Immunogenicity and safety following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine with Matrix-M adjuvant (NVX-CoV2373) versus a primary series in people living with and without HIV-1 infection in South Africa: A randomized crossover phase 2a/2b trial.

COVID-19 remains a global public health issue and an improved understanding of vaccine performance in immunocompromised individuals, including people living with HIV (PLWH), is needed. Initial data from the present study's pre-crossover/booster phase were previously reported. This phase 2a/b clinical trial in South Africa (2019nCoV-501/NCT04533399) revisits 1:1 randomly assigned HIV-negative adults (18-84 years) and medically stable PLWH (18-64 years) who previously received two NVX-CoV2373 doses (5 μg recombinant Spike protein with 50 μg Matrix-M™ adjuvant) or placebo.

Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women.

Background: There are gaps in uptake of, adherence to, and persistence in the use of preexposure prophylaxis for human immunodeficiency virus (HIV) prevention among cisgender women.

Methods: We conducted a phase 3, double-blind, randomized, controlled trial involving adolescent girls and young women in South Africa and Uganda. Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine-tenofovir alafenamide (F/TAF), or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate subcutaneous or oral placebo.

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.

The Importance of the Individual in PrEP Uptake: Multilevel Correlates of PrEP Uptake Among Adolescent Girls and Young Women in Tshwane, South Africa.

Adolescent girls and young women (AGYW) account for 25% of new HIV infections in South Africa. Pre-exposure prophylaxis (PrEP) is approved by the South African Government, but the factors that promote PrEP uptake among AGYW are not well understood. This study examines multilevel factors associated with PrEP uptake among AGYW in six clinic catchment areas in Tshwane (Pretoria), South Africa.

ChAdOx1 nCoV-19 (AZD1222) vaccine-induced Fc receptor binding tracks with differential susceptibility to COVID-19.

Despite the success of COVID-19 vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have emerged that can cause breakthrough infections. Although protection against severe disease has been largely preserved, the immunological mediators of protection in humans remain undefined. We performed a substudy on the ChAdOx1 nCoV-19 (AZD1222) vaccinees enrolled in a South African clinical trial.

Prospective acceptability of a multipurpose technology (MPT) implant in preclinical development to prevent HIV and unplanned pregnancy: Qualitative insights from women end users and health care providers in South Africa and Zimbabwe.

Background: Given the high rates of both HIV and unintended pregnancies in sub-Saharan Africa, the SCHIELD program aims to develop a multipurpose technology implant for HIV and pregnancy prevention. An end-user evaluation was undertaken with young women and health care providers to assess preferences for modifiable implant attributes to improve future adoption and rollout.

Methods: Focus group discussions were conducted with potential women end users, and health care providers experienced in implant insertion or removal participated in in-depth interviews.

Efficacy of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination against SARS-CoV-2 variants of concern: Final analysis of a randomized, placebo-controlled, phase 1b/2 study in South African adults (COV005).

COVID-19 vaccine efficacy (VE) has been observed to vary against antigenically distinct SARS-CoV-2 variants of concern (VoC). Here we report the final analysis of VE and safety from COV005: a phase 1b/2, multicenter, double-blind, randomized, placebo-controlled study of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination in South African adults aged 18-65 years. South Africa's first, second, and third waves of SARS-CoV-2 infections were respectively driven by the ancestral SARS-CoV-2 virus (wild type, WT), and SARS-CoV-2 Beta and Delta VoCs.

Incorporating end-users' voices into the development of an implant for HIV prevention: a discrete choice experiment in South Africa and Zimbabwe.

Background: Input from end-users during preclinical phases can support market fit for new HIV prevention technologies. With several long-acting pre-exposure prophylaxis (PrEP) implants in development, we aimed to understand young women's preferences for PrEP implants to inform optimal design.

Methods: We developed a discrete choice experiment and surveyed 800 young women in Harare, Zimbabwe and Tshwane, South Africa between September-November 2020.

Durability of ChAdOx1 nCoV-19 (AZD1222) vaccine and hybrid humoral immunity against variants including omicron BA.1 and BA.4 6 months after vaccination (COV005): a post-hoc analysis of a randomised, phase 1b-2a trial.

Background: COVID-19 vaccine rollout is lagging in Africa, where there has been a high rate of SARS-CoV-2 infection. We aimed to evaluate the effect of SARS-CoV-2 infection before vaccination with the ChAdOx-nCoV19 (AZD1222) vaccine on antibody responses through to 180 days.

Methods: We did an unmasked post-hoc immunogenicity analysis after the first and second doses of AZD1222 in a randomised, placebo-controlled, phase 1b-2a study done in seven locations in South Africa.

Stigma in the health clinic and implications for PrEP access and use by adolescent girls and young women: conflicting perspectives in South Africa.

