Jun 1, 2007 - CI=0.1, 18.6). Condylomata and trichomoniasis were the most frequent genital infections. Forty-eight (47.5%) of 101 girls with Papanicolaou ...
RESEARCH AND PRACTICE
Reproductive Health of Adolescent Girls Perinatally Infected With HIV | Susan B. Brogly, PhD, D. Heather Watts, MD, Nathalie Ylitalo, MD, Eduardo L. Franco, PhD, George R. Seage III, ScD, James Oleske, MD, Michelle Eagle, PA-C, and Russell Van Dyke, MD
Some girls infected perinatally with HIV early in the HIV/AIDS epidemic now have reached adolescence and become sexually active. The rate of pregnancy in these adolescent girls and the effectiveness of antiretroviral therapy (ART) in preventing second-generation mother-to-child transmission of HIV are not known. Two case reports have described the pregnancy outcomes of a small number of perinatally infected adolescents in the United States,1,2 and pregnancy outcomes in 28 perinatally infected adolescents in India have been reported.3 Although reproductive health outcomes for adolescent girls with behaviorally acquired HIV infection have been studied extensively, little data exist on the reproductive health of girls with perinatal HIV infection. A high risk of genital human papillomavirus infection and its sequelae, cervical squamous intraepithelial lesions (SIL),4–6 as well as other genital infections,7 has been documented in women and adolescents infected with HIV through sexual activity and drug use. Adolescents perinatally infected with HIV are often cared for in pediatric infectious disease clinics, where reproductive health issues may not be routinely addressed. In this study, we estimated rates of pregnancy and pregnancy outcomes, genital infections, and cervical cytological abnormalities in a cohort of perinatally HIV-infected adolescents in the United States.
METHODS Study Population The source population for this study was children enrolled in the Pediatric AIDS Clinical Trials Group (PACTG) protocol 219C. The PACTG was the pediatric counterpart of the AIDS Clinic Trial Group (ACTG), a US multisite clinical HIV/AIDS research organization that has a major role in setting standards of
Objectives. We sought to describe the reproductive health of adolescent girls perinatally infected with HIV. Methods. We estimated the incidence of first pregnancy, genital infections, and abnormal cervical cytology for 638 girls aged 13 years and older in the Pediatric AIDS Clinical Trials Group protocol 219C. Results. Thirty-eight girls became pregnant, for a first pregnancy rate of 18.8/ 1000 person-years; 7 of these girls had additional pregnancies (95% confidence interval [CI] = 13.3, 25.7). Thirty-two pregnancies resulted in live births. All girls received antiretroviral therapy during pregnancy. One infant was HIV infected, 29 were uninfected, and 2 had unknown infection status, for a rate of mother-tochild transmission of HIV in infants with known infection status of 3.3% (95% CI = 0.1, 18.6). Condylomata and trichomoniasis were the most frequent genital infections. Forty-eight (47.5%) of 101 girls with Papanicolaou test examinations had abnormal cervical cytology, including atypical cells of undetermined significance (n = 18), low-grade squamous intraepithelial lesions (SIL; n = 27), and highgrade SIL (n = 3). Many abnormalities persisted despite intervention. Conclusions. Pregnancy rates were lower and cervical abnormalities were higher than among non–HIV-infected adolescents. These findings underscore the importance of Papanicolaou tests and promotion of safer sexual practices in this population. (Am J Public Health. 2007;97:1047–1052. doi:10.2105/AJPH.2005.071910)
care for HIV infection in the United States and the developed world. Protocol 219C has enrolled and followed HIV-infected and non–HIV-infected children at clinical centers—primarily university-affiliated pediatric infectious disease clinics—across the United States since September 2000 to study the long-term effects of in utero, neonatal, and pediatric ART exposure and the complications of pediatric HIV infection. Protocol 219C was a revised version of PACTG protocol 219, which began in 1993; the primary change was to remove the restriction by which protocol 219 enrolled only children who were currently or previously enrolled in an ACTG clinical trial or whose mother was enrolled in an ACTG clinical trial during pregnancy. HIV-infected children enrolled in 219C if they were aged 21 years or younger, able to adhere to protocol visits, and receive medical care at a PACTG clinical site. Children were followed until loss of contact, protocol withdrawal, death, or their 25th
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birthday. The clinical centers involved in protocol 219C obtained approval from their respective review boards for human research, and the child or the child’s parent or guardian provided written informed consent. The study population for our investigation was restricted to perinatally HIV-infected girls aged 13 years or older who participated in protocol 219C. A girl was considered to have perinatally acquired HIV infection if her mother was HIV infected during pregnancy, labor, or delivery according to clinical records; according to HIV DNA polymerase chain reaction or RNA assays, most girls were shown to be HIV positive during infancy or early childhood. Because of the paucity of data on rates of pregnancy and pregnancy outcomes, including mother-tochild transmission of HIV, we sought to include all pregnancies that occurred in the cohort and so used the minimum age of occurrence of pregnancy—13 years—in defining the study base.
Brogly et al. | Peer Reviewed | Research and Practice | 1047
RESEARCH AND PRACTICE
Data Collection A wide range of demographic, clinical, immunologic, and virologic data were obtained at participants’ enrollment in PACTG protocol 219C and at follow-up visits, which took place every 3 months; these data included information on living conditions, diagnostic test results and histories of clinical diagnoses, pregnancies and pregnancy outcomes, ART use, Centers for Disease Control and Prevention (CDC) disease classification,8 CD4-positive T lymphocyte number CD4+ and percentage and plasma HIV viral load copy number (obtained through blood samples), and pelvic tests and cervical Papanicolaou (Pap) tests. The 219C protocol initially requested pelvic examinations—which included a visual inspection of the cervix and vagina and a bimanual examination—every 3 years beginning at age 15 years or the onset of sexual activity, whichever came first. Cervical Pap tests initially were requested of sexually active girls every 3 years. Beginning in 2002, pelvic and Pap tests were administered annually. Pap tests were fixed with a spray preservative and sent to the local PACTG site’s laboratory for reading. Because the protocol 219C participants received their primary care from clinicians at the PACTG site, clinically indicated test results were recorded in addition to those specified in the 219C protocol.
