BACKGROUND A safe, effective vaccine is essential to end HIV. A canarypox/protein HIV vaccine regimen showed modest efficacy at reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus demonstrated potent humoral and cellular responses in a Phase 1/2a trial and triggered a Phase 2b/3 double-blinded trial to assess the safety and efficacy of this regimen in South Africa. METHODS We enrolled and randomized 5,404 healthy, HIV-uninfected 18-35-year olds at 14 sites to vaccine (2,704 participants) or placebo (2,700 participants) between 26 October 2016 and 21 June 2019. The vaccine regimen consisted of two ALVAC-HIV (vCP2438) (expressing HIV-1 subtype C env, clade B gp41 , gag and pro) immunizations at months 0 and 1, with booster immunizations of ALVAC-HIV plus bivalent subtype C gp120 protein/MF59 adjuvant at months 3, 6, 12 and 18. Efficacy was evaluated by HIV testing every 3 months. RESULTS In January 2020, pre-specified non-efficacy criteria were met at an interim analysis; further vaccinations were subsequently halted. The vaccines were safe and well-tolerated in the study population (median age 24, 70% female-sex-at-birth). Over the primary 24-month follow-up, there were 133 infections among placebo recipients and 138 among vaccinees (hazard ratio = 1.02; 95%CI, 0.81-1.30; P=0.84). Pre-specified subgroup analyses demonstrated no difference in efficacy by sex or when restricting to follow-up post-4 th vaccination, and no difference amongst female-sex-at-birth by age, BMI, prevalent STIs, behavioral risk score or region. CONCLUSIONS The ALVAC/gp120 regimen did not prevent HIV infection in South Africans despite prior evidence of immunogenicity. ClinicalTrials.gov (NCT02968849)

BackgroundThe Eastern Cape province of South Africa has one of the highest burdens of HIV in the world. Emergency Departments (EDs) can serve as optimal clinical sites for the identification of new HIV infections and entry into care. We sought to determine the current burden of HIV disease among ED patients in the Eastern Cape.MethodsWe conducted a prospective cross-sectional observational study in the EDs of three Hospitals in the Eastern Cape province of South Africa from June 2017 to July 2018. All adult, non-critical patients presenting to the ED were systematically approached and offered a Point-Of-Care (POC) HIV test in accordance with South African guidelines. All HIV-positive individuals had their blood tested for the presence of antiretroviral therapy (ART) and the presence of viral suppression (≤ 1000 copies/ml). HIV incidence was estimated using a multi-assay algorithm, validated for a subtype C epidemic.FindingsOf the 2901 patients for whom HIV status was determined (either known HIV-positive or underwent POC HIV testing), 811 (28.0%) were HIV positive, of which 234 (28.9%) were newly diagnosed. HIV prevalence was higher in Mthatha [34% (388/1134) at Mthatha Regional Hospital and 28% (142/512) at Nelson Mandela Academic Hospital], compared to Port Elizabeth [22% (281/1255) at Livingstone Hospital]. HIV incidence was estimated at 4.5/100 person-years (95% CI: 2.4, 6.50) for women and 1.5 (CI 0.5, 2.5) for men. Of all HIV positive individuals tested for ART (585), 54% (316/585) tested positive for the presence of ARTs, and for all HIV positive participants with viral load data (609), 49% (299/609) were found to be virally suppressed.InterpretationOur study not only observed a high prevalence and incidence of HIV among ED patients but also highlights significant attrition along the HIV care cascade for HIV positive individuals. Furthermore, despite developing an optimal testing environment, we were only able to enrol a small sub-set of the ED population. Given the high HIV prevalence and high attrition in the ED population, HIV services in the ED should also develop strategies that can accommodate large testing volumes and ART initiation.

Background South Africa faces the highest burden of HIV infection globally. The National Strategic Plan on HIV recommends provider-initiated HIV counselling and testing (HCT) in all healthcare facilities. However, HIV continues to overwhelm the healthcare system. Emergency department (ED)-based HCT could address unmet testing needs. Objectives This study examines the reasons for accepting or declining HCT in South African EDs to inform the development of HCT implementation strategies. Method We conducted a prospective observational study in two rural EDs, from June to September 2017. Patients presenting to the ED were systematically approached and offered a point-of-care test in accordance with national guidelines. Patients demographics, presenting compaint, medical history and reasons for accepting/declining testing, were recorded. A pooled analysis is presented. Results Across sites, 2074 adult, non-critical patients in the ED were approached; 1880 were enrolled in the study. Of those enrolled, 19.7% had a previously known positive diagnosis, and 80.3% were unaware of their HIV status. Of those unaware, 90% patients accepted and 10% declined testing. The primary reasons for declining testing were ‘does not want to know status’ (37.6%), ‘in too much pain’ (34%) and ‘does not believe they are at risk’ (19.9%). Conclusions Despite national guidelines, a high proportion of individuals remain undiagnosed, of which a majority are young men. Our study demonstrated high patient acceptance of ED-based HCT. There is a need for investment and innovation regarding effective pain management and confidential service delivery to address patient barriers. Findings support a routine, non-targeted HCT strategy in EDs.

