Safety of AZD1222 COVID-19 vaccine and low Incidence of SARS-CoV-2 infection in Botswana following ChAdOx1(AZD1222) vaccination: A single-arm open-label interventional study - final study results.

Objectives: We report the final analysis of the single-arm open-label study evaluating the safety and COVID-19 incidence after AZD1222 vaccination in Botswana conducted between September 2021 and August 2022. Methods: The study included three groups of adults (>18 years), homologous AZD1222 primary series and booster (AZ2), heterologous primary series with one dose AZD1222, and AZD1222 booster (HPS), and primary series other than AZD1222 and AZD1222 booster (OPS). We compared the incidence of AEs in participants with and without prior COVID-19 infection using an exact test for rate ratios. Results: Among 10,894 participants, 9192 (84.4%) were enrolled at first vaccine dose, 521 (4.8%) at second vaccine, and 1181 (10.8%) at the booster vaccine. Of 10,855 included in the full analysis set, 1700 received one dose of AZD1222; 5377 received two doses; 98 received a heterologous series including one AZD1222 and a booster; 30 in the HPS group; 1058 in the OPS group; and 2592 in the AZ2 group. No laboratory-confirmed COVID-19 hospitalizations or deaths were reported. The incidence of laboratory-confirmed symptomatic COVID infection for the AZ2 group was 6.22 (95% confidence interval: 2.51-12.78) per 1000 participant-years (1000-PY) and 3.5 (95% confidence interval: 0.42-12.57) per 1000-PY for AZ2+booster group. Most adverse events were mild, with higher incidence in participants with prior COVID-19 infection. Individuals with prior COVID-19 exposure exhibited higher binding antibody responses. No differences in outcomes were observed by HIV status. Conclusion: AZD1222 is safe, effective, and immunogenic for people living with and without HIV.

Feasibility of oral HIV self-testing in female sex workers in Gaborone, Botswana.

BACKGROUND: Oral HIV self-testing (HIVST) may be useful for increasing testing in persons at elevated risk of acquiring HIV. METHODS: We conducted a pilot study to evaluate the feasibility (defined by uptake) of HIVST among FSW in Gaborone, Botswana. FSW age 18 years and above were recruited through a non-governmental organization serving FSW. FSW with unknown or negative HIV status at screening performed HIVST in the study clinic following brief training. FSW testing HIV-negative were each given two test kits to take home: one kit to perform unassisted HIVST and another to share with others. Feasibility (use) of HIVST (and sharing of test kits with others) was assessed in these women at a study visit four months later. RESULTS: Two hundred FSW were screened. Their average age was 34 years (range 18-59), and 115 (58%) were HIV-positive. Eighty-five (42%) tested HIV-negative at entry and were eligible to take part in the HIVST pilot study. All 85 (100%) agreed to take home HIVST kits. Sixty-nine (81%) of these 85 participants had a follow-up visit, 56 (81%) of whom reported performing HIVST at a mean of three and half months after the initial visit. All 56 participants who performed HIVST reported negative HIVST results. Fifty (73%) of the 69 participants who took HIVST kits home shared them with others. Of the 50 women sharing HIVST kits, 25 (50%) shared with their non-client partners, 15 with a family member, 8 with friends, and 3 with a client. One participant did not test herself but shared both her test kits. Most participants 53/56 (95%) found oral HIVST very easy to use whilst 3/56 (5%) felt it was fairly easy. CONCLUSION: Oral HIVST is feasible among FSW in Gaborone, Botswana. The majority of FSW used the HIVST kits themselves and also shared extra HIVST kits with other individuals.

Sexually transmitted infections among HIV serodiscordant partners: A secondary analysis of HIV Prevention Trial Network 052.

Sexually transmitted infections (STIs) remain a public health concern because of their interaction(s) with HIV. In the HPTN 052 study, STIs were evaluated in both HIV-positive index cases and their HIV-negative partners at enrollment and at yearly follow-up visits. Our definition for STI was based on any infection with Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis, or Trichomonas vaginalis. We used log-binomial regression models to identify factors associated with prevalent STIs. Generalized estimating equation models with the Poisson distribution were used to compare STI incidence between HIV-positive index cases and HIV-negative partners. 8.1% of the participants had STIs at enrollment. The prevalence of STIs (8.9 vs. 7.2) was higher in HIV-positive index cases than HIV-negative partners. Being female (prevalence ratio (PR) = 1.61; 95% CI: 1.20-2.16) or unmarried (PR = 1.92; 95% CI: 1.17-3.14) was associated with prevalent STIs. Compared to HIV-negative male partners, HIV-positive female index cases had a higher risk of STI acquisition (incidence rate ratio (IRR) = 2.25; 95% CI: 1.70-2.97). While we are implementing HIV prevention interventions for HIV-negative people, we should also intensify targeted STI prevention interventions, especially among HIV-positive women.

