Discussion
Overall, in our study we observed how, among virally suppressed PWH, COVID-19 vaccination with mRNA-1273 was not associated with increased occurrence of VB in the 12 months after the first vaccine shot, a time-period where two other vaccine doses, and thus several stimuli to the immune system, were provided.
Some studies, other than our previous case report, have reported VB after COVID-19 vaccination. In their cohort of 143 PLH vaccinated with BNT162b2 mRNA COVID-19 vaccine, Levy et al. observed how in 3 (2.1%) patients the viral load increased after the second dose from undetectable levels (<40 copies/mL) to 47, 52 and 92 copies/mL, whereas in 3 patients, who had low-level viraemia at baseline, the viral load did not change significantly following vaccination. Instead, Milano et al. assessed HIV RNA after the second BNT162b2 mRNA COVID-19 vaccine dose among 228 out of 697 enrolled PWH. They found 20 (8.9%) VB among patients who were previously undetectable and reported high adherence to ART. Overall, our study is the first one assessing VB occurrence in PWH vaccinated with mRNA-1273 and it is reporting an incidence, of 15/48 (31.3%), which is quite superior to that reported by other studies. It should be noted that we performed viral load assessment with higher frequency compared to the above-mentioned reports and the main outcome of our study was precisely to assess VB. Our incidence is in line with the data of Joya et al., which reported how 46% of ART recipients in a large American cohort had ≥1 detectable VL without meeting criteria for virologic failure, including both VB and sustained low-level viremia.
Our study has limitations related to its retrospective design. Notably, VL and immunologic profile assessments were performed concomitantly to outpatient clinic visits which leads to a non-homogenous sampling schedule after vaccination. Thus, VB may be underreported and a study with prespecified sampling time points could provide a better description of VB incidence. Nonetheless, having applied the same sampling schedule (every 4 months) before and after vaccination, we can assume a priori the same probability of detecting the occurrence of a VB in the two periods. Moreover, it can be argued that VB in the follow-up period could be related to other conditions than COVID-19 vaccination. The study design, with the evaluation of VB occurrence in an equal timeframe (12 months) before COVID-19 vaccination, should have led to a balance in the impact of these possible confounders. Moreover, anti-N antibody titres were detectable in 7 patients and 11 patients at baseline and T1c, respectively, suggesting very few cases of COVID-19 during the study follow-up and thus a small impact by this infection.
Overall, we can affirm that COVID-19 mRNA vaccination does not lead to an increased risk of VB occurrence, among virally suppressed PWH, with their frequency being comparable before and after vaccination. We can speculate that the immunostimulatory action elicited by mRNA-1273 is not sufficient to reactivate HIV transcription from its latent state. As expected, when we included in our analysis also the PWH previously excluded for not reaching the definition of viral suppression, thus with less efficient control of viral replication, we observed an HIV RNA increase in all of them. This confirms the assumption of vaccines as immunostimulatory agents, more prone to lead to increase viremia in those patients with inadequate viral control and possibly larger viral burden. Interestingly, despite not being significant, a trend toward a higher number of VB among individuals with lower anti-S titres and serum-neutralizing activity was observed. This finding suggests how an immune system able to respond adequately to immunogenic stimuli is less prone to develop VB, probably through a well-controlled HIV infection which led to a reduction in systemic inflammation and immune activation.
COVID-19 mRNA vaccination can be safely performed among PLWH without any issues related to the possible occurrence of VB. Patients concerned about this possibility should be informed that, among individuals who are adherent to ART, this event seems to occur with the same frequency before and after vaccination. Patients with inadequate viral control might experience a higher frequency of HIV RNA increase after vaccination, but this should not prevent them to receive a potential life-saving instrument. Further research is needed to confirm the results of our study in larger cohorts and validate them also with other vaccines.