Rohan Hazra

University of Washington Seattle, Seattle, Washington, United States

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Publications (91)365.71 Total impact

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    ABSTRACT: Objective: To evaluate the association of in utero exposure to highly active antiretroviral therapy (HAART) with left ventricular (LV) function and structure in HIV-exposed uninfected (HEU) children. Design: Prospective multi-site cohort study in HIV-exposed uninfected children conducted by the Pediatric HIV/AIDS Cohort Study (PHACS). Methods: Echocardiographic measures of LV systolic and diastolic function and cardiac structure were obtained from HEU subjects aged ≥ 6 years enrolled in the PHACS Surveillance Monitoring of ART Toxicities (SMARTT) study. Echocardiographic Z-scores were calculated using normative data from an established reference cohort. We used adjusted linear regression models to compare Z-scores for echocardiographic measures from HEU children exposed in utero to HAART with those exposed to non-HAART antiretroviral therapy (ARV), adjusting for demographic and maternal health characteristics. Results: 174 HEU youth with echocardiograms and maternal ARV information were included (mean age 10.9 years; 48% male, 56% Black non-Hispanic). We observed no differences in Z-scores for LV systolic function measures for those exposed in utero to HAART (39%) compared to HAART-unexposed in either unadjusted or adjusted models. In adjusted models, those exposed to HAART had significantly lower mitral late diastolic inflow velocities (adjusted mean Z-score=0.00 vs 0.52, p=0.04) and significantly higher LV mass-to-volume ratio Z-scores (adjusted mean Z-score=0.47 vs 0.11, p=0.03) than HAART-unexposed. Conclusions: Uninfected children with perinatal exposure to HAART had no difference in LV systolic function. However, small but significant differences in LV diastolic function and cardiac structure were observed, suggesting that continued monitoring for cardiac outcomes is warranted in this population.
    No preview · Article · Jan 2016 · AIDS Research and Human Retroviruses
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    ABSTRACT: We sought to determine the prevalence of abnormal acylcarnitine profiles (ACP) in HIV-exposed uninfected (HEU) newborns and explore the association of abnormal ACP with clinical laboratory outcomes and antiretroviral drug exposures. Clinically, ACP are used to assess for fatty acid oxidation (FAO) dysfunction and normal FAO is necessary for optimal fetal/neonatal growth and development. We analyzed serum ACP in 522 HEU neonates enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study (PHACS) and evaluated associations of abnormal ACP with in utero exposure to combination antiretroviral therapy (cART) in logistic regression models, adjusting for maternal demographic, disease and behavioral characteristics. We evaluated associations of abnormal ACP with laboratory parameters and measures of neurodevelopment and growth. Of 522 neonates, 89 (17%) had abnormal ACP. In adjusted analyses, in utero exposure to a protease inhibitor (PI) was associated with higher odds of having an abnormal ACP (adjusted odds ratio (aOR) = 2.35, 95% CI: 0.96, 5.76, p = 0.06) with marginal significance while exposure to a non-nucleoside reverse transcriptase inhibitor (NNRTI) was associated with lower odds (aOR = 0.23, 95% CI: 0.07, 0.80, p = 0.02). Mean ALT levels were slightly higher in those with abnormal ACP, but no differences in lactate, glucose or CPK were observed. ACP status was not associated with neurodevelopment at 1 year or growth at 2 and 3 years of age. Abnormal ACP in HEU neonates are associated with exposure to PI-containing as opposed to NNRTI-containing ARV regimens but are not associated with serious postnatal clinical problems. Further studies are needed to determine the long-term health implications of abnormal acylcarnitine metabolism at birth in HEU children.