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BackgroundIn South Africa the teenage fertility rate is high. About 42% of women have their sexual debut by 18 years of age and 5% by 15. These young women are also at risk of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) infection. Despite widespread availability of contraception, 18% of sexually active teenagers do not use any. Previous research on the knowledge of, attitudes to and practices of contraception by teenagers has focused on older adolescents.ObjectivesThis study explored knowledge, attitudes and practices about contraception amongst 12–14 year old unmarried schoolgirls with a view to inform planning of programmes to assist in reducing teenage pregnancies.MethodsA qualitative study design with purposive sampling was used to select participants from two government-run schools in King Sabata Dalindyebo Municipality. In-depth and focus group interviews were conducted after obtaining written consent from parents and assent from participants. Interviews were audiotaped, transcribed verbatim, translated and analysed thematically.FindingsParticipants reported that young adolescents were sexually active, which included high-risk sexual behaviour such as multiple partners and casual and transactional sex. Knowledge about contraceptives varied widely. Condoms were the most preferred method of contraception, but it is unknown whether they ever used condoms as they professed to talk about the behaviour of others rather than themselves. Injectable contraceptives were believed to have long-term negative effects. Common sources of contraceptive information were friends or peers, school curriculum and to a lesser extent family members.ConclusionsFindings of the study suggest that young adolescents are sexually active and have inadequate knowledge and misconceptions about contraception. These findings should inform educational programmes about risks of early sexual activity and about contraception.

Acute infectious illnesses, while a major cause of morbidity and mortality across the world, disproportionally affect low-resource settings. In fact, >80% of worldwide deaths from infectious diseases, and resulting sepsis, occur in low-and middle-income countries (LMICs). [1,2] Landmark studies for management of life-threatening infectious diseases and septic shock in the emergency department (ED) and intensive care unit (ICU) have largely been conducted and validated in high-income countries (HICs). [3] The three pillars of sepsis management are aggressive fluid resuscitation, early broad-spectrum antimicrobial agents and invasive monitoring. [1,[4][5][6][7] Unfortunately these approaches are not always feasible in LMICs. Blood tests and physiological parameters such as lactic acid, central venous pressure and mixed venous oxygen saturation are logistically challenging and expensive in LMICs, [8] and ventilators to manage complications from aggressive fluid resuscitation are scarce. [8,9] Beyond resource limitations, it also remains unclear how the different causes of acute infectious illness in LMICs impact on the effectiveness of interventions that were previously tested in HICs. Acute infectious illnesses in LMICs include fungal, viral and parasitic infections that are rare in HICs, [1,7,10,11] where most infectious disease mortality is the result of severe bacterial infections. [12] In addition, patients in LMICs frequently have comorbidities such as HIV, tuberculosis (TB) and malnutrition, which alter host immunity and change the course of infectious illness. [9][10][11]13] There are few data on what sepsis management strategies are most effective in settings that do not have advanced diagnostics and monitoring, and do have a higher burden of comorbidities such as malnutrition, HIV and TB. [1] Only a few dedicated studies on sepsis management in LMICs have been conducted, and most of these data are conflicting. Recent randomised controlled trials of This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Background: Emergency Departments (EDs) can serve as clinical sites for identification of new HIV infections and their entry into care. We examined if HIV-positive patients who present to EDs in South Africa are able to successfully link to care. Methods: We conducted a one-year longitudinal prospective cohort study in four hospitals across the Eastern Cape, South Africa, with participants followed between July 2016 and July 2018. All adult, non-critical patients presenting to the ED were systematically approached, asked about their HIV status, and, if unknown, offered a point-of-care (POC) HIV test. All HIV-positive patients were further consented to participate in a follow-up study to assess subsequent linkage to care and distance from "home" to ED. Linkage to care was defined as self-reported linkage (telephonic) or evidence of repeated CD4/viral load testing in the National Health Laboratory System (NHLS) at either the 6-or 12-months post index ED visit. Findings: A total of 983 HIV-positive patients consented to participate in the study. In the 12 months following their ED visit, 34¢1% of patients demonstrated linkage to care (335/983), 23¢8% did not link to care (234/ 983), and 42¢1% (414/983) were lost to follow-up. Though not statistically significant, a high percentage of young men (27/50, 54%) and those presenting with a trauma-related complaints (100/205, 48.8%) did not link to care. A considerable proportion of patients (105/454, 23¢2%,) resided 50 or more kilometers from their index ED sites, though there was not a significant difference in linkage to care rate between those who lived closer or further from the ED. Interpretation: We have shown that strategies to improve linkage to care from the ED should consider the high rates of poor linkage among young men and those presenting to the ED with trauma. Furthermore, innovative linkage to care solutions will need to account for the unique geographical consideration of this population, given that many ED patients will need to continue care at a site distant from the diagnosis site.

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