Varicella-Zoster Vaccines: Five Hot-Off-The-Press Do’s And Don’ts In The HIV Population

By: 

• Valerie Fenelus, PharmD Candidate
  College of Pharmacy, Nova Southeastern University
• Anthony Vasallo, PharmD Candidate
  College of Pharmacy, Nova Southeastern University
• Elizabeth Sherman, PharmD, AAHIVP
  College of Pharmacy, Nova Southeastern University
  South Florida, Southeast AETC

Varicella-zoster virus (VZV), also known as varicella or chickenpox, is a virus that can become latent and reactivate—it is then referred to as herpes zoster, or shingles. Varicella immunization is routine practice in the United States, but some patients may fall through gaps in care and won’t be immunized. Adult persons living with HIV (PLWH) have about a three-fold higher incidence of herpes zoster compared to the general population. (1) Virus reactivation can occur at any CD4 T lymphocyte (CD4) cell count, but the risk is higher with CD4 counts <200 cells/mm3. Therefore, disease prevention strategies in adults with HIV is of utmost importance. There are two available vaccines for the prevention of herpes zoster in adults: a live attenuated vaccine Zostavax® (ZVL) and a recombinant zoster vaccine Shingrix® (RZV). A live vaccine uses a weakened form of the germ that causes the disease while a recombinant vaccine uses genetic engineering to produce a specific piece of the pathogen (like its protein or capsid) to build an immune response. Recent data shed light on new strategies to reduce VZV incidence in adults with HIV. This article provides 5 important updates about VZV vaccines for clinicians managing the care of PLWH.

1. The US Department of Health and Human Services (DHHS) recommends Shingrix® in adults with HIV aged ≥50 years regardless of CD4 count to prevent herpes zoster

The US Department of Health and Human Services (DHHS) recently updated their recommendation to administer the recombinant zoster vaccine (RZV, Shingrix®) to all PLWH ≥50 years old regardless of CD4 count. (1) The approved vaccination schedule consists of one intramuscular (IM) injection dose at 0 and 2 months, for a total of two doses. However, the Advisory Committee on Immunization Practices (ACIP) has not yet recommended the use of Shingrix® in PLWH due to limited data on its use in this patient population.

2. One study supports the use of Shingrix® in PLWH

The DHHS recommendation is based on a Phase 1/2 randomized placebo-controlled study of 123 PLWH (median age was 46 years). (2) HIV-infected adults ≥18 years of age who received a diagnosis of HIV infection at least 1 year before enrollment were included in the study. Patients were divided into three groups: one group of 94 adults with HIV receiving a stable ART regimen for at least 1 year with CD4 count ≥200 cells/mm3 and HIV RNA <40 copies/mL; a second group of 14 adults receiving a stable ART regimen for at least 1 year with CD4 count <200 cells/mm3 (50–199 cells/mm3) and HIV RNA <40 copies/mL; and a third group of 15 ART-naïve adults with CD4 count ≥500 cells/mm3 and HIV RNA ≥1,000 and ≤100,000 copies/mL. Patients in the third group (ART-naïve) could not have received ART or be expected to start ART within the next 7 months.

Participants received three doses of Shingrix® at months 0, 2, and 6. Median cell-mediated immune response responses peaked after dose 2 of Shingrix® but did not increase further after 3. Vaccination was able to increase humoral and cell-mediated immunity after two doses (P<.0001), including in patients with CD4 < 200 cells/mm3. The most common adverse event reported was injection site pain (98.6%); the most common systemic adverse event reported was fatigue (75.3%). Incidence of increase in HIV RNA and decrease in CD4 count was reported in 4.1% of patients and 9.5% of patients, respectively (decrease in CD4 T-cell count was >30%). One case of herpes zoster was reported 83 days after the subject’s first and only vaccine dose.

Results from this small study suggest the vaccine is safe and immunogenic. Given the risk of herpes zoster is high among PLWH, DHHS recommends administration of Singrix® to PLWH aged ≥50 years regardless of CD4 count, following the same FDA-approved scheduled for patients without HIV (IM, at 0 and 2 months). It must be noted that patients enrolled in this study had CD4 of ≥50 cells/mm3.

3. Shingrix® is preferred over Zostavax® by DHHS for prevention of herpes zoster in persons with HIV aged ≥50 years due to enhanced efficacy and a potentially lower risk of infection

In Phase 3 clinical trials, Zostavax® demonstrated 70% efficacy at preventing herpes zoster in adults from the general population aged 50 to 59 years, but efficacy declined with age, to 38% among those aged ≥70 years. (5) In Phase 3 randomized, placebo-controlled clinical trials of 15,411 patients from the general population, Shingrix® efficacy against herpes zoster in vaccinated participants was 97.2% overall and 91.3% in those aged ≥70 years (P<0.001). (4) Additionally, Zostavax® is a live vaccine and Shingrix® is a recombinant vaccine. As a recombinant vaccine, Shingrix ® does not involve a complete pathogen. Instead, a piece of genetic material from the virus is inserted into other cells to produce large quantities of antigen to confer immunogenicity. Thus, the vaccine does not contain whole live virus. Given the enhanced efficacy of Shingrix® and the absence of live virus, experts prefer Shingrix® over Zostavax® in all patients aged ≥50 years including those with HIV.

4. DHHS does not recommend Shingrix® for persons aged <50 years with HIV infection

At this time, there is not enough information to determine the benefits and risks of Shingrix® in patients younger than 50 years of age. Consequently, there are no efficacy data to guide Shingrix® vaccination in PLWH aged <50 years, and the duration of protection is currently not known. Therefore DHHS does not recommend the use of Shingrix® for PLWH aged <50 years. (1)

5. If Shingrix® is not available or cannot be given because of allergy or intolerance, Zostavax® can be administered to PLWH with CD4 counts ≥ 200 cells/mm3

There are limited data available to support the use of Zostavax® in PLWH with CD4 ≥ 200 cells/mm3. A randomized, double-blind, placebo-controlled trial of a 2-dose schedule of Zostavax® (day 0, week 6) was conducted in 395 PLWH with virologic suppression on ART and CD4 ≥ 200 cells/mm3. At 12-weeks post vaccination, VZV antibody titers and cell-mediated immunity had increased and no vaccine-strain herpes zoster cases were reported. (3) DHHS recommend Zostavax® use in PLWH with CD4 ≥ 200 cells/mm3 if Shingrix® is not available or cannot be given because of allergy or intolerance. The FDA-approved dose schedule for Zostavax® is one dose, one time only. It should be noted however, that Zostavax® is contraindicated in patients with HIV and CD4 < 200 cells/mm3 given concerns about the potential for disseminated vaccine strain infection due to the live nature of the vaccine. (1)