    No preview · Article · Nov 2015 · AIDS research and human retroviruses
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    ABSTRACT: Objective: To evaluate the safety of in-utero antiretroviral exposure in children born to mothers with HIV, using a trigger-based design. Design: The Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites to evaluate safety of in-utero antiretroviral drug exposure in HIV-uninfected children born to HIV-infected mothers. Children meeting predefined clinical or laboratory thresholds have more intensive evaluations to determine whether they meet criteria for adverse events. Methods: Adverse event "cases" were defined for the following domains: growth, hearing, language, neurology, neurodevelopment, metabolic, hematologic/clinical chemistry and blood lactate. We used adjusted log-binomial models to calculate relative risks (RR) of case status overall and within individual domains for various antiretroviral exposures during pregnancy. Results: Among 2680 youth enrolled between 2007 and 2012 (48% female, 66% black, 33% Hispanic), 48% met a trigger and 25% were defined as a case in at least one domain. Language (13.2%) and metabolic (11.4%) cases were most common. After adjustment for birth cohort and other factors, there was no association of any antiretroviral regimen, drug class, or individual drug with meeting overall case criteria (case in any domain). Within individual domains, zidovudine (74% exposed) was associated with increased risk of metabolic case [RR = 1.69, 95%confidence interval (CI) 1.08-2.64] and didanosine plus stavudine (<1% exposed) with increased risk of both neurodevelopmental (RR = 12.40, 95%CI 5.29-29.08) and language (RR = 4.84, 95%CI 1.14-20.51) cases. Conclusion: Our findings support current recommendations for combination antiretroviral therapy during pregnancy, although higher risk of metabolic disorder with zidovudine exposure warrants further study.
    No preview · Article · Oct 2015 · AIDS
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    ABSTRACT: Background: Combination antiretroviral therapy (cART) has resulted in a dramatic decrease in human immunodeficiency virus (HIV)-related opportunistic infections and deaths in US youth, but both continue to occur. Methods: We estimated the incidence of complications and deaths in IMPAACT P1074, a long-term US-based prospective multicenter cohort study conducted from April 2008 to June 2014. Incidence rates of selected diagnoses and trends over time were compared with those from a previous observational cohort study, P219C (2004-2007). Causes of death and relevant demographic and clinical features were reviewed. Results: Among 1201 HIV-infected youth in P1074 (87% perinatally infected; mean [standard deviation] age at last chart review, 20.9 [5.4] years), psychiatric and neurodevelopmental disorders, asthma, pneumonia, and genital tract infections were among the most common comorbid conditions. Compared with findings in P219C, conditions with significantly increased incidence included substance or alcohol abuse, latent tuberculosis, diabetes mellitus, atypical mycobacterial infections, vitamin D deficiency or metabolic bone disorders, anxiety disorders, and fractures; the incidence of pneumonia decreased significantly. Twenty-eight deaths occurred, yielding a standardized mortality rate 31.5 times that of the US population. Those who died were older, less likely to be receiving cART, and had lower CD4 cell counts and higher viral loads. Most deaths (86%) were due to HIV-related medical conditions. Conclusions: Opportunistic infections and deaths are less common among HIV-infected youth in the US in the cART era, but the mortality rate remains elevated. Deaths were associated with poor HIV control and older age. Emerging complications, such as psychiatric, inflammatory, metabolic, and genital tract diseases, need to be addressed.
    No preview · Article · Aug 2015 · Clinical Infectious Diseases
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    ABSTRACT: To assess thepharmacokinetic (PK), safety and efficacy of dolutegravir plus optimized background regimen (OBR) in HIV infected treatment-experienced adolescents. Children ≥12 to < 18 yearsreceived dolutegravir weight-based fixed doses at ~1.0 mg/kg once daily in a Phase I/II multicenter open-label 48 week study. Intensive PK evaluation was done at steady state after dolutegravir was added to a failing regimen or started at the end of a treatment interruption. Safety and HIV RNA and CD4 cell count assessments were performed through Week 48. Twenty three adolescents, were enrolled and 22 (96%) completed the 48 week study visit. Median age and weight were 15 years and 52 kg, respectively. Median (IQR) baseline CD4+ cell count was 466 cells/µL (297, 771). Median (IQR) baseline HIV-1 RNA log10 was 4.3 log10 copies/mL (3.9, 4.6). Dolutegravir geometric mean AUC(0-24) and C24 were 46.0 µg.h/mL and 0.90 µg/mL, respectively, which were within the study targets based on adult PK ranges. Virologic success with an HIV RNA < 400 copies/mL was achieved in 74 % (95% CI: 52% to 90%) at Week 48. Additionally, 61% (95% CI: 39% to 80%) had an HIV RNA < 50 copies/mL at Week 48. Median (IQR) gain in CD4 cell count at Week 48 was 84 cells/µL (-81, 238). Dolutegravir was well tolerated, with no Grade 4 AEs, SAEs or discontinuations due to AEs. Dolutegravir achieved target PK exposures in adolescents. Dolutegravir was safe and well tolerated, providing good virologic efficacy through Week 48.
