Correspondence

Hepatitis B Vaccination and Plasma HIV-1 RNA

N Engl J Med 1996; 334:1272May 9, 1996

Article

To the Editor:

We had embarked on a trial of hepatitis B virus (HBV) immunization to clarify the meaning of isolated findings of seropositivity for antibodies against the core hepatitis antigen (anti-HBc) in persons infected with the human immunodeficiency virus (HIV) when we became aware of reports of an increase in the viral load of HIV in association with the administration of influenza vaccine.1,2 Accordingly, we decided to assay serum obtained during our study for HIV type 1 (HIV-1) RNA. Aliquots of serum obtained before the first dose of HBV vaccine (Recombivax HB, Merck Sharp & Dohme, West Point, Pa.) and two and four weeks later and stored at -70°C were shipped on dry ice to the Aaron Diamond AIDS Research Center and assayed by a reverse-transcriptase–polymerase-chain-reaction assay.3

Ten subjects who had no change in antiviral therapy during the study were selected: four from the HBV-negative group, four with isolated seropositivity for anti-HBc, and two who were positive for antibodies against hepatitis B surface antigen (anti-HBs) (included as controls to assess the booster response in HIV-positive subjects). The subjects' most recent CD4 counts ranged from 4 to 1430 cells per cubic millimeter (median, 310). The results for all 10 subjects are shown in Figure 1Figure 1Plasma HIV-1 RNA Levels in the 10 Subjects before Immunization with HBV Vaccine and Two and Four Weeks Afterward.. In 3 of the 10 patients the HIV titer had more than doubled by week 2 and decreased to 0.5 to 1.2 times the base-line level by week 4. In two additional subjects the titer had more than doubled by week 4.

Although one study found no change in the number of HIV RNA copies after the administration of influenza vaccine,4 others have reported median increases of 5.9- to 7.3-fold.1,5 In one of these studies, 83 percent of HIV-1–infected subjects had more than a threefold increase within one to two weeks, and larger increases correlated with higher base-line CD4 counts and better responses to the influenza vaccine.5 Only two of our patients (indicated by dashed lines in Figure 1) had CD4 counts above 500 per cubic millimeter, and one of these should have had a booster response (anti-HBs was present at base line). In these two subjects the number of HIV-1 RNA copies more than tripled in four weeks (from 350 to 1080 and from <200 to 650 HIV-1 RNA copies per milliliter). Overall, we found little increase in the HIV load after immunization with HBV vaccine in this group of patients with moderate-to-severe immunodeficiency.

We are indebted to Carol A. Bova, R.N.-C., and Mark Keroack, M.D., for assistance in the conduct of this study and to David D. Ho, M.D., and Yunzhen Cao, M.D., for performing the reverse-transcriptase–polymerase-chain-reaction assay.

Sarah H. Cheeseman, M.D.
Raul E. Davaro, M.D.
Richard T. Ellison, III, M.D.
University of Massachusetts Medical School, Worcester, MA 01655

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