People Living With HIV Experience a Diminished Immune Response to COVID-19 mRNA Vaccines

Previous studies have shown that people living with HIV (PLWH) have exhibited a diminished immune response to vaccines such as hepatitis B and influenza, leaving investigators concerned that the same could hold true for mRNA SARS-CoV-2 vaccination.

Armed with initial data demonstrating that COVID-19 disease severity appears higher among PLWH and considering that limited data exist on the specific responses to COVID-19 mRNA shots, a team from University of California, San Francisco (UCSF) sought to find out whether there are differences in the immune response to SARS-CoV-2 vaccination by HIV status or by mRNA vaccine type.

Their results, presented in a late-breaking session at IDWeek 2021, show that PLWH measured 43% lower anti-SARS-CoV-2 IgG antibodies post-vaccination compared with those without HIV, meaning clinicians should consider providing supplemental vaccination in the form of boosters for this population.

To conduct the study, investigators worked with a public hospital with a large outpatient HIV clinic and saved residual outpatient laboratory samples from all previously mRNA-vaccinated individuals in May 2021. Any individuals with prior SARS-CoV-2 infection were excluded. A total of 100 PLWH were matched 1:1 with 100 outpatient HIV-negative adults, who were receiving care for chronic medical conditions. Groups were matched based on days since completion of second vaccination (minimum 10), sex, age +/- 5 years, and type of mRNA vaccine.

Overall, 13% of each cohort were female, with a median age of 59. A total of 25% of participants received the mRNA-1273 vaccine and 75% received the BNT162b2 vaccine. The median CD4+ T-cell count was 511 (IQR: 351-796) and 5 individuals had HIV RNA > 200, among PLWH.

Investigators used mixed models to compare non-response by HIV status, with non-response defined as reciprocal pseudovirus neutralizing titer< 10 and anti-RBD IgG< 10 relative fluorescent units.

The odds of pseudovirus neutralizing antibody non-response were 2.4-fold greater among PLWH compared with individuals without HIV (95% CI = 1.1-5.4). Twelve PLWH and 5 people in the non-HIV group did not mount an IgG response (P = 0.08), but continuous anti-RBD IgG concentrations were 43% lower among PLWH (95% CI = 0.36-0.88).

“Major predictors of response were CD4+ count, suppressed viral load, and whether the participant received Moderna (higher response) or Pfizer mRNA vaccine (lower response),” Matt Spinelli, MD, MAS, assistant professor in the Division of HIV, Infectious Diseases, and Global Medicine at UCSF, and presenting author of the study, told Contagion®.

Indeed, receipt of Pfizer’s BNT162b2 vaccine vs Moderna’s mRNA-1273 vaccine was associated with 77% lower neutralizing titers (GMR 0.23; 95% CI = 0.08-0.65) among PLWH. When adjusting for age, sex, and days post-vaccination among PLWH, investigators found that each 100-cell increase in CD4+ T-cell count was associated with 22% higher neutralizing antibody titers (GMR 1.22; 95% CI = 1.09-1.37), and unsuppressed HIV RNA > 200 was associated with 89% lower neutralizing antibody titers (GMR 0.11; 95% CI = 0.01-0.84).

“Plans to provide boosters to people living with HIV, with the data currently available, seem reasonable, particularly to those with lower CD4+ counts or unsuppressed viral loads, although effective antiretroviral therapy is also very important for these patients,” Spinelli said. “Next steps include examining T-cell responses, as well as immune responses, to booster vaccination, which has already started locally among people living with HIV.”

The study, “Lower SARS-CoV-2 IgG and pseudovirus neutralization titers post-mRNA vaccination among people living with HIV,” was presented virtually at IDWeek 2021, held September 29-October 3, 2021.