Vaccination against hepatitis A virus is safe in people with HIV, but the protective effects of the vaccine are determined by CD4 cell count, according to US research published in the electronic edition of the Journal of Infectious Diseases, which is now available on-line.
Although infection with hepatitis A does not have the potential to cause long-term health problems in people with HIV that hepatitis B and hepatitis C does, it can have short-term health consequences, causing severe acute illness and often causing anti-HIV therapy to be interrupted. Outbreaks of hepatitis A are frequently reported amongst HIV-positive gay men, with sexual transmission being the likely route of infection, and people with HIV are advised to be vaccinated against hepatitis A.
There have, however, been concerns about the safety and effectiveness of hepatitis A vaccine in HIV-infected patients. Therefore US researchers in California and Pennsylvania designed a placebo controlled study involving 133 HIV-positive patients to see if vaccination against hepatitis A adversely effected CD4 cell count, HIV viral load, and HIV disease progression, and to see how effective the vaccine was at conferring protection against hepatitis A.
All the patients enrolled to the study were negative for antibodies to hepatitis A and were on stable anti-HIV therapy. Average age was 38 years, and 89% of study patients were male. Baseline CD4 cell counts and HIV viral load were obtained and patients were randomly assigned to receive hepatitis A vaccine in two doses at six monthly intervals or a placebo. CD4 cell count and HIV viral load were broadly comparable in both the treatment and placebo arms of the study (376 cells/mm3 versus 327 cells/mm3, and 3.29 log10 copies versus 3.39 log10 copies/ml).
Overall seroconversion for hepatitis A antibodies amongst vaccine recipients was 49% at month seven and 52% at month nine. However, the effectiveness of the vaccine was found to be linked to baseline CD4 cell count. Amongst patients with a CD4 cell count above 500 cells/mm3 seroconversion was observed in 69% of patients at month seven and 67% at month nine. In patients with a CD4 count below 200 cells/mm3 however, seroconversion was only 11% at month seven and 9% at month nine.
In addition, investigators found that a single dose of hepatitis A vaccine rarely conferred protection against the virus. Even in patients with a CD4 count above 200 cells/mm3only 13% were protected against the virus after their first dose, and nobody with lower CD4 cell counts seroconverted after a single dose.
The vaccine was found to be safe. Only one patient reported that the vaccination made him feel unwell (as did one patient in the placebo group). In both vaccine recipients and the placebo arm of the study, CD4 cell count increased and viral load fell, although the increase in CD cell count was slightly, but not significantly higher in the placebo arm at 52 cells/mm3 versus 31 cells/mm3 in the vaccine arm. Viral load fall was also slightly greater in the placebo arm at (-0.35 log10copies/ml) than in the vaccinated patients (-0.18 log10copies/ml). Again, this difference was not significant.
Nor did vaccine have any impact on HIV disease progression, as “the frequency of HIV-related events during the study was similar between vaccine recipients and those receiving the placebo.”
The investigators note that their study found a lower rate of vaccine response than earlier trials, one of which had a seroconversion of 88% at month nine. They attempt to explain this by suggesting that earlier studies enrolled patients with a younger average age and used a lower cut-off point for hepatitis A seroconversion.
Nevertheless the investigators conclude “hep[atitis] A vaccine was well tolerated and had no apparent effect on the course of HIV infection or plasma HIV RNA levels.” They recommend that doctors should tell their patients that it is necessary to receive both doses of the vaccine and that even then not everybody receives protection from it.
Further information on this website
The liver - factsheet
Vaccinations and immunisations - Overview
HIV and hepatitis - Booklet in the information for HIV-positive people series (PDF)
Kemper CA et al. Safety and immunogenicity of hepatitis A vaccine in HIV-infected patients: A double-blind, randomized, placebo-controlled trial. Journal of Infectious Diseases, 187, on-line edition, 2003.