Background: Globally, an urgent need exists to expand access to HIV prevention among adolescent girls and young women (AGYW), but the need is particularly acute in sub-Saharan Africa. Oral pre-exposure prophylaxis (PrEP) offers an effective HIV prevention method. In many countries, however, accessing PrEP necessitates that AGYW visit their local health clinic, where they may face access challenges.

High Levels of Pretreatment HIV-1 Drug Resistance Mutations Among South African Women Who Acquired HIV During a Prospective Study.

Background: Pretreatment HIV drug resistance (PDR) undermines individual treatment success and threatens the achievement of UNAIDS 95-95-95 targets. In many African countries, limited data are available on PDR as detection of recent HIV infection is uncommon and access to resistance testing is limited. We describe the prevalence of PDR among South African women with recent HIV infection from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.

Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial.

Background: HIV endpoint-driven clinical trials provide oral pre-exposure prophylaxis (PrEP) as HIV prevention standard of care. We evaluated quantifiable plasma tenofovir among South African women who used oral PrEP during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.

Methods: ECHO, a randomized trial conducted in 4 African countries between 2015 and 2018, assessed HIV incidence among HIV-uninfected women, aged 16-35 years, randomized to 1 of 3 contraceptives.

Female and male partner perspectives on placebo Multipurpose Prevention Technologies (MPTs) used by women in the TRIO study in South Africa and Kenya.

Background: Male partner awareness and acceptance of microbicide and family planning product use has been shown to increase women's own acceptance and adherence of a product. However, little is known about preferences regarding potential Multipurpose Prevention Technology (MPT) product delivery forms. As part of the TRIO study, men's reactions to their female partner's TRIO product use and comparisons of men's and women's views of TRIO product attributes and use acceptability were explored to better understand product preferences.

Immunogenicity and safety of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine in people living with and without HIV-1 infection: a randomised, controlled, phase 2A/2B trial.

Background: There is a paucity of data on COVID-19 vaccines in people living with HIV-1, who could be at increased risk of severe illness and death from COVID-19. We evaluated the safety and immunogenicity of a Matrix-M adjuvanted recombinant spike protein nanoparticle COVID-19 vaccine (NVX-CoV2373; Novavax) in HIV-negative people and people living with HIV-1.

Methods: In this randomised, observer-blinded, multicentre, placebo-controlled phase 2A/B trial in South Africa, participants aged 18-84 years, with and without underlying HIV-1, were enrolled from 16 sites and randomly assigned (1:1) to receive two intramuscular injections of NVX-CoV2373 or placebo, 21 days apart.

Genital inflammatory status and the innate immune response to contraceptive initiation.

Problem: Data on the effects of contraceptives on female genital tract (FGT) immune mediators are inconsistent, possibly in part due to pre-existing conditions that influence immune mediator changes in response to contraceptive initiation.

Methods: This study included 161 South African women randomised to injectable depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD), or levonorgestrel (LNG) implant in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. We measured thirteen cytokines and antimicrobial peptides previously associated with HIV acquisition in vaginal swabs using Luminex and ELISA, before, and at 1 and 3 months after contraceptive initiation.

Lung and blood early biomarkers for host-directed tuberculosis therapies: Secondary outcome measures from a randomized controlled trial.

Background: Current tuberculosis treatments leave most patients with bronchiectasis and fibrosis, permanent conditions that impair lung function and increase all-cause post-TB mortality. Host-directed therapies (HDTs) may reduce lung inflammation and hasten eradication of infection. Biomarkers can accelerate tuberculosis regimen development, but no studies have yet examined early biomarkers of TB-HDTs.

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.

HIV Incidence Among Pregnant and Nonpregnant Women in the FACTS-001 Trial: Implications for HIV Prevention, Especially PrEP Use.

Background: During pregnancy and postpartum period, the sexual behaviors of women and their partners change in ways that may either increase or reduce HIV risks. Pregnant women are a priority population for reducing both horizontal and vertical HIV transmission.

Setting: Nine sites in 4 South African provinces.

Immunological non-inferiority of a new fully liquid presentation of the MenACWY-CRM vaccine to the licensed vaccine: results from a randomized, controlled, observer-blind study in adolescents and young adults.

A fully liquid MenACWY-CRM vaccine presentation has been developed, modifying the meningococcal serogroup A (MenA) component from lyophilized to liquid. The safety and immunogenicity of the liquid presentation at the end of the intended shelf-life (aged for 24 or 30 months) were compared to the licensed lyophilized/liquid presentation. This multicenter, randomized (1:1), observer-blind, phase 2b study (NCT03433482) enrolled adolescents and young adults (age 10-40 years).

Giving voice to the end-user: input on multipurpose prevention technologies from the perspectives of young women in Kenya and South Africa.

Unintended pregnancy and unmet need for modern contraception contribute substantially to reproductive health disparities globally. In sub-Saharan Africa they occur in contexts of disproportionately high rates of HIV infection. Multipurpose prevention technologies (MPTs) can address HIV and pregnancy prevention needs in a single "2-in-1" product; however, few studies have solicited end-user views to inform design of new MPTs.