SUMMARY: Individuals who respond well to hepatitis B vaccination have a lower risk of experiencing HIV disease progression, while those who respond poorly are more likely to develop AIDS or die -- independent of CD4 count -- according to a poster presented at the 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010) last month in San Francisco. The researchers suggested that ability to respond to the vaccine reflects many aspects of immune function that may contribute to slower disease progression.

By Liz Highleyman

Michael Landrum and colleagues evaluated the relationship between hepatitis B virus (HBV) vaccine responses and progression to clinical AIDS or death among participants in the U.S. Military HIV Natural History Study.

Response to vaccination is greater in people with healthy immune systems, including several factors known to predict AIDS progression, such as higher CD4 cell count, the researchers noted as background. Prior studies have shown that HIV positive people with advanced immune deficiency tend to respond poorly to the hepatitis B vaccine, producing insufficient numbers of anti-HBV antibodies.

This study included 626 HIV positive participants seen at 7 military health facilities who had received hepatitis B vaccination only after HIV diagnosis. About 90% were men and the median age was just over 30 years.

Based on hepatitis B surface antigen (anti-HBs) testing performed 3-9 months after the last vaccine dose, 217 (35%) were deemed vaccine responders (>10 IU/L) while 409 were non-responders. Participants were followed from the date of the last vaccine dose until they developed AIDS, died, or had their final clinic visit.

Results

	Compared with non-responders, vaccine responders had:
	Significantly higher median current CD4 count (595 vs 480 cells/mm3); Significantly higher nadir or lowest-ever CD4 count (398 vs 352 cells/mm3); Significantly lower median viral load; Significantly higher likelihood of having received 3 or more vaccine doses (70% vs 57%). More recent HBV vaccination.
	During a median 5 years of follow-up (total 3500 person-years), 9% of vaccine responders developed clinical AIDS or died, compared with 25% of non-responders (unadjusted P < 0.001).
	About 75% of all deaths were AIDS-related, 2 were non-AIDS-related, and the remainder were of unknown cause.
	In a multivariate analysis adjusting for other factors including age, number of vaccines doses, CD4 count, and use of ART, vaccine response was associated with a 42% lower risk of clinical AIDS or death (adjusted hazard ratio [HR] 0.58).
	Among participants who had not yet started ART, vaccine response lowered the risk of AIDS or death by 50% (adjusted HR 0.50).
	Among ART-naive individuals with a CD4 count > 350 cells/mL, the risk reduction was also 50% (adjusted HR 0.50).

Based on these findings, the investigators concluded, "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."

The also suggested that HBV vaccine response might help identify untreated individuals at risk for disease progression despite having a CD4 count > 350 cells/mL, who might therefore benefit from earlier ART.

Uniformed Services Univ of the Health Sciences, Bethesda, MD; San Antonio Military Med Ctr, Fort Sam Houston, TX; Univ of Minnesota, Minneapolis, MN; Naval Med Ctr, San Diego, CA; Walter Reed Army Med Ctr, Washington, DC; National Naval Med Ctr, Bethesda, MD; Walter Reed Army Institute of Research, Rockville, MD; Univ of Texas Health Science Ctr at San Antonio, TX.

3/12/10

References
M Landrum, K Huppler Hullsiek, N Crum-Cianflone (IDCRP HIV Working Group). Hepatitis B Vaccine Response Predicts Progression to Clinical AIDS or Death. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. (Abstract 625).