Failure of mRNA vaccines to produce antibody responses in late diagnosed HIV with low CD4 count and high viral load

Simon Collins, HIV i-Base

A letter to the 1 June 2021 edition of the Lancet HIV reports a UK case of someone diagnosed HIV positive in late infection 16 days after the second dose of the Pfizer mRNA vaccine. The vaccine failed to produce antibody responses. [1]

This person was  from HIV positive people on effective ART are also compared to responses in HIV negative controls.

At baseline high HIV viral load was high (831,764 copies/mL) and the CD4 count was low (20 cells/mm3, indicating likely late diagnosis (rather that recent seroconversion). The CD4% was 4.6% and CD4:CD8 ratio was 0.05. No SARS-CoV-2-specific neutralisation or spike-specific T-cell responses were found at days 16 and 44 after the second vaccine.

This case was part of a cohort looking at vaccine responses that included 13 HIV positive people on stable ART (median CD4 count 590 cells/mm3(range: 310 to 940) and 43 HIV-negative controls, [2]

The majority of HIV positive people mounted SARS-specific antibodies with neutralising activity and T cell responses.

The letter suggests careful monitoring for COVID-19 in people with very low CD4 counts and repeating the vaccine schedule after increased CD4 responses to ART.

As follow-up, within one month on ART (bictegravir/TAF/FTC), the CD4 count in this case increased to 70 cells/mm3 and HIV viral load was <50 copies/mL.


Although limited results support the efficacy of COVID-19 vaccines in HIV positive people COVID-19, these data are generally in people with an undetectable viral load in people on stable ART. [3]

The mechanism for caution on vaccine efficacy is that a lower HIV-related CD4 count might be less able to generate B-cell responses to vaccine, which we know is already the case with vaccines against influenza and hepatitis B.

This case highlights the lack of data on vaccine efficacy in the context of HIV viraemia. This is especially when the CD4 count is also low. Although the threshold CD4 count for vaccine response is not known, this should be an additional monitoring recommendation in all cases of late HIV diagnosis.

An interesting paper in the same issue of Lancet HIV (Spinelli et al) reported potentially lower immune responses to natural infection in a cohort of HIV positive people in San Francisco and that they had higher risks of serious outcomes. [4]


  1. Touizer E et al. Failure to seroconvert after two doses of BNT162b2 SARS-CoV-2 vaccine in a patient with uncontrolled HIV. Lancet HIV, correspondence. 8(6):e317–318. DOI: 10.1016/S2352-3018(21)00099-0. (1 June 2021).
  2. Alrubayyi A et al. Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV. bioRxiv. 2021 preprint. DOI: 10.1101/2021.02.15.431215. (16 Feb 2021).
  3. Collins S. Similar immune responses to the Oxford/AZ COVID vaccine reported In HIV positive and HIV negative participants. HTB (3 May 2021).
  4. Spinelli MA et al. SARS-CoV-2 seroprevalence, and IgG concentration and pseudovirus neutralising antibody titres after infection, compared by HIV status: a matched case-control observational study Lancet HIV. 8(6):e334–3421.DOI: 10.1016/S2352-3018(21)00072-2. (1 June 2021).

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