Positive HBV Vaccine Response Halves HIV Progression and Death Risk in US Military

Positive HBV Vaccine Response Halves HIV Progression and Death Risk in US Military

17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco

Mark Mascolini

A positive response to hepatitis B virus (HBV) vaccination approximately halved the risk of HIV disease progression or death in members of the US Military HIV Natural History Study, regardless of antiretroviral exposure or CD4 count [1]. The results underline the critical importance of HBV vaccination among people infected with HIV.

In addition, Michael Landrum and colleagues suggested, "HBV vaccine response may serve as a useful indicator for studying immunological correlates of HIV-related disease progression that are independent of the HIV RNA load or level of immune deficiency reflected by the CD4 count."

Earlier work by these researchers found that HBV vaccination did not lower the overall risk of HBV infection in this cohort, but they linked a vigorous vaccine response to a lower risk of chronic HBV infection, and chronic HBV and HBV vaccine response were associated with CD4 count and HIV load [2-4].

People eligible for this study at seven military care centers had a documented date of HIV infection and had not received an HBV vaccine before their HIV diagnosis. After testing positive for HIV, they received at least one HBV vaccine dose and had anti-hepatitis B surface (HBs) antigen measured 3 to 9 months after their last dose. Landrum and coworkers defined a positive vaccine response at anti-HBs antigen at or above 10 IU/L and nonresponse as a lower anti-HBs antigen level.

Study participants included 217 HBV vaccine responders and 409 nonresponders. Both groups had a median age around 32 years, and about 90% were men. Median CD4 counts stood at 505 in responders and 480 in nonresponders, a significant difference (P < 0.01). Median nadir CD4 count was higher in responders (398 versus 352, P < 0.01), and median viral load was lower (2.30 versus 3.62 log, P < 0.01). A higher proportion of responders than nonresponders got three or more HBV vaccine shots (70% versus 57%, P < 0.01), and responders were vaccinated more recently (median 2000 versus 1997, P < 0.01).

During a median follow-up of 5 years, 19 responders (9%) and 102 nonresponders (25%) had a new AIDS diagnosis or died (P <0.001 in a comparison unadjusted for other progression risk factors). To determine risk of progression or death, Landrum and colleagues devised a multivariate model that considered age, ethnicity, HIV duration before last HBV vaccination, number of vaccines doses, and year of last HBV vaccination.

That model determined that HBV vaccination lowered the risk of progression or death 42% (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.34 to 0.98, P = 0.04). Among people naive to antiretrovirals at their last HBV vaccine dose, vaccination halved the risk of progression or death (HR 0.50, 95% CI 0.27 to 0.91, P = 0.02). And among people naive to antiretrovirals at last vaccination and with a CD4 count above 349, vaccination also halved the risk of progression or death (HR 0.50, 95% CI 0.25 to 1.01, P = 0.05).

Because the study group consisted largely of young men receiving free care, the findings may not apply to all HIV populations.

Landrum and coworkers proposed that "response to HBV vaccine following immunization during HIV infection may be a useful independent predictor of clinical HIV-related disease progression, and may provide a functional assessment of immune function in such individuals."

References
1. Landrum M, Huppler Hullsiek K, Crum-Cianflone N, et al. Hepatitis B vaccine response predicts progression to clinical AIDS or death. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 625. http://www.retroconference.org/2010/PDFs/625.pdf.
2. Landrum ML, Hullsiek KH, Ganesan A, et al. Hepatitis B vaccination and risk of hepatitis B infection in HIV-infected individuals. AIDS. 2009. Epub ahead of print.
3. Landrum ML, Fieberg AM, Chun HM, et al. The effect of human immunodeficiency virus on hepatitis B virus serological status in co-infected adults. PLoS One. 2010;5:e8687. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008687.
4. Landrum ML, Huppler Hullsiek K, Ganesan A, et al. Hepatitis B vaccine responses in a large U.S. military cohort of HIV-infected individuals: another benefit of HAART in those with preserved CD4 count. Vaccine. 2009;27;4731-4738.