Safety and immunogenicity of early measles vaccination in children born to HIV-infected mothers in the United States: results of Pediatric AIDS Clinical Trials Group (PACTG) protocol 225

Abstract

BACKGROUND.: ACTG (Pediatric AIDS Clinical Trials Group) 225, a multicenter, randomized, open-label trial in the United States evaluated reactogenicity and immunogenicity of 2 vaccination regimens: monovalent measles vaccine (Attenuvax) at 6 months of age and measles, mumps, and rubella, live attenuated (MMRII) vaccine at 12 months of age (2D), or only MMRII at 12 months of age (1D) in human immunodeficiency virus-infected (HIV-infected) (POS) and uninfected (NEG) children in the pre-highly active antiretroviral therapy (pre-HAART) period.

Methods: Plaque-reduction neutralization (PRN) of measles-neutralizing antibody titers were evaluated at study weeks 0, 6, 26, 32, 52, and 130 (∼3 years of age).

Results: The 110 subjects included: 65 2DNEG; 30 1DNEG; 7 2DPOS and 8 1DPOS. Vaccinations (n=175) were associated with no adverse experiences >Grade 2 except for Grade 3 fever (n=2, 1 1DPOS and 1 1DNEG). Six weeks after Attenuvax, all 2DPOS subjects (7/7) seroresponded (PRN titers ≥120 mIU/mL) with median titers significantly exceeding 2DNEG titers (2115 vs 628 mIU/mL, respectively; P=.023). At ∼3 years of age, 67% 1DPOS (4/6) and 83% 2DPOS (4/5) subjects maintained titers ≥120 mIU/mL. Prevaccination titers ≥25 mIU/mL among 2DNEG subjects correlated inversely with the likelihood of achieving titers ≥120 mIU/mL (56% vs 90%; P=.004).

Conclusions: Among HIV-infected children pre-HAART, Attenuvax at 6 months was well tolerated and immunogenic. These data support the current World Health Organization (WHO) recommendation to administer a first dose of measles vaccine at 6 months of age to HIV-infected children.

© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Figures

Figure 1.

HIV-infected (POS) and uninfected (NEG) children in PACTG Study 225 were randomized to 1 of 2 measles vaccine regimens: 2D children were given monovalent measles vaccine at 6 months of age (study week 0) followed by MMRII vaccine at 12 months of age; 1D children were only given MMRII at 12 months of age. Subjects were followed through 3 years of age (study week 130). The proportion with follow-up by study week for each group is shown: the inserted table shows the numbers of censored (follow-up <130 weeks) and uncensored (follow-up ≥week 130) subjects in each group and the median time for follow-up. PACTG indicates Pediatric AIDS Clinical Trials Group; MMRII, measles, mumps, and rubella, live attenuated.

Figure 2.

Plasma HIV RNA viral load measurements (HIV-RNA log10 copies/mL) pre- and postvaccination were available for 10 subjects enrolled in PACTG Study 225. Panel A shows the results for 5 2DPOS vaccinees given monovalent measles vaccine at 6 months of age (subjects 1, 2, 3, 4, and 5). Panel B shows the results following MMRII immunization at 12 months of age for 2 2DPOS vaccinees (subjects 3 and 4) and 3 1DPOS vaccinees (subjects 6, 7, and 8). Solid lines represent the pre- and postvaccination HIV RNA load for each subject. Dashed lines in each figure represent the median HIV RNA load for each group. The mean interval between pre- and postvaccination viral load measurements was 59 days after vaccination at 6 months of age, and 112 days after vaccination at 12 months of age. Plasma HIV RNA viral loads were measured using Amplicor assay (Roche Diagnostics) as previously described with a minimum detection level of 400 RNA copies per mL. The y-axis scale for Panel A differs from that of Panel B. HIV indicates human immunodeficiency virus; PACTG, Pediatric AIDS Clinical Trials Group.

Figure 3.

HIV-infected (POS) and uninfected (NEG) children enrolled in PACTG 225 were randomized to 1 of 2 measles vaccine regimens: 2D children were given monovalent measles vaccine at 6 months of age (study week 0) followed by MMRII vaccine at 12 months of age (study week 26); 1D children were only given MMRII at 12 months of age only. Subjects were followed until ∼3 years of age (study week 130). Measles PRN titers were measured in parallel with the Measles International Reference Serum (WHO 66/202) and are expressed in mIU/mL with a titer of 1:8 equivalent to 8 mIU/mL in this assay. Panel A shows pre- and postvaccination measles PRN titers. Bars marked with an asterisk (*) designate the proportion of study subjects with measles PRN titers ≥25 mIU/mL. Bars not marked with an asterisk represent PRN titers ≥120 mIU/mL at study weeks 6, 16, 26, 32, 42, 52, 104, and 130 by treatment group. Panel B is a further analysis of the study week 6 postdose 1 data for 2DNEG subjects only and shows the percent of seroresponders (PRN titer ≥120 mIU/mL) stratified by prevaccination titer ≥25 mIU/mL or <25 mIU/mL. PACTG indicates Pediatric AIDS Clinical Trials Group; MMRII, measles, mumps, and rubella, live attenuated; WHO, World Health Organization; PRN, plaque reduction neutralization.