Esau Joao

Management of human immunodeficiency virus-infected pregnant women at Latin American and Caribbean sites.

OBJECTIVE: To describe the management of a population of human immunodeficiency virus (HIV)–infected pregnant women in Latin America and the Caribbean, and to assess factors associated with maternal viral load of 1,000 copies/mL or more and with infant HIV-1 infection. METHODS: Eligibility criteria were enrollment in the prospective cohort study as of March 2006; delivery of a liveborn, singleton infant; and completion of the 6-month postpartum or postnatal visit. RESULTS: Of 955 women enrolled in Argentina, the Bahamas, Brazil, and Mexico, 770 mother-infant pairs were eligible. At enrollment, most women were relatively healthy (87% asymptomatic, 59% with viral load less than 1,000 copies/mL, 62% with CD4+% of 25% or more). Most (99%) received antiretrovirals during pregnancy (56% prophylaxis, 44% treatment), and 38% delivered by cesarean before labor and before ruptured membranes. Only 18% of women had a viral load of 1,000 copies/mL or more after delivery (associated in adjusted analyses with receipt of antiretrovirals at conception, CD4+% [lower], viral load [higher], and country at enrollment, enrollment late in pregnancy, and inversely related to antiretroviral regimen [two nucleoside or nucleotide analogue reverse transcriptase inhibitors plus one nonnucleoside reverse transcriptase inhibitor] during pregnancy). None of the infants breastfed, and all received antiretroviral prophylaxis. Seven infants became infected (0.91%; 95% confidence interval 0.37–1.86). Low birth weight infants and those whose mothers had a low CD4+% at hospital discharge after delivery and were not receiving antiretrovirals at enrollment were at higher risk of HIV infection. CONCLUSION: Only a minority of women had a viral load of 1,000 copies/mL or more around delivery, and mother-to-child transmission of HIV occurred rarely (1%). LEVEL OF EVIDENCE: II

Pharmacokinetics and Safety of Tenofovir in HIV-Infected Women During Labor and Their Infants During the First Week of Life

Background:Data describing the pharmacokinetics and safety of tenofovir in neonates are lacking. Methods:The HIV Prevention Trials Network 057 protocol was a phase 1, open-label study of the pharmacokinetics and safety of tenofovir disoproxil fumarate (TDF) in HIV-infected women during labor and their infants during the first week of life with 4 dosing cohorts: maternal 600 mg doses/no infant dosing; no maternal dosing/infant 4 mg/kg doses on days 0, 3, and 5; maternal 900 mg doses/infant 6 mg/kg doses on days 0, 3, and 5; maternal 600 mg doses/infant 6 mg/kg daily for 7 doses. Pharmacokinetic sampling was performed on cohort 1 and 3 mothers and all infants. Plasma, amniotic fluid, and breast milk tenofovir concentrations were determined by liquid chromatographic–tandem mass spectrometric assay. The pharmacokinetic target was for infant tenofovir concentration throughout the first week of life to exceed 50 ng/mL, the median trough tenofovir concentration in adults receiving standard chronic TDF dosing. Results:One hundred twenty-two mother–infant pairs from Malawi and Brazil were studied. Tenofovir exposure in mothers receiving 600 and 900 mg exceeded that in nonpregnant adults receiving standard 300 mg doses. Tenofovir elimination in the infants was equivalent to that in older children and adults, and trough tenofovir plasma concentrations exceeded 50 ng/mL in 74%–97% of infants receiving daily dosing. Conclusions:A TDF dosing regimen of 600 mg during labor and daily infant doses of 6 mg/kg maintains infant tenofovir plasma concentration above 50 ng/mL throughout the first week of life and should be used in the studies of TDF efficacy for HIV prevention of mother-to-child transmission and early infant treatment.

Maternal antiretroviral use during pregnancy and infant congenital anomalies: the NISDI perinatal study.

Background:We evaluated the association between maternal antiretrovirals (ARVs) during pregnancy and infant congenital anomalies (CAs), utilizing data from the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study. Methods:The study population consisted of first singleton pregnancies on study, ≥20 weeks gestation, among women enrolled in NISDI from Argentina and Brazil who delivered between September 2002 and October 2007. CAs were defined as any major structural or chromosomal abnormality, or a cluster of 2 or more minor abnormalities, according to the conventions of the Antiretroviral Pregnancy Registry. CAs were identified from fetal ultrasound, study visit, and death reports. Prevalence rates [number of CAs per 100 live births (LBs)] were calculated for specific ARVs, classes of ARVs, and overall exposure to ARVs. Results:Of 1229 women enrolled, 995 pregnancy outcomes (974 LBs) met the inclusion criteria. Of these, 60 infants (59 LBs and 1 stillbirth) had at least 1 CA. The overall prevalence of CAs (per 100 LBs) was 6.2 [95% confidence interval (CI) 4.6 to 7.7]. The prevalence of CAs after first trimester ARVs (6.2; 95% CI 3.1 to 9.3) was similar to that after second (6.8; 95% CI 4.5 to 9.0) or third trimester (4.3; 95% CI 1.5 to 7.2) exposure. The rate of CAs identified within 7 days of delivery was 2.36 (95% CI 1.4 to 3.3). Conclusions:The prevalence of CAs after first trimester exposure to ARVs was similar to that after second or third trimester exposure. Continued surveillance for CAs among children exposed to ARVs during gestation is needed.

