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Infectious Morbidity, Mortality and Nutrition in HIV-exposed, Uninfected, Formula-fed Infants

Results From the HPTN 040/PACTG 1043 Trial

Yeganeh, Nava, MD*; Watts, D. Heather, MD; Xu, Jiahong, PhD; Kerin, Tara, PhD*; Joao, Esau C., MD§; Pilotto, Jose Henrique, MD; Theron, Gerhard, MD; Gray, Glenda, MD**; Santos, Breno, MD††; Fonseca, Rosana, MD‡‡; Kreitchmann, Regis, MD§§; Pinto, Jorge, MD¶¶; Mussi-Pinhata, Marisa M., MD‖‖; Veloso, Valdilea, MD***; Camarca, Margaret, RN; Mofenson, Lynne, MD†††; Moye, Jack, MD‡‡‡; Nielsen-Saines, Karin, MD*

The Pediatric Infectious Disease Journal: December 2018 - Volume 37 - Issue 12 - p 1271–1278
doi: 10.1097/INF.0000000000002082
HIV Reports

Background: HIV-exposed uninfected (HEU) infants are a growing population with potentially poor health outcomes. We evaluated morbidity and mortality in HEU formula-fed infants enrolled in the NICHD HPTN 040/PACTG 1043 trial.

Methods: Infectious morbidity, mortality and undernutrition were evaluated within a cohort of 1000 HEU infants enrolled between April 2004 and April 2010 in Brazil (n = 766) and South Africa (n = 234) as part of the NICHD/HPTN 040 trial of 3 different antiretroviral regimens to decrease intrapartum HIV vertical transmission.

Results: Twenty-three percent of infants had at least 1 infectious serious adverse effect. Infants born to mothers with <12 years of education [adjusted odds ratio (AOR), 2.6; 95% confidence interval [CI], 1.2–5.9), with maternal viral load of >1,000,000 copies/mL at delivery (AOR, 9.9; 95% CI, 1.6–63.1) were more likely to have infectious serious adverse effects. At 6 months, the infant mortality rate per 1000 live births overall was 22 ± 2.6, 9.1 ± 1.8 in Brazil and 64.1 ± 3 in South Africa. Undernutrition and stunting peaked at 1 month of age with 18% having a weight-for-age Z score ≤−2, and 22% with height for Z score ≤−2. The likelihood of infant mortality was greater among infants born in South Africa compared with Brazil (AOR, 6.2; 95% CI, 2.5–15.8), high maternal viral load (AOR, 1.7; 95% CI, 1.01–2.9) and birth weight-for-age Z score ≤−2 (AOR, 5.2; 95% CI, 1.8–14.8).

Conclusions: There were high rates of undernutrition, stunting and infectious serious adverse effect in this study’s formula-fed HEU population. Suppressing maternal HIV viral load during the peripartum period may be a modifiable risk factor to decrease infant mortality.

From the *David Geffen UCLA School of Medicine, Los Angeles, California

Office of the Global AIDS Coordinator and Health Diplomacy, US Department of State, Washington, District of Columbia

Westat, Rockville, MD

§Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil

Hospital Geral de Nova Iguaçu, Nova Iguaçu and Laboratório de AIDS e Imunologia Molecular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, (Fiocruz), Rio de Janeiro, Brazil

Perinatal HIV Research Unit, Stellenbosch University/Tygerberg Hospital, Cape Town, South Africa

**University of Witwatersrand/Chris Hani Baragwanath Hospital, Johannesburg, South Africa

††Hospital Conceicao, Porto Alegre, Rio Grande do Sul, Brazil

‡‡Hospital Femina, Porto Alegre, Rio Grande do Sul, Brazil

§§Irmandade da Santa Casa de Misericordia de Porto Alegre, Rio Grande do Sul, Brazil

¶¶Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

‖‖Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

***Laboratório de Pesquisa Clínica em DST e AIDS - Instituto de Pesquisa Clínica Evandro Chagas - Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil

†††Elisabeth Glaser Pediatric AIDS Foundation, Washington, District of Columbia

‡‡‡Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Accepted for publication March 15, 2018.

The trial is registered with (registration number: NCT00099359).

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) HPTN 040 study was supported by NICHD contract number HHSN267200800001C (NICHD control number N01-HD-8-0001) and U01 AI047986 (Brazilian AIDS Prevention Trials International Network), National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH). N.Y. received funding from the NIAID (K23 AI118584). Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the NIAID (U01 AI068632), the NICHD and the National Institute of Mental Health (NIMH) [AI068632]. In addition, the study was supported in part by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI), and GlaxoSmithKline on behalf of ViiV Healthcare. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors and were fully responsible for all aspects of manuscript development. BIPI and GlaxoSmithKline were given the opportunity to check the data used in the present manuscript for factual accuracy only. Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) was provided by the NIAID of the NIH under award numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC) and UM1AI106716 (IMPAACT LC), with co-funding from the Eunice Kennedy Shriver NICHD and the NIMH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH nor the US Department of State. The authors have no other funding or conflicts of interest to disclose.

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Address for correspondence: Nava Yeganeh, MD, MPH, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA. E-mail:

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