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

SUPPLEMENTARY FIGURE S1: Binding antibody responses to SARS-CoV-2 spike (Anti-S) following vaccination with ChAdOx1 (AZD1222).SUPPLEMENTARY FIGURE S2: SAR-COV-2 variant Dynamics (Fig S2-A) and cumulative number of cases by COVID-19 zones (showing study sites 1 to 5).SUPPLEMENTARY TABLE S1: Line listing of adverse events of special interest.SUPPLEMENTARY TABLE S2: Line listing of serious adverse events.SUPPLEMENTARY TABLE S3: Incidence (per 1,000 participant-years) of AE, localised and systemic adverse events by prior COVID infection status.SUPPLEMENTARY TABLE S4: Sociodemographic characteristics of participants enrolled in the immunogenicity subcohort of the ChAdOx1(AZD1222) study.SUPPLEMENTARY TABLE S5: geometric mean concentrations of Anti-Nucleocapsid antibody levels by dose and time (days) since first-dose.SUPPLEMENTARY TABLE S6: geometric mean concentrations of Anti-Spike antibody levels by dose and time (days) since first-dose.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.AstraZeneca under an externally sponsored collaborative research agreement, partially supported through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE 2.0), by the Bill and Melinda Gates Foundation (INV-033558) and the National Institutes of Health NIH Fogarty International Center.http://www.elsevier.com/locate/ijregihj2024School of Health Systems and Public Health (SHSPH)SDG-03:Good heatlh and well-bein

The impact of free antiretroviral therapy for pregnant non‐citizens and their infants in Botswana

Abstract Introduction In December 2019, the Botswana government expanded free antiretroviral therapy (ART) to include non‐citizens. We evaluated the impact of this policy change on antenatal care (ANC), antiretroviral therapy coverage and adverse birth outcomes. Methods The Tsepamo Surveillance study collects data at up to 18 delivery sites in Botswana. We compared outcomes in citizens and non‐citizens living with HIV before and after antiretroviral therapy expansion to non‐citizens. Adverse birth outcomes included preterm delivery (PTD) <37 weeks, very preterm delivery (VPTD) <32 weeks, small for gestational age (SGA) <10th percentile, very small for gestational age (VSGA) <3rd percentile, stillbirth and neonatal death. Log‐binomial regression models were constructed to generate risk ratios. Results From August 2014 to September 2021, 45,576 (96.5%) citizens and 1513 (3.2%) non‐citizens living with HIV delivered; 954 (62.9%) non‐citizen deliveries were before the antiretroviral therapy expansion, and 562 (37.1%) were after. Non‐citizen ANC attendance among pregnant people living with HIV increased from 79.2% pre‐expansion to 87.2% post‐expansion (p<0.001), and became more similar to citizens (96.0% post‐expansion). Non‐citizens receiving any antenatal antiretroviral therapy increased from 65.5% pre‐expansion to 89.9% post‐expansion (p < 0.001), also more similar to citizens (97.2% post‐expansion). Infants born to non‐citizens with singleton gestations in the pre‐expansion period had significantly greater risk of PTD (aRR = 1.28, 95% CI, 1.11, 1.46), VPTD (aRR = 1.89, 95% CI, 1.43, 2.44) and neonatal death (aRR = 1.69, 95% CI, 1.03, 2.60), but reduced SGA risk (aRR = 0.75; 95% CI, 0.62, 0.89) compared with citizens. Post‐expansion, greater declines in most adverse outcomes were observed in non‐citizens, with largely similar outcomes between non‐citizens and citizens. Non‐significant differences were observed for non‐citizenship in PTD (aRR = 0.84, 95% CI, 0.66, 1.06), VPTD (aRR = 0.57, 95% CI, 0.28, 1.01), SGA (aRR = 0.91, 95% CI, 0.72, 1.13), VSGA (aRR = 0.87, 95% CI, 0.58, 1.25), stillbirth (aRR = 0.71, 95% CI, 0.35, 1.27) and neonatal death (aRR = 1.35, 95% CI, 0.60, 2.62). Conclusions Following the expansion of free antiretroviral therapy to non‐citizens, gaps narrowed in ANC and antiretroviral therapy use in pregnancy between citizens and non‐citizens living with HIV. Disparities in adverse birth outcomes were no longer observed

B and T Cell Phenotypic Profiles of African HIV-Infected and HIV-Exposed Uninfected Infants: Associations with Antibody Responses to the Pentavalent Rotavirus Vaccine

We examined associations between B and T cell phenotypic profiles and antibody responses to the pentavalent rotavirus vaccine (RV5) in perinatally HIV-infected (PHIV) infants on antiretroviral therapy and in HIV-exposed uninfected (PHEU) infants enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials P1072 study (NCT00880698). Of 17 B and T cell subsets analyzed, PHIV and PHEU differed only in the number of CD4+ T cells and frequency of naive B cells, which were higher in PHEU than in PHIV. In contrast, the B and T cell phenotypic profiles of PHIV and PHEU markedly differed from those of geographically matched contemporary HIV-unexposed infants. The frequency of regulatory T and B cells (Treg, Breg) of PHIV and PHEU displayed two patterns of associations: FOXP3+ CD25+ Treg positively correlated with CD4+ T cell numbers; while TGFβ+ Treg and IL10+ Treg and Breg positively correlated with the frequencies of inflammatory and activated T cells. Moreover, the frequencies of activated and inflammatory T cells of PHIV and PHEU positively correlated with the frequency of immature B cells. Correlations were not affected by HIV status and persisted over time. PHIV and PHEU antibody responses to RV5 positively correlated with CD4+ T cell counts and negatively with the proportion of immature B cells, similarly to what has been previously described in chronic HIV infection. Unique to PHIV and PHEU, anti-RV5 antibodies positively correlated with CD4+/CD8+FOXP3+CD25+% and negatively with CD4+IL10+% Tregs. In conclusion, PHEU shared with PHIV abnormal B and T cell phenotypic profiles. PHIV and PHEU antibody responses to RV5 were modulated by typical HIV-associated immune response modifiers except for the association between CD4+/CD8+FOXP3+CD25+Treg and increased antibody production