Full HAV vaccination series highly immunogenic in immunocompromised patients

Hepatitis A virus (HAV) vaccination is highly immunogenic for virologically suppressed patients with HIV infection and for those on immunosuppressive monotherapy, according to findings published in the Journal of Travel Medicine.

Researchers conducted a prospective cohort study to assess the strength of antibody responses associated with HAV vaccination among immunocompromised adult populations. They also aimed to assess booster responses and identify predictors of adequate serologic response. The analysis included virologically suppressed patients with HIV infection, those on immunosuppressive therapy, those on immunosuppressive combination therapy, and a control group of patients not on immunosuppressive therapy. Patients received 2 inactivated HAV vaccine doses (Avaxim^®, Havrix^®, or VAQTA Adult^®) at month 0 and between months 6 and 12, and those with an indication for both HAV and hepatitis B virus (HBV) vaccination received 3 combined HAV/HBV vaccine doses (Twinrix^®) at 0, 1, and 6 to 12 months.

The primary outcome was seroconversion 2 months after vaccination, defined as the percentage of vaccinated patients with HAV antibody levels at or above 20 mIU/mL. Logistic and linear regression models were used to determine predictors of seroconversion and changes in antibody levels.

Among patients in the HIV (n=41), immunosuppressive monotherapy (n=40), immunosuppressive combination therapy (n=35), and control (n=34) groups, the mean (SD) ages were 43 (11.0), 42 (14.2), 36 (14.6), and 35 (12.44) years (P =.017), 80%, 48%, 57%, and 35% were men (P <.001), and median Charlson Comorbidity Index scores were 0, 1, 1, and 0, respectively (P =.011).

All HIV-positive patients were on combination antiretroviral therapy and all but 1 were virologically suppressed at baseline (mean CD4⁺ count, 673 cells/mm³). In patients on immunosuppressive mono- or combination therapy, the most common underlying diagnosis was Crohn disease.

The rate of seroconversion 2 months after completion of the full HAV vaccination series ranged between 83% and 100% across all 4 groups. Compared with patients in the control group, only those on immunosuppressive combination therapy exhibited significantly lower rates of seroconversion (P =.045) but all immunocompromised patients exhibited lower geometric mean concentrations (range, 71.08-221.55 vs 544.24 mIU/mL). Moreover, the researchers observed significantly lower geometric concentrations in patients on immunosuppressive combination therapy vs monotherapy (P <.001).

In the multivariable analysis, a smaller increase in HAV antibodies from baseline to 2 months after completion of the full series was associated with positive HIV status (β, -0.31), use of immunosuppressive mono- (β, -0.40) and combination therapy (β, -0.85), and coadministration of the 13-valent pneumococcal conjugate vaccine (β, -0.22).

At 6 months following full HAV vaccination, seroconversion rates remained high in HIV-positive patients and those on immunosuppressive monotherapy (97% and 88%, respectively). However, the rate of seroconversion was significantly lower for patients in the combination therapy vs control groups (69% vs 97%; P =.002). Overall, the researchers noted significantly reduced antibody levels across all 4 groups in the 6 months after vaccination (P <.001).

Predictors significantly associated with waning immunity included female sex (β, 0.18), immunosuppressive combination therapy use (β, -0.32), and tumor necrosis factor-a inhibitor use (β, -0.37). Most patients who experienced waning immunity exhibited adequate booster responses, with the exception of those on immunosuppressive combination therapy.

In regard to safety, the researchers noted 59 adverse events across 32 (23%) unique patients and most (88%) were of mild to moderate severity. The most common were local reactions (24%), musculoskeletal events (14%), gastrointestinal events (10%), fever (10%), and headache or fatigue (8%).

Study limitations include the use of correlates of immunity to assess disease protection conferred by HAV vaccination, small sample sizes, and the decision to restrict the analysis to measurements of humoral response.

“[S]imultaneous vaccination with pneumococcal conjugate vaccines seems to be detrimental for the antibody response to hepA vaccination,” the researchers noted. “The potential benefit of expanded vaccination schedules among ICPs [immunocompromised populations] needs to be further investigated,” they concluded.

By Jessica Nye, PhD

References:

Schnyder JL, Garrido HMG, Tanck MW, et al. Hepatitis A vaccine immunogenicity and boostability in adults receiving immunosuppressive therapy and adults living with HIV: a prospective single-centre cohort study. J Travel Med. Published online September 11, 2024. doi:10.1093/jtm/taae125