Correspondence
Antiretroviral Therapy during Pregnancy and the Risk of an Adverse Outcome
N Engl J Med 2003; 348:471-472January 30, 2003
- Article
To the Editor:
The findings of Tuomala et al. (June 13 issue)1 contradict earlier results from Europe2 showing that exposure to highly active antiretroviral therapy increases the risk of premature delivery by a factor of nearly three. The cumulative percentage of women delivering at each period of gestation was higher among women receiving combination therapy with protease inhibitors than among those receiving no therapy or monotherapy, and the risk of premature delivery was greatest among women in whom combination therapy with protease inhibitors was initiated before pregnancy or in the early stages of pregnancy.2
Although both analyses adjusted for maternal CD4 count and antenatal illicit-drug use, there are differences between Europe and the United States in both the population of illicit-drug users and the population of persons with human immunodeficiency virus (HIV) infection. In the United States, HIV-infected women come predominantly from minority groups, with problems of access to care and higher rates of premature delivery; this is not the case in Europe.3 Infants in the European studies had the appropriate birth weight for their gestational age, whereas in the United States, this was less likely to be the case.1,2
Both European studies demonstrated associations between combination therapy with protease inhibitors and duration of pregnancy. Furthermore, in Europe, the increase in the rate of emergency cesarean sections among HIV-infected women was due to early labor in women who had received highly active antiretroviral therapy before their scheduled cesarean section.4 Highly active antiretroviral therapy not only reduces viral load but also affects metabolic pathways. Further investigation of potential mechanisms may shed light on these contradictory findings and could inform the care of HIV-infected pregnant women in all settings.
4 ReferencesClaire Thorne, Ph.D.
Simona Fiore, M.D.
Institute of Child Health, London WC1N 1EH, United KingdomChristoph Rudin, M.D.
University Children's Hospital, CH-4008 Basel, Switzerland1
Tuomala RE ,Shapiro DE ,Mofenson LM , et al. Antiretroviral therapy during pregnancy and the risk of an adverse outcome. N Engl J Med 2002;346:1863-1870
Full Text | Web of Science | Medline2
European Collaborative Study, Swiss Mother+Child HIV Cohort Study
CrossRef | Web of Science | Medline3
Martin JA, Hamilton BE, Ventura SJ, et al. Births: final data for 2000. National vital statistics reports. Vol. 50. No. 5. Hyattsville, Md.: National Center for Health Statistics, 2002.
4
Coll O ,Fiore S ,Floridia M , et al. Pregnancy and HIV infection: a European consensus on management. AIDS 2002;16:Suppl 2:S1-S18
CrossRef | Web of Science | Medline
Author/Editor Response
We agree with Thorne et al. that there are differences between our results and those of the European studies. Without specific data from the European cohorts, we cannot assess differences between studies in ethnic background, illicit-drug use, access to care, infants' birth weight, or reasons for cesarean delivery. However, the rates of premature delivery among women in the United States and Europe who were not receiving antiretroviral therapy were similar (16 percent and 17 percent, respectively), which argues against major differences in risk factors for an adverse outcome of pregnancy, and we controlled for illicit-drug use. A mismatch between gestational age and birth weight should not affect our findings in regard to premature delivery. Premature delivery itself is not an indication for delivery by cesarean section, and premature labor should not be an indication for cesarean delivery in HIV-infected women. Data from women in the United States receiving care at clinical-trial sites do not show an increase in the rate of indications for cesarean delivery associated with prematurity, such as breech presentation or chorioamnionitis.
In the European studies, women who began receiving combination antiretroviral therapy before pregnancy rather than in the third trimester were more likely to delivery prematurely. We have no data on the use of antiretroviral drugs before pregnancy; however, 30 percent of the women in our study began receiving antiretroviral drugs during the third trimester — a percentage that is similar to that in the European studies (46 percent). The number of patients who were receiving combination therapy in the European studies was smaller than that in our study (323 vs. 533).
We agree that highly active antiretroviral therapy can affect metabolic pathways and immune function. Further study is needed to define more clearly the risks associated with the use of highly active antiretroviral therapy during pregnancy. For the present, our data provide reassurance that the risks of adverse outcomes associated with such therapy are low and are outweighed by the benefits in terms of maternal health and the reduction in the likelihood of vertical transmission.
Ruth E. Tuomala, M.D.
Brigham and Women's Hospital, Boston, MA 02115
retuomala@partners.org David E. Shapiro, Ph.D.
Harvard School of Public Health, Boston, MA 02115Lynne M. Mofenson, M.D.
National Institutes of Health, Rockville, MD 20852- Citing Articles (11)
Citing Articles
1
C Rudin, A Spaenhauer, O Keiser, M Rickenbach, C Kind, K Aebi-Popp, MWG Brinkhof, . (2011) Antiretroviral therapy during pregnancy and premature birth: analysis of Swiss data. HIV Medicine 12:4, 228-235
CrossRef2
CL Townsend, J Schulte, C Thorne, KL Dominguez, PA Tookey, M Cortina-Borja, CS Peckham, B Bohannon, M-L Newell, . (2010) Antiretroviral therapy and preterm delivery-a pooled analysis of data from the United States and Europe. BJOG: An International Journal of Obstetrics & Gynaecology 117:11, 1399-1410
CrossRef3
Claire L Townsend, Mario Cortina-Borja, Catherine S Peckham, Pat A Tookey. (2007) Antiretroviral therapy and premature delivery in diagnosed HIV-infected women in the United Kingdom and Ireland. AIDS 21:8, 1019-1026
CrossRef4
Haritini Petropoulou, Alexander J. Stratigos, Andreas D. Katsambas. (2006) Human immunodeficiency virus infection and pregnancy. Clinics in Dermatology 24:6, 536-542
CrossRef5
Athena P Kourtis, Pooja Bansil, Melissa McPheeters, Susan F Meikle, Samuel F Posner, Denise J Jamieson. (2006) Hospitalizations of pregnant HIV-infected women in the USA prior to and during the era of HAART, 1994–2003. AIDS 20:14, 1823-1831
CrossRef6
Claire Thorne, Marie-Louise Newell. (2005) Managing mother-to-child transmission of HIV infection in developed-country settings. Women's Health 1:3, 385-399
CrossRef7
Claire Thorne, Marie-Louise Newell. (2005) The safety of antiretroviral drugs in pregnancy. Expert Opinion on Drug Safety 4:2, 323-335
CrossRef8
Augusto E Semprini, Alessandra Vucetich, Lital Hollander. (2004) Sperm washing, use of HAART and role of elective Caesarean section. Current Opinion in Obstetrics and Gynecology 16:6, 465-470
CrossRef9
Augusto E Semprini, Simona Fiore. (2004) HIV and reproduction. Current Opinion in Obstetrics and Gynecology 16:3, 257-262
CrossRef10
(2003) Current awareness in prenatal diagnosis. Prenatal Diagnosis 23:8, 694-700
CrossRef11
(2003) Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiology and Drug Safety 12:5, 431-446
CrossRef
