Maternal Viral Load Research Articles

Missed opportunities for prevention of mother-to-child transmission of HIV-1 in the NISDI Perinatal and LILAC cohorts

ObjectiveTo evaluate cases of mother-to-child transmission of HIV-1 at multiple sites in Latin America and the Caribbean in terms of missed opportunities for prevention. MethodsPregnant women infected with HIV-1 were eligible for inclusion if they were enrolled in either the NISDI Perinatal or LILAC protocols by October 20, 2009, and had delivered a live infant with known HIV-1 infection status after March 1, 2006. ResultsOf 711 eligible mothers, 10 delivered infants infected with HIV-1. The transmission rate was 1.4% (95% CI, 0.7–2.6). Timing of transmission was in utero or intrapartum (n=5), intrapartum (n=2), intrapartum or early postnatal (n=1), and unknown (n=2). Possible missed opportunities for prevention included poor control of maternal viral load during pregnancy; late initiation of antiretrovirals during pregnancy; lack of cesarean delivery before labor and before rupture of membranes; late diagnosis of HIV-1 infection; lack of intrapartum antiretrovirals; and incomplete avoidance of breastfeeding. ConclusionEarly knowledge of HIV-1 infection status (ideally before or in early pregnancy) would aid timely initiation of antiretroviral treatment and strategies designed to prevent mother-to-child transmission. Use of antiretrovirals must be appropriately monitored in terms of adherence and drug resistance. If feasible, breastfeeding should be completely avoided. Presented in part at the XIX International AIDS Conference (Washington, DC; July 22-27, 2012); abstract WEPE163.

Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV Infection

BackgroundThe safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants.MethodsWithin 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth.ResultsA total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan–Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two- and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P<0.001 for both comparisons with the other groups).ConclusionsIn neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two- or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.)

Antiretroviral Adherence During Pregnancy and Postpartum in Latin America

Adherence to antiretrovirals by pregnant women (and postpartum women if breastfeeding) is crucial to effectively decrease maternal viral load and decrease the risk of mother-to-child transmission of HIV. Our objectives were to describe self-reported adherence to antiretrovirals during the antepartum (after 22 weeks of pregnancy) and postpartum periods (6-12 weeks and 6 months), and identify predictors of adherence among HIV-infected women enrolled and followed in a prospective cohort study from June 2008 to June 2010 at multiple sites in Latin America. Adherence was evaluated using the number of missed and expected doses during the 3 days before the study visit. At the pre-delivery visit, 340 of 376 women (90%) reported perfect adherence. This rate significantly decreased by 6-12 weeks (171/214 [80%]) and 6 months postpartum (163/199 [82%], p<0.01). The odds for less than perfect adherence at the pre-delivery visit was significantly higher for pregnant women with current tobacco use (odds ratio [OR]=2.9, 95% confidence interval [CI]: 1.46-6.14; p=0.0029). At 6-12 weeks postpartum, the probability of non-perfect adherence increased by 6% for each 1 year increase in age (OR=1.06, 95% CI: 1.00-1.12, p=0.0497). At 6 months postpartum, the odds of nonperfect adherence was higher for those who were currently using alcohol (OR=3.04, 95% CI: 1.34-6.90; p=0.0079). Although a self-report measure of adherence based on only 3 days may lead to overestimation of actual adherence over time, women with perfect adherence had lower viral loads and higher CD4 counts. Adherence to antiretrovirals decreased significantly postpartum. Interventions should target women at high risk for lower adherence during pregnancy and postpartum, including tobacco and alcohol users.