    Full-text · Article · Aug 2015 · The Pediatric Infectious Disease Journal

  • No preview · Article · Jul 2015 · JAIDS Journal of Acquired Immune Deficiency Syndromes
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    ABSTRACT: Objective: This study compared 12-month CD4 and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies. Design: This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C. Methods: Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4% and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models. Results: Virologic failure occurred in 939 out of 2373 (40%) children. At 12 months, children switching to new cART (16%) had a nonsignificant increase in CD4% from baseline, 0.59 percentage points [95% confidence interval (95% CI) -1.01 to 2.19], not different than those who continued failing cART (71%) (-0.64 percentage points, P = 0.15) or switched to a drug-sparing regimen (5%) (1.40 percentage points, P = 0.64). Children discontinuing all ART (7%) experienced significant CD4% decline -3.18 percentage points (95% CI -5.25 to -1.11) compared with those initiating new cART (P = 0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log10VL by 12 months, the new cART group having the largest drop (-1.15 log10VL). Conclusion: In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring.
    Full-text · Article · Jul 2015 · AIDS (London, England)
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    ABSTRACT: Background: Fetal bone effects of maternal tenofovir use have not been well studied. We sought to compare whole-body bone mineral content (BMC) of newborns exposed vs not exposed to tenofovir in utero. Methods: We enrolled participants from April 2011 to June 2013 at 14 US clinical sites. Singleton infants of women with human immunodeficiency virus (HIV) infection who took tenofovir in late pregnancy (tenofovir-exposed) or no tenofovir during pregnancy (tenofovir-unexposed) were enrolled during late pregnancy or within 72 hours of birth. Infants born before 36 weeks gestation or with confirmed HIV infection were excluded. Whole-body BMC was measured in the first month of life and compared with that of the tenofovir-exposed and tenofovir-unexposed newborns, unadjusted and adjusted for covariates. Results: Seventy-four tenofovir-exposed and 69 tenofovir-unexposed infants had evaluable BMC measurements. Tenofovir-exposed mothers were more likely to be married (31% vs 22%; P = .04) and to use boosted protease inhibitors (84% vs 62%; P = .004). Tenofovir-exposed newborns did not differ from unexposed newborns on mean gestational age (38.2 vs 38.1 weeks) or mean length (-0.41 vs -0.18) or weight (-0.71 vs -0.48) Z-scores. The mean (standard deviation) BMC of tenofovir-exposed infants was 12% lower than for unexposed infants (56.0 [11.8] vs 63.8 [16.6] g; P = .002). The adjusted mean bone mineral content was 5.3 g lower (95% confidence interval, -9.5, -1.2; P = .013) in the tenofovir-exposed infants. Conclusions: Maternal tenofovir use is associated with significantly lower neonatal BMC. The duration and clinical significance of this finding should be evaluated in longitudinal studies. Clinical trials registration: NCT01310023.
