High prevalence of asymptomatic Omicron carriage and correlation with CD4+ T cell count among adults with HIV enrolling in COVPN 3008 Ubuntu clinical trial in sub-Saharan Africa


BACKGROUND: The COVID-19 wave driven by the SARS-CoV-2 Omicron variant prompted the need to explore asymptomatic carriage among HIV-immunocompromised adults.
METHODS: In the trial we are assessing COVID-19 mRNA-1273 vaccine efficacy in persons with HIV (PWH) or another COVID-19-associated comorbidity across 7 sub-Saharan African countries. Previously vaccinated persons were excluded. Baseline testing included HIV screening, CD4+ T-cell count and HIV viral load (if HIV+), anti-SARS-CoV-2 antibodies, and nasal swab SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR). Participants had to be without COVID-19 signs/symptoms to be vaccinated at enrollment. Here we examine December 2021-April 2022 data to characterize asymptomatic SARS-CoV-2 infections and assessed correlation with CD4 count.
RESULTS: 6397 adults, including 4437 PWH, were enrolled (median age: 38 years; female: 75%). Baseline nasal swab data were available for 5772/6397 (90.2%). 336/5772 (6%) had asymptomatic SARS-CoV-2 infection, more frequent among SARS-CoV-2 seronegative than seropositive participants (9% vs 4%, p<0.001). Infection was detected among 98/1463 (7%) of PWH with a CD4 count<500 cells/mm3 vs 152/2974 (5%) with counts '¥500 cells/mm3 (p=0.037), an association irrespective of SARS-CoV-2 serostatus. A 10-fold CD4 decrease corresponded to 1.72-fold higher odds of PCR positivity, adjusting for serostatus, sex, and non-linear temporal trends (95% confidence interval [CI]:1.09-2.72-fold higher, p=0.019,Figure 1). Over time, the adjusted odds of PCR positivity were highest during the Omicron surge in December 2021 and 44% lower in men than women (95% CI: 17%-62% lower, p=0.004). Gene sequencing on a subset confirmed Omicron.

CONCLUSIONS: Our study of the largest cohort of PWH in a COVID-19 vaccine clinical trial to date reports the asymptomatic SARS-CoV-2 carriage rate was 3-6-fold higher than COVID-19 vaccine trials before Omicron. Additionally, lower CD4 count in PWH strongly correlated with increased odds of SARS-CoV-2 PCR positivity. These data highlight the urgent need for larger studies to better characterize how HIV-associated immunocompromise influences infection acquisition/clearance.