COVID-19, tuberculosis, and HIV triad: a prospective observational study in ambulatory patients in Kenya, Uganda, and South Africa

People living with HIV (PLHIV) have an increased risk of tuberculosis (TB) and severe COVID-19. TB and COVID-19 present with overlapping symptoms and co-infection can lead to poor outcomes. We assessed the frequency of SARS-CoV-2 positive serology and SARS-CoV-2 infection and the risk of mortality at 6 months in PLHIV with TB disease and SARS-CoV-2 infection. This multi-country, prospective, observational study, conducted between 7th September 2020 and 7th April 2022, included ambulatory adult PLHIV investigated for TB (with symptoms of TB or advanced HIV disease) in Kenya, Uganda, and South Africa. Testing included CD4 cell count, Xpert MTB/RIF Ultra assay (sputum), Determine TB LAM Ag assay (urine), chest X-ray, blood SARS-CoV-2 serology test and SARS-CoV-2 PCR (only if TB or COVID-19 symptoms). Individuals were followed for 6 months. Among 1254 participants, 1204 participants had SARS-CoV-2 serology (54% women, median CD4 344 cells/µL [IQR 132-673]), and 487 had SARS-CoV-2 PCR. SARS-CoV-2 serology positivity was 27.0% (325/1204), lower in PLHIV with CD4 counts <200 cells/µL (19.9%, 99/497) than in those with CD4 counts ≥200 cells/µL (31.6%, 222/703), p<0.001. SARS-CoV-2 PCR positivity was 8.6% (42/487) and 27.7% (135/487) had probable or confirmed SARS-CoV-2 infection. Among PLHIV with symptoms of TB or of COVID-19, 6.6% (32/487) had SARS-CoV-2 infection and TB disease. In multivariable analyses, the risk of death was higher in PLHIV with both SARS-CoV-2 infection and TB compared to those with only SARS-CoV-2 infection (adjusted hazard ratio [aHR] 8.90, 95%CI 1.47-53.96, p=0.017), with only TB (aHR 3.70, 95%CI 1.00-13.72, p=0.050) or with none of them (aHR 6.83, 95%CI 1.75-26.72, p=0.006). These findings support SARS-CoV-2 testing in PLHIV with symptoms of TB, and SARS-CoV-2 vaccination, especially for those with severe immunosuppression. PLHIV with COVID-19 and TB have an increased risk of mortality and would benefit from comprehensive management and close monitoring.