HIV RNA Suppression Among HIV-Infected Ugandan Children With Measles

Publisher Website
Google Scholar
Abstract
To the Editor: In the course of HIV disease, coincident infections by several agents have been associated with transient increases in plasma HIV RNA levels,1 but only a few, such as scrub typhus (Orientia tsutsugamushi),2 have been associated with transient decreases. Low plasma HIV RNA levels during measles virus infection were first noted by Moss et al3 in a cross-sectional study of hospitalized Zambian children. When a recent measles outbreak occurred among HIV-infected children participating in a longitudinal observational cohort, we evaluated HIV RNA levels before, during, and after the measles episode. Because measles virus can elicit an immune response without manifesting the classic clinical syndrome,4 we also sought to determine whether such “subclinical” measles infection caused changes in plasma HIV RNA levels in this cohort. Finally, we evaluated HIV RNA levels among children without measles who received live-attenuated measles vaccine. From October 2005 through September 2006, 300 HIV-infected children aged 1 to 10 years were enrolled into the Children with HIV and Malaria Project (CHAMP) from a dedicated pediatric HIV clinic at Mulago Hospital, Kampala, Uganda.5 The guardians of all children provided informed consent. The research was approved by the Uganda National Council of Science and Technology, the Makerere University Research and Ethics Committee, and the University of California, San Francisco Committee on Human Research and was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2000. Children with clinical measles were identified from the study clinic from June through December 2006. The World Health Organization (WHO) criteria of fever ≥38.0°C and maculopapular rash with cough, coryza, and/or conjunctivitis were used as our case definition of measles.6 To identify cases of subclinical measles infection, dried blood spots (DBSs) that had been routinely collected from a convenience sample of 94 participants were screened for measles immunoglobulin M (IgM). To determine if vaccination affected HIV RNA level, the children who had routine laboratory tests coincidentally obtained in the 14-day period following measles vaccination (Sanofi Pasteur, Lyon, France) were retrospectively identified. Plasma HIV RNA (Roche Amplicor Version 1.5 [level of detection of 400 copies/mL] Pleasanton, CA), absolute CD4 cell count, CD4 percent (CD4%), and total lymphocyte count were determined routinely at 12-week intervals and additionally obtained at the time of clinical presentation. DBSs were tested for measles antibodies using Measles Enzygnost ELISA IgM Kits (Dade Behring, Marburg, Germany); the kit protocols were modified for use with DBSs, as per Riddell et al,7,8 yielding qualitative results of negative, equivocal, and positive for the presence of antibodies. For all statistical analyses, the log transformation of plasma HIV RNA (log10 [copies/mL]) was used. To determine the acute change in plasma viral load, the HIV RNA level during measles was subtracted from the HIV RNA level obtained at the most recent preceding visit; these acute changes in HIV RNA level were then tested against the null hypothesis of no change, using the nonparametric Wilcoxon signed rank test. To determine if this acute change with measles differed from normal variation in HIV RNA level, a list of the changes in HIV RNA level between sequential visits on which participants reported no illness was generated from all available CHAMP data, randomly selecting 1 value per participant. The median changes with measles were then compared with the median changes between these routine visits, using the nonparametric Wilcoxon 2-sample test. To determine if the HIV RNA set point changed as a result of measles illness, the most recent HIV RNA level from before measles illness was subtracted from the first level available after the resolution of illness.