To the Editor: Because the great majority of HIV-1-infected women worldwide are of reproductive age, both intended and unintended pregnancies occur relatively frequently in this population1,2 and may be increasing in the context of highly active antiretroviral therapy (HAART) compared with earlier eras.1,3 Many HIV-1-infected women desire childbearing.4 However, unintended pregnancies may result in inadvertent exposure of the developing fetus to potentially teratogenic drugs such as efavirenz or to newer medications of unknown risk. Prevention of unintended pregnancy among HIV-1-infected women is a high priority. We evaluated the rate and potential predictors of repeat pregnancy during 2 years of postpartum follow-up among women enrolled to a clinical trial that compared 2 initial antiretroviral regimens in pregnancy. These women had intensive follow-up during and after pregnancy, including extensive contraceptive counseling, and were specifically counseled to avoid subsequent pregnancies on study. We hypothesized that occurrence of repeat pregnancies might be predicted by specific demographic and/or clinical characteristics. By identifying these characteristics, we hoped to target HIV-infected women most at risk for repeat pregnancy with more focused contraceptive counseling. Pediatric AIDS Clinical Trials Group protocol 1022 (P1022) was a randomized open-label study to determine the better antiretroviral strategy (protease inhibitor-based [nelfinavir] versus protease inhibitor-sparing [nevirapine]) for HIV-infected pregnant women initiating antiretroviral therapy during pregnancy. Women initiated assigned therapy between 10 and 30 weeks of gestation and were followed through 2 years after delivery. More details have been published.5 Enrollment was terminated early because of greater than expected toxicity in the nevirapine arm,5 but enrolled women continued study follow-up. After delivery, women were seen for visits at 2, 8, 16, 24, 32, 40, 48, 56, 72, 88, and 104 weeks. At each visit, except the 2-week visit, a urine pregnancy test was completed. Women received contraceptive counseling during pregnancy and at each postpartum visit. Current contraceptive use was queried at each visit after delivery. Condom use was reinforced, and women were provided with additional methods or referred for contraceptive services if necessary. If a subsequent pregnancy was diagnosed, study medications were discontinued until a pregnancy outcome occurred. Women were followed on study and received antiretrovirals from their prenatal care provider. We assessed the number of subsequent pregnancies per 100 person-years using the exact binomial method.6 Characteristics of women with or without a subsequent pregnancy were compared using t tests for normally distributed continuous variables, Mann-Whitney test for nonnormally distributed continuous variables, and χ2 or Fisher exact test for categorical data. Thirty-nine women were enrolled, 21 randomized to nelfinavir and 18 to nevirapine, both with zidovudine and lamivudine. One subject withdrew before treatment was dispensed and 1 woman died in the early postpartum period of fulminant hepatic failure, leaving 37 women eligible for postpartum follow-up. Eleven subsequent pregnancies occurred among 9 women during follow-up for a pregnancy rate of 16.5 per 100 woman-years of follow-up [95% confidence interval (CI): 8.5% to 27.5%]. Censoring women at the first subsequent pregnancy, the rate was 15.3 per 100 woman-years (95% CI: 7.2% to 26.9%). Outcomes of the subsequent pregnancies included 3 spontaneous abortions, 2 induced abortions, 3 live births, and 3 ongoing pregnancies, 2 in the third trimester and 1 in the early second trimester. There were no significant differences in demographic characteristics, pregnancy history, smoking, drug or alcohol use, CD4+ lymphocyte count, HIV RNA level, or treatment arm between women with or without a subsequent pregnancy. However, women with subsequent pregnancies were significantly less likely to use a second contraceptive method in addition to male condoms. Of the 35 women with complete contraception information, only 1 of 8 women in the group with repeat pregnancies used a hormonal method of contraception in the postpartum period compared with 21 of 27 women without repeat pregnancies who used an additional method (P = 0.002, Fisher exact test). Eight women (22%) underwent sterilization and 13 (35%) chose oral contraceptives or depot medroxyprogesterone (DMPA) during the postpartum period in addition to condoms. Excluding the 8 women who chose to be sterilized postpartum, the subsequent pregnancies occurring among 9 women during follow-up gave a pregnancy rate of 21.4 per 100 woman-years of follow-up (95% CI: 11.3% to 35.3%). Censoring women at the first subsequent pregnancy, the rate was 20.8 per 100 woman-years (95% CI: 10.0% to 36.0%). The pregnancy rate among HIV-infected women in this study of 15-21 per 100 person-years is generally higher than that reported for similar HIV-infected women in the United States and Europe. In a report from the Womens' Interagency HIV Study (WIHS), an ongoing cohort of women in the United States, the pregnancy rate among HIV-infected women was 7.4 per 100 person-years compared with 15.2 per 100 person-years among similar HIV-uninfected women.1 The pregnancy rate was stable over time among HIV-infected women, but the rate of induced abortion decreased in the HAART era.1 A study of women with known seroconversion date in Europe compared the pregnancy rate before and after the diagnosis of HIV infection and