By June 2009, 10 493 cases of AIDS among adolescents aged 13–19 years had been reported to the Department of sexually transmitted disease (STD) and AIDS of Brazilian Ministry of Health . This group comprises individuals infected perinatally, those infected through sexual contact or transfusion of blood products, and those with an unknown source of infection. On the contrary, between 2000 and 2008, 4900 HIV-1-infected pregnant adolescents aged 10–19 years were reported in Brazil , where the mother-to-child transmission (MTCT) rate is presently less than 2% in sites where specialized care is available .
Combination antiretroviral therapy regimens have significantly improved the prognosis of HIV-1 infection in countries where it has been successfully implemented. For example, HIV-1 mortality in children and adolescents has decreased by over 80–90% since the introduction of protease inhibitor-containing combination regimens, [3–7] and the results of a recent randomized trial support early initiation of antiretroviral drugs as a protective factor for disease progression .
With the development of better therapeutic strategies, improvement in the quality of life and life span of HIV-1-infected children with symptomatic infection has been observed. Despite difficulties in achieving viral suppression during treatment of infected infants and children, this population is reaching adolescence, becoming sexually active, and procreating [9–12]. This new generation of HIV-1-exposed infants brings with it the need for specialized pediatric care.
Since 1998, there have been some published reports from different parts of the world regarding pregnancy among women who themselves acquired HIV-1 infection perinatally [11,13–16]. In Brazil, most individuals with perinatally acquired HIV-1 infection are still being followed at pediatric or adolescent clinics, although many of them are young adults. Our objective was to describe the characteristics and infant outcomes of pregnancies among adolescents and young women with perinatally acquired HIV-1 infection in Brazil.
Patients and methods
We performed a retrospective chart review of pregnant girls with perinatally acquired HIV-1 infection at six centers for HIV-1 adolescent care in Brazil. The study was approved by the Institutional Review Board at Hospital dos Servidores do Estado do Rio de Janeiro, Brazil.
Since the neonatal records of adolescents generally were not available, perinatally acquired HIV-1 infection was defined by a positive maternal HIV-1 serology result or maternal death prior to diagnosis in cases when the adolescent had no other risk factor for HIV-1 infection (e.g. sexual abuse or blood transfusions).
Data abstracted from the medical records included information: before pregnancy (maternal prenatal care, age at HIV-1 diagnosis, previous antiretroviral use and initiation of sexual activity); during pregnancy (CDC classification, antiretroviral use, CD4, viral load, gynecologic and obstetric complications); mode of delivery; infant characteristics (gestational age, sex, birth weight, birth length); and infant HIV-1 infection status defined by two positive HIV-1 RNA polymerase chain reaction (PCR) tests performed at 1 and 4 months of age, and HIV-1 antibody tests between 12 and 18 months of age, according to Brazilian guidelines . Lower limits of HIV-1 RNA detection were 80 copies/ml from 2002 to 2006 and 50 copies/ml from 2007 onwards. Data were analyzed using SPSS 12.0 (SPSS Inc., Chicago, Illinois, USA).
Fifteen pregnancies in 11 adolescents with perinatally acquired HIV-1 infection were followed from 2002 to 2009 at six medical centers (five in Rio de Janeiro and one in São Paulo). One youth had three pregnancies and two adolescents had two pregnancies each. Eight patients (73%) were non-White. The median age of diagnosis of HIV-1 infection was 10.1 years (range 1.3–20) and disclosure of diagnosis occurred at a median age of 12 years (range 9.5–13). Six HIV-1-infected grandmothers are still alive but only one received antiretroviral drugs during prenatal care.
These 11 girls with perinatally acquired HIV-1 infection had their sexual debut at median age of 15 years (range 13–19) and the median age at first pregnancy was 16.9 years (range 14–21.5). One patient had two previous spontaneous abortions. Patients had been under medical follow-up for a median 8.5 years (range 2.9–15.8) when their (first) pregnancy was diagnosed. The median duration of antiretroviral use was 7.8 years (range 0–15.3), and the median number of antiretroviral regimens used was three (range 0–7). The median gestational age at the beginning of specialized prenatal care was 13 weeks (range 8–26) and four patients (36.4%) had presented with an AIDS-defining illness (CDC clinical category C). Most of the girls were referred for specialized prenatal care in the same healthcare unit in which they had been followed, and their HIV-1 infection status was known by healthcare providers since the beginning of prenatal care.
Ten of 11 patients had previously been exposed to zidovudine (ZDV) during childhood. Seven patients had been treated with three or more antiretroviral regimens before pregnancy. Antiretroviral drugs were prescribed for all pregnancies and used in 14 cases (93.3%). Protease inhibitor-based regimens were used during 11 pregnancies, and one patient received a nonprotease inhibitor-based regimen. In two pregnancies, a dual nucleoside reverse transcriptase inhibitor (NRTI) regimen was used [ZDV/didanosine (DDI) and ZDV/lamivudine, respectively].
