Zika virus infection during pregnancy and vertical transmission: case reports and peptide-specific cell-mediated immune responses.

Zika virus (ZIKV) infection in pregnant women is associated with birth defects, which are more prevalent and severe the earlier in pregnancy the infection occurs. Pregnant women at risk of possible ZIKV exposure (n = 154) were screened using ELISA for ZIKV IgM and IgG. Nine of 154 (5.84%) pregnant women who underwent screening exhibited positive ZIKV serology. Of these, two maternal infections were confirmed by real-time RT-PCR and five were considered probable, but only three of those were retained for further analysis based on strict diagnostic criteria. Plaque reduction neutralization tests (PRNT) confirmed ZIKV infection in nine cases (5.84%). Two cases of vertical ZIKV transmission were confirmed by PCR. One infant showed no signs of congenital ZIKV syndrome and had a normal developmental profile despite first-trimester maternal infection. In the second case, pregnancy was terminated. Production of interferon γ (IFN-γ) by peripheral blood mononuclear cells obtained from pregnant women and umbilical cord blood was measured using enzyme-linked immunospot assay (ELISpot) after stimulation with panels of synthetic peptides derived from the sequence of ZIKV proteins. This analysis revealed that, among all peptide pools tested, those derived from the ZIKV envelope protein generated the strongest IFN-γ response.

Successful Pediatric Heart Transplantation from a Deceased Donor with SARS-Cov-2 Infection: A Case Report.

We report the case of a 3-year-old who was highly sensitized and received cardiac transplantation from a donor in the acute phase of SARS-CoV-2 infection. Despite maximal immunosuppression owing to a positive cross-match and desensitization protocol, the patient's course was favorable.

Identifying Clinical Criteria for an Expanded Targeted Approach to Screening for Congenital Cytomegalovirus Infection-A Retrospective Study.

Targeted screening for congenital CMV infection (cCMV), which entails CMV testing of infants who fail newborn hearing screening (NBHS), has become common practice. However, this strategy misses nearly all infected infants with normal hearing at birth who are nonetheless at high risk of subsequent hearing loss and would benefit from timely cCMV diagnosis. The objective of this study was to identify expanded criteria predictive of cCMV to increase the scope and utility of targeted newborn CMV screening. In this retrospective study, 465 newborns were tested for cCMV at a single tertiary care center with a targeted screening program between 2014 and 2018. Twenty-two infants were diagnosed with cCMV, representing 0.2% of the 12,189 births over this period and 4.7% of the infants tested. The highest prevalence of cCMV infection was among infants tested because of primary maternal CMV infection (8/42, 19%), followed by failed initial NBHS (10/88, 11.4%), maternal HIV infection (3/137, 2.2%), and clinical suspicion alone (5/232, 2.2%). The symptoms with the highest prevalence of infection among all infants tested included an enlarged liver and/or spleen (33.3%) (3/9), followed by petechiae (33.3%), microcephaly (9.4%), direct hyperbilirubinemia (7.7%), thrombocytopenia (6%), and growth impairment (4.3%). In addition to CMV screening of newborns who fail the NBHS, these data suggest that certain clinical signs of cCMV-in particular: thrombocytopenia, growth impairment, and HIV exposure in pregnancy-should be additional criteria for expanded targeted newborn CMV screening, where universal screening is not yet the standard of care.

Mitigating healthcare staffing shortages: Should healthcare workers with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) household exposures work?

In a tertiary-care, pediatric healthcare center in Québec, Canada, healthcare workers who reported a household exposure to confirmed coronavirus disease 2019 (COVID-19) cases were allowed to work. On repeated testing, 15% became severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-positive by reverse-transcription polymerase chain reaction (RT-PCR), with no nosocomial transmission. Being asymptomatic and receiving a booster dose >7 days prior to exposure was protective against becoming SARS-CoV-2-positive by PCR.

Prenatal findings, neonatal symptoms and neurodevelopmental outcome of congenital cytomegalovirus infection in a university hospital in Montreal, Quebec.

