Effects of COVID-19 mRNA vaccination on HIV viremia and reservoir size

Abstract

Objective: The immunogenic nature of COVID-19 mRNA vaccines led to some initial concern that these could stimulate the HIV reservoir. We analyzed changes in plasma HIV loads (pVL) and reservoir size following COVID-19 mRNA vaccination in 62 people with HIV (PWH) receiving antiretroviral therapy (ART), and analyzed province-wide trends in pVL before and after the mass vaccination campaign.

Design: Longitudinal observational cohort and province-wide analysis.

Methods: 62 participants were sampled pre-vaccination, and one month after their first and second COVID-19 immunizations. Vaccine-induced anti-SARS-CoV-2-Spike antibodies in serum were measured using the Roche Elecsys Anti-S assay. HIV reservoirs were quantified using the Intact Proviral DNA Assay; pVL were measured using the cobas 6800 (LLOQ:20 copies/mL). The province-wide analysis included all 290,401 pVL performed in British Columbia, Canada between 2012-2022.

Results: Pre-vaccination, the median intact reservoir size was 77 (IQR:20-204) HIV copies/million CD4+ T-cells, compared to 74 (IQR:27-212) and 65 (IQR:22-174) post-first and -second dose, respectively (all comparisons p>0.07). Pre-vaccination, 82% of participants had pVL<20 copies/mL (max:110 copies/mL), compared to 79% post-first dose (max:183 copies/mL) and 85% post-second dose (max:79 copies/mL) (p>0.4). The magnitude of the vaccine-elicited anti-SARS-CoV-2-Spike antibody response did not correlate with changes in reservoir size nor detectable pVL frequency (p>0.6). We found no evidence linking the COVID-19 mass vaccination campaign to population-level increases in detectable pVL frequency among all PWH in the province, nor among those who maintained pVL suppression on ART.

Conclusion: We found no evidence that COVID-19 mRNA vaccines induced changes in HIV reservoir size nor plasma viremia.

Keywords: COVID-19 vaccine; HIV; IPDA; mRNA; plasma viral load; reservoir size.

Figure 1:. Plasma HIV loads following one- and two-dose COVID-19 vaccination.

HIV plasma viral loads prior to vaccination (left), one month after the first dose (middle), and one month following the second dose (right). A black dashed line indicates the assay LLOQ of 20 HIV copies/mL, while light grey dashed lines indicate clinically relevant pVL thresholds of 50 and 200 HIV copies/mL. For graphing purposes, undetectable viral loads were plotted as 10 HIV copies/mL, while viral loads that were detectable yet below the LLOQ were plotted as 15 HIV copies/mL. As the vast majority of pVL measurements were below the LLOQ, violin plots help visualize the data distribution. Each participant is identified by a unique color that is consistent throughout all figures. P-values were calculated using the Wilcoxon sum rank test for paired data.

Figure 2:. Measures of intact reservoir size, and total, 5’-defective, 3’-defective proviral burdens after one- and two-dose COVID-19 vaccination.

Intact reservoir size (panel a), total proviral burden (panel b), 5’-defective proviral burden (panel c), and 3’-defective proviral burden (panel d) measured at baseline (pre-vaccine), one month after the first vaccine dose, and one month after the second vaccine dose, using the Intact Proviral DNA Assay (IPDA). Each participant is identified by a unique color that is consistent throughout all figures. P-values were calculated using the Wilcoxon sum rank test for paired data.

Figure 3.. Relationship between reservoir size, plasma viral load and COVID-19 vaccine immune response magnitude.

Panel a: Anti-SARS-CoV-2-Spike (S) serum antibody levels one month following the first COVID-19 vaccine dose in participants with pVL >20 HIV RNA copies/mL (top group) versus <20 HIV RNA copies/mL (bottom group) at this time point. P-value calculated using the Mann-Whitney U-test. Panel b: same as a, but for anti-S serum antibody levels and pVL one month after the second dose. Panel c: Relationship between Anti-S serum antibody levels one month following the first COVID-19 vaccine dose, and the fold-change in intact reservoir size from baseline, assessed using Spearman’s correlation. Panel d: same as c, but depicting the relationship between Anti-S serum antibody levels one month following the second COVID-19 vaccine dose, and the fold-change in intact reservoir size since the previous time point. Each participant is identified by a unique color that is consistent throughout all figures.

Figure 4.. Population-level analysis of pVL test results in BC.

Panel a: The percentage of all pVL tests performed in BC that returned a detectable result (defined as >40 HIV RNA copies/mL; see methods) was computed for every month between 2012–2022 and depicted as a smoothed mauve curve. The numbers underneath the x-axis denote the total number of pVL tests performed each year. The smoothed blue line depicts the number of COVID-19 vaccine doses administered in BC weekly, as retrieved from the COVID-19 Vaccine Tracker [36]. The shaded rectangle denotes the period when pVL load testing of long-term ART-suppressed PWH was temporarily curtailed to preserve capacity for COVID-19 diagnostic testing. Panel b: The percentage of PWH in BC receiving uninterrupted ART who experienced at least one detectable pVL measurement (defined as >40 HIV RNA copies/mL; see methods) for the given year. The total number of pVL tests included in each year’s analysis, as well as the total number of PWH from whom these pVL data are derived, are shown on the x-axis.