Immunogenicity, immunologic memory, and safety following measles revaccination in HIV-infected children receiving highly active antiretroviral therapy

Abstract

Background: Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)-infected children in the absence of highly active antiretroviral therapy (HAART).

Methods: HIV-infected children 2 to <19 years old receiving HAART and with HIV loads <30,000 copies/mL, CD4% ≥15, and ≥1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN). A subset was given another MMR 4-5 years later, and PRN antibody was measured before and 7 and 28 days later.

Results: At entry, 52% of 193 subjects were seroprotected (PRN ≥120 mIU/mL). Seroprotection increased to 89% 8 weeks postvaccination, and remained at 80% 80 weeks postvaccination. Of 65 subjects revaccinated 4-5 years later, 85% demonstrated memory based on seroprotection before or 7 days after vaccination. HIV load ≤400 copies/mL at initial study vaccination was associated with higher seroprotection rates, greater antibody concentrations, and memory. Grade 3 fever or fatigue occurred in 2% of subjects.

Conclusions: Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression.

Clinical trials registration: NCT00013871 (www.clinicaltrials.gov).

Figure 1.

P1024 geometric mean concentration (GMC) according to immunologic strata. GMCs of measles neutralizing antibody are shown at each P1024 study visit for all subjects combined and according to immunologic stratum. The GMC of stratum 4 was higher than that of strata 2 and 3 at entry (P < .001); differences among strata were not significant after study MMR vaccination, administered at study week 16. Time point 0 on the x-axis reflects the GMC of serum samples obtained at entry. Eight, 32, and 80 weeks postvaccination correspond to study weeks 24, 48, and 96, respectively. Abbreviations: Ndr, nadir; Scr, screening.

Figure 2.

P1024 proportion of subjects with antibody concentration ≥120 mIU/mL according to P1024 HIV RNA group and P1024 geometric mean concentration (GMC) according to P1024 HIV RNA group. Proportion of subjects with protective measles neutralizing antibody concentrations (top panel, A) and GMCs of measles neutralizing antibody (bottom panel, B) are shown at each P1024 study visit according to P1024 HIV viral load group. The proportion with protective (≥120 mIU/mL) antibody concentrations was higher for subjects with ≤400 copies/mL than for each of the other viral load groups at each time point after study MMR vaccination, administered at study week 16. The GMC of subjects with a viral load ≤400 copies/mL was higher than that of subjects with a viral load >5000 copies/mL at entry (P = .004) and higher than that of each of the other 2 viral load groups at each time point after study MMR vaccination (P ≤ .004). Time point 0 on the x-axis reflects results of serum samples obtained at entry. Eight, 32, and 80 weeks postvaccination correspond to study weeks 24, 48, and 96, respectively. Bars represent 95% confidence intervals.

Figure 3.

P1061s geometric mean concentration (GMC) according to immunologic strata. GMCs of measles neutralizing antibody are shown at each P1061s study visit for all subjects combined and according to immunologic stratum. A trend toward higher GMCs with increasing stratum was present at P1061s entry and day 7, but differences were not significant. MMR vaccine was administered on P1061s day 0.

Figure 4.

P1061s geometric mean concentration (GMC) according to P1024 HIV RNA group. GMCs of measles neutralizing antibody are shown at each P1061s study visit for all subjects combined and according to HIV viral load ≤400 copies/mL vs >400 copies/mL at the P1024 MMR visit. The GMC of subjects with a viral load ≤400 copies/mL was higher than that of subjects with a viral load >400 copies/mL at P1061s entry and day 7. MMR vaccine was administered on P1061s day 0.