Background Outcome of congenital cytomegalovirus (cCMV) infection in the absence of routine CMV screening and third-trimester scan in North America is scarcely documented. The aim of this study was to assess the severe outcomes related to cCMV according to the indication for screening. Methods This was a retrospective study of 84 mother-child pairs followed for cCMV between 2003 and 2017 at CHU Sainte-Justine in Montreal, Canada. Prenatal ultrasound, neonatal symptoms, neuroimaging and severe outcomes (cerebral palsy, severe cognitive impairment, bilateral hearing loss or neonatal death) were reviewed. Results Among 38 cases with abnormal prenatal ultrasound, 41.9% of live-born infants developed severe outcomes. Sixteen (42.1%) were detected in the third trimester. Among 16 cases diagnosed prenatally because of maternal history, all had normal prenatal ultrasound, and none developed severe outcomes. Among cases diagnosed postnatally because of neonatal symptoms, 25% developed severe outcomes. All infants who developed severe outcomes had moderate/severe neonatal symptoms. Conclusion Outcome of cCMV infection varies according to the reason for screening and timing of diagnosis. Any prenatal ultrasound anomaly might indicate a risk of severe outcome, and warrants a detailed ultrasound scan. However, late detection, or postnatal diagnosis, represented more than half of the cases, and awareness of this will help ensuring optimal management.

Pregnancies Among the First Generation of Survivors of Perinatal HIV Infection.

OBJECTIVE: Little is known about pregnancy outcomes among women who have acquired human immunodeficiency virus (HIV) through perinatal infection and survived into adulthood. The objectives of this study were to describe pregnancy outcomes among women with perinatal HIV infection (PHIV) in Canada and to identify potential challenges in the prevention of perinatal HIV transmission in this population. METHODS: A retrospective review of all pregnancies among women with PHIV who were previously followed as children at two tertiary care centres in Montréal, Québec, was conducted. Data were extracted from pediatric and obstetrical records. RESULTS: There were 21 pregnancies among 11 women, and 18 of these pregnancies were unintentional. Mean age at first pregnancy was 19.5 years (range 15-29 years). At the first prenatal visit, 79% had a detectable viral load, 36% were immunosuppressed (CD4 T cell count <200 mm3), and only 36% were receiving antiretroviral therapy (ART). At the time of delivery, although all were prescribed ART, 50% of these women still had a detectable viral load, and 36% remained immunosuppressed. All of the women harboured mutations conferring drug resistance to zidovudine and lamivudine, and the majority (73%) were also resistant to nevirapine. None of the infants were HIV infected, although all received prophylaxis with agents to which their mother's virus was resistant. CONCLUSION: Unplanned pregnancies, difficulties with adherence to ART, and drug resistance were identified challenges in the management of pregnancies among women with PHIV. This study highlights a gap in the reproductive counselling of adolescents with PHIV and the need for close follow-up and adherence support during pregnancy in this population.

Blood viral load in the diagnostic workup of congenital cytomegalovirus infection.

BACKGROUND: There is limited data on the role of cytomegalovirus (CMV) blood quantitative polymerase chain reaction (qPCR) in the diagnostic workup of congenital CMV (cCMV) infection. OBJECTIVES: The objective of this study was to determine if CMV blood qPCR at the time diagnosis could differentiate between symptomatic and asymptomatic infants according to the recent consensus classification. STUDY DESIGN: Retrospective study of children diagnosed with cCMV infection at CHU Sainte-Justine, Montreal, Canada, between 2008 and 2016. Cases for whom qPCR was done at baseline (<4 weeks of age) alongside a complete diagnostic workup were included. The association between CMV blood viral load (VL) and clinical severity group was determined. The probability of having moderate to severe symptoms was assessed using univariate logistic regression analysis. RESULTS: Forty-seven patients were included in the analysis. Median VL was significantly higher among infants with moderate to severely symptomatic disease vs. those asymptomatic or asymptomatic with isolated sensorineural hearing loss (SNHL) (13 736 vs. 1876 copies/ml, p = 0.004), infants with moderate to severe disease or asymptomatic with isolated SNHL vs. asymptomatic (17 736 vs. 1496 copies/ml, p < 0.001), and in infants with baseline neurological involvement vs. those without (17 317 vs. 2641 copies/ml, p = 0.03). Using logistic regression, an infant would have a >75 % probability of being moderate to severely symptomatic above 18 770 copies/ml, with a threshold of 100 000 copies/ml approaching a 100 % probability. CONCLUSIONS: Our baseline assessment of CMV blood VL suggests that that the level of CMV viremia correlates with symptom severity.

