Reduced antibody responses to first dose of mRNA COVID-19 vaccines in HIV positive people with a lower CD4 count

NOTE: Please see comments below for updated information on this study.

Simon Collins, HIV i-Base

Results from a small prospective study in HIV positive volunteers showed reduced antibody responses following the first dose of an mRNA vaccine against COVID-19 (6 Pfizer and 6 Moderna) to CD4 count. [1]

Although these data are interesting, the important results will be after the second dose, and also to see data from other authorised vaccines.

The 12 volunteers (all men, 11 were white) were recruited between January and March 2021. Median age was 64 years (IQR: 57 to 70). All were on ART ≥ 6 months with HIV viral load <50 copies/mL.

Distribution by CD4 count was 2, 1, 3 and 6 for <200, 200 to 349, 350 to 499 and ≥500 cells/mm3 respectively.

Although antibody results were all positive (>0.8 U/mL), levels ranged from 2.12 to >250 U/mL

Unfortunately, the specific CD4 counts were not included in this study, reported as a letter to the journal AIDS. It would help to know the far below 200 the two participants with <200 CD4 counts were. Similarly, although beyond the range of the test, it would be useful to know how high antibody levels reached in those with the highest CD4 counts.

There were no significant adverse reactions to the vaccines.

Table 1: Mean antibody levels by CD4 count *

CD4 (cells/mm3) N Ages Days to antibody test mean titre (U/mL) range
<200 2 61, 75 27, 21 2.3 2.1 to 2.5
200 to 349 1 70 15 >250 NA
350 to 499 3 55, 65, 72 19, 20, 27 50.1 4.6 to 128
≥500 6 33 to 68 16 to 28 138.0 44 to >250

* Test sensitivity: range 0.4 to >250 U/mL, positive = >0.8.


Although vaccine can also protect from cellular responses, the emphasis on humoral responses in the development of these vaccines suggests caution given the very low and often undetectable responses in people with severely reduced immune function. 

This is supported by a recent article in Nature Medicine reporting antibody levels are highly predictive of immune protection. Further data is clearly needed urgently. [2]

This small phase 1/2 study highlights other data that are needed. This includes getting the results from the second vaccine dose. It also includes similar data from other authorised vaccines. These studies need to include a range of low CD4 counts and results in people with detectable viral load to understand the thresholds for concern.

In a similar way the age threshold of +/– 80 years-old could drop lower in general population and might be lower still for HIV positive people. [3]

NOTE: The results after the second vaccine dose significantly improved for all participants, are now published. One participant with a CD4 count < 200 cells/mm3 reported levels that at 239 U/mL. The absolute CD4 counts were not available. [4]

Further research is needed to understand durability of the results.


  1. Ruddy JA et al. Safety and antibody response to the first dose of SARS-CoV-2 messenger RNA vaccine in persons with HIV. AIDS, ahead of print – Issue -doi: 10.1097/QAD.0000000000002945. (14 May 2021).
  2. Khoury DS et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nature Medicine. (17 May 2021).
  3. Collins S. Low responses to mRNA COVID-19 vaccines in those older than 80 vs <60 years and in recipients of solid organ transplants. HTB (3 May 2021).
  4. Ruddy J et al. Safety and antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in persons with HIV. AIDS, research letter. doi: 10.1097/QAD.0000000000003017. (8 July 2021).

This report was first published on 20 May 2021.

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