Similar immune responses to the Oxford/AZ COVID vaccine reported In HIV positive people with high CD4 counts

Simon Collins, HIV i-Base

On 20 April 2021, a UK paper reported the first results in HIV positive people of both T cell and B cell responses to the Oxford/AstraZeneca vaccine.

The study, published as a preprint on the Lancet SSRN website, reports no significant differences in humoral and cell-mediated immune responses in HIV positive people on ART with an undetectable viral load, compared to an HIV negative control group in the same phase 2/3 study. [1]

A second related paper, also published ahead of review, also reports no significant differences in responses to the same vaccine in HIV positive people in South Africa. [2]

The UK study was an open label, single arm, sub-study in 54 adult men living with HIV. Median age was 42 years (IQR: 37 to 49), 81% were white and median CD4 count was 694 cells/mm³ (IQR: 562 to 864). All participants received two standard doses of the ChAdOx-1 vaccine as prime/boost 4 to 6 weeks apart.

Primary outcomes were safety, with immunogenicity as secondary endpoints.

There were also no significant differences in self-reported side effects between HIV positive and negative participants over seven days after each vaccine. This included injection site pain (49%), fatigue (47%), headache (47%), malaise (34%), chills (23%), and muscle or (36%) joint pain 77 (9%). The second vaccine (the boost dose) was linked to slightly fewer side effects.

Humoral responses were measured by anti-spike IgG ELISA and antibody-mediated neutralisation of live virus. Cell-mediated responses were measured by ex-vivo ELISpot and T-cell proliferation.

Antibodies to the spike protein peaked at day 42 (14 days after the boost dose) and were sustained to day 56, similar to HIV negative controls, with no correlation with CD4 count or age.

Virus neutralisation in a randomly selected subset of 15 participants was reported in 4/15 by day 28 and in 13/15 by day 56.

CD4 T-cell responses peaked at day 14 after the prime does and were sustained at a reduced level until day 56. Again, there were no significant differences to the HIV negative control group (for all comparisons p>0.05).

Although there was a theoretical concern that chronic immune activation might impact vaccine responses in the HIV positive group, the vaccine had no impact on activation of either CD4 or CD8 cells at any time point.

Although these results are preliminary, further follow-up is planned after 6 and 12 months.

The researchers noted limitations of gender (the control group were 50% women) and that more data are needed for people with lower CD4 counts. They concluded that the lack of difference by HIV status was “highly encouraging and reinforces the message that people living with HIV should be supported to receive vaccination”.

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Although most phase 3 studies for current COVID-19 vaccines enrolled some HIV positive people, numbers were generally too low to produce clinical efficacy data and immunogenicity data have also not been released.

Also, although clinical results were released for HIV positive participants in the Novavax study in South Africa, vaccine recipients were more likely to report infections (n=4 with vaccines vs n=2 in the placebo arm).

It is also important that the analysis of responses in HIV positive people (with high CD4 counts and undetectable viral load on ART) receiving the Oxford/AZ vaccine in South Africa showed no significant differences compared to people who are HIV negative.

Both results from the Oxford/AZ vaccine are therefore especially welcome – and other companies should also publish their HIV analysis.

It also becomes more urgent to have data on people with a wide range of lower CD4 counts and also for people with detectable viral load.

References

Frater J et al for the Oxford VaccineTrial Group. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection. Lancet pre-print. (19 April 2021).
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3829931
Madhi S et al. ChAdOx1 nCoV-19 (AZD1222) vaccine in people living with and without HIV. DOI: 10.21203/rs.3.rs-322470/v1. (17 March 2021).
https://www.researchsquare.com/article/rs-322470/v1

This report was first posted on 20 April 2021.