Infant Outcomes After Maternal Antiretroviral Exposure in Resource-Limited Settings

The impact of maternal antiretrovirals (ARVs) during pregnancy, labor, and postpartum on infant outcomes is unclear. Infants born to HIV-infected mothers in ARV studies were followed for 18 months. Between June 2006 and December 2008, 236 infants enrolled from Africa (n = 36), India (n = 47), Thailand (n = 152), and Brazil (n = 1). Exposure to ARVs in pregnancy included ≥ 3 ARVs (10%), zidovudine/intrapartum ARV (81%), and intrapartum ARV (9%). There were 4 infant infections (1 in utero, 3 late postpartum) and 4 deaths with 1.8% mortality (95% confidence interval [CI], 0.1%-3.5%) and 96.4% HIV-1-free survival (95% CI, 94.0%-98.9%). Birth weight was ≥ 2.5 kg in 86%. In the first 6 months, Indian infants (nonbreastfed) had lowest median weights and lengths and smallest increases in growth. After 6 months, African infants had the lowest median weight and weight-for-age z scores. Infants exposed to highest maternal viral load had the lowest height and height-for-age z scores. Serious adverse events occurred in 38% of infants, did not differ by country, and correlated with less maternal ARV exposure. Clinical diagnoses were seen in 84% of Thai, 31% of African, and 9% of Indian infants. Congenital defects/inborn errors of metabolism were seen in 18 (7.6%) infants, of which 17 were Thai (11%: 95% CI, 6.7%-17.0%); none had first trimester ARV exposure. Infant follow-up in large international cohorts is feasible and provides important safety and HIV transmission data following maternal ARV exposure. Increased surveillance increases identification of congenital/inborn errors.

Hepatitis C infection in childhood

Hepatitis C infection in children has a different course than in adults, with higher rates of spontaneous clearance. Prenatal (vertical) transmission is the most common route of transmission in childhood. Only a high maternal viral load and HIV co-infection have been proven to increase the risk of infection in the offspring. There is thus no evidence to recommend abstinence from breastfeeding, or elective C-section to prevent transmission. Standard interferon, pegylated interferon and ribavirin are the only approved therapies in children. Severe liver disease is extremely rare in childhood, and described mainly in patients contaminated through blood transfusion.

A rare case of non immune fetal hydrops secondary to parvovirus B19 infection in only one twin in a dichoronic-diamniotic twin pregnancy

Non Immune Fetal Hydrops (FH) caused by Parvovirus B19 in one dichorionic-diamnotic (DCDA) twin has been reported but remains extremely rare.1 2 We describe FH affecting one twin in a...

477 HIV CO-INFECTION IS AN INDEPENDENT FACTOR IN DETERMINING VACCINE SCAPE MUTANTS AMONG HEPATITIS B CHRONIC PATIENTS IN BRAZIL

Trabalho apresentado no The International Liver Congress, 2012; Annual Meeting of The European Association for The Study of The Liver, 47., 2012. Barcelona

HIV Infection in Infants and Children - An Updated Review

DOI: http://dx.doi.org/10.3329/bjch.v34i2.10219 BJCH2010; 34(2): 62-66

Risk factors for mother‐to‐child transmission of hepatitis C virus: Maternal high viral load and fetal exposure in the birth canal

Mother-to-child transmission (MTCT) is the major transmission pathway of hepatitis C virus (HCV) in children. However, its risk factors remain unsettled for introduction of putative intervention. Pregnant women screened for HCV and MTCT in children born to antibody-positive mothers were prospectively studied in Tottori, Japan. Among 41 856 screened women, 188 (0.45%) were HCV antibody-positive, of whom 61% had detectable HCV RNA. While 10 of the 34 children (29%) born to high viral load (HVL: ≥6.0 × 10(5) IU/mL) mothers were infected, none born to RNA-detectable but non-HVL mothers were infected (P < 0.001). MTCT among vaginally delivered children born to HVL mothers was analyzed. Children delivered after 4 h or more of labor were more frequently infected than were those born within 4 h of labor (P = 0.019). Premature rupture of fetal membranes was significantly more common in infected children than in uninfected children (P < 0.001). Durations of membrane rupture and labor were longer in infected children than in uninfected children (P = 0.008 and P = 0.040, respectively). Elective cesarean section that eliminates these risk factors, other than HVL, significantly reduced MTCT from nine of 22 (41%) to none of nine children (0%) (P = 0.032). Our data suggest that contamination of the fetus in the birth canal with infected maternal blood is a major risk factor for HCV MTCT, in addition to maternal HVL. To rationalize intervention by elective cesarean section, the natural history of infected children should be carefully evaluated.

