Objectives: The aim was to investigate if there is synergy in HIV infection and COVID-19 in their influence on human immunity, if there is an exacerbation of HIV patients’ immune status caused by SARS-CoV-2; and if HIV infection without antiretroviral therapy (ART) leads to a more serious COVID-19 course than HIV infection with ART. Design: Anonymised blood samples and clinical data were collected in 47 hospitals, clinics and medical centres in six Russian cities/regions in the period from 20 March to 15 June 2020. Three hundred and seventy-six HIV/COVID-19 patients were studied (171 without ART and 205 with ART). The control group consisted of 382 SARS-CoV-2-positive patients without HIV infection. Lymphocyte and cytokine amounts were measured by flow cytometry and ELISA. This work is a retrospective study. Results: COVID-19 led to rapid augmentation of the process of T-cell exhaustion initially caused by HIV, and this T cell degradation was most pronounced in patients without ART. A rise in IL-10 and TGFβ serum concentrations was observed. Diminishing CD4+/CD8+ cell and Th1/Th2 cell ratios characteristic for HIV progression were accompanied by a surge in exhausted T cell count with simultaneous exacerbation of COVID-19-related respiratory distress. Conclusions: HIV infection without ART may be a very serious comorbidity of COVID-19, whereas immunity of HIV/COVID-19 patients with proper ART is not generally affected by SARS-CoV-2. HIV-1 and SARS-CoV-2 are likely to exhibit a synergic effect, and exhausted T lymphocyte dynamics may be its effective marker. © 2020 The Author(s)