Canadian study finds minimal evidence of weaker COVID-19 vaccine responses in people with HIV

Moderna vaccine as a third dose produced especially strong responses
Marco Verch. Creative Commons licence.

People with undetectable HIV who received SARS-CoV-2 vaccines didn’t experience faster antibody declines than people without HIV after two vaccine doses and had equivalent or better antibody responses compared to a control group after a third dose, especially those who received the Moderna vaccine as their third dose, Canadian researchers report in a pre-print article released before peer review.

The study found no evidence of weaker virus neutralisation nor any evidence of weaker vaccine responses in people with a history of a low CD4 cell count. Most people in this study received the Pfizer or Moderna mRNA vaccines but there was some evidence that the Oxford-AstraZeneca vaccine was associated with weaker responses after the first two doses.

Although numerous studies have looked at vaccine responses in people with HIV, there is still a lack of information about the impact of a third vaccine dose, or booster dose, as well as immune responses in vaccinated people with HIV to the Omicron variant. As Omicron and variants descended from it are now becoming the dominant form of SARS-CoV-2 worldwide, and vaccines are less effective in preventing infection with these variants, it is especially important to know if vaccines produce weaker responses in people with HIV.


control group

A group of participants in a trial who receive standard treatment, or no treatment at all, rather than the experimental treatment which is being tested. Also known as a control arm.

multivariable analysis

Statistical technique often used to reduce the impact of confounding factors, in order to attempt to identify the real association between a factor of interest and an outcome. 

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.


In cell biology, a structure on the surface of a cell (or inside a cell) that selectively receives and binds to a specific substance. There are many receptors. CD4 T cells are called that way because they have a protein called CD4 on their surface. Before entering (infecting) a CD4 T cell (that will become a “host” cell), HIV binds to the CD4 receptor and its coreceptor. 

Professors Mark Brockman and Zabrina Brumme from Simon Fraser University in British Columbia investigated antibody responses after two and three doses of vaccine in 99 people with HIV and a control group of 152 people without HIV, most of whom were health care workers.

The research group reported previously on vaccine responses shortly after the second dose in this population, finding that most people with HIV had similar antibody levels to people without HIV. People who had received two doses of the Oxford Astra-Zeneca vaccine, older people and people with multiple health conditions were more likely to have lower antibody levels.

The follow-up study reported on antibody responses one, three and six months after the second dose of vaccine and one month after the third dose, to both the original form of SARS-CoV-2 and the Omicron variant.

All people with HIV were receiving antiretroviral treatment and had undetectable viral loads. The median CD4 count of people with HIV was 715 and the median lowest-ever count was 280. A quarter of people with HIV had a lowest-ever CD4 count below 123.

Compared to the control group, people with HIV were more likely to be male (88% vs 33%), to be White (69% vs 51%) and to be obese (15% vs 19%) but did not have a higher prevalence of chronic health conditions associated with severe COVID-19 outcomes.

In terms of the initial two-dose regimen, most participants had received an mRNA vaccine (Pfizer or Moderna) but eight people with HIV received the Oxford-AstraZeneca vaccine followed by an mRNA vaccine and eight people with HIV received two doses of the Oxford-AstraZeneca vaccine.

Use of different vaccines for the first and second dose was common in Canada because a second dose using a mRNA vaccine was recommended for everyone who had received the Oxford/AstraZeneca vaccine after reports of rare thrombotic events associated with it.

In October 2021 a third vaccine dose began to be offered to people with HIV who were over 65, or who had a history of AIDS-defining illness, or a previous CD4 count below 200, or a detectable viral load during 2021. In January 2022, all adults in British Columbia became eligible for a third dose six months after their second dose.

Everyone received a mRNA vaccine as their third dose, including 70% of people with HIV who received the Moderna vaccine as their third dose. People aged 70 and over, and people with HIV who met any of the priority criteria, received a higher dose of 100mcg rather than the standard booster dose of 50mcg.

Three and six months after the second dose, receptor binding domain antibody concentrations declined in both people with HIV and the control group. In a multivariable analysis that controlled for sociodemographic-, health- and vaccine-related variables, lower antibody concentrations at both time points were associated with a greater number of chronic conditions and receipt of the Oxford-AstraZeneca vaccine, but not HIV. Age ceased to be associated with weaker antibody responses at six months.

The study also found no difference in the rate of decline of antibodies after the second dose between people with HIV and the control group.

One month after the third dose, antibody levels had risen above the concentrations observed one month after the second dose and in almost half of cases, concentrations were above the upper limit of the antibody assay. There was no difference between people with HIV and the control group in antibody levels. Current or lowest-ever CD4 count did not affect antibody concentrations.

Virus neutralisation (the capacity of antibodies to stop virus replication) had also declined by three months after the second dose in both groups. Receipt of the Oxford-AstraZeneca vaccine was the only factor associated with lower neutralising activity. By six months after the second dose, neutralising activity was no longer detectable in 52% of participants with no history of COVID-19.

A third vaccine dose resulted in a fourfold increase in neutralising activity compared to peak levels after the second dose. Improved neutralising activity was associated with receiving the Moderna vaccine as the third dose. No HIV-related factor affected neutralising activity after the third dose.

The study also looked at responses to the Omicron variant in people who had no history of COVID-19. Although levels of antibodies capable of binding to the Omicron variant were lower after both the second and third doses than antibodies to wild-type viruses, antibody levels improved significantly after the third dose. Multivariable analysis showed that compared to the control group, people with HIV had significantly higher concentrations of antibodies that could bind to the Omicron variant.

The study investigators say their findings provide reassurance that a previous history of low CD4 count does not compromise vaccine responses and that people with well-treated HIV have just as good, if not better, responses to a third vaccine dose than people without HIV.