HIV-1 mother-to-child transmission and drug resistance among Brazilian pregnant women with high access to diagnosis and prophylactic measures

BackgroundA high-coverage public health prenatal program (70,000 women/year) from central western Brazil/Goias State has represented a unique opportunity for the early diagnosis of HIV-1 and implementation of strategies to prevent mother-to-child transmission (MTCT). ObjectivesTo investigate MTCT among a prospective cohort of HIV-1 infected mothers/exposed infants. Study design142 mothers/their 149 infants (2008–2010) were investigated regarding maternal viral load, CD4+cell counts, HIV-1 pol sequences; infants’ HIV-1 RNA tests (30/120days), sequential anti-HIV-1/2 serology. HIV-1 subtypes were assigned by REGA. Transmitted drug resistance was identified by the Calibrated Population Resistance tool, secondary resistance by Stanford HIV-1 Drug Resistance/International AIDS Society databases. ResultsMothers (median age=24 years; 25/142 adolescents) were diagnosed during prenatal care (2008–2010) or previously (1994–2007). Recent cases were younger, mostly asymptomatic. Undetectable viremia and MTCT prophylaxis predominated in formerly diagnosed mothers. Recent cases had higher subtype C prevalence. One naive patient had transmitted resistance; ten antiretroviral-experienced patients had secondary resistance: 6 from MTCT prophylaxis, 4 under HAART. Late disclosure of diagnosis, vaginal delivery, breastfeeding, lack of oral zidovudine were observed in the three MTCT cases (3/149; 2.01%). Two of three infected infants harbored subtype C; infected infants/mothers did not have drug resistance mutations. Two of the transmitting-mothers had viremia <1000 copies/ml. Among exposed-uninfected infants the median time to seroreversion was 12 months. ConclusionsIn this study delayed disclosure of diagnosis, partial/no preventive measures, drug resistance among asymptomatic women under prophylaxis and MTCT in low viremic mothers raise concerns. The expansion of subtype C infection corroborates surveillance of HIV-1 diversity in this region.

The role of G protein gene GNB3 C825TPolymorphism in HIV-1 acquisition, progression and immune activation

BackgroundThe GNB3 C825T polymorphism is associated with increased G protein-mediated signal transduction, SDF-1α-mediated lymphocyte chemotaxis, accelerated HIV-1 progression, and altered responses to antiretroviral therapy among Caucasian subjects. The GNB3 825T allele is highly prevalent in African populations, and as such any impact on HIV-1 acquisition or progression rates could have a dramatic impact. This study examines the association of the 825T polymorphism with HIV-1 acquisition, disease progression and immune activation in two African cohorts. GNB3 825 genotyping was performed for enrolees in both a commercial sex worker cohort and a perinatal HIV transmission (PHT) cohort in Nairobi, Kenya. Ex vivo immune activation was quantified by flow cytometry, and plasma chemokine levels were assessed by cytokine bead array.ResultsGNB3 genotype was not associated with sexual or vertical HIV-1 acquisition within these cohorts. Within the Pumwani cohort, GNB3 genotype did not affect HIV-1 disease progression among seroconverters or among HIV-1-positive individuals after adjustment for baseline CD4 count. Maternal CD4 decline and viral load increase in the PHT cohort did not differ between genotypes. Multi-parametric flow cytometry assessment of T cell activation (CD69, HLA-DR, CD38) and Treg frequency (CD25+FOXP3+) found no differences between genotype groups. Plasma SDF-1α, MIP-1β and TRAIL levels quantified by cytokine bead array were also similar between groups.ConclusionsIn contrast to previous reports, we were unable to provide evidence to suggest that the GNB3 C825T polymorphism affects HIV-1 acquisition or disease progression within African populations. Ex vivo immune activation and plasma chemokine levels were similarly unaffected by GNB3 genotype in both HIV-1-negative and HIV-1-positive individuals. The paucity of studies investigating the impact of GNB3 polymorphism among African populations and the lack of mechanistic studies make it difficult to assess the true biological significance of this polymorphism in HIV-1 infection.

