Fully vaccinated HIV patients may be less susceptible to develop severe breakthrough SARS-CoV-2 infection

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Scientists from the USA and Canada have recently estimated the prevalence and risk of severe coronavirus disease 2019 (COVID-19) among human immunodeficiency virus (HIV)-positive patients with vaccine breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Study: Analysis of severe illness after post-vaccination COVID-19 breakthrough among adults with and without HIV in the United States. Image Credits: Explode/Shutterstock

The study finds that the risk of severe breakthrough infection is low among fully vaccinated HIV patients. However, the risk could be high among HIV patients with moderate-to-severe immune suppression.

The study is currently available on the medRxiv* preprint server.


Currently available COVID-19 vaccines have shown good efficacy in preventing SARS-CoV-2 infection, severe COVID-19, hospitalization, and mortality. However, due to waning vaccine efficacy with time, several breakthrough infections have been detected in many countries across the world. The risk of breakthrough infections is estimated to be higher among immunocompromised patients, including those with HIV infections.

The risk of severe COVID-19 is believed to be higher among people with HIV infection because of suppressed immune system functioning. However, there are studies indicating comparable COVID-19 severity among people with and without HIV infections. Because of suppressed immune functions, HIV-positive people may be less likely to develop hyper inflammation, which is a major hallmark of severe COVID-19.

According to the US Centers for Disease Control and Prevention (CDC) guidelines, advanced or untreated HIV patients are advised to take an additional primary dose as well as a booster dose of the COVID-19 vaccine to reduce the risk of disease severity and mortality.

In the current study, the scientists have estimated the prevalence and risk of severe breakthrough SARS-CoV-2 infection among HIV patients who were fully vaccinated against COVID-19.

Study design

The study population included 33,029 HIV patients and 80,965 non-HIV patients who had received either two doses of the mRNA-based COVID-19 vaccine (Pfizer or Moderna), or the single dose of Johnson & Johnson adenoviral vector-based vaccine. The participants with vaccine breakthrough SARS-CoV-2 infections were included in the final analysis.

The study primarily aimed to estimate the prevalence and risk of severe breakthrough COVID-19 among participants with and without HIV infection. Severe COVID-19 was defined as hospitalization within 28 days of infection detection.

Important observations

The vaccine breakthrough SARS-CoV-2 infection was identified in 1,241 HIV patients and 2,408 non-HIV participants. The majority of participants with breakthrough infections were male and aged above 55 years. The proportion of HIV patients with obesity, diabetes, or hypertension was lower than non-HIV participants. About 49% of infections occurred during the delta variant-dominated wave, whereas 41% occurred at the beginning of the omicron variant-dominated wave.

About 6% of HIV-positive participants and 7% of non-HIV participants were admitted to the hospital due to severe COVID-19, indicating comparable disease severity. The average duration of hospital stay was 4 days and 5 days for participants with and without HIV infection, respectively. Overall, mechanical ventilation was applied to 10% of such participants and death occurred in 1% of hospitalized patients with and without HIV infection.

Prevalence of severe COVID-19

A comparable prevalence of severe COVID-19 was observed among patients with and without HIV infection. However, HIV patients with low CD4 count had a higher risk of developing severe COVID-19 compared to those with high CD4 count. No significant correlation was observed between HIV viral load and risk of severe COVID-19.

Considering both HIV positive and negative participants, the highest risk of severe COVID-19 was found to be associated with Johnson & Johnson primary vaccination, followed by Pfizer and Moderna primary vaccination. However, participants boosted with an additional vaccine dose showed a lower risk of severe COVID-19, irrespective of HIV status and vaccine type.

Risk factors for severe COVID-19

HIV-positive patients with low CD4 count showed a significantly higher risk of severe COVID-19 compared to HIV-positive patients with high CD4 count and those without HIV infection. In both HIV-positive and negative participants, increasing age was found to be a risk factor for severe COVID-19. Female patients with HIV infection showed 3-fold higher risk of severe COVID-19 than male patients. In addition, a diagnosis of cancer was found to increase the risk of disease severity by 2-fold.

The proportion of HIV-positive patients with low CD4 count who required mechanical ventilation or died during hospital stay was higher compared to patients with high CD4 count. These critically ill patients were mostly male, non-Hispanic Black, aged above 55 years, with high numbers of comorbidities, and without booster vaccination. Among HIV-positive patients who died during the course of severe COVID-19, 50% had a history of acquired immunodeficiency syndrome (AIDS) and a low CD4 count.

Study significance

The study indicates that the risk of severe breakthrough COVID-19 and related mortality is low among HIV-positive patients who have been fully vaccinated against COVID-19. However, a low CD4 count can increase the risk of disease severity in these patients.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Source: News Medical

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