Challenges to achieving and maintaining viral suppression among children living with HIV.

OBJECTIVES: The objective of this study was to determine the time to, and durability of, viral suppression, among Canadian children living with HIV after initiation of combination antiretroviral therapy (cART). DESIGN: Prospective, multicenter Canadian cohort study (Early Pediatric Initiation Canada Child Cure Cohort), using both prospective and retrospectively collected data. METHODS: Kaplan-Meir survival estimates with Cox regression were used to determine the time to and risk factors for viral suppression, defined as two consecutive undetectable viral loads (<50 copies/ml) at least 30 days apart after initiation of cART. RESULTS: A total of 228 children were enrolled between December 2014 and December 2018. The time to viral suppression was significantly shorter among children initiating cART after 5 ≤ 5 vs. years or less of age [adjusted hazard ratio (aHR) 1.57, 95% confidence interval (CI) 1.13-2.20], among those born after 2010 vs. prior (aHR 1.71, 95% CI 1.04-2.79), and among those without child protection services involvement (aHR 1.44, 95% CI 1.03-2.01). Overall, 27% of children had a viral rebound within 3 years of achieving viral suppression; the risk of viral rebound was significantly lower among children initiating cART after 5 vs. 5 years or less of age [adjusted odds ratio (aOR): 0.32, 95% CI 0.13-0.81], those whose families had not received social assistance (aOR 0.16, 95% CI 0.06-0.46), and females vs. males (aOR 0.51, 95% CI 0.26-0.99). CONCLUSION: Only 73% of the children in the Early Pediatric Initiation Canada Child Cure Cohort had maintained viral suppression 3 years after it was first achieved. Age at cART initiation, and socioeconomic factors were predictors of both time to viral suppression and risk of viral rebound in this cohort.

Head ultrasound, CT or MRI? The choice of neuroimaging in the assessment of infants with congenital cytomegalovirus infection.

BACKGROUND: Despite growing interest in universal screening for congenital CMV infection (cCMV), and data to support treatment for cases with central nervous system (CNS) involvement, there is limited regarding the optimal imaging modalities to identify CNS involvement. The objective of this study was to assess the concordance between head ultrasound (US) and magnetic resonance imaging (MRI) or computed tomography (CT), in identifying neurological abnormalities in infants with cCMV infection, and to determine whether the addition of advanced neuroimaging after US had an impact on clinical management. METHODS: Retrospective review of infants with cCMV infection, referred to the Centre d'Infectiologie Mère-Enfant (CIME) at Sainte-Justine Hospital Center in Montreal, between 2008 and 2016. Only patients who underwent head US followed by and brain MRI or CT scan were included in this analysis. RESULTS: Of 46 cases of cCMV identified during the study period, 34 (74%) had a head US followed by MRI (n = 28, 61%), or CT scan (n = 6, 13%). In the majority of cases (n = 24, 71%), both images were concordant (11 both reported abnormal, 13 both reported normal). In 5 cases, US was reported normal and subsequent imaging (MRI = 4, CT = 1); reported abnormal. In all 5 cases patients were clinically symptomatic and met treatment criteria even in the absence of neuroimaging findings. In 5 cases, US was reported abnormal with a subsequent normal MRI (4) or CT (1); in 2 of these cases, patients were clinically symptomatic and met treatment criteria regardless of neuroimaging findings. However, in 3 cases, the patients were clinically asymptomatic, and in 2 of these cases, treated based only on the abnormal US findings. CONCLUSIONS: In this study, we found that that sequential US and MRI were concordant in the majority (71%) of cases in detecting abnormalities potentially associated with cCMV infection. While the addition of MRI to baseline head ultrasound did not influence the decision to treat in clinically symptomatic infants, the addition of MRI to infants with abnormal HUS imaging who are clinically asymptomatic could help refine treatment decisions in these cases.

