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Risk Factors for Adverse Birth Outcomes in the PROMISE 1077BF/1077FF Trial

Sebikari, Dorothy MBChB, MPHa; Farhad, Mona MSb; Fenton, Terry EdDb; Owor, Maxensia MBChBa; Stringer, Jeffrey S. A. MDc; Qin, Min PhDb; Chakhtoura, Nahida MDd; Chi, Benjamin H. MD, MScc; Saidi, Friday MBBSe; Nevrekar, Neetal MDf; Violari, Avy MDg; Chipato, Tsungai MBChB, MCEh; McIntyre, James A. MBChB, FRCOGi,j; Moodley, Dhayendre PhDk; Taha, Taha E. MBBS, MCM, MPH, PhDl; Theron, Gerhard MDm; Fowler, Mary Glenn MD, MPHn

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 15, 2019 - Volume 81 - Issue 5 - p 521–532
doi: 10.1097/QAI.0000000000002072
Prevention Research

Background: In the multicountry PROMISE 1077BF/1077FF trial, the risk of low birth weight (LBW; <2500 g) and preterm delivery (PTD; <37 weeks) was significantly higher among women initiating a protease inhibitor–based antiretroviral treatment (ART) regimen than those receiving ZDV alone. Among those assigned to a protease inhibitor regimen, tenofovir/emtricitabine was associated with the more severe outcomes of very LBW (<1500 g) and very PTD (<34 weeks) compared with zidovudine/lamivudine.

Methods: We used multivariate logistic regression to further explore these treatment findings, taking into account demographic baseline clinical and postentry obstetrical factors. We evaluated individual adverse outcomes and composites that included stillbirth and early loss/spontaneous abortion.

Results: Among 3333 women delivering at least 1 live infant, median maternal age at enrollment was 26 years; 661 (20%) were primiparous, and 110 (3.3%) reported at least 1 previous PTD. Seventeen percent of newborns were LBW, 1% were very LBW, 17% had PTD, and 3% had very PTD. Treatment allocation remained strongly associated with multiple adverse outcomes after controlling for other risk factors with both ART regimens exhibiting increased risk relative to ZDV alone. Other risk factors remaining significant in at least one of the multivariate models included the following: country, gestational age at entry, maternal age, maternal body mass index, previous PTD, history of alcohol use, baseline HIV viral titer, multiple gestation, and several obstetric risk factors.

Conclusions: ART effects on adverse pregnancy outcomes reported in the randomized PROMISE trial remained strongly significant even after controlling for demographic, baseline clinical, and obstetrical risk factors, which were also associated with these outcomes.

aClinical Department, Makerere University—Johns Hopkins University Research Collaboration, Kampala, Uganda;

bHarvard T.H. Chan School of Public Health, Center for Biostatistics in AIDS Research, Boston, MA;

cDepartment of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC;

dNational Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Maternal and Paediatric Infectious Diseases Branch, Bethesda, MD;

eDepartment of Obstetrics and Gynaecology, University of North Carolina (UNC) Project Lilongwe, Lilongwe, Malawi;

fClinical Research Department, Byramiee Jeeieebhoy Government Medical College, Pune, India;

gPerinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;

hDepartment of Obstetrics and Gynecology, University of Zimbabwe, Harare, Zimbabwe;

iAnova Health Institute, Johannesburg, South Africa;

jDivision of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, South Africa;

kDepartment of Obstetrics and Gynecology, School of Clinical Medicine, Centre for AIDS Research in South Africa, University of KwaZulu Natal, Durban, South Africa;

lDepartment of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD;

mDepartment of Obstetrics and Gynecology, Stellenbosch University, Cape Town, South Africa; and

nDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.

Correspondence to: Dorothy Sebikari, MBChB, Makerere University—Johns Hopkins University Research Collaboration, Upper Mulago Hill Road, P.O. Box 23491, Kampala, Uganda (e-mail:

Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC), and UM1AI106716 (IMPAACT LC), with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Additional investigator support was also provided by NIAID (K24 AI120796). The study products for the PROMISE 1077BF/1077FF trial were provided free of charge by Abbott/Abbvie, Gilead Sciences, Boehringer Ingelheim, and GlaxoSmithKline/Viiv with the exception of some nevirapine that was purchased at a discounted rate by a contractor to the Eunice Kennedy Shriver National Institute of Child Health and Human development for use in the trial. None of the pharmaceutical companies had any role in the trial design, data collection, data analysis, or manuscript writing.

M.F. owns some Gilead stocks, and J.A.M. reports grants during the conduct of the study. The remaining authors have no conflicts of interest to disclose.

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Received November 20, 2018

Accepted March 27, 2019

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