Our study data showed that 3 weeks after the first dose of COVID-19 vaccine, 45 out of 78 (57.7%) participants had positive SARS-CoV-2 anti-Spike IgG test results. This differs remarkably from the 100% anti-Spike IgG seroconversion noted in the Phase 1/2 clinical trial studies of the BNT162b2 vaccine, which includes an overall healthier population and relatively smaller subset of PLWH. Another study has demonstrated that in subjects who received the BNT162b2 vaccine, 143 PLWH had decreased immune response at 14 days after the initial vaccination dose, compared with the control group. In this study, at 14 days, 51% of PLWH developed antibodies, while 59% of those without HIV developed antibodies. Our results differ from a study of SARS-CoV-2 immunogenicity in PLWH after single dose of mRNA COVID-19 vaccination (50% BNT162b2, 50% mRNA-1273), which demonstrated that all subjects developed antibodies to SARS-CoV-2 Spike receptor binding domain after the initial dose. However, that study also had a small sample size (n = 12) and participants were demographically different from our study subjects [all subjects were male; 92% were white; median age = 64 years (range 57–70)]. Antibody responses after single-dose COVID-19 vaccine have been described in immunocompetent hosts as well as immunocompromised solid organ transplant recipients with decreased antibody detection of 31% and 69% after single-dose Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines, respectively. Another study demonstrated decreased memory B-cell and plasma cell responses (including decreased IgG) among dialysis and renal transplant recipients after BNT162b2 vaccination, in comparison with healthy controls with 100% seroconversion; in that study, dialysis patients had 70.5% anti-S1 IgG at 3–4 weeks after vaccination boost and renal transplant recipients did not develop IgG positivity, aside from one with prior infection. Furthermore, a study demonstrated that only 52 of 93 (56%) multiple myeloma patients had detectable SARS-CoV-2 IgG antibodies at 21 days or more after the initial dose of COVID-19 vaccine. For PLWH, HIV infection-driven immune activation and dysregulation may result in impaired B-cell responses that impact vaccine-induced seroconversion rates.[13,14] Impaired vaccine responses have been noted in PLWH (including those virologically suppressed on ART) which is attributed to impaired B-cell and T-follicular helper-cell function and can be enhanced by the process of ageing.[15,16] Poor antibody responses to vaccines in PWLH may be attributed to HIV infection, leading to dysregulation of T-follicular helper cells, as well as an array of B cell-specific defects that have been noted in the setting of HIV infection.
Therefore, more attention needs to be paid to these groups of patients who potentially may not experience similar levels of protection from COVID-19 vaccine as their healthy peers. A caveat is that many of these studies did not evaluate T-cell responses which do confer protection against COVID-19 infection. Nonetheless, the almost complete seroconversion noted after the second vaccination suggests that the diminished responsiveness among PLWH can be overcome with subsequent booster vaccinations and should be an option explored not just for those who do not seroconvert after a single dose, but also after the second dose in certain circumstances. It also begs the question as to the use of higher vaccine dosage or additional booster doses for immunocompromised patients, which is a tantalizing question that has yet to be rigorously explored or evaluated. This is particularly important for certain SARS-CoV-2 variants which are less susceptible to vaccine-induced immunity. The one subject who did not seroconvert had multiple overlapping explanations for the absence of an immune response to the vaccine, being both a transplant patient and a PLWH, further adding complexity among patients with multiple immunocompromising conditions.
Despite the relatively small sample size, we found that those with lower CD4 counts and cancer or other immunosuppressive conditions (other than HIV) may be less likely to seroconvert after the first dose of COVID-19 vaccine. Although these findings did not reach statistical significance (possibly in part due to our small sample size), the direction of the effects are not surprising as these are known conditions that may impact immune responsiveness to vaccine antigens. Our data also demonstrated that participants who were on an antiretroviral regimen containing INSTIs were more likely to seroconvert, although the association did not reach statistical significance. These observations merit evaluation in larger cohorts of PLWH to confirm our exploratory findings and analyses.
This study had several limitations. First, our small sample size may have reduced the power of this study to detect statistically significant differences in risk factors for seroconversion, but the differences in immune responses in the two time periods reported remain noteworthy and the directions of our effect estimates are consistent with prior studies that associate immunocompromised conditions with lack of seroconversion.[7–9] Second, 50% of participants were lost to follow-up by visit 2. We attribute this to loss of convenience to study participants, as visit 1 took place at a community-based vaccination site but visit 2 was relocated to the HIV clinic at our hospital. This required complex logistical planning. Some participants were unable to, or did not want to, come to the clinic because of concern regarding SARS-COV-2 infection risk or for other reasons, including time constraints, for follow-up or cited scheduling conflicts when approached. However, as 67% of participants in visit 1 who had a negative IgG test returned for follow-up, we were able to record very high rates of new seroconversion (97.5%) that allowed us to assess immunogenicity of the vaccine in that subset following a second dose of vaccine. Furthermore, demographic and immunological characteristics were similar between those who were retained in visit 2, compared with those who did not receive the second dose in the requisite time period; thus, we believe the conclusions that could be drawn from higher subject retention at visit 2 would probably not change the results significantly (Table S1). Third, our cohort consisted of PLWH aged ≥ 55 years and findings from this study may not be generalizable to a younger population. A significant proportion of our study subjects (12.8%) had immunocompromising conditions other than HIV that could have explained relatively lower immunogenicity results after the first vaccination, such that it may not be attributable to their HIV status alone. An additional limitation is that we utilized a qualitative immunoassay that detects SARS-CoV-2 anti-spike antibody, but does not measure neutralizing antibody, and the results cannot distinguish between prior COVID-19 infection and vaccine-induced immunity. We excluded patients with prior history of COVID-19, although without baseline antibody testing, those with asymptomatic infection may have been missed. However, this would have led to an underestimation and not an overestimation of non-seroconversion to the vaccine. Although there was no HIV-negative matched control group, we used robust historical data for comparison. Having a control immunocompetent group at an external site would have been ideal, but the feasibility and practicality of this option were unfortunately limited by resources and the HIV-specific clinic study site. Lastly, further immunogenicity data regarding other types of COVID-19 vaccines included would provide additional information about a broad range of vaccines and vaccine-induced immunity; however, administration of a single type of COVID-19 vaccine has the advantage of demonstrating the immune response to a single vaccine type with less confounding factors. Nevertheless, the findings from our study lend importance to future larger studies to evaluate immunogenicity, including vaccine-related seroconversion rates and durability of immune responses following COVID-19 vaccine among PLWH. Although recognizing these limitations, we present this study because of its relevance in a population with immune dysregulation affected by both current epidemics of HIV and COVID-19 globally and in the expectation that it will stimulate additional study and relevant information in the near future.
In conclusion, our study suggests that the completion of a two-dose series of BNT162b2 is critical for individuals living with HIV, especially those with low CD4 counts or who have other concurrent immunocompromising conditions.
We would like to acknowledge the staff who supported our study at the Yale Nathan Smith HIV Clinic of the Yale New Haven Health System in New Haven, CT, and at the Floyd Little Field House in Hillhouse High School in New Haven, CT.
HIV Medicine. 2022;23(2):178-185. © 2022 Blackwell Publishing