Use of Triple Combination Antiretroviral Therapy With Raltegravir as Empiric HIV Therapy in the High-risk HIV-exposed Newborn.

The recent approval of raltegravir granules for suspension in the newborn population offers a new option for the antiretroviral prophylaxis of newborns for the prevention of perinatal transmission. However, there are little data on its use in preterm infants, nor on outcomes following its use as empiric HIV therapy for newborns subsequently found to be infected. We describe here the use of RAL granules for suspension in these cases.

Quasispecies Diversity Is a Major Risk Factor for Vertical Hepatitis C Virus Transmission.

BACKGROUND: Vertical transmission is the major cause of pediatric hepatitis C virus (HCV) infection. The objective of this study was to better understand HCV pathogenesis in pregnant women and provide insights into risk factors and mechanisms involved in vertical transmission. METHODS: Evolutionary dynamics of HCV variant spectra and HCV-specific neutralizing antibody responses were examined using high-throughput sequencing and pseudoparticle-based assays in pregnant women monoinfected with HCV (n = 17) or coinfected with HCV and human immunodeficiency virus (HIV)-1 (n = 15). RESULTS: Overall, statistically significant associations were found between HCV quasispecies diversity, selective pressure exerted on the HCV E2 envelope protein, and neutralizing activity of maternal immunoglobulins. Women with low quasispecies diversity displayed significantly higher mean aspartate aminotransferase and alanine aminotransferase levels throughout pregnancy, but this difference was restricted to monoinfected participants. Low quasispecies diversity and inefficient neutralizing activity were also significantly associated with vertical transmission, but only in the monoinfected group. CONCLUSIONS: These results indicate that maternal neutralizing antibody responses play a role in the prevention of vertical HCV transmission, but not in presence of HIV-1 coinfection, and suggest that the mechanism of vertical transmission may be different between monoinfected and coinfected women. These findings could inform management strategies for the prevention of vertical HCV transmission.

Use of Cytomegalovirus-Specific Hyperimmunoglobulins in Pregnancy: A Retrospective Cohort.

OBJECTIVE: There is no consensus on the use of cytomegalovirus (CMV)-specific hyperimmunoglobulins (CSHIGs) for suspected congenital CMV infections during pregnancy, but this therapy is currently used in some countries. The objectives of this study were to describe tolerability and pregnancy outcome following treatment with monthly intravenous CSHIG and compare rates of positive PCR and postnatal symptoms according to whether CSHIGs were given or not. METHODS: This retrospective cohort study included all pregnant women who were diagnosed with primary CMV infection or congenital CMV infection at the Centre Hospitalier Universitaire Sainte-Justine (Montreal, QC) between 2005 and 2016. CSHIG was discussed with pregnant women who received positive CMV PCR results from amniotic fluid or if ultrasound anomalies suggested congenital infection and there was serologic evidence of maternal primary infection (therapeutic group). CSHIG was also offered as prophylaxis in pregnant women without fetal ultrasound anomalies but with evidence of maternal primary infection, when amniocentesis either had negative results or was not performed (prophylactic group). A matched analysis was performed to control for timing of maternal infection, amniocentesis, and type and timing of ultrasound anomaly. RESULTS: Sixteen women received CSHIG, and 55 had no CMV-specific treatment. CSHIG treatment was well-tolerated. In bivariate analyses, the risk of congenital CMV infection and postnatal symptoms did not significantly decrease with CSHIG treatment, in both the therapeutic and the prophylactic groups. After matching, there was still no difference in outcomes between CSHIG-treated and untreated women. CONCLUSION: The effectiveness of CSHIG in preventing congenital CMV infection and its clinical manifestations could not be demonstrated.

