Only a fraction of HIV-positive individuals for whom vaccination against hepatitis B virus (HBV) and hepatitis A virus (HAV) is appropriate are receiving these vaccinations, according to research conducted in the US and published in the May 15th edition of Clinical Infectious Diseases. The US investigators stress that greater efforts need to be made to screen and vaccinate individuals against these infections when they first enter HIV care.
Liver-related causes have emerged as a major cause of illness and death amongst HIV-positive individuals since the advent of HAART. Treatment guidelines in both the US and UK specify that HIV-positive individuals should, when clinically appropriate, receive vaccinations against both HBV and hepatitis A. In the US, the vaccinations are particularly recommended for individuals at high risk of these infections, including gay men, injecting drug users and heterosexuals with multiple sexual partners. In the UK they are recommended for all HIV-positive patients who lack immunity. In addition, the vaccinations are recommended on both sides of the Atlantic for all HIV-positive individuals who are coinfected with hepatitis C virus.
Investigators from the US HIV Outpatients Study (HOPS) wished to establish how many HIV-positive individuals were being screened for these infections, and then received either partial or complete courses of vaccination, and had tests to assess the success of the vaccinations. They also wished to determine the clinical and demographic features of individuals who were receiving vaccination. When individuals were not vaccinated, the investigators gathered informal information from clinicians about their decisions not to offer vaccination.
A total of 1,071 individuals from nine HIV treatment centres in large US cities were included in the investigators’ analysis. A total of 877 (81.9%) were screened for HBV and 613 (57.2%) were screened for hepatitis A. Of the individuals screened, 612 (57.1%) were considered eligible for vaccination against HBV (the others having immunity to HBV or current or previous HBV disease), and 716 (66.8%) were eligible for vaccination against hepatitis A.
Hepatitis B vaccination
Only 198 (32.4%) of the individuals considered candidates for HBV vaccination received at least one dose of the three-dose vaccine, and only 104 patients received all three recommended doses. Of the individuals who received all three doses, only 51 had postvaccination testing for HBV surface antigen. Of the 19 patients who responded to vaccination, the majority (84.2%) had a nadir CD4 cell count above 200 cells/mm3. Responders also had higher median CD4 cell counts (584 cells/mm3 versus 384 cells/mm3, p=0.08), and were more likely to have an undetectable baseline viral load (63.2% versus 33.3%, p=0.04). Although responders were more likely to be taking HAART (84% versus 68%), the difference was not statistically significant.
There were significant demographic differences between individuals receiving vaccination and those who did not. In multivariate analysis, high school education or less (OR 1.68, 95% CI, 1.01-2.81), being heterosexual rather than a gay man or injecting drug user (OR 2.43, 95% CI, 1.23 - 4.81), and a median higher number of clinic visits a year, were found to be significantly associated with an increased risk of receiving HBV vaccination.
An informal survey of doctors about their reasons for not offering HBV vaccination revealed that these included irregular clinic attendance by the patient, lack of perceived patient risk, CD4 cell count too low to generate an immune response, and the refusal of an insurance company to pay for vaccination.
Hepatitis A vaccination
Rates of vaccination against hepatitis A were even lower. Of the 716 individuals eligible for vaccination, only 167 (23%) received at least one of the two recommended doses of the vaccine, and only 90 individuals received both doses. Women (OR 1.83, 95% CI 1.06-3.17, p=0.03), individuals from an HIV risk group other than gay men or injecting drug users (OR 2.46, 95% CI, 1.34-4.50, p=0.003), and individuals with an undetectable HIV viral load (p=0.01) were significantly more likely to receive vaccination compared to patients with other characteristics.
Investigators comments and conclusions
“In this analysis of ambulatory sites providing HIV care in the era of HAART, there was a low rate of administration of preventative vaccines for HAV and HBV,” comment the investigators. They note that there are similarly low rates of vaccination amongst HIV-positive individuals in the US for other recommended immunisations, including influenza and pneumonia.
Concern is also expressed by the investigators about how little postvaccination testing was conducted by treatment centres to assess the success of the HAV and HBV vaccinations.
When testing was carried out, it was found that patients with a nadir CD4 cell count above 200 cells/mm3 and an undetectable HIV viral load were more likely to gain an immune response to HBV after vaccination. However, they also note that “HAART per se, although greater in the vaccinated group, was not significantly associated with the detection of antibody responses” and suggest that if clinicians delay vaccination until the immune system has improved after the initiation of HAART, an individual may never receive HBV vaccination.
Commenting on clinicians' reasons for not vaccinating patients, the investigators state that rates of vaccination were significantly higher for patients receiving free HIV care at Ryan White-funded clinics than amongst individuals whose HIV care was paid for by private insurance.
A lack of HBV and HAV preventative screening and vaccination is criticised by the investigators, who note that gay men and injecting users still account for the majority of new HBV cases each year. They emphasise, “screening and vaccination are especially important for [HIV] coinfected patients with hepatitis C, who are not only are likely to have behaviours that place them at risk of HBV and HAV, but whose chronic liver disease places them at increased risk of morbidity and mortality from hepatitis A.”
The investigators conclude that routine screening, vaccination, and postvaccination testing should be included in the care of all newly-diagnosed HIV-positive individuals, and that both providers and patients should be reminded about the importance of these vaccinations.
Further information on this website
AIDS deaths down, but new causes of death at largest UK HIV clinic - news story
Hepatitis B - overview
Tedaldi EM et al. Hepatitis A and B vaccination practices for amulatory patients infected with HIV. Clinical Infectious Diseases 38: 1483-1489, 2004.