CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

801LB Cotrimoxazole and Reduced Infectious Morbidity in HIV-Exposed Uninfected Infants Nicole L. Davis 1 ; JeffreyWiener 2 ; Sascha Ellington 2 ; Charles Chasela 3 ; Dumbani Kayira 4 ; Michael Hudgens 5 ; Charles van der Horst 5 ; Denise Jamieson 2 ; Athena P. Kourtis 2 1 US Cntrs for Disease Control and Prevention, Atlanta, GA, USA; 2 CDC, Atlanta, GA, USA; 3 Univ of the Witwatersrand, Johannesburg, South Africa; 4 Univ of North Carolina Project Malawi, Lilongwe, Malawi; 5 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: Diarrhea and respiratory infections are among the leading causes of global morbidity and mortality in young children, with HIV-exposed infants at increased risk. Cotrimoxazole prophylaxis (CPT) may reduce such morbidity in the growing population of HIV-exposed, uninfected infants. Methods: A cohort study was conducted using data from the Breastfeeding, Antiretrovirals and Nutrition (BAN) clinical trial (conducted 2004-2010, Malawi) to assess the association of CPT with respiratory and diarrheal morbidity. All HIV-exposed infants in the BAN trial began receiving CPT (240 mg once daily) in June 2006, in accordance with WHO and Malawi guidelines, from 6-36 weeks of age or until weaning occurred and HIV infection was ruled out. We included all infants who were HIV-uninfected at 8 weeks of age (n=1984). CPT was treated as a time-varying exposure, with infants attending BAN study visits prior to June 2006 considered CPT-unexposed. Outcomes included all documented diarrhea or respiratory infection events occurring from 8-48 weeks of age; events occurring more than two weeks apart were treated as separate events. Conditional gap-time proportional hazards models were used to estimate associations between CPT and diarrheal or respiratory morbidity from 8-48 weeks of age. Results: A total of 1984 infants contributed 1414 person-years (PY) of follow-up (CPT-unexposed: 260 PY, CPT-exposed: 1154 PY). CPT-exposed infants experienced 5.32 respiratory events and 2.87 diarrhea events per 100 person-weeks. The incidence rate of respiratory and diarrheal morbidity among CPT-unexposed infants was 8.09 and 4.39 per 100 person-weeks, respectively. CPT was associated with a 36% relative reduction in respiratory morbidity and a 41% relative reduction in diarrheal morbidity (respiratory HR 0.64, 95%CI 0.60-0.69; diarrheal HR 0.59, 95% CI 0.54-0.65). Adjustment for rainy season (Nov-Mar) and randomization arm resulted in similar findings. Conclusions: CPT was associated with a significant reduction in respiratory and diarrheal morbidity in HIV-exposed, uninfected infants. We have previously shown CPT to also be associated with reduced risk of both clinical and asymptomatic malaria, severe infectious morbidity, and mortality in HIV-exposed, uninfected infants in Malawi. CPT may have an important role to play in reducing the leading global causes of morbidity and mortality in the growing population of HIV-exposed, uninfected infants in malaria-endemic resource- limited settings. 802 HIV-Exposed Children Account for More Than Half of 24-Month Mortality in Botswana Rebecca Zash 1 ; Jean Leidner 2 ; Sajini Souda 3 ; Kelebogile Binda 4 ; Heather J. Ribaudo 5 ; Sikhulile Moyo 6 ; Kathleen Powis 7 ; Joseph Makhema 4 ; Shahin Lockman 8 ; Roger L. Shapiro 5 1 Beth Israel Deaconess Med Cntr, Boston, MA, USA; 2 Goodtables Consulting, Oklahoma, OK, USA; 3 Univ of Botswana, Gaborone, Botswana; 4 Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana; 5 Harvard Sch of PH, Boston, MA, USA; 6 Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana; 7 Massachusetts General Hosp, Boston, MA, USA; 8 Brigham and Women’s Hosp, Harvard Med Sch, Boston, MA, USA Background: The relative contribution of HIV-exposure and HIV-infection to childhood mortality in a programmatic setting with widespread antiretroviral treatment (ART) use in pregnancy is not well described. Methods: FromMarch 2012-March 2013, women and their children were enrolled within 48 hours of delivery in 5 geographically diverse government-run postpartumwards in Botswana. Maternal obstetric and medical history, demographics and socioeconomic status were collected at enrollment. Women were interviewed every 1-3 months for 24 months by phone (or home visit if not reachable) to assess child HIV status, feeding modality, food security and child and maternal mortality. Mothers and children received all care, including ART, through the government health system. Child feeding was according to Botswana guidelines. Risk factors for 24-month survival were assessed by Cox proportional hazard modeling. Results: A total of 3000 women (1499 HIV-infected) and their 3033 children (1515 HIV-exposed) were enrolled. Among HIV-infected women, 58%were on ART, 23% on zidovudine (ZDV) alone, 11% received no ARVs during pregnancy, and 8%were unknown. Incidence of Mother-to-child HIV transmission (MTCT) was 2.1% through 24 months. Vital status at 24 months was known for 3018 (99.5%) children and there were 106 (3.5%) deaths overall. Mortality differed by HIV exposure status (Figure 1): 12 (38%) among HIV-infected, 70 (4.7%) among HIV-exposed uninfected (HEU), and 24 (1.6%) among HIV-unexposed uninfected (HUU). The only independent risk factors for mortality in adjusted analysis were child HIV-infection (aHR 22.6, 95%CI 10.7, 47.5%), child HIV-exposure (aHR 2.7, 95% CI 1.7,4.5) and maternal death (aHR 7.7, 95%CI 1.9,31.9). Although the risk of replacement feeding was significant when modeled separately from HIV-exposure status (aHR 2.3, 95% CI 1.5, 3.6), feeding and HIV-exposure status were co-linear (99.7% of HIV-unexposed but only 13% of HIV-exposed children breastfed) and could not be modeled together. Given 26% HIV prevalence among pregnant women in Botswana, more than half of all 24-month child mortality is accounted for by HEU (46%) plus HIV-infected (8%) children. Conclusions: In a programmatic setting with widespread maternal and child ART availability, HIV-exposed children contribute approximately half the overall deaths at 24 months. Lack of breastfeeding could not be assessed independently of HIV-exposure status, but was a likely contributor to excess mortality among HEUs.

Poster Abstracts

803 Mortality Risk AssociatedWith Preterm and SGA Stratified by Maternal HIV Status Ayesha Sania 1 ; Emily Smith 2 ;WafaieW. Fawzi 2 1 ICAP, Columbia Univ Mailman Sch of PH, New York, NY, USA; 2 Harvard Sch of PH, Boston, MA, USA

Background: Preterm and small-for-gestational-age (SGA), two distinct biological processes leading to low birth weight (LBW), are associated with increased risk of mortality during infancy. The risk of mortality due to these conditions among vulnerable populations such as HIV exposed infants are yet to be estimated. Using the recent intergrowth standard to define SGA, we have evaluated the relative risk of mortality due to preterm and SGA in Tanzania, stratified by maternal HIV status. Methods: Data from five individually randomized trials of multivitamins were pooled. Of the cohorts, two enrolled HIV-positive pregnant women, two enrolled HIV-negative women and one included both HIV-negative and positive women. Preterm birth (gestational age <37 weeks) was defined using date last menstrual period, and SGA (birthweight <10th percentile for gestational age) was defined using the recently published intergrowth standard. We used Cox proportional hazard models to estimate the risk of mortality. Effect modification by maternal HIV status was assessed using the likelihood ratio test.

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CROI 2016