Chlamydia and Gonorrhea in HIV-Infected Pregnant Women and Infant HIV Transmission.

Background Sexually transmitted infections (STIs) such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) can lead to adverse pregnancy and neonatal outcomes. The prevalence of STIs and its association with HIV mother-to-child transmission (MTCT) were evaluated in a substudy analysis from a randomized, multicenter clinical trial. Methodology Urine samples from HIV-infected pregnant women collected at the time of labor and delivery were tested using polymerase chain reaction testing for the detection of CT and NG (Xpert CT/NG; Cepheid, Sunnyvale, CA). Infant HIV infection was determined by HIV DNA polymerase chain reaction at 3 months. Results Of the 1373 urine specimens, 249 (18.1%) were positive for CT and 63 (4.6%) for NG; 35 (2.5%) had both CT and NG detected. Among 117 cases of HIV MTCT (8.5% transmission), the lowest transmission rate occurred among infants born to CT- and NG-uninfected mothers (8.1%) as compared with those infected with only CT (10.7%) and both CT and NG (14.3%; P = 0.04). Infants born to CT-infected mothers had almost a 1.5-fold increased risk for HIV acquisition (odds ratio, 1.47; 95% confidence interval, 0.9–2.3; P = 0.09). Conclusions This cohort of HIV-infected pregnant women is at high risk for infection with CT and NG. Analysis suggests that STIs may predispose to an increased HIV MTCT risk in this high-risk cohort of HIV-infected women.

Trends in a Cohort of HIV-infected pregnant women in Rio de Janeiro, 1996-2004

OBJECTIVE: To describe trends in sociodemographic, immunological and virological profiles and interventions to decrease the risk of mother-to-child HIV transmission. METHODS: Retrospective cohort study conducted at a tertiary institution in Rio de Janeiro, Brazil from January 1996 to December 2004. Analysis was performed by stratification in three time periods: 1996-1998 (P1), 1999-2001 (P2) and 2002-2004 (P3). RESULTS: In 9 years, 622 pregnancies occurred. Complications included: maternal mortality 0.3%, stillbirths 2.5%, miscarriages 0.6%, neonatal mortality 1.1%, prematurity 9.9%, low birth weight (LBW) 16.5%, congenital malformations 2.2%. The number of HIV-infected pregnant patients grew threefold over time reflecting increased prevalence of disease and patient identification. HIV diagnosis before pregnancy increased from 30% in P1 to 45% in P3. The proportion of pregnant women receiving highly active antiretroviral therapy increased from none (P1) to 88% (P3) with a significant trend towards women delivering at undetectable viral loads in later years despite a higher frequency of advanced disease. Scheduled cesarean deliveries increased from 35% in P1 to 48% in P3. Perinatal transmission rates were 2.4% with a decline from 3.5% in P1 to 1.6% in P3. Neonatal outcomes tended to remain constant or improve with time. A slight rise in LBW and congenital malformations were observed. CONCLUSIONS: During the observational period, HIV+ pregnant women presented with more advanced disease and lower socio-economic status. However, improved management of HIV-infected patients (associated with increased identification and increased availability of treatment) resulted into very low transmission rates similar to those of developed countries with overall improvement of patient outcomes.

Pregnancy in HIV vertically infected adolescents and young women: a new generation of HIV-exposed infants.

