significant progress has been achieved with regards to reaching the UNAIDS 90-90-90 targets. The third 90, viral suppression in people on ART, was achieved among women and men. However, gaps persist in HIV diagnosis and ART coverage particularly in men and individuals younger than 30 years. Achieving 90-90-90 is feasible but requires additional investment to reach youth and men.

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

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

Strengthening HIV surveillance in the antiretroviral therapy era: rationale and design of a longitudinal study to monitor HIV prevalence and incidence in the uMgungundlovu District, KwaZulu-Natal, South Africa.

BACKGROUND: South Africa has over 6,000,000 HIV infected individuals and the province of KwaZulu-Natal (KZN) is the most severely affected. As public health initiatives to better control the HIV epidemic are implemented, timely, detailed and robust surveillance data are needed to monitor, evaluate and inform the programmatic interventions and policies over time. We describe the rationale and design of the HIV Incidence Provincial Surveillance System (HIPSS) to monitor HIV prevalence and incidence. METHODS/DESIGN: The household-based survey will include a sample of men and women from two sub-districts of the uMgungundlovu municipality (Vulindlela and the Greater Edendale) of KZN, South Africa. The study is designed as two sequential cross-sectional surveys of 10,000 randomly selected individuals aged 15-49 years to be conducted one year apart. From the cross sectional surveys, two sequential cohorts of HIV negative individuals aged 15-35 years will be followed-up one year later to measure the primary outcome of HIV incidence. Secondary outcomes include the laboratory measurements for pulmonary tuberculosis, sexually transmitted infections and evaluating tests for estimating population-level HIV incidence. Antiretroviral therapy (ART) access, HIV-1 RNA viral load, and CD4 cell counts in HIV positive individuals will assess the effectiveness of the HIV treatment cascade. Household and individual-level socio-demographic characteristics, exposure to HIV programmatic interventions and risk behaviours will be assessed as predictors of HIV incidence. The incidence rate ratio of the two cohorts will be calculated to quantify the change in HIV incidence between consecutive samples. In anticipation of better availability of population-level HIV prevention and treatment programmes leading to decreases in HIV incidence, the sample size provides 84% power to detect a reduction of 30% in the HIV incidence rate between surveys. DISCUSSION: The results from HIPSS will provide critical data regarding HIV prevalence and incidence in this community and will establish whether HIV prevention and treatment efforts in a "real world", non-trial setting have an impact on HIV incidence at a population level. Importantly, the study design and methods will inform future methods for HIV surveillance.

Exploring the validity of routine individuated service data for antenatal HIV surveillance in the Western Cape.

Background: In the Western Cape, South Africa, public-sector individual-level routine data are consolidated from multiple sources through the Provincial Health Data Centre (PHDC). This enables the description of temporal changes in population-wide antenatal HIV seroprevalence. We evaluated the validity of these data compared to aggregated program data and population-wide sentinel antenatal HIV seroprevalence surveys for the Western Cape province. Methods: We conducted a retrospective cohort analysis of all pregnancies identified in the PHDC from January 2011 to December 2020. Evidence of antenatal and HIV care from electronic platforms were linked using a unique patient identifier. HIV prevalence estimates were triangulated and compared with available survey estimates and aggregated programmatic data from registers as recorded in the District Health Information System. Provincial, district-level and age-group HIV prevalence estimates were compared between data systems using correlation coefficients, absolute differences and trend analysis. Results: Of the 977800 pregnancies ascertained, PHDC HIV prevalence estimates from 2011-2013 were widely disparate from aggregate and survey data (due to incomplete electronic data), whereas from 2014 onwards, estimates were within the 95% confidence interval of survey estimates, and closely correlated to aggregate data estimates (r = 0.8; p = 0.01), with an average prevalence difference of 0.4%. PHDC data show a slow but steady increase in provincial HIV prevalence from 16.7% in 2015 to 18.6% in 2020. The highest HIV prevalence was in the Cape Metro district (20.3%) Prevalence estimates by age group were comparable between sentinel surveys and PHDC from 2015 onwards, with prevalence estimates stable over time among younger age-groups (15-24 years) but increased among older age-groups (> 34 years). Conclusions: This study compares sentinel seroprevalence surveys with both register-based aggregate data and consolidated individuated administrative data. We show that in this setting linked individuated data may be reliably used for HIV surveillance and provide more granular estimates with greater efficiency than seroprevalence surveys and register-based aggregate data.