Identification of Reproductive Outcomes All pregnancies and pregnancy outcomes recorded in the 219C database were identified and confirmed by the clinical site. Liveborn infants were classified by the primary care provider as HIV infected or uninfected on the basis of HIV DNA polymerase chain reaction or RNA assays. Diagnoses of atypical squamous cells of undetermined significance (ASCUS), low-grade SIL, or high-grade SIL were made according to the Bethesda system for cervical cytological diagnosis.9 Although screening for genital infections was not performed routinely as part of protocol 219C, the physician attending the pelvic examination frequently diagnosed symptomatic cases. The diagnostic procedures for genital condylomata, trichomoniasis, chlamydial infection, gonorrhea, and syphilis were based on the PACTG site’s standard diagnostic procedures and were conducted at the institution’s local
laboratory, all of which were accredited by the Colleges of American Pathology. Girls were identified as sexually active through disclosure or occurrence of pregnancy or genital infection.
Statistical Methods We estimated the cumulative incidence of first pregnancy and the incidence rate per 1000 person-years from the girl’s 13th birthday to the date of the conception of the first pregnancy or the last cohort visit, whichever occurred first. The date of conception was determined by subtracting the gestational age of the fetus or infant from the date of the pregnancy outcome. In estimating the rate of mother-to-child transmission of HIV, pregnancies that yielded multiple births were assessed as a single transmission if any infants were HIV infected and as a single nontransmission if none were infected. The cumulative incidence of first genital condylomata, trichomoniasis, chlamydial infection, gonorrhea, and syphilis also were estimated; girls with a diagnosis of the genital infection before age 13 years were excluded from analyses for that particular outcome. Incidence rates of pregnancy and cumulative incidence of genital infections were estimated for all girls and for girls known to be sexually active. Analysis of abnormal cervical cytology was restricted to 101 girls for whom Pap tests were given. The cumulative incidence of low- or high-grade SIL was estimated for 40 girls whose first Pap test was indicative of normal cervical cytology and who then received at least 1 subsequent Pap test (with normal or abnormal result). The treatment and persistence of cervical abnormalities were described. Differences in CDC disease classification, CD4+ percentage, HIV RNA copy number, in utero ART exposure, and ART use according to sexual activity, pregnancy, and cervical cytology were assessed using the Kruskal–Wallis, χ2, and Fisher exact tests as appropriate.
RESULTS Of 1317 perinatally HIV-infected girls enrolled in PACTG protocol 219C from September 2000 to December 2005, 638 were aged 13 years or older and were included in
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the study population. These 638 girls were from 75 pediatric infectious disease clinics in 24 states and districts across the United States. A total of 174 (27.3%) were known to be sexually active on the basis of disclosure, pregnancy, or genital infection. Sexually active girls were significantly older and significantly more likely to be Hispanic, to live on their own, and to have a higher HIV RNA copy number and a lower CD4+ percentage than were girls who were not known to be sexually active (Table 1). Sexually active girls were less likely to be on ART than non–sexually active girls; however, among girls on ART, there was no significant difference in the proportions on the 3 highly active antiretroviral therapies described in Table 1.
Pregnancy Thirty-eight girls experienced a first pregnancy between the age of 13 years and their last cohort visit (2026.2 person-years of follow-up). The overall incidence rate of first pregnancy was 18.8 per 1000 person-years (95% confidence interval [CI] = 13.3, 25.7), and the incidence among girls aged 15 to 19 years was 33.5 per 1000 person-years (95% CI = 22.8, 47.6). At the 19th birthday, the cumulative incidence of first pregnancy was 17.2% (95% CI = 11.1, 23.2) among all 638 girls in the study population and 24.2% (95% CI = 16.6, 31.8) among 174 girls known to be sexually active (Figure 1). Girls who became pregnant were significantly older than those who did not, and in general, the differences in characteristics between the 2 groups paralleled the differences between sexually active and non–sexually active girls shown in Table 1. In addition, among girls known to be sexually active, those who became pregnant were more likely to have abnormal cervical cytology during follow-up than those who did not become pregnant. In addition to the 38 first pregnancies, 6 girls had a second pregnancy, and 1 had a third pregnancy. Twenty-eight of the first pregnancies resulted in live births (including one set of twins), 2 spontaneously aborted, and 8 were therapeutically aborted. Three of the second pregnancies were therapeutically aborted, and 3 resulted in live births; the single third pregnancy resulted in a live birth. Of the 32 pregnancies that resulted in live
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RESEARCH AND PRACTICE
TABLE 1—Characteristics of Perinatally HIV-Infected Adolescent Girls (n = 638), by Sexual Activity Level: PACTG Protocol 219C, 2000–2005 Characteristica Mean age (range),c y Race/ethnicity,c no. (%) Black Hispanic White Other/unknown Living conditions,c no. (%) With biological parent(s) With other adult(s) With adoptive parent(s) Foster care or residential facility On own CDC disease classification,d no. (%) A or N B C Unknown HIV RNA, copies/mL,c no. (%)