Background:Vertically infected individuals are reaching childbearing age and the new generation of HIV-exposed infants is coming to pediatric care. Methods:Chart review of pregnancies among HIV vertically infected adolescents and young women. Results:Fifteen pregnancies were reviewed. Girls had HIV diagnosis at median age 10.1 years (range 1.3–20). They started sexual life at median age 15 years (range 13–19); median age at pregnancy was 16.9 years (range 14–21.5); 36.4% had presented an AIDS-defining clinical event; have been followed for median 8.5 years (range 2.9–15.8) and had used median two antiretroviral regimens (range 0–7). Fourteen (93.3%) received antiretroviral drugs during pregnancy; median CD4 cell count during pregnancy was 394 (range 117–651) cells/μl and median viral load was 4800 copies/ml (range 50–100 000); 54% had undetectable viral load near delivery. All patients delivered by elective c-section. Median birth weight was 2650 g (range 2085–3595), median length was 47.3 cm (range 42–51) and median gestational age 38 weeks (range 37–39). All newborn received zidovudine for 6 weeks of life and none was breastfed. Fourteen (93%) infants were considered HIV-uninfected; one was lost to follow-up. Conclusions:This group of adolescents seems to have sexual behavior similar to that of HIV-uninfected. Since this is an experimented antiretroviral population, new drugs may be necessary for adequate viral suppression to avoid HIV mother-to-child transmission. Follow-up of this third generation of HIV-exposed infants needs to be addressed within HIV adolescent care.

HIV rapid testing as a key strategy for prevention of mother-to-child transmission in Brazil

OBJECTIVE To assess the feasibility of HIV rapid testing for pregnant women at maternity hospital admission and of subsequent interventions to reduce perinatal HIV transmission. METHODS Study based on a convenience sample of women unaware of their HIV serostatus when they were admitted to delivery in public maternity hospitals in Rio de Janeiro and Porto Alegre, Brazil, between March 2000 and April 2002. Women were counseled and tested using the Determine HIV1/2 Rapid Test. HIV infection was confirmed using the Brazilian algorithm for HIV infection diagnosis. In utero transmission of HIV was determined using HIV-DNA-PCR. There were performed descriptive analyses of sociodemographic data, number of previous pregnancies and abortions, number of prenatal care visits, timing of HIV testing, HIV rapid test result, neonatal and mother-to-child transmission interventions, by city studied. RESULTS HIV prevalence in women was 6.5% (N=1,439) in Porto Alegre and 1.3% (N=3.778) in Rio de Janeiro. In Porto Alegre most of women were tested during labor (88.7%), while in Rio de Janeiro most were tested in the postpartum (67.5%). One hundred and forty-four infants were born to 143 HIV-infected women. All newborns but one in each city received at least prophylaxis with oral zidovudine. It was possible to completely avoid newborn exposure to breast milk in 96.8% and 51.1% of the cases in Porto Alegre and Rio de Janeiro, respectively. Injectable intravenous zidovudine was administered during labor to 68.8% and 27.7% newborns in Porto Alegre and Rio de Janeiro, respectively. Among those from whom blood samples were collected within 48 hours of birth, in utero transmission of HIV was confirmed in 4 cases in Rio de Janeiro (4/47) and 6 cases in Porto Alegre (6/79). CONCLUSIONS The strategy proved feasible in maternity hospitals in Rio de Janeiro and Porto Alegre. Efforts must be taken to maximize HIV testing during labor. There is a need of strong social support to provide this population access to health care services after hospital discharge.OBJETIVO: Analisar a viabilidade da testagem rapida para o HIV entre gestantes na admissao a maternidade e de intervencoes para reduzir a transmissao perinatal do HIV. METODOS: Amostra de conveniencia de mulheres que desconheciam sua situacao sorologica para o HIV quando admitidas para o parto em maternidades publicas do Rio de Janeiro, RJ, e de Porto Alegre, RS, entre marco de 2000 e abril de 2002. As mulheres foram aconselhadas e testadas com teste rapido Determine HIV1/2 na maternidade. Infeccao pelo HIV foi confirmada pelo algoritmo brasileiro para o diagnostico da infeccao pelo HIV. A transmissao intra-utero foi determinada pelo PCR-DNA-HIV. Foram realizadas analises descritivas dos dados sociodemograficos, numero de gestacoes e de abortos previos, numero de visitas de pre-natal, momento da testagem para o HIV, resultado do teste rapido para o HIV, intervencoes recebidas pelos recem-natos e de transmissao vertical do HIV, de acordo com cada cidade. RESULTADOS: A prevalencia de HIV entre as mulheres foi 6,5% (N=1.439) em Porto Alegre e 1,3% (N=3.778) no Rio de Janeiro. A maioria foi testada durante o trabalho de parto em Porto Alegre e no pos-parto, no Rio de Janeiro. Cento e quarenta e quatro criancas nasceram de 143 mulheres infectadas pelo HIV. Todos os recem-natos receberam ao menos a profilaxia com zidovudina oral, exceto um em cada cidade. Foi possivel evitar qualquer exposicao ao leite materno em 96,8% e 51,1% dos recem-natos em Porto Alegre e no Rio de Janeiro, respectivamente. A zidovudina injetavel foi administrada durante o trabalho de parto para 68,8% dos recem-natos em Porto Alegre e 27,7% no Rio de Janeiro. Entre aqueles com amostras de sangue coletadas ate 48 horas do nascimento, a transmissao intra-utero foi confirmada em quatro casos no Rio de Janeiro (4/47) e em seis casos em Porto Alegre (6/79). CONCLUSOES: A estrategia mostrou-se factivel nas maternidades do Rio de Janeiro e de Porto Alegre. Esforcos devem ser empreendidos para maximizar a testagem durante o trabalho de parto. Forte suporte social precisa ser acoplado a essa estrategia para garantir o acesso dessa populacao ao sistema de saude apos a alta da maternidade.

