ABSTRACT
Background: The tolerability of mRNA COVID-19 vaccines among people living with HIV (PLWH) has been understudied in vaccine trials. CoVPN 3008 (Ubuntu) is the largest multicenter Phase 3 efficacy trial of mRNA vaccines in sub-Saharan Africa. Method(s): We enrolled adults age >=18 years living with HIV or another comorbidity associated with severe COVID-19. Previously vaccinated individuals were excluded. Baseline testing included HIV, CD4 count and HIV viral load (VL) (if HIV+), anti-SARS-CoV-2 antibodies, and nasal swab SARS-CoV-2 nucleic acid amplification test (NAAT). All participants receive vaccinations at months 0 and 6, and SARS-CoV-2 seronegative individuals also receive vaccination at month 1. This analysis includes mRNA-1273 vaccinations at months 0 and 1. Reactogenicity (solicited adverse events [AEs]) was assessed among a representative subset of participants (Safety Subset, SS) for 7 days post-vaccination. Baseline characteristics associated with moderate/severe reactogenicity events were assessed by univariate and multivariate logistic regression. Result(s): 14002 participants were enrolled in the trial (1510 into the SS) at 46 sites from 2 Dec 2021 to 9 Sep 2022. At baseline in the SS, 71% (1065) were female, median age 38 years (IQR 32-46), and median BMI 25.0 (IQR 20.7-30.2). 73% (1108) were SARS-CoV-2 seropositive, and 8.7% (131) had a positive nasal NAAT swab. 16% (197) had a history of tuberculosis. 84% (1267) were PLWH, with median CD4 count of 614 cells/muL (IQR 414-861);7.8% had CD4 count < 200. 21% (238) had detectable HIV VL (>=50 copies/mL), with median VL 1660 (IQR 182-23932). 14% (172/1262) and 12% (64/542) of PLWH reported moderate/severe reactogenicity after the 1st and 2nd vaccination (Figure), with no hospitalizations. Female PLWH and CD4 count >500 had 35% (p=0.03) and 44% (p=0.04) increased odds of moderate/severe reactogenicity, respectively. Other baseline characteristics were not associated with the odds of reporting moderate/severe reactogenicity among PLWH after 1st vaccination. Similar trends were seen after the 2nd vaccination, but none reached statistical significance. In multivariate models, female sex remained associated with increased odds of moderate/severe reactogenicity after the 2nd vaccination. Conclusion(s): Similar to observations in HIV-negative populations, mRNA-1273 was well tolerated by PLWH with more reactogenicity in females. Impaired inflammatory responses among participants with CD4 counts < 500 cell/muL may explain less moderate/severe reactions.
ABSTRACT
Background: SARS-CoV-2 seroprevalence data in women living with HIV (WLHIV), their infants and associated risk factors in this subpopulation remain limited. We retrospectively measured SARS-CoV-2 seroprevalence from 09/2019- 12/2021 among WLHIV and their children in the PROMOTE observational cohort in Uganda, Malawi, and Zimbabwe prior to widespread SARS-CoV-2 vaccination in those countries. Method(s): Sociodemographic, clinical data and blood were collected q6 months. Plasma stored during 3 waves of the COVID-19 pandemic in East/ Southern Africa were tested for SARS-CoV-2 specific IgG antibodies (Ab) using serological assays that detect adaptive immune responses to SARS-CoV-2 spike protein. Modified-Poisson regression models were used to calculate prevalence rate ratios (PRR) and 95% confidence intervals (CI) to identify sociodemographic and clinical risk factors. Result(s): Plasma samples from 979 PROMOTE mothers and 1332 children were analysed. We found no significant differences in baseline characteristics between participants testing positive (+) and negative (-) for SARS-CoV-2 Ab. Overall maternal SARS-CoV-2 seroprevalence was 57.6% (95%CI: 54.5-60.7) and 39.3% (95%CI: 36.7-41.9) for infants. The earliest + result was detected from a sample collected on 09/2019, in Malawi. Factors significantly associated with SARS-CoV-2 seropositivity were country of origin (reference Uganda, aPRR 1.45, 95%CI: 1.24-1.69) and non-breastfeeding mother (aPRR=1.22, 95%CI: 1.02-1.48). Children above 5 years had a 10% increased risk of SARS-CoV-2 seropositivity (aPRR=1.10, 95%CI: 0.90-1.34) when compared to younger children. We found no statistically significant association with sanitation, household density, distance to clinic, maternal employment, ART regimen or viral load. Mother/infant SARS-CoV-2 serostatuses were discordant in 373/865 (43.1%) families tested: mothers+/children- in 51.2%;mothers-/children+ in 12%;child+/sibling+ concordance was 21.4%. Conclusion(s): These SARS-CoV-2 seroprevalence data indicate that by late 2021, about half of mothers and about a third of children in a cohort of HIV-affected families in eastern/southern Africa had been infected with SARS-CoV-2. Breastfeeding was protective for mothers, likely because of the need to stay home for young children. Discordant results between children within same families underscores the need to further understand transmission dynamics within households.