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      Pregnancy outcomes among HIV-infected women who conceived on antiretroviral therapy

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          Abstract

          As antiretroviral therapy (ART) expands in resource-limited settings, understanding the impact of ART on pregnancy outcomes is critical. We analyzed women who became pregnant on ART while enrolled in a clinical trial (HPTN 052, ACTG A5208, and ACTG A5175); the majority of women were from Africa, with a median age of 29 years. Eligible women were on ART at conception and had a documented date of a last menstrual period and a pregnancy outcome. The primary outcome was non-live birth (stillbirth; spontaneous abortion; elective termination; or ectopic pregnancy) versus live birth. Preterm birth (<37 weeks completed gestation) was a secondary outcome. We used Cox proportional hazards regression models with time-varying covariates. 359 women became pregnant, of whom 253 (70%) met inclusion criteria: 127 (50%) were on NNRTI-based ART, 118 (47%) on PI-based ART, and 8 (3%) on 3-NRTIs at conception. There were 160 (63%) live births (76 term and 84 preterm), 11 (4%) stillbirths, 51 (20%) spontaneous abortions, 28 (11%) elective terminations, and 3 (1%) ectopic pregnancies. In multivariable analysis adjusted for region, parent study, and pre-pregnancy ART class, only older age was associated with increased hazard of preterm birth [HR: 2.49 for age 25–30 years; 95% CI: 1.18–5.26; p = 0.017]. Women conceiving on ART had high rates of preterm birth and other adverse pregnancy outcomes. Despite the benefits of ART, studies designed to investigate the effects of preconception ART on pregnancy outcomes are needed.

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          Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention.

          Background Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. Methods We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. Results The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated with higher rates than zidovudine-based ART of very preterm delivery before 34 weeks (6.0% vs. 2.6%, P=0.04) and early infant death (4.4% vs. 0.6%, P=0.001), but there were no significant differences between tenofovir-based ART and zidovudine alone (P=0.10 and P=0.43). The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART. Conclusions Antenatal ART resulted in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes. (Funded by the National Institutes of Health; PROMISE ClinicalTrials.gov numbers, NCT01061151 and NCT01253538 .).
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            Comparative Safety of Antiretroviral Treatment Regimens in Pregnancy.

            Maternal antiretroviral treatment (ART) started before conception may increase the risk for adverse birth outcomes among women with human immunodeficiency virus (HIV) infection, but whether the risk differs by ART regimen is unknown.
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              Timing of initiation of antiretroviral therapy and adverse pregnancy outcomes: a systematic review and meta-analysis

              Although lifelong combination antiretroviral therapy (ART) is recommended for all individuals with HIV, few data exist for pregnancy outcomes associated with ART initiation before conception. We assessed adverse pregnancy outcomes associated with ART initiated before conception compared with that of ART started after conception.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysis
                Role: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysis
                Role: ConceptualizationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                18 July 2018
                2018
                : 13
                : 7
                : e0199555
                Affiliations
                [1 ] Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, United States of America
                [2 ] Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America
                [3 ] Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, Boston, MA, United States of America
                [4 ] Division of Infectious Diseases, Department of Medicine University of Colorado School of Medicine, Aurora, CO, United States of America
                [5 ] Division of Infectious Diseases, Department of Pediatrics David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America
                [6 ] Kenya Medical Research Institute (KEMRI), United States Army Medical Research Directorate-Kenya (USAMRD-K), Henry Jackson Foundation Medical Research International (HJFMRI), Kericho, Kenya
                [7 ] Director, Providence/Boston Center for AIDS Research, Director, Brown Global Health Initiative, Brown University, Providence, RI, United States of America
                [8 ] Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America
                University of New South Wales, AUSTRALIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-4210-381X
                Article
                PONE-D-18-01120
                10.1371/journal.pone.0199555
                6051581
                30020964
                0446d29e-14d5-490e-aa4f-613ab972a6e6
                © 2018 Stringer et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 January 2018
                : 7 June 2018
                Page count
                Figures: 2, Tables: 4, Pages: 12
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100006492, Division of Intramural Research, National Institute of Allergy and Infectious Diseases;
                Award ID: U01-A1068619/UMI-A1068619
                Funded by: funder-id http://dx.doi.org/10.13039/100006492, Division of Intramural Research, National Institute of Allergy and Infectious Diseases;
                Award ID: U01A1068636/A168634/A138838
                Research reported in this publication was supported by the National Institutes of Health grants to the HIV Prevention Trials Network as well as grants to the AIDS Clinical Trials Group, and Division of Intramural Research, National Institute of Allergy and Infectious Diseases, U01-A1068619/UMI-A1068619 and U01A1068636/A168634/A138838. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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