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

Gibb, Diana M., Kizito, Hilda, Russell, Elizabeth C., Chidziva, Ennie, Zalwango, Eva, Nalumenya, Ruth, Spyer, Moira, Tumukunde, Dinah, Nathoo, Kusum, Munderi, Paula, Kyomugisha, Hope, Hakim, James, Grosskurth, Heiner, Gilks, Charles F., Walker, A. Sarah and Musoke, Phillipa (2012) Pregnancy and Infant Outcomes among HIV-Infected Women Taking Long-Term ART with and without Tenofovir in the DART Trial. PLoS Medicine, 9 5: . doi:10.1371/journal.pmed.1001217

Author Gibb, Diana M.
Kizito, Hilda
Russell, Elizabeth C.
Chidziva, Ennie
Zalwango, Eva
Nalumenya, Ruth
Spyer, Moira
Tumukunde, Dinah
Nathoo, Kusum
Munderi, Paula
Kyomugisha, Hope
Hakim, James
Grosskurth, Heiner
Gilks, Charles F.
Walker, A. Sarah
Musoke, Phillipa
Title Pregnancy and Infant Outcomes among HIV-Infected Women Taking Long-Term ART with and without Tenofovir in the DART Trial
Journal name PLoS Medicine   Check publisher's open access policy
ISSN 1549-1676
Publication date 2012-05
Year available 2012
Sub-type Article (original research)
DOI 10.1371/journal.pmed.1001217
Open Access Status DOI
Volume 9
Issue 5
Total pages 16
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2012
Language eng
Formatted abstract
 Background: 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.

Methods and Findings: 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.

Conclusions: 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
Keyword Bone Mineral Density
To Child Transmission
Antiretroviral Therapy
Disoproxil Fumarate
Premature Delivery
United Kingdom
Double blind
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Public Health Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 43 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 51 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 07 Jun 2013, 20:09:14 EST by System User on behalf of School of Public Health