Vertical Transmission of Hepatitis C Virus: Variable Transmission Bottleneck and Evidence of Midgestation In Utero Infection.

Hepatitis C virus (HCV) can be transmitted from mother to child during pregnancy and childbirth. However, the timing and precise biological mechanisms that are involved in this process are incompletely understood, as are the determinants that influence transmission of particular HCV variants. Here we report results of a longitudinal assessment of HCV quasispecies diversity and composition in 5 cases of vertical HCV transmission, including 3 women coinfected with human immunodeficiency virus type 1 (HIV-1). The population structure of HCV variant spectra based on E2 envelope gene sequences (nucleotide positions 1491 to 1787), including hypervariable regions 1 and 2, was characterized using next-generation sequencing and median-joining network analysis. Compatible with a loose transmission bottleneck, larger numbers of shared HCV variants were observed in the presence of maternal coinfection. Coalescent Bayesian Markov chain Monte Carlo simulations revealed median times of transmission between 24.9 weeks and 36.1 weeks of gestation, with some confidence intervals ranging into the 1st trimester, considerably earlier than previously thought. Using recombinant autologous HCV pseudoparticles, differences were uncovered in HCV-specific antibody responses between coinfected mothers and mothers infected with HCV alone, in whom generalized absence of neutralization was observed. Finally, shifts in HCV quasispecies composition were seen in children around 1 year of age, compatible with the disappearance of passively transferred maternal immunoglobulins and/or the development of HCV-specific humoral immunity. Taken together, these results provide insights into the timing, dynamics, and biologic mechanisms involved in vertical HCV transmission and inform preventative strategies.IMPORTANCE Although it is well established that hepatitis C virus (HCV) can be transmitted from mother to child, the manner and the moment at which transmission operates have been the subject of conjecture. By carrying out a detailed examination of viral sequences, we showed that transmission could take place comparatively early in pregnancy. In addition, we showed that when the mother also carried human immunodeficiency virus type 1 (HIV-1), many more HCV variants were shared between her and her child, suggesting that the mechanism and/or the route of transmission of HCV differed in the presence of coinfection with HIV-1. These results could explain why cesarean section is ineffective in preventing vertical HCV transmission and guide the development of interventions to avert pediatric HCV infection.

Health outcomes and the transition experience of HIV-infected adolescents after transfer to adult care in Québec, Canada.

BACKGROUND: Little is known on outcomes after transition to adult care among adolescents with perinatal HIV infection. Though there is data from other chronic pediatric diseases suggesting increased morbidity and mortality following transfer to adult care, this has not well been studied among the first wave of survivors of perinatal HIV infection. The primary objective of this study was to determine outcomes after transition to adult care among a cohort of HIV-infected adolescents in Québec, Canada. Secondary objectives were to document participant experiences with the transition process, identify barriers to successful transition, and potential changes to improve the transition process. METHODS: Clinic records were reviewed to identify all perinatally-infected youth who transitioned from the Centre Maternel et Infantile sur le Sida pediatric HIV clinic (Montreal) at age 18 to an adult care provider between 1999 and 2012. Transitioned patients were contacted using last available patient or parental listed phone number on hospital record, internet based telephone directory, or social media. A standardized questionnaire was administered by telephone or in-person interview, and copies of current medical records obtained from treating physicians. RESULTS: Forty-five patients were transferred between 1999 and 2012, among whom 25 consented to the study, eight were lost to follow-up, eight refused participation, and four were deceased. Overall 76 % of patients remained engaged in care, defined by at least one physician visit within 6 months of the interview. Over 50 % reported difficulty with adherence to their current drug regimens. At one-year post-transfer, there was a decrease in the proportion of patients with CD4 count >500 cells/mm(3) from 64 to 29 %, and a statistically significant decrease in absolute CD4 count (mean 370 vs 524 cells/mm(3), p = 0.04.). The majority (92 %) of participants felt that 18 was too young an age to transfer to adult care, and provided suggestions for improving the transition process. CONCLUSIONS: This group of perinatally-infected youth remained engaged in care after transition, however difficulties with adherence and assuming responsibility for their own care were identified as issues in their post-transition care. The high rate of mortality among them and the changes to their health status post-transition suggest that further work is necessary to document the health outcomes of this group in larger, more diverse cohort settings.