Postexposure Infant Prophylaxis in High-risk Situations of Human Immunodeficiency Virus Type 1 Transmission

To the Editors: We read with great interest the article by Stern and Muniz entitled “Fever and rash in an 8-month-old girl” published in “Your diagnosis, please” section.1 Much progress has been made in recent years in preventing mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Postexposure infant prophylaxis (PIP), through administration of antiretroviral drugs to the infant starting within hours of birth, could be important in preventing the infection from viruses that entered the fetus.2 However, cases of perinatal HIV infection still occur, mainly when available preventive interventions are not provided.3,4 The authors described a case of a full-term infant with high risk of HIV infection: the mother was prescribed highly active antiretroviral therapy (HAART) during pregnancy but had not taken the medications consistently and had an HIV viral load of 22,500 copies/mL during her third trimester of pregnancy. The infant was ultimately HIV infected. We want to focus on the role of the PIP in these situations. The authors noted that “AZT was prescribed, but the child did not complete the recommended 6-week course.” In the United States, the Public Health Service Task Force guidelines recommend that infants born to HIV-infected women should receive 6 weeks of oral zidovudine (AZT) alone, irrespective of the risk of transmission.5 However, other guidelines from European countries recommend combination antiretroviral prophylaxis for infants born to mothers with high-level viremia.6,7 Although well-designed studies of combined antiretroviral prophylaxis for infants born to women receiving HAART but with persistent high-level viremia are admittedly lacking, there is increasing evidence in other high-risk situations of HIV transmission suggesting that children born to mothers with high-level viremia, even if receiving HAART, should receive combination antiretroviral prophylaxis. Maternal viral load is considered the best predictor of the risk of vertical transmission of HIV. In the HAART era, MTCT risk is associated with high maternal viral load (for viral load ≥10,000 copies/mL, adjusted odds ratio = 12.1; P = 0.003).8 When women presented at delivery with unknown HIV status, PIP with nevirapine plus AZT reduced transmission of HIV more than did a regimen of nevirapine alone.9 Neonatal PIP with 2 or 3 antiretroviral drugs was also superior to AZT alone for prevention of intrapartum HIV transmission among infants born to women not receiving antiretroviral drugs before labor in a recent study.10 Although higher rates of anemia and neutropenia have been reported with combination antiretroviral PIP, this approach has been well tolerated in full-term infants from cohort studies.11 Therefore, in this high risk of HIV transmission situation, we believe that the use of 2 or 3 antiretroviral drugs could be justified to further reduce the risk of HIV MTCT compared with the reduction in risk achieved by use of AZT alone. Luis M. Prieto, MD Pablo Rojo, MD Paediatrics Department Jose T. Ramos, MD Department of Pediatric Infectious Diseases Hospital Universitario de Getafe Madrid, Spain

Pregnancy outcomes in adolescents in the UK and Ireland growing up with HIV

Adolescents with HIV infection acquired perinatally or in early childhood are becoming sexually active, but little is known about fertility and pregnancy outcomes. Multicentre data on pregnancy outcomes in this population are described here. A retrospective case note review of pregnant women with perinatal/early acquired HIV infection, conceiving before 1 September 2009 and attending participating centres in the UK and Ireland, was carried out. Among 252 women with perinatal/early acquired infection aged 12 years and older under follow-up in 21 centres, 42 pregnancies were reported in 30 women (19 women with a single pregnancy, 10 women with two pregnancies, and one woman with three pregnancies). Fifteen women (50%) had previous AIDS-defining diagnoses. The median age at first reported pregnancy was 18 years (range 14-22 years). Of the 42 pregnancies, 34 (81%) were reportedly unplanned, 31 (74%) involved regular partners, and in 21 (50%) of the 42 pregnancies the partners were reported to be unaware of maternal HIV status. Fifteen of the 42 pregnancies (36%) were electively terminated, six of the 42 (14%) resulted in first-trimester miscarriages and 21 of the 42 (50%) resulted in live births. Maternal viral load was detectable close to delivery in seven of 21 pregnancies (33%). Four infants required neonatal intensive care, three of whom were delivered preterm. One infant is HIV infected, there are ongoing concerns about the development of three of 21 infants (14%), and two of 21 (10%) have been fostered. Despite access to ongoing sexual health and contraceptive services, unplanned pregnancies are occurring in young women growing up with HIV. Pregnancy care and prevention of onward transmission require complex case management for this emerging population.

