Measles Vaccine, HIV Infection, and Antiretroviral Therapy—A Window of Opportunity

Measles virus infection, a systemic rash illness commonly acquired in infancy and early childhood, is one of the most contagious infectious diseases in humans [1]. Measles is also an important cause of global morbidity and mortality, primarily among infants and children living in resource-limited settings [2]. Since the development of measles vaccines in the 1960s, intensive vaccination efforts, especially in the 21st century, have led to substantial reductions in measles-related deaths on a global scale, resulting in a reduction in mortality from almost 750 000 childhood deaths worldwide in 2000 to 164 000 in 2008 [3]. Eradication of measles infection on a global scale can, in theory, be accomplished because measles virus has no nonhuman reservoirs, and vaccination strategies to prevent transmission are available and feasible [4]. However, because of the highly contagious nature of measles virus, at least 95% vaccination coverage with at least 1 dose (and preferably 2 doses) of measles vaccine must be achieved to suppress and eventually eradicate continued global measles transmission [5]. One important characteristic of measles infection is that it produces more serious illness and increased mortality among immunocompromised individuals, primarily those with defects in T-cell immunity [6]. Because >90% of human immunodeficiency virus (HIV)–infected children live in regions where measles is still endemic [7, 8], achieving high rates of measles vaccine coverage is especially important among these populations to suppress excess measles-associated morbidity and mortality. However, live virus vaccines may also result in disease and, in general, are not recommended for administration to severely immunocompromised individuals. Measles vaccines are also known to induce short-term immunosuppressive effects and, therefore, the risk of further adverse events among HIV-infected infants and children is of concern. Moreover, it is well known that the immunogenicity of live virus vaccines, including measles vaccines, among HIV-infected children is limited and primarily related to degree of immunocompromise [9]. Knowledge gaps in understanding measles immunogenicity among HIV-infected children arise because the preponderance of studies regarding measles vaccine immunogenicity are derived from domestic settings, and generally from healthy infants and children. In contrast, data from resourcelimited settings rarely include populations of HIV-infected children, and may also be confounded by other factors, such as malnutrition and other environmental factors that may affect information about safety and immunogenicity of measles vaccines. In addition, the impact of HIV-related immunocompromise and subsequent effects of antiretroviral therapy (ART) on immune reconstitution and, ultimately, on vaccine immunogenicity are unclear. In this issue of the Journal, Abzug and colleagues describe the safety and immunogenicity of 1 or 2 measles vaccine booster doses administered to HIV-infected children, living in the United States, who had received at least 1 prior measles-mumps-rubella (MMR) vaccine, and after stable administration of ART [10]. They investigated the baseline and long-term humoral immunity to measles, as measured by measles plaque reduction neutralizing antibodies, among 193 HIV-infected children aged 2–18 years before and after 1 booster dose of measles vaccine administered at least 6 months after initiation of ART for HIV infection. Not surprisingly, the investigators found that baseline measles seroprotection was only 52%, as defined by measles neutralizing antibody levels ≥120 mIU/mL. However, after 1 booster dose of measles vaccine, seroprotective measles antibody titers increased to 89% eight weeks later, and were sustained in 80% of children 80 weeks after the booster. Among a subset of 65 children Received and accepted 9 April 2012; electronically published 12 June 2012. Correspondence: Yvonne Maldonado, MD, Department of Pediatrics, Stanford University School of Medicine, Rm G312, MC 5208, Stanford, CA 94305 (bonniem@stanford.edu). The Journal of Infectious Diseases 2012;206:466–8 © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/infdis/jis392