Impact of SARS-CoV-2 breakthrough infection on short-term CD4 count among adults with HIV in the United States from 2020-2022

Background CD4 T cells are critical for reducing disease severity and viral clearance of SARS-CoV-2, which is particularly important among immune-compromised populations, including people with HIV (PWH). While vaccines are effective, risk and severity of COVID-19 breakthrough infections are higher in people with versus without HIV. Little is known about the effects of SARS-CoV-2 on CD4 counts among PWH after a breakthrough infection. Methods We evaluated the impact of COVID-19 breakthrough infection on immediate (0-60 days) and short-term (61-180 days) CD4 count from 2020-2022 among PWH vaccinated for COVID-19 in the CIVETs-II study. We utilized pre-post paired t-tests to test for statistically significant changes in CD4 count before and after breakthrough infection, and linear mixed effect models to quantify changes in CD4 count following SARS-CoV-2 breakthrough infection. Results Among 152 PWH, 37% were white and 40% were 55+ years of age. Median CD4 count pre-breakthrough was 614 cells/mm3, while median post-breakthrough CD4 count was 612 cells/mm3. Most patients had an undetectable HIV viral load (62%). Paired pre-post t-test indicated no change in CD4 count before breakthrough infection to CD4 counts 0-60 days (-40 [-86, 5] cells/mm3) or 61+ days (25 [-11, 61] cells/mm3) following breakthrough infection. Longitudinal trajectories indicated CD4 count rebound 61+ days following breakthrough infection (112 cell/mm3 increase per 60-day increase; p<0.05). Conclusion While changes in CD4 counts were observed post-breakthrough infection, these results are likely not clinically significant, suggesting that among PWH vaccinated for COVD-19, CD4 count is not substantially impacted by breakthrough infections.