Strategies to Close the PrEP Uptake Gap Among Transgender People and Men Who Have Sex with Men in Tshwane, South Africa: Perspectives from the Community.

HIV Pre-exposure Prophylaxis (PrEP) uptake among transgender (TG) people and gay men and other men who have sex with men (MSM) remains low, despite South Africa being the first African country to approve PrEP. This mixed-methods study used a two-phase explanatory sequential design: (1) quantitative analysis of cross-sectional surveys followed by (2) qualitative in-depth interviews. This study explored facilitators and barriers to PrEP uptake to identify strategies to increase utilization in these key populations. We conducted 202 cross-sectional surveys and 20 in-depth interviews between July 2021 and March 2022 in Soshanguve, Tshwane, Gauteng. Quantitative data were analyzed using univariate logistic regression; thematic analysis was performed for qualitative data. Findings show high willingness to use PrEP but low PrEP uptake. We outline strategies to facilitate PrEP use: (1) demystify daily PrEP by deploying community-engaged PrEP education campaigns; (2) capitalize on existing peer networks; and (3) expand accessible and culturally responsive PrEP service delivery models. We provide feasible recommendations to close the PrEP uptake gap in these key populations in South Africa.

Risk Factors Associated with HIV Acquisition in Males Participating in HIV Vaccine Efficacy Trials in South Africa.

In South Africa, HIV acquisition risk has been studied less in people assigned male at birth. We studied the associations between risk behaviors, clinical features and HIV incidence amongst males in two South African HIV preventive vaccine efficacy trials. We used Cox proportional hazards models to test for associations between demographics, sexual behaviors, clinical variables and HIV acquisition among males followed in the HVTN 503 (n = 219) and HVTN 702 (n = 1611) trials. Most males reported no male sexual partners (99.09% in HVTN 503) or identified as heterosexual (88.08% in HVTN 702). Annual HIV incidence was 1.39% in HVTN 503 (95% CI 0.76-2.32%) and 1.33% in HVTN 702 (95% CI 0.80-2.07%). Increased HIV acquisition was significantly associated with anal sex (HR 6.32, 95% CI 3.44-11.62), transactional sex (HR 3.42, 95% CI 1.80-6.50), and non-heterosexual identity (HR 16.23, 95%CI 8.13-32.41) in univariate analyses and non-heterosexual identity (HR 14.99, 95% CI 4.99-45.04; p < 0.01) in multivariate analysis. It is appropriate that prevention efforts in South Africa, although focused on the severe epidemic in young women, also encompass key male populations, including men who have sex with men, but also men who engage in anal or transactional sex.

Establishing communication challenges and preferences among clinical trial participants in an under-resourced setting to improve adherence to study visits and participant retention.

BACKGROUND: Ensuring protocol visit compliance and maintaining high participant retention remain critical elements of clinical trials. In the HVTN 702 HIV vaccine trial, Setshaba Research Centre in Soshanguve, Tshwane, South Africa, experienced challenges in communicating with participants to remind them about their study visits. In order to improve participants adhering to their study visits, and study retention, we aimed to identify challenges in mobile communication, and to establish preferences in communication methods and interest in receiving study information via cellphones. METHODS: We conducted a paper-based survey among HVTN 702 HIV vaccine trial participants at Setshaba Research Centre. The survey comprised of dichotomous and scale questions and was completed voluntarily and anonymously. The questions included those on their primary form of communication (calling, SMS and WhatsApp), the best time of day for the site to communicate with them, whether they were interested in receiving regular general study information updates via their cellular phone, how often they changed their cellular phones and/or network, whether they experienced any challenges with their cellular phones and what these challenges were, if any. All participants scheduled to visit the clinic from February to May 2019 were invited to participate. Thus, 90 of 380 (24%) participants enrolled by May 2019 were surveyed. RESULTS: The majority (68%) of participants were 26-35 years old and almost three-quarters (73%) were female. Almost all participants (99%) had a personal cellphone. Half of the participants experienced some challenge related to cellphones, these being poor network signal at home (12%), battery running flat frequently (11%), sharing their phone (9%), lack of data (9%), challenges with use of applications (6%) and their cellphones being unreliable (3%). Annually, 20% of participants made a single or multiple network changes. Communication preferences were calls by site staff (80%), SMS (16%) and WhatsApp (3%). Most preferred to be contacted in the morning (49%) or afternoon (31%). Site contact was rated as 'very helpful' (87%), and 97% were interested in receiving regular general study information updates via their cellphone. CONCLUSION: Despite participants owning cellphones, there are still technical challenges, for example, network signals, battery-charging and applications. The majority of participants preferred being called rather than communicating by text messages or WhatsApp. Future studies need to include addressing participant challenges in maintaining contact and training of participants on use of cellphone applications to optimise communication. Noting the preferred time of day for participants to be called might improve the likelihood of making contact with them. The willingness to receive updates will aid in keeping participant interest high and enhance retention.

Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity.

