COVID-19 Outcomes in HIV-Infected Populations

The intersection of HIV infection and COVID-19 presents a complex clinical picture influenced by the degree of immune suppression, antiretroviral treatment status, and the presence of co-morbidities such as tuberculosis. People living with well controlled HIV generally experience COVID-19 outcomes comparable to HIV-uninfected individuals, whereas those with advanced immunodeficiency face higher risks of severe disease, prolonged viral shedding and in-hospital mortality. Antiretroviral therapy not only restores immune competence but also facilitates viral clearance of SARS-CoV-2, reducing the likelihood of persistent infection and the emergence of novel variants. Vaccination in this population is effective and safe, yet immune responses in some people with HIV may be attenuated, with faster waning of antibody levels and lower neutralising activity. Global data from hospitalised cohorts underscore that HIV remains an independent risk factor for both severe presentation and death, even when viral suppression is maintained. These observations have driven updated clinical guidelines advocating prioritisation of booster doses for immunocompromised individuals, intensified surveillance in high-burden settings and integrated management strategies addressing HIV, tuberculosis and COVID-19 concurrently.

Research from Nature Portfolio

In regions with high burdens of HIV and tuberculosis, clinical studies have demonstrated that dual infection exacerbates lymphopenia and elevates inflammatory markers such as D-dimer and ferritin, leading to poorer COVID-19 outcomes and higher fatality rates. Patients co-infected with HIV and tuberculosis display diminished SARS-CoV-2 antibody levels when CD4 counts are low, while initiation of antiretroviral therapy can restore antiviral immunity and promote viral clearance. In the context of vaccination, administration of a third mRNA dose in people living with HIV markedly boosts anti-spike antibody titres well beyond levels achieved after the second dose, with particularly robust responses following heterologous booster schedules. Cell-mediated immunity, assessed by interferon-γ production, remains stable after the third dose, supporting the safety and immunogenicity of additional boosters in this group. These findings emphasise the value of tailored vaccine strategies and the importance of maintaining antiretroviral therapy to optimise COVID-19 protection in immunocompromised populations.

COVID-19 Outcomes in HIV-Infected Populations publication trend

The graph below shows the total number of articles in covid-19 outcomes in hiv-infected populations across all publications each year (not limited to Nature Index journals).

Technical terms

Antiretroviral therapy (ART): Combination of drugs that suppress HIV replication and restore immune function.

CD4 T cell count: Measure of immune competence, indicating the number of helper T cells per microlitre of blood.

Neutralising antibody: Antibody capable of preventing viral entry into host cells, a key marker of protective immunity.

Viral load: Quantity of viral RNA in the bloodstream, used to assess level of active infection.

Breakthrough infection: SARS-CoV-2 infection occurring despite prior vaccination, often associated with waning immunity.

References

1. The immune response to SARS-CoV-2 in people with HIV. Cellular & Molecular Immunology (2023).
2. Effects of tuberculosis and/or HIV-1 infection on COVID-19 presentation and immune response in Africa. Nature Communications (2023).
3. SARS-CoV-2 humoral immunity in people living with HIV-1. Trends in Immunology (2024).
4. Epidemiology and outcomes of COVID-19 in HIV-infected individuals: a systematic review and meta-analysis. Scientific Reports (2021).
5. Clinical features of, and risk factors for, severe or fatal COVID-19 among people living with HIV admitted to hospital: analysis of data from the WHO Global Clinical Platform of COVID-19. The Lancet HIV (2022).
6. Relationship of SARS-CoV-2-specific CD4 response to COVID-19 severity and impact of HIV-1 and Tuberculosis co-infection. Journal of Clinical Investigation (2021).
7. Immunogenicity to COVID-19 mRNA vaccine third dose in people living with HIV. Nature Communications (2022).
8. Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV. Nature Communications (2021).