found the rate of pregnancy decreased from 8.6 per 100 person-years before HIV diagnosis to 8.2 in the first 4 years after diagnosis and 6.0 after 4 years.2 The proportion of induced abortions increased significantly after HIV diagnosis (P < 0.05), although the majority of the follow-up period was in the pre-HAART or early HAART era. The pregnancy rate in the Adult/Adolescent Spectrum of HIV Disease Project (AASHDP) among 8857 women was 5.5 per 100 person-years with an increased rate during 1997-2001 compared with earlier periods (relative risk 1.2, 95% CIs: 1.1 to 1.4).3 Women enrolled to the current study were all receiving HAART, which may have influenced the pregnancy rate because of improved maternal health and decreased rate of transmission, but rates were still higher than recent rates in WIHS or the AASHDP. Rates in the current study are more similar to those reported among HIV-infected adolescents, as for example in the Reaching for Excellence in Adolescent Care and Health, where the rate among HIV-infected adolescents was 20.6 per 100 person-years.7 However, only 6 women (16%) in the current study were under age 20. The relatively high pregnancy rates in P1022 compared with WIHS and AASHDP were seen despite the fact that the women were enrolled during pregnancy, were specifically advised to avoid recurrent pregnancy because of potential teratogenic risk, and received ongoing contraceptive counseling and obstetrical and gynecologic care facilitated through the study. Women who conceived during follow-up were more likely to be using condoms alone for contraception, underscoring the need for dual method use for enhanced contraceptive efficacy. Although pregnancy rates with perfect condom use are estimated at 2% per year, rates with typical use are thought to be closer to 15% per year.8 Many of the women reported condom use less than 100% of the time with sexual activity. The reasons for lack of uptake of dual method use for women enrolled to this study were not explored but would be important to understand to enhance dual method use in the future. One potential reason for lack of dual method use may be provider or patient concerns regarding the interactions of HIV infection or antiretroviral therapy and contraceptive methods. Indeed both nelfinavir and nevirapine have been shown to decrease levels of ethinyl estradiol from oral contraceptives, and nelfinavir has been shown to lower norethindrone levels, which may affect contraceptive efficacy.9 It is unclear whether drug interactions contributed to the pregnancy that occurred in the 1 woman on oral contraceptives in the study. DMPA did not demonstrate clinically significant pharmacokinetic interactions with nelfinavir, efavirenz, or nevirapine, but data are limited regarding interactions of other antiretrovirals with DMPA.10 Further study of potential interactions between hormonal contraceptive formulations and antiretroviral agents is needed to be able to provide appropriate counseling to HIV-infected women on antiretrovirals. An additional concern is the potential effect of pharmacologic doses of reproductive hormones in contraceptives on HIV disease progression. A recent randomized trial, initially designed to compare contraceptive efficacy and patient acceptance of the intrauterine device (IUD) to hormonal contraceptives among HIV-infected women, found an increased risk of HIV disease progression among women using hormonal contraception (hazard ratio 1.7, 95% CI: 1.1 to 2.5).11 Further study is required to assess this effect and to evaluate whether differences in HIV progression are seen by contraceptive method among women on antiretroviral therapy. This study and a previous study from Kenya have both demonstrated the safety of the IUD as a contraceptive option for selected HIV-infected women desiring a method in addition to condoms, despite initial concerns regarding the potential for increased risk of pelvic infections among HIV-infected women.11,12 Pending further data, both IUDs and hormonal contraceptives may be offered to appropriately screened HIV-infected women who desire added contraceptive efficacy. The repeat pregnancy rate among women enrolled to P1022, a study of optimal therapy during and after pregnancy, was higher than expected based on previous studies.1,3 The only risk factor identified for a repeat pregnancy was use of male condoms as the sole contraceptive agent. Women should be counseled regarding appropriate condom use and offered additional methods of contraception if pregnancy is not desired. In addition, prevention of unintended pregnancies in HIV-infected women will reduce the number of HIV-infected infants.13 Concerns regarding interactions of hormonal contraceptives with antiretrovirals and HIV disease progression point to an increasing role for IUDs and female barrier methods such as the diaphragm and cervical cap among HIV-infected women and underscore the need for additional research in this area. Details of study funding and participants appear online (see Supplemental Digital Content 1,https://links.lww.com/A1037) D. Heather Watts, MD* Sharon Huang, MS† Susan E. Cohn, MD, MPH‡ Laura Smith, MPH§ Jane Hitti, MD, MPH‖ *Pediatric, Adolescent and Maternal AIDS Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD †Statistical and Data Analysis Center, Harvard School of Public Health, Boston, MA ‡Department of Medicine, University of Rochester School of Medicine, Rochester, NY §Frontier Science and Technology Research Foundation, Amherst, NY ∥Department of Obstetrics and Gynecology, University of Washington, Seattle, WA