Further evidence that COVID breakthrough infections are more common in people living with HIV

Jeyaratnam Caniceus/Pixabay. Image is for illustrative purposes only.

A new study provides more evidence that people living with HIV who are vaccinated against COVID-19 are more likely to experience a breakthrough COVID infection compared to HIV-negative people. The good news is that – across the board – fully vaccinated people had less severe COVID illness than unvaccinated people.

The study, by Dr Jing Sun at Johns Hopkins University, follows another report showing that COVID-vaccinated people with HIV were more likely to experience breakthrough cases than HIV-negative people, regardless of CD4 counts or viral suppression.

The current research followed over 650,000 people throughout the US, 5% of whom had compromised immune systems, including over 8,500 people living with HIV. The cohort was mostly female (57%), had a median age of 51, and included participants from diverse racial and ethnic backgrounds. No data were available on CD4 count, viral load or HIV treatment.



Having a weakened immune system, therefore, a reduced ability to fight infections and other diseases.

immune system

The body's mechanisms for fighting infections and eradicating dysfunctional cells.


An infection that can be spread easily, by casual contact.

bone marrow

Cells in the middle of bones which are responsible for producing blood cells.


Inflammation of one or more joints, characterised by pain, swelling, warmth, redness of the overlying skin, and diminished range of joint motion.

The time frame covered in this analysis (December 2020 to September 2021) was similar to the previous report, including portions of infection waves where the Delta and previous variants were dominant in the US, but not including more recent periods when Omicron has become the most prevalent.

The researchers reported that COVID breakthrough infections were generally low at 2.8% six months after full vaccination (meaning all recommended doses of a particular vaccine had been administered).

However, vaccinated people with HIV (including both fully and partially vaccinated individuals) were 33% more likely to experience breakthrough cases compared to HIV-negative people, independent of other risk factors such as age and pre-existing medical conditions. This result is similar to the previous analysis, which showed a 44% higher likelihood in breakthrough cases, but the current report did not evaluate whether CD4 count or viral loads affected the risk of breakthrough or disease severity.

Between June and September 2021, when the Delta variant dominated, about seven breakthrough cases occurred each month for every 1000 fully vaccinated people with healthy immune systems. In the same time period, about nine breakthrough cases occurred each month for every 1000 fully vaccinated people with HIV. That number jumped to 12 breakthroughs each month for every 1000 partially vaccinated people with HIV, illustrating the benefit of full vaccination. Furthermore, across all participants and the entire evaluation period (pre- and post-Delta), those fully vaccinated were 28% less likely to experience breakthrough cases than those who were partially vaccinated.

In this analysis, a severe COVID outcome meant requiring mechanical ventilation, use of an artificial lung to deliver oxygen, or dying. In people with compromised immune systems (including people with HIV, multiple sclerosis, rheumatoid arthritis as well as those who’d received organ and bone marrow transplants), fewer COVID infections were severe after full vaccination. While the analysis did not specifically break out people with HIV, severe outcomes occurred in 6.6% of unvaccinated immunocompromised people and reduced to 3.3% in those fully vaccinated.

However, vaccinated immunocompromised people were still significantly more likely to experience severe COVID illness compared to vaccinated people with healthy immune systems (less than 1% of whom had severe outcomes). The authors state this disparity warrants continuing behavioural protections for immunocompromised people, such as wearing masks, social distancing and avoiding crowded indoor settings.

These behavioural measures may be even more important in the face of the Omicron variant, which is more contagious and better at infecting vaccinated people than previous variants. While no research yet tells us how Omicron will impact people with HIV, the results in this study demonstrating that full vaccination protects against severe disease look to be true in the case of Omicron as well. Furthermore, an additional vaccine dose appears to boost the immune system of the general population enough to provide even better protection against Omicron.

The bottom line is that it’s even more important for people living with HIV to get fully vaccinated if they can, obtain a third dose if they’re eligible, and continue masking and social distancing behaviours as much as possible.


Sun J et al. Association Between Immune Dysfunction and COVID-19 Breakthrough Infection After SARS-CoV-2 Vaccination in the US. JAMA Internal Medicine, online ahead of print, 28 December 2021 (open access).

DOI: 10.1001/jamainternmed.2021.7024