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Introduction: The prevention strategies for MTCT of HIV proposed by the World Health Organization (WHO) and other agencies have significantly reduced the number of infected children, child morbidity and mortality associated with HIV, and have improved maternal health. However, the detection rate of pregnant women with HIV in Brazil significantly increased in the last decade10. Objective: To evaluate factors that may interfere in mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Methods: A historical cohort study with a sample of 299 HIV-infected mothers and their newborns who delivered at the Obstetric Center of the Hospital de Clínicas de Porto Alegre, southern Brazil, from January 2010 to December 2014. Results: Of the 299 newborns of HIV-infected mothers, 3.7% (n = 11) were infected. Of those, 90.9% (n = 10) were born by cesarean section; 90.9% (n = 10) had ≥ 37 weeks; 54.6% (n = 6) received zidovudine starting within the first 4 hours after birth; and 45.4% (n = 5) received zidovudine and nevirapine. Four women whose newborns were infected with HIV had syphilis during pregnancy (36.4%). Poor adherence to highly active antiretroviral therapy (HAART) (p < 0.003), viral load ≥ 1000 copies/mL or ignored in the third trimester (p < 0.000), and CD4 count < 500 cells/mm3 in the third trimester (p < 0.046) were significantly associated with an increased risk of MTCT. Conclusions: Lack of control of risk factors may contribute to unfavorable rates of MTCT of HIV. [ABSTRACT FROM AUTHOR]