COVID-19 vaccines in people with HIV

Vaccines work by stimulating two arms of the immune system to provide protection. The humoral response produces antibodies, which are the first line of defence against COVID-19 and other infections. The cellular response produces T-cells that recognise and kill the virus. The T-cell response may be especially important for avoiding serious COVID-19 illness.

It’s well established that older people and immunosuppressed people have weaker responses to vaccines and these responses tend to dwindle faster than in younger people. As a result, people with HIV are recommended to have booster shots to ensure long-term protection against COVID-19 illness.

Several types of vaccines are in use to protect against COVID-19. All these vaccines are highly effective in preventing severe COVID-19 but somewhat less effective in preventing infection with SARS-CoV-2, the virus that causes COVID-19 illness.

The vaccines use either modified virus proteins to stimulate an immune response (the Oxford/AstraZeneca, the Johnson & Johnson and the Novavax vaccines) or viral mRNA, which instructs cells to make a non-infectious fragment of the virus so that the immune system can react to it (the Pfizer and Moderna vaccines).

The vaccines do not introduce infectious virus into the body and do not cause changes to human genes. They are broken down shortly after administration and do not stay in the body.

The Pfizer and Moderna vaccines in people with HIV

Studies of the Pfizer and Moderna mRNA vaccines have reported on responses to vaccination in large groups of people with HIV. These studies show consistently that after two doses of these vaccines, almost all people with HIV developed antibodies to SARS-CoV-2. Some, but not all, studies found that antibody levels were lower in people with HIV. Antibody levels and T-cell responses tended to be lower in people with CD4 counts below 500 and responses were usually sub-optimal in people with CD4 counts below 200. (Levy) (Antinori, July 2022) (Tomasoni) (Spinelli) (Xu). A study which looked at antibody levels or T-cell responses six months after vaccination showed that responses dwindled in all people with HIV. People with CD4 counts below 200 experienced greater loss of antibodies and T-cell responses six months after vaccination. (Antinori, CROI 2022) Studies which looked at side effects found that people with HIV did not experience reactions to vaccination more frequently.

The Oxford/AstraZeneca vaccine in people with HIV

The initial Oxford/AstraZeneca vaccine studies recruited 54 people with HIV in the UK and 103 people with HIV in South Africa. Two reports have been published on the HIV-positive participants. They show that the vaccine produced the same strength of immune response in people with HIV and people without HIV. There was no difference between people with HIV and others in the common vaccine side effects of sore injection site, headache, chills, tiredness or muscle and joint pains. People in both studies had high CD4 counts (above 500) and were on antiretroviral treatment. Six months after completing the full vaccination course, the people with HIV in this study showed a decline in antibody and T-cell responses to the vaccine. However, there was no significant difference to HIV-negative people in the studies. (Frater) (Madhi) (Ogbe)

The Johnson & Johnson vaccine in people with HIV

A large trial of the Johnson & Johnson (Janssen) vaccine in 477,102 South African healthcare workers found no difference in vaccine effectiveness between people with HIV (8.3% of those vaccinated) and HIV-negative people. The study assessed vaccine effectiveness against hospitalisation due to COVID-19, severe COVID-19 or death from COVID-19. (Bekker)

A small study of 99 healthcare workers in South Africa who received the vaccine (26 living with HIV) showed no difference in neutralising antibody activity against the Delta variant of SARS-CoV-2 between people with HIV and HIV-negative people approximately two months after vaccination. In this study, vaccinated people with HIV had high CD4 counts (median 735) and all but one had an undetectable viral load. (Khan)

Other vaccines in people with HIV

Novavax recruited 201 people with HIV for one of the studies into its COVID-19 vaccine in South Africa (6% of all participants). No difference in side effects between HIV-positive and HIV-negative participants was reported. Overall efficacy of the vaccine was 49.4% (95% confidence interval 6.1-72.8), with a higher efficacy when the HIV-positive participants were excluded (60%, 95% confidence interval 19.9-80.1). The very wide confidence intervals indicate that these results should be treated with caution. (Shinde)

There is limited information on the effectiveness of other World Health Organization-approved vaccines (CoronaVac, Covaxin or Sinopharm's VeroCell BIBP vaccine) in people with HIV.

