HIV risk from some COVID-19 vaccines might be unlikely due to rarity of vector viruses involved

Simon Collins, HIV i-Base

On 19 October 2020 a letter to the Lancet from researchers involved in an HIV vaccine study more than a decade ago called STEP raised cautions about COVID vaccines that use an adenovirus (specifically Ad5). [1]

Although the HIV vaccine was not effective, an unexpected outcome was that uncircumcised men who received the active vaccine, and who have naturally previously been exposed to Ad5, were later found to be at slightly higher risk of becoming HIV positive compared to the placebo group (5.1% vs 2.2% per year for Ad5 positive and 5.2% vs 1.4% for uncircumcised men, respectively). This was not reported for women or circumcised men. [2] Similar results were also reported in a second HIV study. [3]

In their letter, the researchers question whether using a similar Ad5 platform for a vaccine against COVID-19 might also increase the risk of HIV in countries where HIV incidence is still high. They do not suggest that the vector might increase the risk of coronavirus.

Currently, several leading COVID vaccine candidates use an adenovirus platform (including those from CanSino, Oxford/AstraZeneca and Johnson & Johnson/Janssen), though only CanSino is using Ad5. [4, 5, 6, 7] 

Although there is no evidence that any of these vaccines are likely to increase the risk of HIV infection, as yet, the letter has not been answered by researchers involved in COVID vaccines using Ad5.

Professor Lucy Dorrell from the Nuffield Department of Medicine emphasised that researchers had already considered the issues from STEP including the very low likelihood that people would have previously come into contact with the viral vectors used for COVID-19 vaccines:

“It is understandable that there is concern specifically around the use of Ad5, and the potential risks and uncertainties should be discussed fully with trial participants. In selecting other viral vectors such as Ad26 (JnJ) and ChAdOx1 (Oxford/AstraZeneca), vaccine developers rigorously applied the lessons learnt from the STEP trial. Very few people around the world have been exposed to these viruses, therefore, it is extremely unlikely that people living in high prevalence areas for HIV would be at increased risk of infection if they receive these vaccines.”


The potential risk of increased susceptibility to HIV is acknowledged in the CanSino paper published in the Lancet in May 2020, even though the potential mechanism is unclear. It includes a comment that the researchers plans “to monitor the participants in our upcoming phase 2 and phase 3 studies to assess the indication for any such [HIV] acquisition”. [4]

It might therefore be important for other studies to include a similar safety approach even though effective vaccines will only have limited follow-up time for the placebo arm (as participants should roll over to the active vaccine.

An important caution might be that if CD4 T cell responses to adenoviruses are cross-reactive and recognise multiple adenovirus variants – as reported in some studies – then pre-existing CD4 T cell responses induced by a natural Ad5 infection might be boosted by a different adenovirus vector and it might not matter whether this was Ad26 or chimpanzee etc. [8, 9] 

Luckily, the signal from the STEP study was generally recognised as modest. However, the plans for universal access to COVID vaccines might make even a small increase in risk important.


  1. Buchbinder AP et al. Use of adenovirus type-5 vectored vaccines: a cautionary tale. Lancet 396 (10260): E68-E69. DOI: 10.1016/S0140-6736(20)32156-5. (19 October 2020).
  2. Buchbinder AP et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008; 372: 1881-1893
  3. Gray GE et al. Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind randomised placebo-controlled test-of-concept phase 2b study. Lancet Infect Dis. 2011; 11: 507-515.
  4. Zhu FC et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet. 2020; 395: 1845-1854.
  5. Folegatti PM et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.Lancet, 2000: 396 (10249): 467-478.  DOI: 10.1016/S0140-6736(20)31604-4. (20 July 2020).
  6. Johnson & Johnson press release. Johnson & Johnson initiates second global phase 3 clinical trial of its Janssen COVID-19 vaccine candidate. (15 November 2020.
  7. Jannsen website. Our innovative vaccine technology platform.
  8. Heemskerk B et al. Extensive cross-reactivity of CD4+ adenovirus-specific T cells: implications for immunotherapy and gene therapy. J Virol. 2003 Jun 77(11): 6562–6566. DOI: 10.1128/JVI.77.11.6562-6566.2003. (June 2003).
  9. Hutnick NA et al. Adenovirus-specific human T cells are pervasive polyfunctional and cross reactive. Vaccine. 2010 Feb 23 28(8): 1932–1941. DOI: 10.1016/j.vaccine.2009.10.091. (23 February 2010).

This article was first posted on 30 November 2020. The comments were updated to include references 8 and 9.

Links to other websites are current at date of posting but not maintained.