Host factors that influence mother-to-child transmission of HIV-1: genetics, coinfections, behavior and nutrition.

Mother-to-child transmission (MTCT) is the most important mode of HIV-1 acquisition among infants and children and it can occur in utero, intrapartum and postnatally through breastfeeding. Great progress has been made in preventing MTCT through use of antiretroviral regimens during gestation, labor/delivery and breastfeeding. The mechanisms of MTCT, however, are multifactorial and remain incompletely understood. This review focuses on select host factors affecting MTCT, in particular genetic factors, coexisting infections, behavioral factors and nutrition. Whereas much emphasis has been placed on decreasing maternal HIV-1 viral load, an important determinant of MTCT, through use of antiretroviral agents, complementary focus on overall maternal health is often neglected. By addressing coinfections in mothers and infants, improving the mother's nutritional status and modifying risky behaviors and practices, not only is maternal and child health improved, but a direct benefit in reducing MTCT can be derived. The study of genetic variations in susceptibility to HIV-1 infection is rapidly evolving, and the future is likely to bring revolutionary changes in HIV-1 prevention by enhancing natural resistance to infection and by individually tailoring pharmacologic regimens.

Interaction between nk cells and HLA-G1 at the placental interface of HIV-1 infected pregnant women: additional risk factors or physiological association?

Background: Human Leucocyte Antigen-G (HLA-G) molecules are involved in the inhibition of cell-mediated immune responses and could promote the propagation of HIV-1 infection across the placental interface thus increasing the risk of vertical transmission. Therefore, the objective of this study was to assess whether the Major Histocompatibility Complex (MHC) - coded molecule HLA-Ginhibits Natural Killer (NK) cell activity thereby, assisting viral penetration across the placental barrier in HIV-1 positive pregnant women. Study Design & Methods: Natural Killer (CD56+) cell activity and placental HLA-G1 expression was assessed using immunohistochemistry and real-time polymerase chain reaction (RT-PCR) techniques, respectively. Studies were performed on a total of fifty five placental samples obtained from HIV-1 infected mothers at birth. Results: Low numbers of NK cells increased risk of vertical transmission [OR = 3.424 (95%CI 0.65-17.89)]. The risk of babies becoming infected increased by 1.3 with every 1 unit increase in HLA-G1 expression. A positive correlation was observed between mothers’ log viral load and transmission of infection to the baby (p = 0.047; 95%CI 1.029-11.499). Conclusion: Low NK cell activity at the placental interface increased the risk of vertical transmission. Maternal viral load remained a strong predictor of viral transmission.

Quantifying the impact of nevirapine-based prophylaxis strategies to prevent mother-to-child transmission of HIV-1: a combined pharmacokinetic, pharmacodynamic, and viral dynamic analysis to predict clinical outcomes.