    Full-text · Article · Jun 2015 · Clinical Infectious Diseases
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    ABSTRACT: To investigate whether prenatal atazanavir (ATV) exposure, assessed by meconium antiretroviral (ARV) quantification, predicts early child language outcomes. Prenatal ATV exposure previously was associated with poorer language development in 1-year olds. Pregnant women with HIV and their uninfected infants enrolled in the Surveillance Monitoring of Antiretroviral Therapy Toxicities study. Meconium ARV concentrations were quantified by liquid chromatography-tandem mass spectrometry. Language development at 1 year was assessed with MacArthur-Bates Communicative Development Inventory (CDI) and Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). Late language emergence was defined as ≥1 of 4 CDI scores ≤10th percentile for age. Associations between fetal ATV exposure timing and duration, meconium ATV concentration, and language outcomes were evaluated, adjusting for potential confounders. Through 2013, meconium samples were available from 175 of 432 infants with prenatal ATV exposure. Valid Bayley-III (n = 93) and CDI (n = 106) assessments also were available. After adjustment for potential confounders, higher ATV meconium concentrations were associated with lower late language emergence risk (P = 0.04) and cumulative ATV exposure duration also was associated with higher Bayley-III Language scores (P = 0.03). Maternal ATV duration and initiation week correlated with ATV meconium concentrations (positively and negatively, respectively). Higher meconium ATV concentrations were protective against developmental language delays at 1 year, suggesting the importance of fetal ATV detoxification into meconium. This information supports ATV exposure safety for infant language development. ATV is a preferred ARV for pregnant women with HIV, suggesting the importance of ATV safety investigations. Additionally, further pursuit of the influences on language development in HIV-exposed uninfected infants is required.
    Full-text · Article · Jun 2015 · JAIDS Journal of Acquired Immune Deficiency Syndromes
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    ABSTRACT: Maternal tenofovir disoproxil fumarate (TDF) treatment among HIV-infected pregnant women results in fetal tenofovir (TFV) exposure. Fetal TFV toxicity was demonstrated in animals, but most clinical investigations have not observed toxicity in humans. We evaluated HIV-exposed, uninfected infants in the SMARTT cohort of the Pediatric HIV/AIDS Cohort Study whose mothers were prescribed TDF for ≥8 third trimester weeks. Infant dual-energy X-ray absorptiometry (DXA) scans were obtained at 0-4 weeks to measure whole body bone mineral content (BMC). Meconium TFV concentrations were quantified by liquid chromatography-tandem mass spectrometry. Fifty-eight TFV-exposed infants had meconium TFV quantified. Detectable concentrations were 11-48,100 ng/g; 3 infants had undetectable concentrations. Maternal TDF prescription duration ranged from 8-41 gestational weeks; infant gestational ages were 36-41 weeks. Meconium TFV concentrations were not correlated with TFV exposure duration or timing and did not vary by concomitant prescription of protease inhibitors. Increased meconium TFV concentrations were associated with greater gestational ages (ρ=0.29, P=0.03) and lower maternal plasma HIV RNA before delivery (ρ=-0.29, P=0.04). Meconium TFV concentrations were not associated with infant weight, length (n=58), or BMC (n=49). For the first time, we explored associations between meconium TFV concentrations and infant growth and bone measurements; we did not observe a meconium concentration-dependent relationship for these infant outcomes. These findings support other clinical research failing to show dose-response relationships for growth and bone outcomes among intrauterine TFV-exposed infants. High meconium TFV concentrations correlated with low maternal viral load, suggesting maternal TDF adherence significantly contributes to meconium TFV concentrations.
    Full-text · Article · May 2015 · The Pediatric Infectious Disease Journal
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    ABSTRACT: Some perinatally infected children do not regain normal CD4 T-cell counts despite suppression of HIV-1 plasma viremia by antiretroviral therapy (ART). The frequency, severity and significance of these discordant treatment responses remain unclear. We examined the persistence of CD4 lymphocytopenia despite virologic suppression in 933 children (≥5 years of age) in the USA, Latin America and the Caribbean. CD4 T-cell trajectories were examined and Kaplan-Meier methods used to estimate median time to CD4 T-cell count at least 500 cells/μl. After 1 year of virologic suppression, most (99%) children achieved a CD4 T-cell count of at least 200 cells/μl, but CD4 T-cell counts remained below 500 cells/μl after 1 and 2 years of virologic suppression in 14 and 8% of children, respectively. Median times to first CD4 T-cell count at least 500 cells/μl were 1.29, 0.78 and 0.46 years for children with less than 200, 200-349 and 350-499 cells/μl at the start of virologic suppression. New AIDS-defining events occurred in nine children, including four in the first 6 months of virologic suppression. Other infectious and HIV-related diagnoses occurred more frequently and across a wide range of CD4 cell counts. ART improved CD4 cell counts in most children, but the time to CD4 cell count of at least 500 cells was highly dependent upon baseline immunological status. Some children did not reach a CD4 T-cell count of 500 cells/μl despite 2 years of virologic suppression. AIDS-defining events occurred in 1% of the population, including children in whom virologic suppression and improved CD4 T-cell counts were achieved.