The median CD4 cell count during pregnancy was 394 (range 117–651) cells/μl and the median viral load was 4800 copies/ml (range 50–100 000); 54% (6/11) had an undetectable viral load near delivery.
All patients were delivered by cesarean section before labor and before ruptured membranes, in 60% of cases for prevention of MTCT and in 40% of cases for obstetric reasons (including one patient's choice). No postpartum complications were observed.
The median birth weight of the infants was 2650 g (range 2085–3595), and the median length was 47.3 cm (range 42–51). Gestational age was available for seven infants [median 38 weeks (range 37–39)]. One newborn had severe perinatal anoxia. All newborns received ZDV for the first 6 weeks of life, and none were breastfed. Fourteen (93%) infants were considered HIV-1-uninfected, and there was one lost to follow-up. Table 1 shows characteristics of perinatally infected mothers and infant HIV status.
We report the first case series of pregnancies among Brazilian adolescents with perinatally acquired HIV-1 infection. In these 15 cases, there were favorable outcomes, even though viral suppression near delivery had not been achieved in many cases. The Brazilian Ministry of Health advises follow-up of HIV-1-exposed children until adolescence , and this third generation of HIV-exposed infants needs to be addressed within HIV-1-specialized adolescent care settings.
The late HIV-1 diagnosis at a median age of 10 years in this group of vertically infected patients has been found in other cohorts in Latin America , and suggests that the study population have survived many years with reasonably good health before being tested for HIV-1. The fact that only one grandmother had received antiretroviral drugs during pregnancy reinforces the fact that, in Brazil, many HIV-1-infected adolescents presently in care were born before HIV-1 prenatal screening had been integrated into the standard of care for pregnant women.
The timing of sexual debut and pregnancy among vertically infected girls are comparable to what is observed in the general adolescent population. According to reports from the Pan American Health Organization, in Latin America 50% of youths below 17 years are sexually active and up to 25% of all babies are born to adolescents . Finding such reproductive capacity among HIV-1-infected individuals, most of whom have advanced disease and who have grown up and matured with antiretroviral treatment, is another extremely positive result of the use of available potent antiretroviral regimens.
In general, the antiretroviral management of these girls during pregnancy was similar to that of women whose HIV-1 infection status was first discovered during pregnancy. Although most patients received highly active antiretroviral therapy (HAART) during pregnancy, only 54% had undetectable viral load near delivery and the majority of cesarean deliveries were performed because of inadequate viral suppression. Difficulty in achieving suppression of HIV-1 replication in these patients can be caused by poor adherence or by the existence of viral mutations associated with resistance to antiretroviral drugs. In fact, most patients had previously used antiretroviral drugs and 64% (7/11) had been treated with three or more antiretroviral regimens before pregnancy. It is very likely that these previous changes in antiretroviral regimens were due to sequential failures and this situation is frequently associated with the presence of viral mutations associated with antiretroviral resistance. Williams et al. observed a viral load below 400 copies/ml near delivery in only 38.5% of the 13 pregnancies of vertically infected women. Unique behavioral characteristics of adolescents make them a group with greater difficulty in adhering to complex regimens [21–23]. It is true that inadequate viral suppression due to inadequate adherence is frequently seen in HIV-1-infected adolescents, but we also have to consider the possibility of viral resistance since these patients have been treated for many years and exposed to different drug regimens. Unfortunately, we do not have data on HIV genotyping of this group of pregnant adolescents.
There were no cases of MTCT of HIV-1 in our cohort. These findings are in concurrence with the Puerto Rican study of a cohort of 10 pregnancies in eight adolescents with perinatally acquired HIV-1 infection among adolescents and young adults , and with the Indian study of 30 pregnancies of asymptomatic, adolescent and young adult primigravidas with perinatally acquired HIV-1 infection . In both studies, no cases of MTCT were reported. Williams et al. have described MTCT rates for 13 pregnancies in 10 perinatally infected adolescents; only one child was infected (transmission rate of 7.7%). In this case, the mother refused antiretroviral drugs as well as cesarean delivery . Table 2 describes the characteristics of the pregnancy outcomes of vertically HIV-1-infected adolescents and young adults in other studies in different parts of the world.
The group of adolescents receiving antiretroviral treatment seems to have sexual behavior similar to that of HIV-1-uninfected adolescents. As more effective antiretroviral regimens become available, increasing numbers of HIV-1-infected children enter adolescence and will initiate sexual activity and reproduction. For those who become pregnant, reinforcement of the importance of adherence and provision of new antiretroviral drugs may be necessary to achieve viral suppression, avoid cesarean section, and prevent MTCT of HIV-1.
The authors gratefully acknowledge Dr Jennifer Read from the National Institutes of Health for the time devoted to review this study and comments.
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