Single-dose nevirapine (sd-NVP) and extended NVP prophylaxis are widely used in resource-constrained settings to prevent vertical HIV-1 transmission. We assessed the pharmacokinetics of sd-NVP in 62 HIV-1-positive pregnant Ugandan woman and their newborns who were receiving sd-NVP prophylaxis to prevent mother-to-child HIV-1 transmission. Based on these data, we developed a mathematical model system to quantify the impact of different sd-NVP regimens at delivery and of extended infant NVP prophylaxis (6, 14, 21, 26, 52, 78, and 102 weeks) on the 2-year risk of HIV-1 transmission and development of drug resistance in mothers and their breast-fed infants. Pharmacokinetic parameter estimates and model-predicted HIV-1 transmission rates were very consistent with other studies. Predicted 2-year HIV-1 transmission risks were 35.8% without prophylaxis, 31.6% for newborn sd-NVP, 19.1% for maternal sd-NVP, and 19.7% for maternal/newborn sd-NVP. Maternal sd-NVP reduced newborn infection predominately by transplacental exchange, providing protective NVP concentrations to the newborn at delivery, rather than by maternal viral load reduction. Drug resistance was frequently selected in HIV-1-positive mothers after maternal sd-NVP. Extended newborn NVP prophylaxis further decreased HIV-1 transmission risks, but an overall decline in cost-effectiveness for increasing durations of newborn prophylaxis was indicated. The total number of infections with resistant virus in newborns was not increased by extended newborn NVP prophylaxis. The developed mathematical modeling framework successfully predicted the risk of HIV-1 transmission and resistance development and can be adapted to other drugs/drug combinations to a priori assess their potential in reducing vertical HIV-1 transmission and resistance spread.

Expression of HLA-G1 at the placental interface of HIV-1 infected pregnant women and vertical transmission of HIV

Objectives The ability of Human Leucocyte Antigen-G (HLA-G) to inhibit the cytolytic effect to immunocompetent cell types, suggests that HLA-G has an immunomodulatory role. In view of this concept the objective of the study was to assess whether the Major Histocompatibility Complex -coded molecule HLA-G mRNA is a risk factor at the placental barrier in HIV-1 positive pregnant women. Design Placental HLA-G1 levels in HIV-1 infected mothers and viral loads in both mothers and their babies were performed on fifty-five participants. Methods Synthesis of complementary deoxyribose nucleic acid (cDNA) was performed using ribose nucleic acid (RNA) extracted from placental tissue samples. Amplification of cDNA using specifically designed primers complementary to the full length HLA-G1 isoform was quantified using real time-polymerase chain reaction (RT-PCR). Viral load assays (Amplicor Version 1.5, Roche Diagnostics) were performed on all plasma samples. Results HLA-G1 primers detected the full length isoform HLA-G1 PCR product at 86.5 °C. Logistic regression calculations indicated that the risk of babies becoming infected increased by 1.3 with every 1 unit increase in HLA-G1 expression. Female babies were 3.7 times more likely to become infected than male. There was a positive correlation between mothers’ log viral load and transmission of infection to the baby ( p = 0.047; 95%CI 1.029–11.499). Conclusion Maternal viral load was a strong predictor of viral transmission. Placental HLA-G1 expression was up-regulated 3.95 times more in placentas of HIV-1 infected mothers with infected babies when compared to uninfected babies.

Use of Zidovudine-Sparing HAART in Pregnant HIV-Infected Women in Europe: 2000–2009

Increasing numbers of women in resource-rich settings are prescribed zidovudine (ZDV)-sparing highly active antiretroviral therapy (HAART) in pregnancy. We compare ZDV-sparing with ZDV-containing HAART in relation to maternal viral load at delivery, mother-to-child transmission (MTCT) of HIV, and congenital abnormality. This is an analysis of data from the National Study of HIV in Pregnancy and Childhood and the European Collaborative Study. Data on 7573 singleton births to diagnosed HIV-infected women between January 2000 and June 2009 were analyzed. Logistic regression models were fitted to estimate adjusted odds ratios (AORs). Overall, 15.8% (1199 of 7573) of women received ZDV-sparing HAART, with increasing use between 2000 and 2009 (P < 0.001). Nearly a fifth (18.4%) of women receiving ZDV-sparing HAART in pregnancy had a detectable viral load at delivery compared with 28.6% of women on ZDV-containing HAART [AOR 0.90; 95% confidence interval (CI): 0.72 to 1.14, P = 0.4]. MTCT rates were 0.8% and 0.9% in the ZDV-sparing and ZDV-containing groups, respectively (AOR 1.81; 95% CI: 0.77 to 4.26, P = 0.2). The congenital abnormality rate was the same in both groups (2.7%, AOR 0.98; 95% CI: 0.66 to 1.45, P = 0.9), with no significant difference between the groups in a subanalysis of pregnancies with first trimester HAART exposure (AOR 0.79; 95% CI: 0.48 to 1.30, P = 0.4). We found no difference in risk of detectable viral load at delivery, MTCT, or congenital abnormality when comparing ZDV-sparing with ZDV-containing HAART. With increasing use of ZDV-sparing HAART, continued monitoring of pregnancy outcomes and long-term consequences of in utero exposure to these drugs is required.