A Phase 2b Study to Evaluate the Safety and Efficacy of VRC01 Broadly Neutralizing Monoclonal Antibody in Reducing Acquisition of HIV-1 Infection in Women in Sub-Saharan Africa: Baseline Findings.

BACKGROUND: HIV Vaccine Trials Network 703/HIV Prevention Trials Network 081 is a phase 2b randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of passively infused monoclonal antibody VRC01 in preventing HIV acquisition in heterosexual women between the ages of 18 and 50 years at risk of HIV. Participants were enrolled at 20 sites in Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania, and Zimbabwe. It is one of the 2 Antibody Mediated Prevention efficacy trials, with HIV Vaccine Trials Network 704/HIV Prevention Trials Network 085, evaluating VRC01 for HIV prevention. METHODS: Intense community engagement was used to optimize participant recruitment and retention. Participants were randomly assigned to receive intravenous VRC01 10 mg/kg, VRC01 30 mg/kg, or placebo in a 1:1:1 ratio. Infusions were given every 8 weeks with a total of 10 infusions and 104 weeks of follow-up after the first infusion. RESULTS: Between May 2016 and September 2018, 1924 women from sub-Saharan Africa were enrolled. The median age was 26 years (interquartile range: 22-30), and 98.9% were Black. Sexually transmitted infection prevalence at enrollment included chlamydia (16.9%), trichomonas (7.2%), gonorrhea (5.7%), and syphilis (2.2%). External condoms (83.2%) and injectable contraceptives (61.1%) were the methods of contraception most frequently used by participants. In total, through April 3, 2020, 38,490 clinic visits were completed with a retention rate of 96% and 16,807 infusions administered with an adherence rate of 98%. CONCLUSIONS: This proof-of-concept, large-scale monoclonal antibody study demonstrates the feasibility of conducting complex trials involving intravenous infusions in high incidence populations in sub-Saharan Africa.

Acceptability of oral HIV self-testing among female sex workers in Gaborone, Botswana.

BACKGROUND: HIV prevalence among female sex workers (FSW) in sub-Saharan Africa is much higher than in the general population. HIV self-testing (HIVST) may be useful for increasing testing rates in FSW. METHODS: We conducted semi-structured in-depth interviews among FSW, nurses and lay counsellors providing services to FSWs in Botswana. We aimed to gain understanding of perceived acceptability, anticipated barriers, and preferred approaches to HIVST among FSW. Interviews were audio-recorded, transcribed and translated. Transcripts were reviewed and coded independently by two investigators; high inter-coder agreement was achieved (Kappa = 0.80). RESULTS: We interviewed five care providers whose average age was 40 years (SD = 2,64, range = 37-43); three nurses and two counsellors. Thirty FSW were interviewed, with mean age 34 years (range = 20-52). Most (27; 90%) FSW expressed great interest in using HIVST kits. Facilitators of HIVST were: awareness of own risky sexual behaviours, desire to stay healthy, and perceived autonomy over one's healthcare decisions. Perceived advantages of HIVST included convenience, privacy, and perception of decreased stigma. Identified barriers to HIVST included lack of knowledge about the HIVST kit, fear of testing due to anticipated stigma, mistrust of the test's accuracy, doubt of self-competency to perform HIVST, and concerns about not linking to care. Assisting someone to test was noted as good for providing emotional support, but there were concerns about confidentiality breaches. Providers expressed concerns over low literacy among FSWs which could affect comprehension of testing instructions, and competency to perform testing and interpret results. Participants' recommendations for implementation of HIVST included: ensuring wide dissemination of information on HIVST, engaging peers in information-sharing and education, making test kits accessible in FSW-friendly centres, and having clear instructions for linkage to healthcare and support. CONCLUSION: HIVST shows high acceptability among FSWs in Gaborone Botswana, with providers expressing some concerns. Implementation should be peer-driven with healthcare provider oversight.