Awareness of cytomegalovirus and risk factors for susceptibility among pregnant women, in Montreal, Canada.

BACKGROUND: Advances in diagnostic and therapeutic modalities for congenital cytomegalovirus (CMV) infection have generated a mounting interest in identifying mothers susceptible to CMV. The objectives of this study were to evaluate the prevalence and socio-demographic determinants of CMV susceptibility and CMV awareness, among pregnant women, in Montreal, Quebec. METHODS: Between April and December 2012, women delivering at Centre Hospitalier Universitaire Sainte Justine were recruited for the study. Stored serum from the first trimester of pregnancy was tested for CMV IgG. Knowledge about CMV and socio-demographic characteristics were collected via standardized questionnaire. RESULTS: Four hundred and ninety one women were enrolled in the study. Overall, 225 mothers (46%) were seronegative for CMV, and 85% (n = 415) were unaware of CMV or the associated risks in pregnancy. Significant risk factors for CMV seronegative status included Canadian vs. foreign born (aOR 6.88, 95% CI 4.33-10.94), and high vs. low family income (aOR 4.68, 95% CI 2.09-10.48). Maternal employment status was the only significant predictor of CMV unawareness, with unemployed mothers at the highest risk (aOR 85.6, 95% CI 17.3-421.3). CONCLUSIONS: Nearly half of pregnant women studied were at risk of primary infection, and yet, the majority was unaware of potential risks associated with CMV. Canadian born mothers and those with a high socioeconomic status were more likely to be CMV seronegative. Increased education about CMV infection, through public health interventions and obstetrician/pediatric counseling, is needed for all pregnant women.

Risk factors for pre-term birth in a Canadian cohort of HIV-positive women: role of ritonavir boosting?

BACKGROUND: The risk of pre-term birth (PTB) associated with the use of protease inhibitors (PIs) during pregnancy remains a subject of debate. Recent data suggest that ritonavir boosting of PIs may play a specific role in the initiation of PTB, through an effect on the maternal-fetal adrenal axis. The primary objective of this study is to compare the risk of PTB among women treated with boosted PI versus non-boosted PIs during pregnancy. METHODS: Between 1988 and 2011, 705 HIV-positive women were enrolled into the Centre Maternel et Infantile sur le SIDA mother-infant cohort at Centre Hospitalier Universitaire Sainte-Justine in Montreal, Canada. Inclusion criteria for the study were: 1) attendance at a minimum of two antenatal obstetric visits and 2) singleton live birth, at 24 weeks gestational or older. The association between PTB (defined as delivery at <37 weeks gestational age), antiretroviral drug exposure and maternal risk factors was assessed retrospectively using logistic regression. RESULTS: A total of 525 mother-infant pairs were included in the analysis. Among them, PI-based combination anti-retroviral therapy was used in 37.4%, boosted PI based in 24.4%, non-nucleoside reverse transcriptase inhibitor (NNRTI) or nucleoside reverse transcriptase inhibitor based in 28.1%, and no treatment was given in 10.0% of cases. Overall, 13.5% of women experienced PTB. Among women treated with antiretroviral therapy, the risk of PTB was significantly higher among women who received boosted versus non-boosted PI (OR 2.01, 95% CI 1.02-3.97). This remained significant after adjusting for maternal age, delivery CD4 count, hepatitis C co-infection, history of previous PTB, and parity (aOR 2.17, 95% CI 1.05-4.51). There was no increased risk of PTB with the use of unboosted PIs as compared to NNRTI- or NRTI-based regimens. CONCLUSION: While previous studies on the association between PTB and PI use have generally considered all PIs the same, our results would indicate a possible role of ritonavir boosting as a risk factor for PTB. Further work is needed to understand the pathophysiologic mechanisms involved, and to identify the safest ARV regimens to be used in pregnancy.