In Uteroand Postnatal Exposure to Antiretrovirals Among HIV-Exposed But Uninfected Children in the United States

An increasing number of antiretroviral agents (ARVs) are approved for use, but their use during pregnancy in the United States has not been completely described. We used data from the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring for ART Toxicities (SMARTT) study, a United States-based prospective cohort study of HIV-exposed but uninfected children, to assess temporal trends and maternal characteristics associated with the use of ARVs during pregnancy. The proportion of children exposed in utero to ARVs was calculated over time. A multivariable logistic regression model was used to estimate associations of maternal characteristics with use of highly active antiretroviral therapy (HAART) during pregnancy. We studied 1768 HIV-exposed but uninfected children born between 1995 and 2009 and enrolled in SMARTT. Prenatal HAART exposure increased from 19% in 1997 to 88% in 2009. Of children born in 2009, 99% had prenatal exposure to NRTIs (including zidovudine, 73%; lamivudine, 72%; tenofovir, 39%; and emtricitabine, 37%). Exposure to protease inhibitors increased from 15% in 1997 to 86% in 2009, while exposure to non-nucleoside reverse transcriptase inhibitors (NNRTIs) declined from 33% in 2003 to 11% in 2009. Higher maternal HIV RNA viral load (VL) concentration, lower maternal CD4 count, and earlier timing of the first maternal CD4 or VL measurement during pregnancy were associated with increased odds of HAART exposure. Prenatal HAART exposure has increased but is not universal. As ARV use during pregnancy continues to evolve, follow-up of children is needed to assess long-term effects of ARV exposures.

Genetic variation in interleukin 28B with respect to vertical transmission of hepatitis C virus and spontaneous clearance in HCV-infected children

The vertical transmission of hepatitis C virus (HCV-VT) is a major route of HCV infection in children, but the risk factors remain incompletely understood. This study analyzed the role of interleukin 28B (IL28B) in HCV-VT and in the spontaneous clearance of HCV among infected infants. Between 1991 and 2009, 145 mothers were recruited for this study: 100 were HCV-RNA+ve / human immunodeficiency virus negative (HIV-ve), with 128 children, and 33 were HCV-RNA-ve/HCV antibody+ve, with 43 children. The infants were tested for HCV-RNA at birth and at regular intervals until the age of 6 years. IL28B (single nucleotide polymorphism rs12979860) was determined in the mothers and children. HCV-VT was assumed when children presented HCV-RNA+ve in two subsequent blood samples. HCV-VT-infected infants were categorized as: (1) transient viremia with posterior HCV-RNA-ve and without serum-conversion; (2) persistent infection with serum-conversion. Of the 31 mothers with CC polymorphism, 19 (61%) were HCV-RNA+ve, whereas among the 68 mothers with non-CC polymorphism, 56 (82%) were HCV-RNA+ve. In all, 26 of 128 (20%) infants born to the HCV-RNA+ve mothers acquired HCV infection, but only 9 (7%) were chronically infected. The rate of HCV-VT was higher among the mothers with higher HCV viremia. No HCV-VT was detected in the HCV-RNA-ve women. Neither the mothers' nor the childrens' IL-28 status was associated with an increased risk of HCV-VT. The factors influencing viral clearance among the infected children were genotype non-1 and genotype CC of IL28B. In logistic regression, child CC polymorphism was the only predictor of HCV-clearance in HCV genotype-1. High maternal viral load is the only predictive factor of HCV-VT. IL28B plays no role in HCV-VT, but IL28B CC child polymorphism is associated independently with the spontaneous clearance of HCV genotype-1 among infected children.