A common viral immune evasion strategy involves mutating viral surface proteins in order to evade host neutralizing antibodies. Such immune evasion tactics have not previously been intentionally applied to the development of novel viral gene delivery vectors that overcome the critical problem of anti-vector immunity. Recombinant, replication-incompetent adenovirus serotype 5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens have proved highly immunogenic in preclinical studies but will probably be limited by the high prevalence of pre-existing anti-Ad5 immunity in human populations, particularly in the developing world. Here we show that rAd5 vectors can be engineered to circumvent anti-Ad5 immunity. We constructed novel chimaeric rAd5 vectors in which the seven short hypervariable regions (HVRs) on the surface of the Ad5 hexon protein were replaced with the corresponding HVRs from the rare adenovirus serotype Ad48. These HVR-chimaeric rAd5 vectors were produced at high titres and were stable through serial passages in vitro. HVR-chimaeric rAd5 vectors expressing simian immunodeficiency virus Gag proved comparably immunogenic to parental rAd5 vectors in naive mice and rhesus monkeys. In the presence of high levels of pre-existing anti-Ad5 immunity, the immunogenicity of HVR-chimaeric rAd5 vectors was not detectably suppressed, whereas the immunogenicity of parental rAd5 vectors was abrogated. These data demonstrate that functionally relevant Ad5-specific neutralizing antibodies are focused on epitopes located within the hexon HVRs. Moreover, these studies show that recombinant viral vectors can be engineered to circumvent pre-existing anti-vector immunity by removing key neutralizing epitopes on the surface of viral capsid proteins. Such chimaeric viral vectors may have important practical implications for vaccination and gene therapy.

A statewide hepatitis B vaccination program for school children in Hawaii: vaccination series completion and participation rates over consecutive school years.

OBJECTIVE: The authors assessed a statewide school-based Hepatitis B (HepB) vaccination program for preadolescents in Hawaii over three consecutive school years. Factors assessed included number of schools and students participating and number of students receiving three doses of hepatitis B vaccine. METHODS: Records of the program, which targeted 4th and/or 5th graders in public and private schools, were reviewed for the period from 1996 to 1999. RESULTS: The proportion of participating schools increased from 76% of all schools in the state in School Year 1 to 94% in School Year 3. The proportion of children with completed consent forms who received three doses of HepB vaccine at school exceeded 80% throughout the project. In School Year 1, 10,003 (70%) of 14,333 children enrolled at participating schools received three vaccine doses in school; however, this proportion declined over subsequent school years to 51% (7,722/15,013) in School Year 2 and 24% (7,344/30,429) in School Year 3. A survey of 477 parents not consenting to school vaccination indicated that 84% of their children completed the vaccine series at a private provider office. CONCLUSION: Statewide school-based HepB vaccination campaigns for at-risk populations can result in a majority of children in targeted age groups receiving three doses of hepatitis B vaccine, though declining participation may be observed as uptake in the private sector increases.

Lack of patient registration in the electronic TB register for sputum smear-positive patients in KwaZulu-Natal, South Africa.

Analysis of diagnostic smear positive records from the laboratory from KwaZulu-Natal in South Africa shows that not all patients are counted in surveillance efforts. However, review of paper-based patient records suggests the majority of identified TB patients are being treated. Directly linking laboratory and clinical records would enhance surveillance information.

International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations.

Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for HIV-1 and other pathogens have been shown to be limited by high titers of Ad5 neutralizing antibodies (NAbs) in the developing world. Alternative serotype rAd vectors have therefore been constructed. Here we report Ad5, Ad26, Ad35, and Ad48 NAb titers in 4381 individuals from North America, South America, sub-Saharan Africa, and Southeast Asia. As expected, Ad5 NAb titers were both frequent and high magnitude in sub-Saharan Africa and Southeast Asia. In contrast, Ad35 NAb titers proved infrequent and low in all regions studied, and Ad48 NAbs were rare in all regions except East Africa. Ad26 NAbs were moderately common in adults in sub-Saharan Africa and Southeast Asia, but Ad26 NAb titers proved markedly lower than Ad5 NAb titers in all regions, and these relatively low Ad26 NAb titers did not detectably suppress the immunogenicity of 4×10(10)vp of a rAd26-Gag/Pol/Env/Nef vaccine in rhesus monkeys. These data inform the clinical development of alternative serotype rAd vaccine vectors in the developing world.

Aerosol and subcutaneous measles vaccine: measles antibody responses 6 years after re-vaccination.

There are no large-scale data on the long-term persistence of measles antibody after vaccination by the aerosol route. We therefore followed-up South African schoolchildren 6 years after their re-vaccination with Edmonston-Zagreb (EZ) and Schwarz (SW) measles vaccine given by aerosol and subcutaneous routes. Measles antibody levels and the proportion of children who were seropositive at year 6 remained significantly higher in the Edmonston-Zagreb aerosol group compared to the groups that received Schwarz or Edmonston-Zagreb vaccine subcutaneously. Measles re-vaccination by aerosol evokes a stronger and much longer lasting antibody response than injected vaccine and should thus provide more durable protection against measles.

Age dependence of adenovirus-specific neutralizing antibody titers in individuals from sub-Saharan Africa.

We assessed neutralizing antibody titers to adenovirus serotype 5 (Ad5) and six rare adenovirus serotypes, serotypes 11, 35, 50, 26, 48, and 49, in pediatric populations in sub-Saharan Africa. We observed a clear age dependence of Ad5-specific neutralizing antibody titers. These data will help to guide the development of Ad vector-based vaccines for human immunodeficiency virus type 1 and other pathogens.