Changes in Measles Serostatus Among HIV-Infected Zambian Children Initiating Antiretroviral Therapy Before and After the 2010 Measles Outbreak and Supplemental Immunization Activities

Measles remains an important cause of child mortality despite an effective vaccine that protects approximately 85% of recipients after a single dose at 9 months of age [1]. Over the past decade, the Measles and Rubella Initiative and partners dedicated resources to reduce measles incidence and mortality. This effort proved largely successful in Africa where the number of reported measles cases declined >90% between 2001 and 2008 [2]. In 2010, however, large measles outbreaks occurred throughout sub-Saharan Africa that continued through 2011 [3, 4], underscoring the importance of maintaining high levels of population immunity and surveillance activities. Children born to women infected with human immunodeficiency virus (HIV) have lower concentrations of maternal antibodies to measles virus [5, 6] and are at increased risk of measles at younger ages [7]. Measles-containing vaccine is recommended at 9 months of age in countries with circulating measles virus and may be administered as young as 6 months of age to HIV-infected children who are not severely immunosuppressed [8]. HIV infection, however, can adversely impact immune responses to measles vaccine [9]. A meta-analysis indicated that fewer HIV-infected children responded to measles vaccination at 9 and 12 months of age compared to uninfected children [10], and antibody levels to measles virus waned over 2–3 years in children infected with HIV [11]. In addition to quantitative differences, the quality of antibody responses to measles virus is impaired in HIV-infected children. Antibody avidity, a functional measure of a mature B-cell response that is correlated with the development of long-lived antibody-secreting plasma cells, decreased 3 months following measles vaccination in HIV-infected Zambian children [12]. Prior to the availability of highly active antiretroviral therapy (HAART), high rates of HIV-related mortality maintained a low proportion of HIV-infected children susceptible to measles virus infection. However, with the rapid scale-up of HAART, HIV-related mortality has declined [13], allowing for accumulation of measles-susceptible HIV-infected children [14]. Antibodies to multiple vaccine-preventable diseases, including measles, are frequently below protective levels in children receiving HAART [15], suggesting that revaccination may be needed to maintain high levels of population immunity. Additionally, cellular reconstitution of HIV-infected children after HAART initiation likely occurs via a predominance of naive T lymphocytes, with only a small contribution through expansion of memory lymphocytes [16]. To evaluate the effect of HAART and revaccination on measles immunity, we measured immunoglobulin G (IgG) antibody levels to measles virus in HIV-infected Zambian children initiating HAART before and after the 2010 measles outbreak and supplemental immunization activities (SIAs).