Key points
- COVID-19 vaccination is recommended for people living with HIV and they are a priority group in vaccination programmes.
- There is no evidence that people with HIV have a higher rate of side effects after vaccination or unusual side effects.
- COVID-19 vaccines stimulate strong antibody responses in people with HIV with higher CD4 counts, although vaccine protection may dwindle faster in people with CD4 counts below 200.
- People with HIV are priority groups for third doses and booster doses.
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.
Studies show that people with immunosuppression caused by HIV, as indicated by a low CD4 count, have weaker responses to COVID-19 vaccines. A CD4 count below 200 appears to raise the risk of a weaker response or no response to vaccination, although this has only been established for the Pfizer and Moderna mRNA vaccines.
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
Registration studies of the Pfizer and Moderna mRNA vaccines in use in Europe and North America did not report on vaccine safety and effectiveness in the small numbers of people with HIV who took part in those trials, but subsequent studies have reported on responses to vaccination in larger groups of people with HIV.
Israeli clinicians have reported results in 143 people living with HIV who received the Pfizer vaccine. All were taking HIV treatment, 95% had an undetectable viral load and the average CD4 cell count was 700. Two doses of the vaccine were able to trigger the production of antibodies in 98% of participants, including in the small number (12) of people with CD4 cell counts below 350. Side effects were generally mild.
An Italian study compared responses to the Pfizer and Moderna vaccines after the first and second dose in 166 people with HIV and a control group of HIV-negative healthcare workers. The study showed that people with CD4 counts above 500 had strong antibody responses to vaccination and these responses were just as strong as those of HIV-negative healthcare workers. People with CD4 counts between 200 and 500 had somewhat weaker responses and people with CD4 counts below 200 had much weaker antibody and T-cell responses.
Longer-term follow-up of the same study population showed that antibody responses to SARS-CoV-2 had declined significantly approximately six months after the second dose in people with CD4 counts below 200 when compared to people with CD4 counts above 500. Neutralising antibody and T-cell responses to SARS-CoV-2 were more likely to be absent or sub-optimal in people with CD4 counts below 200 but the investigators are uncertain about how this affects future risk of severe COVID-19.
Another Italian study looked at side effects of the Moderna vaccine in 453 people with HIV. Fifty-one per cent reported at least one symptom after the first dose and 73% after the second dose. No serious adverse events were reported. The local and systemic reactions to vaccination were consistent with clinical trials; pain, swelling and redness at the injections site, and muscle pains, headaches, chills and fevers. Younger people were more likely to experience moderate or severe symptoms after each dose, while women and people with viral load above 50 copies/ml were more likely to experience moderate or severe symptoms after the first dose.
A US study of responses to the Pfizer or Moderna vaccines in 100 people with HIV showed that one month after the second dose, antibody responses in people with HIV depended on CD4 count. The higher the CD4 count, the stronger the antibody response. In this study, all seven participants with CD4 counts below 200 failed to generate an adequate antibody response. People who received the Moderna vaccine had stronger antibody responses than people who received the Pfizer vaccine.
A Swedish study of 90 people living with HIV and 90 HIV-negative people found that people with HIV who received two doses of the Pfizer vaccine has significantly lower antibody responses than people without HIV. Antibody levels in people with HIV were not affected by CD4 count but people with unsuppressed viral load had weaker antibody responses a month after receiving a second dose.
Two smaller studies carried out in the United States in which most participants had high CD4 counts showed that people with HIV produced strong antibody responses to the Pfizer or Moderna vaccines after the first and second doses and these responses were similar to those in control groups of HIV-negative people. One of these studies also reported on side effects. Almost all participants reported pain at the injection site after each vaccination. Systemic symptoms such as fatigue were common, occurring in around 60-70% of participants after each vaccination. Only one of these reactions was considered severe (headache in one participant after the second vaccination).
The Oxford/AstraZeneca vaccine in people with HIV
The 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.
The Johnson & Johnson vaccine in people with HIV
The Janssen (Johnson & Johnson) vaccine study has involved the largest number of people with HIV so far: 1218 people or 2.8% of all participants. The study was conducted in the United States, South Africa and six Latin American countries. There were two cases of COVID-19 in people with HIV receiving the vaccine and four in people with HIV receiving the placebo. However, due to the small numbers of cases, this difference is not statistically significant and we cannot draw any conclusions about efficacy specifically in people with HIV.
A small study of 99 healthcare workers in South Africa who received the Johnson & Johnson 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.
A large trial of the 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.
Other vaccines in people with HIV
The Novavax vaccine is awaiting approval. 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.
There is limited information on the effectiveness of other WHO-approved vaccines (CoronaVac, Covaxin or Sinopharm's VeroCell BIBP vaccine) in people with HIV.
A small study of people with HIV in China who received either of the inactivated SARS-CoV-2 vaccines (CoronaVac or Sinopharm's VeroCell BIBP vaccine) found lower antibody and T-cell responses after vaccination compared to HIV-negative people. A second study, of a cohort of 42 people living with HIV with high CD4 counts, found that people with HIV had similar antibody and cellular immune responses after vaccination to those observed in a control group of 28 HIV-negative people.
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 a fourth booster dose from March 2022.
The British HIV Association issued a statement on 29 March 2022 that, following a recommendation by the UK's Joint Committee on Vaccination and Immunisation, people who are aged 12 years and over who are immunosuppressed, including all people with HIV, should have a first or second booster dose six months after their last vaccine dose - even if they have already had a booster. This could therefore be a third, fourth or even fifth dose.
Even if you previously had the Oxford/AstraZeneca vaccine, the third dose or booster dose(s) should be of the Pfizer or Moderna vaccine. (In limited circumstances, the Oxford/AstraZeneca vaccine may be given to people who have received this vaccine previously.) 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 have recommended that people with advanced HIV (CD4 count below 200) or unsuppressed HIV should have an additional vaccine dose at least 28 days after their previous vaccination. If they had the Pfizer or Moderna vaccine, this will be a third dose. The first course of the Johnson & Johnson vaccine only has one dose, so recipients will have a second dose.
Concerning booster doses, people with HIV with CD4 counts above 200 can receive a booster at least six months after the second dose of the Pfizer or Moderna vaccine or two months after receiving the Johnson & Johnson vaccine.
The HIV Medicine Association has produced a briefing on US guidance regarding COVID-19 vaccines for people with HIV.
A large US study looking at breakthrough infections in people with HIV in 2021 prior to the emergence of the Omicron variant found that fully vaccinated but unboosted people with HIV had a 41% higher risk of a breakthrough infection than a comparable group of HIV-negative people. However, the absolute number of breakthrough infections was low; only 2.8% of people with HIV experienced a breakthrough infection after being fully vaccinated, compared to 2.1% of HIV-negative people. These findings indicate that people with HIV are likely to benefit from a booster dose of vaccine, but the study did not cover the period when the more infectious Omicron variant began to circulate in the United States.
Several studies have shown that booster doses are effective in people with HIV and other immunocompromised people. An Italian study found that two weeks after a booster dose, people with HIV experienced substantial increases in antibody levels regardless of CD4 count. 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.
The US study found that immunocompromised people who received a third dose were 80% less likely to be hospitalised and 44% less likely to experience a breakthrough infection nine months after receiving their initial vaccination course.
Israel started giving a fourth dose of the Pfizer vaccine in people aged 60 or older on 2 January 2022. A study 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.
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.