Reduced responses to COVID-19 vaccines at low CD4 counts

Simon Collins, HIV i-Base

New data were presented at EACS 2021 on immune responses to COVID-19 vaccines in people with lower CD4 counts. Until now, nearly all results have been in people with median CD4 counts >500 cells/mm3, reporting similar responses to HIV negative people.

This study, by Andrea Antinori from the National Institute for Infectious Diseases in Rome and colleagues, included 166 people living with HIV (16% women; median age 56 (49 to 60). Of these, 32 had CD4 counts <200, 56 were between 200 to 500 and 78 were >500 cells/mm3.

Dr Andrea Antinori, EACS 2021.

This prospective study at a single centre compared both neutralising antibody titres and cell-mediated immune responses in whole blood samples taken a month after the second of two doses of mRNA vaccines. Results were compared to 169 unmatched HIV negative health workers (72% women; median age 42 years (IQR 32 to 53).

At baseline, median (IQR) counts in the HIV groups were 140 (100 to 163), 335 (245 to 441) and 727 (585 to 856) cells/mm3 respectively. The low CD4 group had a significantly lower median CD4:CD8 ratio (0.16 vs 0.44 vs 0.90) and was less likely to have undetectable viral load (68% vs 92% vs 100%); both p<0.001.

Median (IQR) RBD binding response levels were 20 (5 to 40), 40 (10 to 150), 80 (40 to 160) and 80 (40 to 160) across the four groups respectively. The percentage of neutralising antibody levels >10 were 70%, 88%, 93% and 98% respectively.

All immune responses were significantly lower in the CD4 <200 group compared to both the high CD4 and HIV negative controls (all p<0.001). By comparison, responses in the high CD4 group were all roughly comparable to HIV negative controls.

The magnitude of overall humoral and cellular antibody responses strongly correlated with higher CD4 counts. Differences between the <200 and 200 to 500 CD4 groups were significant for humoral (anti-RBD, p<0.05) and cellular (IFN-gamma, p<0.01) responses.

Table 1: Humoral responses by study group (from the abstract, n=127)

                                                        CD4 <200            CD4 200-500       HIV neg

Neutralisation activity                     69% (p <0.001)*   87% (p<0.007)*   (99 to 100%)

Detectable anti-RBD response       87% (p <0.001)*   99% (p=0.177)*   (99 to 100%)           

* p-values compared to HIV negative control group 

In multivariate analysis, having a CD4 count <200 was significantly associated with anti-RBD (Beta –0.64 [95%CI: –0.94 to –0.34], p<0.001), neutralising (Beta –0.41 [95%CI –0.70 to –0.12], p<0.006) and cell-mediated (Beta –.74 [95%CI: –1.13 to –0.34], p<0.001) responses.

Longer follow-up is needed to be able to comment on durability of immune responses.

In questions after the presentation it was noted that no breakthrough infections have been reported. However, the data suggest a role for earlier use of a third dose in those with low CD4 counts.


Antinori A et al. Immunogenicity of mRNA vaccination against SARS-CoV-2 in persons living with HIV (PLWHs) with low CD4 count or previous AIDS. 18th EACS, 27-30 October 2021, London. Oral abstract OS4/3. (webcast – for delegates). (abstract) (full abstract book)

This article was first posted on 28 October 2021.


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