Acceptability and performance of dual HIV/syphilis testing in male circumcision clients, 2021.

Background: Dual HIV/syphilis testing may be an acceptable intervention to identify men with sexually transmitted infections (STIs) and at risk of HIV acquisition. Objectives: We sought to determine the acceptability, and performance of dual HIV/syphilis testing among men attending voluntary medical male circumcision (VMMC) services at six public sector facilities in Gauteng. Method: This was a cross-sectional study at VMMC facilities. Men ≥ 18 years were enrolled. The men had (1) a questionnaire administered, (2) on-site dual HIV/syphilis testing with First Response HIV1+2/Syphilis Combo Card Test by routine lay counsellors, and (3) a blood specimen collected for centralised laboratory testing for HIV and syphilis serology. We evaluated pre-test and post-test acceptability and performance compared to serological testing. Results: Of the 679 men analysed (median age 32.1 years), 96.7% of HIV-negative men preferred testing for HIV and syphilis simultaneously. Of the 675 men tested for syphilis, 28 (4.7%) tested positive (past or recent). In the laboratory, 43/609 (7.1%) had syphilis infection detected, with 9/609 (1.5%) having recent syphilis. There was sub-optimal sensitivity for HIV detection (90.9%; 95% confidence interval [CI]: 88.5% - 93.3%), and for past/recent syphilis (55.8%; 95% CI: 51.9% - 59.8%), improving to 88.9% (95% CI: 86.4% - 91.4%) for recent syphilis. Specificities were > 99% for HIV and syphilis (past or recent). Post-test acceptability was 96.6% and willingness to pay for future testing was 86.1%. Conclusion: Dual HIV/syphilis testing was acceptable but had sub-optimal sensitivity for HIV and syphilis. Syphilis detection was adequate for recent infection.

Correlates of viral suppression among sexual minority men and transgender women living with HIV in Mpumalanga, South Africa.

Sexual minority men (SMM) and transgender women in South Africa engage in HIV care at lower rates than other persons living with HIV and may experience population-specific barriers to HIV treatment and viral suppression (VS). As part of a pilot trial of an SMM-tailored peer navigation (PN) intervention in Ehlanzeni district, South Africa, we assessed factors associated with ART use and VS among SMM at trial enrolment. A total of 103 HIV-positive SMM and transgender women enrolled in the pilot trial. Data on clinical visits and ART adherence were self-reported. VS status was verified through laboratory analysis (<1000 copies/ml). We assessed correlates of VS at baseline using Poisson generalized linear model (GLM) with a log link function, including demographic, psychosocial, clinical, and behavioral indicators. Among participants, 52.4% reported ART use and only 42.2% of all participants had evidence of VS. Of the 49.5% who reported optimal engagement in HIV care (consistent clinic visits with pills never missed for ≥ 4 consecutive days) in the past 3-months, 56.0% were virally suppressed. In multivariable analysis, SMM were significantly more likely to be virally suppressed when they were ≥ 25 years of age (Adjusted prevalence ratio [APR] = 2.0, CI 95%:1.0-3.8); in a relationship but not living with partner, as compared to married, living together, or single (APR = 1.7, CI 95%:1.0-2.7), and optimally engaged in care (APR = 2.1, 95% CI:1.3-3.3). Findings indicate a need for targeted treatment and care support programming, especially for SMM and transgender women who are young and married/living with their partners to improve treatment outcomes among this population.