Safety and Immunogenicity of Hepatitis A Vaccine in HIV-Infected Patients: A Double-Blind, Randomized, Placebo-Controlled Trial

The use of an inactivated hepatitis A (HepA) vaccine provides affordable protection against HAV infection, which may be of particular importance in those who are HIV-infected. One of the inactivated HepA vaccines, HAVRIX, is highly immunogenic in non HIV-infected adults, resulting in seroconversion in up to 90 percent to 94 percent and 100 percent of persons after the first and second doses, respectively, of vaccine.

However, antibody responses to HepA vaccine are lessened in patients with HIV infection. The authors determined the safety and immunogenicity of two doses of HepA vaccine (HAVRIX; 1440 EIU) in a group of HIV-infected adults with varying levels of immunodeficiency who were seronegative for anti-HAV antibodies. The researchers examined whether two doses of vaccine, administered six months apart, adversely affected CD4 cell counts, plasma HIV RNA levels, or the clinical course of HIV-infection.

A group of HIV-infected adults 18 years old or older who were prescreened for the lack of anti-HAV antibody were assessed in the study. Criteria for study inclusion were receipt of stable antiretroviral therapy or no therapy for at least one month prior to entry, no signs or symptoms of active infections, no fever greater than 37.8° C, and no active HIV-related opportunistic infection or malignancy.

A total of 270 adults were screened, 133 of whom were HAV seronegative and enrolled in the study (mean age, 38 years; range, 22-65 years). Of the 68 subjects (51.1 percent) who were randomly assigned to receive HepA vaccine, 48 (70.6 percent) completed the nine-month study. Of the 65 (48.9 percent) who received placebo, 51 (78.5 percent) completed the study. Baseline demographics were similar between treatment groups, although CD4 cell counts were somewhat higher at baseline in vaccine recipients, compared with placebo recipients (376 vs. 327 CD4 cells/mmÒ; P, not significant). Mean HIV RNA levels were also similar (3.29 vs. 3.39 log10 copies/mL). Sixty-two patients (91 percent) in the vaccine group were receiving antiretroviral therapy at the time of entry to the study, compared with 60 (92 percent) in the placebo group. Half the patients were receiving at least two agents, reflecting the pattern of antiretroviral use at the time of enrollment.

The overall frequency of seroconversion among subjects receiving vaccine was 49 percent at month seven and 52 percent at month nine. Among patients with baseline CD4 cell counts of 200-499 or greater than or equal to 500 cells/mmÒ, seroconversion was observed in 53 percent and 73 percent at month seven and in 69 percent and 67 percent at month nine, respectively. When all three groups were compared, the frequency of seroconversion among patients with CD4 cell counts of less than 200 cells/mmÒ was significantly lower at month seven (11 percent; P =.023) and at month nine (9 percent; P = .004). After the first dose of vaccine, seroconversion at month six was observed in only four (13 percent) of 31 subjects with CD4 cell counts greater than or equal to 200 cells/mmÒ and in no subjects with CD4 cell counts less than 200 cells/mmÒ.

The authors found no transient increases in plasma HIV loads after administration of HepA vaccine on HIV RNA levels. Increases in CD4 cell counts and decreases in HIV loads were observed in both subject groups throughout the study. Furthermore, the study demonstrated that the frequency of seroconversion and the magnitude of the resulting antibody titer varied significantly, depending on the initial CD4 cell count. Patients with less immune system impairment were more likely to seroconvert and to have higher antibody titers, suggesting that a success rate of response to HepA vaccine is somewhat lower than those found in earlier studies of HIV infection.

The authors concluded: "HepA was well tolerated and had no apparent effect on the course of HIV infection or plasma HIV RNA levels. Approximately two-thirds of our patients responded to two doses of vaccine administered six months apart. Compared with uninfected persons and with the results of other studies of HIV-infected persons, this relatively lower response rate was unexpected and remains unexplained. ... Clinicians may wish to counsel patients that vaccination may not provide uniform protection against HAV. Whether vaccine response can be improved by the use of adjuvants or a third dose of vaccine or by delaying vaccination until there is evidence of improvement in the immune system in response to more highly active antiretroviral therapy, deserves further study."

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