Syphilis in HIV-infected mothers and infants: results from the NICHD/HPTN 040 study.

Background: Untreated syphilis during pregnancy is associated with spontaneous abortion, stillbirth, prematurity and infant mortality. Syphilis may facilitate HIV transmission, which is especially concerning in low- and middle-income countries where both diseases are common. Methods: We performed an analysis of data available from NICHD/HPTN 040 (P1043), a study focused on the prevention of intrapartum HIV transmission to 1684 infants born to 1664 untreated HIV-infected women. This analysis evaluates risk factors and outcomes associated with a syphilis diagnosis in this cohort of HIV-infected women and their infants. Results: Approximately, 10% of women (n = 171) enrolled had serological evidence of syphilis without adequate treatment documented and 1.4% infants (n = 24) were dually HIV and syphilis infected. Multivariate logistic analysis showed that compared with HIV-infected women, co-infected women were significantly more likely to self-identify as non-white (adjusted odds ratio [AOR] 2.5, 95% CI: 1.5–4.2), to consume alcohol during pregnancy (AOR 1.5, 95% CI: 1.1–2.1) and to transmit HIV to their infants (AOR 2.1, 95% CI: 1.3–3.4), with 88% of HIV infections being acquired in utero. As compared with HIV-infected or HIV-exposed infants, co-infected infants were significantly more likely to be born to mothers with venereal disease research laboratory titers ≥1:16 (AOR 3, 95% CI: 1.1–8.2) and higher viral loads (AOR 1.5, 95% CI: 1.1–1.9). Of 6 newborns with symptomatic syphilis, 2 expired shortly after birth, and 2 were HIV-infected. Conclusion: Syphilis continues to be a common co-infection in HIV-infected women and can facilitate in utero transmission of HIV to infants. Most infants are asymptomatic at birth, but those with symptoms have high mortality rates.

Missed opportunities for prevention of mother-to-child transmission of human immunodeficiency virus type 1 in Latin America and the Caribbean: the NISDI perinatal study.

Cases of mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) in a prospective cohort study in Latin America and the Caribbean were analyzed. Eight of 820 eligible infants became infected [transmission rate, 0.98% (95% CI = 0.45–1.96%)]. Five cases (62%) represented missed opportunities for prevention of MTCT of HIV-1, suggesting the need for ongoing training and education of clinicians regarding prevention of MTCT of HIV-1.

Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes

Background: Sexually transmitted infections (STIs) in pregnancy such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may lead to adverse infant outcomes. Methods: Individual urine specimens from HIV-infected pregnant women diagnosed with HIV during labor were collected at the time of infant birth and tested by polymerase chain reaction for CT and NG. Infant HIV infection was determined at 3 months with morbidity/mortality assessed through 6 months. Results: Of 1373 maternal urine samples, 277 (20.2%) were positive for CT and/or NG; 249 (18.1%) for CT, 63 (4.6%) for NG and 35 (2.5%) for both CT and NG. HIV infection was diagnosed in 117 (8.5%) infants. Highest rates of adverse outcomes (sepsis, pneumonia, congenital syphilis, septic arthritis, conjunctivitis, low birth weight, preterm delivery and death) were noted in infants of women with CT and NG (23/35, 65.7%) compared with NG (16/28, 57.1%), CT (84/214, 39.3%) and no STI (405/1096, 37%, P = 0.001). Death (11.4% vs. 3%, P = 0.02), low birth weight (42.9% vs. 16.9%, P = 0.001) and preterm delivery (28.6% vs. 10.2%, P = 0.008) were higher among infants of CT and NG-coinfected women. Infants who had any adverse outcome and were born to women with CT and/or NG were 3.5 times more likely to be HIV infected after controlling for maternal syphilis (odds ratio: 3.5, 95% confidence interval: 1.4–8.3). By adjusted multivariate logistic regression, infants born to mothers with any CT and/or NG were 1.35 times more likely to have an adverse outcome (odds ratio, 1.35; 95% confidence interval, 1.03–1.76). Conclusions: STIs in HIV-infected pregnant women are associated with adverse outcomes in HIV-exposed infected and uninfected infants.