    No preview · Article · Mar 2015 · AIDS
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    ABSTRACT: Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of human immunodeficiency virus-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with human immunodeficiency virus viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable' viral load (<400copies/mL). At enrollment, 90.8% of participants were perfectly (100%) adherent, compared to 87.6% at the 6-month and 92.0% at the 12-month visit; the proportion with perfect adherence did not differ over time (p=0.1). Perfect adherence was associated with a higher probability of undetectable viral load at the 12-month visit (odds ratio=4.1, 95% confidence interval: 1.8-9.1; p<0.001), but not at enrollment or the 6-month visit (p>0.3). Last time missed any antiretroviral therapy dose was reported as "never" for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p<0.001 for test of trend). The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p≤0.005), but not at the 6-month visit (p=0.2). While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.
    No preview · Article · Mar 2015 · The Brazilian journal of infectious diseases: an official publication of the Brazilian Society of Infectious Diseases
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    ABSTRACT: Objective: To estimate the association of age of viral suppression and central nervous system penetration effectiveness (CPE) score with neurocognitive functioning among school-age children with perinatally acquired HIV infection (PHIV+). Design: We analyzed data from two US-based multisite prospective cohort studies. Methods: Multivariable general linear regression models were used to evaluate associations of age at viral suppression and CPE scores (of initial antiretroviral therapy regimen and weighted average) with the Wechsler Intelligence Scale for Children, Third or Fourth Edition neurocognitive assessments [Full-Scale Intelligence Quotient (FSIQ); Performance IQ/Perceptual Reasoning Index (PIQ/PRI); and Verbal IQ/Verbal Comprehension Index (VIQ/VCI)], adjusted for demographic and clinical covariates. Sensitivity analyses were stratified by birth cohort (before versus after 1996). Results: A total of 396 PHIV+ children were included. Estimated differences in mean FSIQ (comparing virally suppressed versus unsuppressed children) by each age cutoff were 3.7, 2.2, 3.2, 4.4, and 3.9 points at ages 1, 2, 3, 4, and 5, respectively. For PIQ/PRI, estimated mean differences were 3.7, 2.4, 2.2, 4.6, and 4.5 at ages 1 through 5, respectively. In both cases, these differences were significant only at the age 4 and 5 thresholds. After stratifying by birth cohort, the association between age at suppression and cognitive function persisted only among those born after 1996. Age at viral suppression was not associated with VIQ/VCI; CPE score was not associated with FSIQ, verbal comprehension, or perceptual reasoning indices. Conclusion: Virologic suppression during infancy or early childhood is associated with improved neurocognitive outcomes in school-aged PHIV+ children. In contrast, CPE scores showed no association with neurocognitive outcomes.
    Full-text · Article · Jan 2015 · AIDS
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    ABSTRACT: Background Limited data are available for once-daily (QD) darunavir (DRV)/ritonavir (r) in the pediatric population. Coadministration of etravirine (ETR) may alter the pharmacokinetics (PK) of DRV. We evaluated the PK interactions between DRV/r (QD) and ETR QD or twice-daily (BID) in children, adolescents, and young adults.