Brief Report: High Rates of Adverse Birth Outcomes in HIV and Syphilis Coinfected Women in Botswana.

BACKGROUND: Little is known about the combined impact of HIV/syphilis coinfection on birth outcomes. METHODS: Antenatal HIV and syphilis test results, obstetric history, and infant birth outcomes were collected from obstetric records in maternity wards in Botswana between 2008 and 2011 (5 sites) and 2014 and 2016 (8 sites). We used logistic regression to compare adverse birth outcomes by HIV and syphilis status. Outcomes included stillbirth, preterm delivery, low birth weight, and in-hospital neonatal death. RESULTS: Of 76,466 women, 75,770 (99.1%) had HIV test results, and 20,520 (27.1%) were HIV positive. Syphilis test results were available for 67,290 (88.0%), and 697 (1.0%) had reactive rapid plasma reagin. Among 692 women with syphilis and an HIV test result, 261 (37.7%) were coinfected. HIV-infected women were more likely to be infected with syphilis than HIV-uninfected women [odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.44 to 1.96]. From 2008-2011 to 2014-2016, the proportion of women with syphilis remained constant (1.1% vs. 1.0%, P = 0.41), but HIV/syphilis coinfection declined from 45% to 27% (P < 0.0001). Stillbirth occurred in 5.8% of coinfected women, compared with 1.9% with no HIV/syphilis (OR = 3.09; 95% CI: 1.83 to 5.23); 3.4% with HIV alone (OR = 1.75; 95% CI: 1.03 to 2.97), or 3.7% with syphilis alone (OR = 1.58; 95% CI: 0.77 to 3.25). Low birth weight occurred in 24.1% of coinfected women, compared with 12.1% with no HIV/syphilis (OR 2.31; 95% CI: 1.74 to 3.08; 20% with HIV alone (OR = 1.27; 95% CI: 0.96 to 1.69); or 14.6% with syphilis alone (OR = 1.85; 95% CI: 1.26 to 2.74). CONCLUSIONS: Although HIV/syphilis coinfection in pregnancy has declined in the past decade, coinfection was associated with adverse birth outcomes.

Risky Sexual Behavior Among Individuals Receiving Buprenorphine/Naloxone Opiate Dependency Treatment: HIV Prevention Trials Network (HPTN) 058.

INTRODUCTION: Understanding the role of opiate dependency treatment in risky sexual behavior could help optimize interventions for people who inject drugs (PWID). OBJECTIVES: We evaluated whether long-term medication-assisted treatment (LT-MAT) of opiate dependency with buprenorphine/naloxone influenced risky sexual behavior among HIV-uninfected PWID and identified predictors of risky sexual behavior. METHODS: We used data from HPTN 058, a randomized controlled trial of LT-MAT vs. short-term medication-assisted treatment among PWID in China and Thailand. We evaluated associations between randomized opiate dependency treatment group and self-reported risky sexual behaviors within the past month: condomless sex with primary partner, condomless sex with nonprimary partner, multiple partners, and more than 3 sexual acts. We used generalized estimating equations to conduct intention-to-treat, as-treated, and exploratory analyses of these associations. RESULTS: Of 1250 participants included in the analysis, 92% were male, with median age of 34 years (interquartile range 28-39). At baseline, referring to the past month, 36% of participants reported condomless sex with primary partner, 4% reported condomless sex with nonprimary partner, 6% reported multiple sex partners, and 30% reported more than 3 sexual acts. Risky sexual behaviors did not differ significantly between treatment groups at any point. Significant predictors (P < 0.05) of condomless sex with nonprimary partner were history of incarceration and noninjection drug use. Number of needle-sharing partners, noninjection drug use, and higher income were predictors for multiple sexual partners. CONCLUSIONS: LT-MAT did not significantly modify risky sexual behavior among HIV-uninfected PWID. Interventions that reduce sexual risk should target PWID with history of incarceration, alcohol use, and needle sharing.

Virologic outcomes in early antiretroviral treatment: HPTN 052.

INTRODUCTION: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. OBJECTIVE: To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. METHODS: 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350-550 cells/mm3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 < 250 cells/mm3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs > 1000 copies/mL > 24 weeks after ART initiation. RESULTS: Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. CONCLUSIONS: Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.