Pregnancy and Infant Outcomes among HIV-Infected Women Taking Long-Term ART with and without Tenofovir in the DART Trial

MRC Clinical Trials Unit, London, UK.
PLoS Medicine (Impact Factor: 14.43). 05/2012; 9(5):e1001217. DOI: 10.1371/journal.pmed.1001217
Source: PubMed


Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART) in pregnancy. This is particularly true for World Health Organization (WHO)-recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure.
Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models. 382 pregnancies occurred in 302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0-4.9]). 226/390 (58%) outcomes were live-births, 27 (7%) stillbirths (≥22 wk), and 137 (35%) terminations/miscarriages (<22 wk). Of 226 live-births, seven (3%) infants died <2 wk from perinatal causes and there were seven (3%) congenital abnormalities, with no effect of in utero tenofovir exposure (p>0.4). Of 219 surviving infants, 182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age at last visit was 25 (12-38) months. From mothers' ART, 62/9/111 infants had no/20%-89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested). Only 73/182(40%) infants were breast-fed for median 94 (IQR 75-212) days. Overall, 14 infants died at median (IQR) age 9 (3-23) months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three), sepsis (two), burns (one), measles (one), unknown (one). During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16) or two (three) in 14 children with no effect of in utero tenofovir (p>0.1). There was no evidence that in utero tenofovir affected growth after 2 years (p = 0.38). Attained height- and weight for age were similar to general (HIV-uninfected) Ugandan populations. Study limitations included relatively small size and lack of randomisation to maternal ART regimens.
Overall 1-year 5% infant mortality was similar to the 2%-4% post-neonatal mortality observed in this region. No increase in congenital, renal, or growth abnormalities was observed with in utero tenofovir exposure. Although some infants died untested, absence of recorded HIV infection with combination ART in pregnancy is encouraging. Detailed safety of tenofovir for pre-exposure prophylaxis will need confirmation from longer term follow-up of larger numbers of exposed children. ISRCTN13968779

Download full-text


Available from: Diana M Gibb
  • Source
    • "A recent retrospective study from Malawi showed that longer time on ART was associated with an increased probability of pregnancy, but desire and/or intent for children was not specifically measured (Tweya et al., 2013). There is evidence that ART increases fertility (Gibb et al., 2012; Myer et al., 2010; Zaba & Gregson, 1998), and better studies are needed to disentangle the role of ART on fertility desire and intent and pregnancy rates that may result from return to health and increase in fertility. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Improved health outcomes have resulted in people with HIV facing decisions about childbearing. We sought to understand the factors associated with desire for a child among men and women in Malawi. HIV-infected men and women ages 18-40 were invited to participate in a brief interview about fertility desires. Single variable logistic regression was used to evaluate the factors associated with the outcome of fertility desire. Additionally, multiple logistic regression was used to assess the relationship of all the factors together on the outcome of fertility desire. In-depth interviews with women were performed to understand experiences with reproductive health care. A total of 202 brief interviews were completed with 75 men (37.1%) and 127 women (62.9%), with 103 (51.0%) of respondents desiring a child. Being in a relationship (OR: 3.48, 95% CI: 1.58-7.65, p = 0.002) and duration of HIV more than two years (OR: 2.00, 95% CI: 1.08-3.67, p = 0.03) were associated with increased odds of desire for a child. Age 36-40 years (OR: 0.64, 95% CI: 0.46-0.90, p = 0.009) and having a living child (OR: 0.24, 95% CI: 0.07-0.84, p = 0.03) were associated with decreased odds of desire for a child. Seventy percent of women (n = 19 of 27 respondents) completing semistructured interviews who responded to the question about decision-making reported that their male partners made decisions about children, while the remainder reported the decision was collaborative (n = 8, 30%). Eighty-six percent of women (n = 36 of 42 respondents) reported no discussion or a discouraging discussion with a provider about having children. HIV-infected women and men in Malawi maintain a desire to have children. Interventions are needed to integrate safer conception into HIV care, to improve male participation in safer conception counseling, and to empower providers to help patients make decisions about reproduction free of discrimination and coercion.
    Full-text · Article · Nov 2013 · AIDS Care
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of human immunodeficiency virus (HIV)-positive pregnant women in the UK. The scope includes guidance on the use of antiretroviral therapy (ART) both to prevent HIV mother-to-child transmission (MTCT) and for the welfare of the mother herself, guidance on mode of delivery and recommendations in specific patient populations where other factors need to be taken into consideration,such as coinfection with other agents. The guidelines are aimed at clinical professionals directly involved with, and responsible for, the care of pregnant women with HIV infection.
    Full-text · Article · Sep 2012 · HIV Medicine
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE:: To describe the pharmacokinetics of tenofovir and emtricitabine in the third trimester of pregnant HIV-infected women and at postpartum. DESIGN:: A non-randomized, open-label, multi-centre phase-IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. METHODS:: HIV-infected pregnant women treated with the nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF 300 mg; equivalent to 245 mg tenofovir disoproxil) and/or emtricitabine (FTC 200 mg) were included in the study. 24 h pharmacokinetic curves were recorded in the 3 trimester (preferably week 33) and postpartum (preferably week 4-6). Collection of a cord blood sample and maternal sample at delivery was optional. Pharmacokinetic parameters were calculated using WinNonlin software version 5.3. Statistical analysis was conducted using SPSS version 16.0. RESULTS:: 34 women were included in the analysis. Geometric mean ratios of 3 trimester vs. postpartum (90% confidence interval) were 0.77 (0.71-0.83) for TDF AUC0-24h; 0.81 (0.68-0.96) for TDF Cmax and 0.79 (0.70-0.90) for TDF C24h, and 0.75 (0.68-0.82) for FTC AUC0-24h; 0.87 (0.77-0.99) for FTC Cmax and 0.77 (0.52-1.12) for FTC C24h. The viral load close to delivery was <200 copies/mL in all but one patient, the average gestational age at delivery was 38 weeks. All children were tested HIV-negative and no congenital abnormalities were reported. CONCLUSIONS:: Although PK exposure of the NRTIs TDF and FTC during pregnancy is approximately 25% lower, this was not associated with virological failure in this study and did not result in mother to child transmission.
    No preview · Article · Nov 2012 · AIDS (London, England)
Show more