    No preview · Article · Jan 2015
  • Peter L Havens · Rohan Hazra

    No preview · Article · Jan 2015 · The Pediatric Infectious Disease Journal
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    Full-text · Article · Jan 2015 · Clinical Infectious Diseases
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    ABSTRACT: Background: The CD4 cell count or percent (CD4%) at the start of combination antiretroviral therapy (cART) is an important prognostic factor in children starting therapy and an important indicator of program performance. We describe trends and determinants of CD4 measures at cART initiation in children from low-, middle-, and high-income countries. Methods: We included children aged <16 years from clinics participating in a collaborative study spanning sub-Saharan Africa, Asia, Latin America, and the United States. Missing CD4 values at cART start were estimated through multiple imputation. Severe immunodeficiency was defined according to World Health Organization criteria. Analyses used generalized additive mixed models adjusted for age, country, and calendar year. Results: A total of 34,706 children from 9 low-income, 6 lower middle-income, 4 upper middle-income countries, and 1 high-income country (United States) were included; 20,624 children (59%) had severe immunodeficiency. In low-income countries, the estimated prevalence of children starting cART with severe immunodeficiency declined from 76% in 2004 to 63% in 2010. Corresponding figures for lower middle-income countries were from 77% to 66% and for upper middle-income countries from 75% to 58%. In the United States, the percentage decreased from 42% to 19% during the period 1996 to 2006. In low- and middle-income countries, infants and children aged 12-15 years had the highest prevalence of severe immunodeficiency at cART initiation. Conclusions: Despite progress in most low- and middle-income countries, many children continue to start cART with severe immunodeficiency. Early diagnosis and treatment of HIV-infected children to prevent morbidity and mortality associated with immunodeficiency must remain a global public health priority.
    No preview · Article · Jan 2015 · JAIDS Journal of Acquired Immune Deficiency Syndromes
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    ABSTRACT: Importance Most studies examining the association of prenatal antiretroviral (ARV) exposures with congenital anomalies (CAs) in children born to human immunodeficiency virus (HIV)–infected women have been reassuring, but some evidence suggests an increased risk with specific ARV agents.Objective To evaluate the association of in utero ARV exposures with CAs in HIV-exposed uninfected children.Design, Setting, and Participants Prospective cohort study design. The Pediatric HIV/AIDS Cohort Study’s Surveillance Monitoring of ART Toxicities (SMARTT) Study was performed at 22 US medical centers among 2580 HIV-exposed uninfected children enrolled in the SMARTT Study between March 23, 2007, and June 18, 2012.Exposures First-trimester exposure to any ARV and to specific ARV medications.Main Outcomes and Measures The primary end point was a CA based on physician review of infant physical examinations according to the Antiretroviral Pregnancy Registry modification of the Metropolitan Atlanta Congenital Defects Program. Rates of CAs were estimated overall and by birth year. Logistic regression models were used to evaluate the association of CAs with first-trimester ARV exposures, adjusting for demographic and maternal characteristics.Results Congenital anomalies occurred in 175 of 2580 children, yielding a prevalence of 6.78% (95% CI, 5.85%-7.82%); 242 major CAs were confirmed, including 72 musculoskeletal and 55 cardiovascular CAs. The prevalence of CAs increased significantly among successive birth cohorts (3.8% for children born before 2002 and up to 8.3% for those born 2008-2010). In adjusted models, no association of first-trimester exposures with CAs was found for any ARV, for combination ARV regimens, or for any drug class. No individual ARV in the reverse transcriptase inhibitor drug classes was associated with an increased risk of CAs. Among protease inhibitors, higher odds of CAs were observed for atazanavir sulfate (adjusted odds ratio [aOR], 1.95; 95% CI, 1.24-3.05) and for ritonavir used as a booster (aOR, 1.56; 95% CI, 1.11-2.20). With first-trimester atazanavir exposure, risks were highest for skin (aOR, 5.23) and musculoskeletal (aOR, 2.55) CAs.Conclusions and Relevance Few individual ARVs and no drug classes were associated with an increased risk of CAs in HIV-exposed infants after adjustment for calendar year and maternal characteristics. While the overall risk remained low, a relative increase was observed in successive years and with atazanavir exposure. Given the low absolute CA risk, the benefits of recommended ARV therapy use during pregnancy still outweigh such risks, although further studies are warranted.
