CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

endpoint using real-time quantitative PCR and serology in stored specimens. Timing of CMV infection was compared between arms using Kaplan Meier and Cox proportional hazards models. In utero transmission was defined as CMV DNA detection within 2 weeks of birth and intrapartum transmission was defined as first CMV detection between 2 and 6 weeks. Non-breastfeeding transmissions were defined as those with first CMV DNA detection after the 6-week study visit in FF infants, and infections through breast milk were estimated as the excess infections between the BF and FF infants after the 6-week study visit. Results: A subset of 138 infants randomized to breastfeed and 134 randomized to formula feed were assessed for CMV infection. Baseline characteristics including maternal HIV disease status and sociodemographics were similar between arms. BF infants acquired CMV at an earlier median age (4.26 months, SD=0.97) than FF infants (9.87 months, SD=1.27; log rank p<0.001) and the probability of infection by 1 year was 0.89 (SD=0.03) in the BF and 0.69 (SD=0.05) in the FF infants (p<0.001; Figure). Overall, breastfeeding was associated with a 1.67-fold increased risk of infant CMV infection (hazard ratio (HR): 1.67, 95% CI: 1.24-2.23, p=0.001) and was independent of infant HIV infection status (multivariate HR: 1.61, 95% CI: 1.20-2.16, p=0.002). Among BF infants assessed over 1 year, we estimated 9% of CMV infections occurred in utero, 23% intrapartum, 36% through breastfeeding, and 31% through non-breast milk postpartummodes such as saliva and urine.

Conclusions: More than a third of CMV infections in BF infants of HIV-infected mothers occur through breast milk transmission. Vaccine strategies for this population will need to consider the very high rate of transmissions during the first months of life. 885 Is the Prevalence of M. tuberculosis Infection Higher in HIV-Exposed Children? Palwasha Y. Khan 1 ; Katherine L. Fielding 1 ; Dominic Mulawa 2 ; Regina Chiumya 2 ;Themba Mzembe 2 ; Olivier Koole 1 ; Judith R. Glynn 1 ; Amelia C. Crampin 1 1 London School of Hygiene and Tropical Medicine, London, United Kingdom; 2 Karonga Prevention Study, Karonga, Malawi Background: The effect of HIV exposure on the risk of Mycobacterium tuberculosis (M.tb) infection and tuberculosis (TB) in children is not well understood. HIV-exposed uninfected children have an increased risk of morbidity and mortality in sub-Saharan Africa. In high HIV/TB burden settings increased susceptibility and/or exposure to M.tb in children born to HIV-positive mothers may contribute to ill health despite PMTCT. Study hypothesis: Prevalence of M.tb infection is higher in HIV-exposed children compared to HIV-unexposed Methods: Setting: Demographic surveillance site, northern Malawi. Adult HIV prevalence ~8% Eligibility: Children aged 2 to 5 years Dates: January 2012 - July 2014 Design and procedures: Cross-sectional study of tuberculin skin testing (TST) (2TU of purified protein derivative RT23). A positive TST was defined as induration ≥ 15mm. Maternal HIV sero-status, BCG vaccination, household socio-economic status, household contact with a TB case and smear-positive TB notification data were available from related studies. Children whose mothers were known to be HIV-positive at the time of delivery were defined as HIV-exposed. Children <2 years were not included to minimise misclassification due to BCG-attributable induration. Results: 3707 children were eligible, of whom 3302 (89.0%) were enrolled. Of these, 3296 had a TST placed and read within 48-72hrs. 106 (3.2%) had a TST ≥ 10mm and 35 (1.1%) had a TST ≥ 15mm. 92/3296 (2.8%) of children were classified as HIV-exposed and 469 (14.2%) had unknown HIV exposure status. Documented BCG vaccination date was available for 2673 (81.1%). See table. Random effects logistic regression analysis showed that the odds of a positive TST was 4 times higher in children who had been exposed to HIV before birth, adjusting for age and community M.tb exposure [aOR 4.1 (1.2 – 14.0, p=0.024)].

Poster Abstracts

Table showing univariable and multivariable analysis of risk factors associated with TST positivity

533

CROI 2015