Double-dose hepatitis B revaccination has good results in HIV-positive patients not responding to standard vaccine

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Use of a double-dose of hepatitis B virus vaccine in HIV-positive patients who did not respond to standard vaccination has a 50% success rate, according to a Dutch study published in the January 15th edition of the Journal of Infectious Diseases.

HIV and hepatitis B are transmitted in similar ways, and it is estimated that approximately 6% - 10% of HIV-positive gay men are infected with hepatitis B virus. Patients infected with HIV and hepatitis B virus are often said to be coinfected. High rates of HIV/hepatitis B coinfection are also present in HIV-positive patients in many resource-limited countries.

Antiretroviral therapy can mean a longer, healthier life for HIV-positive patients, but since effective anti-HIV treatment became available, liver disease caused by hepatitis B and hepatitis C virus has become a major cause of illness and death in people with HIV. It is estimated that individuals coinfected with HIV and hepatitis B virus have an eight-fold increased risk of death compared to individuals who are only infected with HIV.

Glossary

hepatitis B virus (HBV)

The hepatitis B virus can be spread through sexual contact, sharing of contaminated needles and syringes, needlestick injuries and during childbirth. Hepatitis B infection may be either short-lived and rapidly cleared in less than six months by the immune system (acute infection) or lifelong (chronic). The infection can lead to serious illnesses such as cirrhosis and liver cancer. A vaccine is available to prevent the infection.

response rate

The proportion of people asked to complete a survey who do so; or the proportion of people whose health improves following treatment.

intramuscular

Injected into a muscle.

immune system

The body's mechanisms for fighting infections and eradicating dysfunctional cells.

nadir

Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.

Patients who are coinfected with HIV and hepatitis B are also less likely to clear hepatitis B surface antigen and hepatitis B e antigen, have a higher rate of hepatitis B replication and therefore have an increased risk of passing on hepatitis B to others. Coinfected patients also have a greater risk of progression to cirrhosis and of experiencing flare-ups of hepatitis.

Preventing hepatitis B in HIV-positive patients is therefore a priority. A vaccine against the virus exists and it is recommended that all HIV-positive patients should receive this. However, compared to individuals with a strong immune system, HIV-positive patients have a poor response to hepatitis B vaccination with only 40% - 76% developing protective antibodies against the infection.

All asymptomatic HIV-positive patients in the Netherlands are provided with hepatitis B vaccination consisting of three 10 µg doses of HBvaxPro. These are provided by intramuscular injection. But approximately 50% of patients do not develop a protective level of antibodies against the infection.

To try and achieve a higher rate of response investigators revaccinated 144 non-responders at monthly intervals with double the recommended dose of the vaccine.

Most of the patients (108, 75%) were men and the mean age was 43 years. At the time of revaccination, 96 patients (67%) were receiving antiretroviral therapy and 89 patients (62%) had an undetectable HIV viral load. Median nadir (lowest ever) CD4 cell count was 204 cells/mm3 and at the time the first course of hepatitis B vaccination was offered, median CD4 cell count was 360 cells/mm3. Median CD4 cell count was similar when revaccination was provided.

Revaccination was successful in 74 of the 144 patients, a response rate of 51%. Median hepatitis B antibody titers were 107.9 iu/l in these patients, well above the protective threshold of 10 iu/l.

Female patients were found to have a significantly better response rate (p = 0.03). A response was also more likely in patients under 40 years, irrespective of their HIV viral load. For patients aged 40 and above, revaccination was significantly more likely to be successful in patients with an undetectable HIV viral load (p = 0.005).

“To our knowledge, this is the first study describing the results of double-dose hepatitis B virus rechallenge vaccination at monthly intervals in HIV-infected patients not responding to their initial vaccination,” write the investigators, “we revaccinated 144 patients who had failed to have an antibody response after standard vaccination and found a 50.7% response rate.”

The investigators conclude that such a response rate shows that their strategy of double-dose revaccination was justified and call for further prospective studies.

References

De Vries-Sluijs TEMS et al. A prospective open study of the efficacy of high-dose recombinant hepatitis B rechallenge vaccination in HIV-infected patients. J Infect Dis 197: 292 – 294, 2008.