    No preview · Article · Nov 2014 · JAMA Pediatrics
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    ABSTRACT: Background: Long-term effects of in utero and neonatal antiretroviral (ARV) exposure on cognitive and academic development in HIV-exposed, uninfected school-age children are unknown. Methods: HIV-exposed, uninfected children, ages 5-13 years, in Pediatric HIV/AIDS Cohort Study Surveillance Monitoring for Antiretroviral Treatment Toxicities, a US-based multisite cohort study, completed age-appropriate Wechsler intelligence and academic scales (WPPSI-III, WASI, WIAT-II-A). Associations between cognitive and academic outcomes and in utero ARV exposure by regimen, class and individual ARVs were evaluated, adjusting for potential confounders. Results: Children completing WPPSI-IIIs (n = 350) were 49% male, 74% Black, 25% Hispanic; WASI (n = 337) and WIAT-II-A (n = 415) cohorts were similar. The percentage exposed to combination ARV (cARV) was 84% (WPPSI-III), 64% (WASI) and 67% (WIAT-II-A). Among ARV-exposed children, there were no significant associations between any ARV regimen or class and any cognitive or academic outcome. In addition, in both unadjusted models and after adjustment for caregiver IQ, sociodemographic factors and maternal health and substance use during pregnancy, no individual ARV drug was associated with significantly lower cognitive or academic scores. Factors typically associated with lower cognitive and academic scores in the general population, such as prematurity, small for gestational age, maternal alcohol use and lower maternal cognitive status, were also associated with lower scores in this study. Conclusions: Overall, the safety of prenatal and neonatal ARV use was supported.
    No preview · Article · Nov 2014 · The Pediatric Infectious Disease Journal
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    ABSTRACT: Objective To evaluate the occurrence, clinical presentations and diagnostic methods for tuberculosis in a cohort of HIV-infected infants, children and adolescents from Latin America. Methods A retrospective analysis of children with tuberculosis and HIV was performed within a prospective observational cohort study conducted at multiple clinical sites in Latin America. Results Of 1114 HIV-infected infants, children, and adolescents followed from 2002 to 2011, 69 that could be classified as having confirmed or presumed tuberculosis were included in this case series; 52.2% (95% CI: 39.8–64.4%) had laboratory-confirmed tuberculosis, 15.9% (95% CI: 8.2–26.7%) had clinically confirmed disease and 31.9% (95% CI: 21.2–44.2%) had presumed tuberculosis. Sixty-six were perinatally HIV-infected. Thirty-two (61.5%) children had a history of contact with an adult tuberculosis case; however information on exposure to active tuberculosis was missing for 17 participants. At the time of tuberculosis diagnosis, 39 were receiving antiretroviral therapy. Sixteen of these cases may have represented immune reconstitution inflammatory syndrome. Conclusions Our study emphasizes the need for adequate contact tracing of adult tuberculosis cases and screening for HIV or tuberculosis in Latin American children diagnosed with either condition. Preventive strategies in tuberculosis-exposed, HIV-infected children should be optimized.
    Full-text · Article · Oct 2014 · Brazilian Journal of Infectious Diseases

Publication Stats

1k Citations
365.71 Total Impact Points


  • 2015
    • University of Washington Seattle
      Seattle, Washington, United States
  • 2008-2015
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development
      Роквилл, Maryland, United States
  • 2013
    • National Institute of Child Health and Human Development
      베서스다, Maryland, United States
  • 2005-2013
    • National Cancer Institute (USA)
      • • HIV and AIDS Malignancy Branch
      • • Pediatric Oncology Branch
      베서스다, Maryland, United States
  • 2012
    • University of Illinois at Chicago
      • Department of Pediatrics (Peoria)
      Chicago, Illinois, United States
    • Beverly Hospital, Boston MA
      BVY, Massachusetts, United States
  • 2011
    • Northwestern University
      • Division of Infectious Diseases (Dept. of Medicine)
      Evanston, Illinois, United States
  • 2007-2009
    • National Institutes of Health
      • Branch of HIV and AIDS Malignancy
      Maryland, United States
  • 2006
    • Children's National Medical Center
      Washington, Washington, D.C., United States