Quantification of risk factors for herpes zoster: population based case-control studyBMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g2911 (Published 13 May 2014) Cite this as: BMJ 2014;348:g2911
All rapid responses
Forbes et al. report the results from an interesting large case-control study in the UK, assessing the risk of herpes zoster (HZ) reactivation associated with a number of conditions. Both in the manuscript and the accompanying press release, the point is made that the greatest risk of reactivation was found in individuals with conditions causing severe immunosuppression and therefore in groups that are not currently able to benefit from Zostavax® (Merck), as it is a live attenuated vaccine, which is contraindicated in these populations. One of these conditions highlighted is HIV, which along with lymphoma and haematopoietic stem cell transplantation, conferred one of the highest relative risks of HZ reactivation.
The authors rightly highlight the need to find alternative risk reduction strategies in these patients. We feel, however, that in the case of HIV infection, a few additional points are worth making. The CDC-Advisory Committee on Immunisation Practices (ACIP) state that Zostavax® is contraindicated in ‘Persons with AIDS or other clinical manifestations of HIV, including persons with CD4+ T-lymphocyte values <200 per mm3 or <15% of total lymphocytes’(1). No specific recommendations are given about the use of the vaccine in those with asymptomatic HIV and higher CD4 counts. The Shingles Prevention Study(2) excluded patients with HIV and there are no currently published data on this matter. However, final results from the AIDS Clinical Trial Group (ACTG) 5247 study are awaited (http://clinicaltrials.gov/show/NCT00851786). This phase II, randomised, double-blind, placebo-controlled study evaluated the safety and immunogenicity of Zostavax® in HIV-infected adults with CD4 counts ≥ 200 per mm3 and virologically suppressed on antiretroviral therapy (ART) and, importantly, subjects were required to have a history varicella or HZ >1 year ago or be varicella zoster virus (VZV) seropositive prior to entry. Preliminary results reported on safety are encouraging, showing no greater risk of rash or fever in the Zostavax® arm compared to placebo, although there was a higher incidence of injection site reactions(3). The vaccine was also immunogenic, as demonstrated by VZV antibody titres, while the results of cell-mediated immunity assays are awaited.
While the full results of this study will hopefully provide appropriate data to help make an informed decision about the use of Zostavax® in HIV-infected patients with higher CD4 counts, a point worth making is that not all live vaccines are contraindicated in this group. The recently published Infectious Diseases Society of America (IDSA) guidelines on vaccinations in immunocompromised hosts include recommendations for the rotavirus vaccine in HIV-infected infants, as well as yellow fever vaccine, MMR and varicella vaccine in HIV-infected children and adults without severe immunosuppression(4). Although the varicella vaccine and Zostavax® contain the same strain of VZV, the latter contains approximately 15 times higher viral titres. Thus the ACTG 5247 safety evaluations are important.
With an increasingly ageing HIV-infected population in the UK in the era of highly effective ART, it is important that we consider the best options available for preventing HZ reactivation in this group. In those with asymptomatic HIV infection on ART with higher CD4 counts, this may, in time, be the same standard of care afforded to HIV-uninfected subjects. For those who are more immunosuppressed, strategies such as the heat-treated zoster vaccine look promising and need further evaluation(5). In addition, it may be wise to ensure that effective clinical strategies are put in place for guaranteeing that those HIV-infected patients with more profound immune deficiency at the outset are, as their immune system reconstitutes in response to ART, given the option of receiving Zostavax® at the earliest possible “safe” opportunity.
Thushan de Silva
NIHR Academic Clinical Lecturer in Infectious Diseases & Microbiology
Consultant/honorary Professor in International Health
Professor/honorary consultant in Infectious Diseases
1. Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2008;57(RR-5):1-30; quiz CE2-4.
2. Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 2005;352(22):2271-84.
3. Benson C, Hua, L., Andersen, J., Jiang, J., Bozzolo, D., Bergstrom, K., Annunziato, P., Read, S., Pollard, R., Rusin, D. and Lennox, J. Zostavax is Generally Safe and Immunogenic in HIV+ve Adults Virologically Suppressed on ART: Results of a Phase 2 Randomised, Double-blind, Placebo-controlled Trial. 19th Conference on Retroviruses and Opportunistic Infections. Seattle, USA, 2012.
4. Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):309-18.
5. Mullane KM, Winston DJ, Wertheim MS, Betts RF, Poretz DM, Camacho LH, et al. Safety and immunogenicity of heat-treated zoster vaccine (ZVHT) in immunocompromised adults. J Infect Dis 2013;208(9):1375-85.
Competing interests: No competing interests