HIV-Infected Patients Respond Poorly to Pneumococcal Vaccine

Daniel M. Keller, PhD

November 04, 2011

November 4, 2011 (Boston, Massachusetts) — Antibody responses to pneumococcal vaccine are low among HIV-infected individuals, whether they receive it before they begin antiretroviral therapy (ART) or after at least 6 months of ART, Maria Rodriguez-Barradas, MD, director of the HIV clinic at the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston, Texas, told delegates during a poster session here at the Infectious Diseases Society of America 49th Annual Meeting.

Dr. Rodriguez-Barradas told Medscape Medical News that the recommendations for pneumococcal vaccination in HIV-infected patients are mostly based on expert opinion. "Right now, the recommendation is to vaccinate everybody with a CD4 count of more than 200 cells/μL," she said, "but from what we know, it would make sense to think that patients who are virally suppressed on treatment would have a better immune response, because data have shown in vitro that their B cell immunity improves."

Therefore, in this prospective double-blind study, the researchers looked to see if it is worth waiting to vaccinate until after patients have been on ART and their viral loads are suppressed. Inclusion criteria were a CD4 count of at least 200 cells/μL, no ART, no pneumococcal vaccine in the previous 3 years, and no acute illness in the previous 2 weeks.

Patients were randomized to receive the recommended single dose of 23-valent pneumococcal vaccine prior to the start of treatment (baseline) and placebo at 12 months (immediate group; n = 41 at baseline), or to receive placebo at baseline and the vaccine at 12 months (delayed group; n = 68 at baseline). Delayed administration was based on a time point, not on the achievement of a target viral load or CD4 cell count.

There were no significant demographic differences between the 2 groups. The mean age of subjects in the immediate group was 40.7 years and in the delayed group was 44.1 years; 87% of the immediate group was 87% male, as was 77% of the delayed group. CD4 counts and viral loads were statistically equivalent.

Immunoglobulin (Ig)G levels against capsular polysaccharides were determined at baseline, at 1 month, and at 6 months, when there were 24, 24, and 16 subjects in the immediate group, respectively, and 30, 30, and 6 in the delayed group. Initial enrollment was 109 subjects, but a high rate of attrition limited the number of evaluable subjects. The characteristics of the evaluable participants were similar in the 2 groups, and not different from the initial enrollees overall.

With still more samples to analyze, Dr. Rodriguez-Barradas said the preliminary results indicate that "the delayed group — the patients who have been on [ART] — have not been shown to have a much better response than those who received the vaccine after starting treatment.... Overall for the 2 groups, the response rate to the vaccine was not very good."

Five serotypes of pneumococcal capsular polysaccharides were tested (1, 3, 4, 6B, and 23F), but IgG antibody responses were significant 1 month after active vaccination for only 3 serotypes in the immediate group and 2 serotypes in the delayed group. A response was defined as a 2-fold or greater increase in IgG after vaccination with a level that was at least 1 μg/mL. "Only 20% of the subjects had good responses to 2 or more serotypes," Dr. Rodriguez-Barradas reported. At 6 months, the responses had essentially fallen back to the baseline level.

At the 1-year visit, 69% of the immediate group and 50% of the delayed group had nondetectable viral loads.

In another study of older, non-HIV-infected subjects, Dr. Rodriguez-Barradas said that the IgG responses were better than were seen in the HIV-infected individuals. In published studies, she said, even at 5 years, the IgG levels were still "a little bit higher than their prevaccine levels."

This study measured only IgG levels. Dr. Rodriguez-Barradas said the next step is to see if immune function improves in the patients who have been on treatment, using opsonophagocytosis assays, which have been shown to be the best functional correlates of immune protection.

For a population of patients not likely to have good retention in care, Dr. Rodriguez-Barradas warned that clinicians might miss an opportunity for vaccination if they wait until ART begins. "In those [patients], the first opportunity you have to vaccinate might be the opportunity that you have to take...since waiting did not improve the response. If the patient has a CD4 count [above 200 cells/μL], you might as well give the vaccine when you're seeing them the first time, even if that's before treatment.... Overall, probably starting treatment is just the best intervention to prevent bacterial pneumonia in HIV patients."

Joel Gallant, MD, professor of medicine and epidemiology in the division of infectious diseases at Johns Hopkins University School of Medicine in Baltimore, Maryland, and vice chair of the HIV Medicine Association, who was not involved in this study, told Medscape Medical News that the study is interesting and goes against what has been seen with some other vaccines in other studies in which CD4, viral load, or both were big predictors of immune response to vaccination.

"Many of us, based on those studies, have been assuming that we should extrapolate to just about every vaccine and wait until people are on antiretroviral therapy and have had a good response," he said. "I think it would have been more useful to know that these people['s viral loads] were suppressed and that they had a good CD4 increase — to look at those as predictors rather than time on therapy."

Dr. Gallant said that deciding on whether to vaccinate at the beginning of ART or later depends somewhat on risk. As an example, he explained that if he has a patient about to start ART in November, "I'm still going to vaccinate them against the flu, rather than waiting until flu season is over and they've had a good immune response."

But pneumococcal vaccine might be a different situation and one in which there might be no urgency to vaccinate. "It seems to me, based on previous studies, that it makes sense to wait a little bit. This study argues against that, but I think the bulk of evidence would suggest that waiting probably will increase the chances of response," he advised, suggesting that "the other approach is to revaccinate. Pneumovax is already recommended for vaccination after a 5-year period, but that would be a long time to wait."

Finally, he said, he was surprised by the low antibody responses in this study, "although I think there have been concerns about this particular vaccine in HIV-positive people in the past with other studies, so it could be consistent."

The study had no outside funding. Dr. Rodriguez-Barradas and Dr. Gallant have disclosed no relevant financial relationships.

Infectious Diseases Society of America (IDSA) 49th Annual Meeting: Abstract LB-10. Presented October 22, 2011.

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