Impact of maternal HIV-1 viremia on lymphocyte subsets among HIV-exposed uninfected infants: protective mechanism or immunodeficiency.

BACKGROUND: Reports of increased morbidity and mortality from infectious diseases among HIV Exposed Uninfected (HEU) infants have raised concern about a possible underlying immunodeficiency among them. The objective of this study was to assess the immunological profile of HEU infants born to mothers exhibiting different levels of HIV-1 viremia at the time of delivery. METHODS: Study subjects were enrolled in the Centre maternel et infantile sur le SIDA (CMIS) mother-child cohort between 1997 and 2010 (n =585). Infant CD4+ T cell, CD8+ T cell and CD19+ B cell counts were assessed at 2 and 6 months of age, and compared among HEU infants in groups defined by maternal viral load (VL) at the time of delivery (VL < 50 copies/ml, VL 50-1000 copies/ml, and VL > 1000 copies/ml) in a multivariable analysis. RESULTS: At 2 months of age, infants born to mothers with VL > 1000 copies/ml had lower CD4+ T cell counts compared to those born to mothers with VL < 50 copies/ml at the time of delivery (44.3% versus 48.3%, p = 0.007, and 2884 vs. 2432 cells/mm3, p = 0.02). These differences remained significant after adjusting for maternal and infant antiretroviral drug use, gender, race and gestational age, and persisted at 6 months of age. There were no differences in CD8+ T cell count or absolute CD19+ B cell count between groups, though higher CD19+ B cell percentage was seen among infants born to mothers with VL > 1000 copies/ml. CONCLUSIONS: These results suggest that exposure to high levels of HIV-1 viremia in utero, even in the absence of perinatal transmission, may affect the infant's developing immune system. While further work needs to be done to confirm these findings, they reinforce the need for optimal treatment of HIV infected pregnant women, and careful follow-up of HEU infants.

The Young and the Resistant: HIV-Infected Adolescents at the Time of Transfer to Adult Care.

Combined antiretroviral therapy allows children with human immunodeficiency virus (HIV) to reach adulthood. We studied 45 adolescents at the time of transfer to adult care. Despite universal healthcare access, over two-thirds of the adolescents were failing treatment, which was manifested by detectable HIV-1 viral load, CD4 counts <200 cells/ mm(3), and/or triple-class drug resistance.

Leukocyte telomere length in HIV-infected and HIV-exposed uninfected children: shorter telomeres with uncontrolled HIV viremia.

OBJECTIVES: Nucleoside reverse transcriptase inhibitors (NRTIs) used in HIV antiretroviral therapy can inhibit human telomerase reverse transcriptase. We therefore investigated whether in utero or childhood exposure to NRTIs affects leukocyte telomere length (LTL), a marker of cellular aging. METHODS: In this cross-sectional CARMA cohort study, we investigated factors associated with LTL in HIV-1-infected (HIV(+)) children (n = 94), HIV-1-exposed uninfected (HEU) children who were exposed to antiretroviral therapy (ART) perinatally (n = 177), and HIV-unexposed uninfected (HIV(-)) control children (n = 104) aged 0-19 years. Univariate followed by multivariate linear regression models were used to examine relationships of explanatory variables with LTL for: a) all subjects, b) HIV(+)/HEU children only, and c) HIV(+) children only. RESULTS: After adjusting for age and gender, there was no difference in LTL between the 3 groups, when considering children of all ages together. In multivariate models, older age and male gender were associated with shorter LTL. For the HIV(+) group alone, having a detectable HIV viral load was also strongly associated with shorter LTL (p = 0.007). CONCLUSIONS: In this large study, group rates of LTL attrition were similar for HIV(+), HEU and HIV(-) children. No associations between children's LTL and their perinatal ART exposure or HIV status were seen in linear regression models. However, the association between having a detectable HIV viral load and shorter LTL suggests that uncontrolled HIV viremia rather than duration of ART exposure may be associated with acceleration of blood telomere attrition.