Third vaccine doses and booster doses for people with HIV

Doctors draw a distinction between a third vaccine dose and a booster dose.

A third vaccine dose is needed if you are less likely than other people to have had a satisfactory response to the recommended two-dose course. This is regarded as part of the standard vaccination course for people at higher risk of sub-optimal vaccine responses.

In the United Kingdom, you should be offered a third dose at least eight weeks after your second dose if you have any of the following:

• A CD4 count below 200
• HIV-related symptoms or active tuberculosis, regardless of CD4 count
• A detectable viral load after being on HIV treatment for at least a year
• No current antiretroviral treatment.

A booster dose protects against the gradual loss of vaccine protection that typically occurs. It is taken after a person’s first vaccine course has been completed.

A booster dose may be needed six months or more after a two- or three-dose course, even by people who had a satisfactory response to the course.

If you had a three-dose course in the UK, you will be offered booster doses on a regular basis. The British HIV Association strongly encourages all people with HIV to have booster doses when offered. 

Even if you previously had the Oxford/AstraZeneca vaccine, the third dose or booster dose(s) should be of the Pfizer or Moderna vaccine. Using different types of vaccine may improve the immune response; this is quite a common practice when giving vaccinations.

In the United States, the Centers for Disease Control and Prevention emphasises the importance of keeping up to date with booster doses for all people with HIV, especially those who have CD4 counts below 350.

The HIV Medicine Association has produced a briefing on US guidance regarding COVID-19 vaccines for people with HIV.

Several studies have shown that booster doses are effective in people with HIV and other immunocompromised people, leading to substantial increases in antibody levels. A large US study that covered the period when the Delta and Omicron variants were circulating in the United States showed that immunocompromised people – including people living with HIV – who received a third vaccine dose were significantly less likely to be admitted to hospital with severe COVID-19 or experience a breakthrough infection when compared to immunocompromised people who had been vaccinated without boosting (Sun). An Israeli study of the effects of a fourth vaccine dose showed that by the sixth week after receiving this fourth dose, recipients were 77% less likely to develop severe COVID-19 disease than people of the same age who had only received three doses (Bar-On).

The fourth dose also offered protection against SARS-CoV-2 infection, but this was short-lived: their risk of infection compared with three-dose recipients had halved by the fourth week after their fourth vaccination, but had returned to previous levels by week eight. In contrast, the protection against severe disease did not wane.

Summary

• Vaccines against COVID-19 are highly effective in preventing serious illness. COVID-19 vaccination is recommended for people living with HIV and people with HIV are a priority group for COVID-19 vaccination.
• COVID-19 vaccines are safe in people with HIV. There is no evidence that people with HIV have a higher rate of side effects after vaccination or unusual side effects. There is no evidence that any COVID-19 vaccine interacts with HIV treatment or causes HIV viral load to increase.
• COVID-19 vaccines are effective in most people with HIV. They stimulate strong antibody responses in people with HIV with higher CD4 counts. People with lower CD4 counts (below 200) have weaker responses to vaccination and their antibody responses after vaccination may dwindle faster than those of people with higher CD4 counts.
• People with lower CD4 counts who have already received two vaccine doses are advised to have a third dose of a COVID-19 vaccine at least eight weeks after their second dose. A third dose improves immune responses and reduces the risk of severe COVID-19 and breakthrough infection.
• People with any HIV-related symptoms should also have a third dose, regardless of CD4 count, as should anyone with unsuppressed viral load.
• In the United Kingdom, a booster dose is recommended for all people with HIV at least six months after a second or third dose.