Rohan Hazra

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Maryland, United States

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Publications (76)312.07 Total impact

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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.
    The Brazilian journal of infectious diseases: an official publication of the Brazilian Society of Infectious Diseases 03/2015; DOI:10.1016/j.bjid.2015.01.004 · 1.04 Impact Factor
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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.
    AIDS 01/2015; 29(3):295. DOI:10.1097/QAD.0000000000000528 · 6.56 Impact Factor
  • Peter L Havens, Rohan Hazra
    The Pediatric Infectious Disease Journal 01/2015; DOI:10.1097/INF.0000000000000650 · 3.14 Impact Factor
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    ABSTRACT: Objectives: 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. Design: 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. Methods: CD4+ T-cell trajectories were examined and Kaplan-Meier methods used to estimate median time to CD4+ T cell count at least 500 cells/[mu]l. Results: After 1 year of virologic suppression, most (99%) children achieved a CD4+ T cell count of at least 200 cells/[mu]l, but CD4+ T cell counts remained below 500 cells/[mu]l 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/[mu]l were 1.29, 0.78 and 0.46 years for children with less than 200, 200-349 and 350-499 cells/[mu]l 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. Conclusion: 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/[mu]l 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.
    AIDS 01/2015; DOI:10.1097/QAD.0000000000000598 · 6.56 Impact Factor
  • JAIDS Journal of Acquired Immune Deficiency Syndromes 01/2015; 68(1):62-72. DOI:10.1097/QAI.0000000000000380 · 4.39 Impact Factor
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    ABSTRACT: Objective: To investigate whether prenatal atazanavir (ATV) exposure, assessed by meconium antiretroviral quantification, predicts early child language outcomes. Prenatal ATV exposure previously was associated with poorer language development in one-year-olds. Methods: Pregnant women with HIV and their uninfected infants enrolled in the SMARTT study. Meconium antiretroviral 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 (LLE) was defined as >= one of four 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. Results: 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 LLE 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). Conclusions: 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 HEU infants is required.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 01/2015; DOI:10.1097/QAI.0000000000000558 · 4.39 Impact Factor
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    ABSTRACT: 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.
    JAMA Pediatrics 11/2014; 169(1). DOI:10.1001/jamapediatrics.2014.1889 · 4.25 Impact Factor
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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.
    The Pediatric Infectious Disease Journal 11/2014; 33(11):1128-33. DOI:10.1097/INF.0000000000000410 · 3.14 Impact Factor
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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.
    Brazilian Journal of Infectious Diseases 10/2014; DOI:10.1016/j.bjid.2014.08.007 · 1.10 Impact Factor
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    ABSTRACT: BACKGROUND: Individuals with long-term human immunodeficiency virus (HIV) infection are at risk for premature vasculopathy and cardiovascular disease (CVD). We evaluated coronary vessel wall thickening, coronary plaque, and epicardial fat in patients infected with HIV early in life compared with healthy controls. METHODS: This is a prospective cross-sectional study of 35 young adults who acquired HIV in early life and 11 healthy controls, free of CVD. Time resolved phase-sensitive dual inversion recovery black-blood vessel wall magnetic resonance imaging (TRAPD) was used to measure proximal right coronary artery (RCA) wall thickness, and multidetector computed tomography (CT) angiography was used to quantify coronary plaque and epicardial fat. RESULTS: RCA vessel wall thickness was significantly increased in HIV-infected patients compared with sex- and race-matched controls (1.32 ± 0.21 mm vs 1.09 ± 0.14 mm, P = .002). No subject had discrete plaque on CT sufficient to cause luminal narrowing, and plaque was not related to RCA wall thickness. In multivariate regression analyses, smoking pack-years (P = .004) and HIV infection (P = .007) were independently associated with thicker RCA vessel walls. Epicardial fat did not differ between groups. Among the HIV-infected group, duration of antiretroviral therapy (ART) (P = .02), duration of stavudine exposure (P < .01), low-density lipoprotein cholesterol (P = .04), and smoking pack-years (P < .01) were positively correlated with RCA wall thickness. CONCLUSIONS: This investigation provides evidence of subclinical coronary vascular disease among individuals infected with HIV in early life. Increased duration of ART, hyperlipidemia, and smoking contributed to proximal RCA thickening, independent of atherosclerotic plaque quantified by CT. These modifiable risk factors appear to influence early atherogenesis as measured by coronary wall thickness and may be important targets for CVD risk reduction.
    Clinical Infectious Diseases 08/2014; 59(12). DOI:10.1093/cid/ciu672 · 9.42 Impact Factor
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    ABSTRACT: Renal toxicity is a concern in HIV-infected children receiving antiretrovirals. However, the prevalence (1.7%; 95% confidence interval [CI]: 1.0-2.6%) and incidence of kidney dysfunction (0.17 cases/100 person-years; 95% CI: 0.04-0.30) were rare in this multicenter cohort study of 1032 perinatally HIV-infected Latin American and Caribbean children, followed from 2002-2011.
    AIDS Research and Human Retroviruses 05/2014; 30(10). DOI:10.1089/AID.2013.0276 · 2.46 Impact Factor
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    ABSTRACT: Tenofovir (TDF) is associated with phosphaturia and elevated 1,25 dihydroxy vitamin D (1,25-OH(2)D). Fibroblast growth factor 23 (FGF23) causes phosphaturia and increases in response to elevated 1,25-OH(2)D. Vitamin D binding protein (VDBP) binds to 1,25-OH(2)D, decreasing its biologic activity, and is elevated in persons with higher plasma tenofovir concentrations. We compared FGF23 and VDBP before and after vitamin D3 (VITD) supplementation in youth treated with combination antiretroviral therapy (cART) containing or not containing TDF. A randomized controlled trial in HIV+ youth ages 18-25 years enrolled participants based on cART treatment with TDF (TDF, N=118) or without TDF (no-TDF, N=85) and randomized within those groups to VITD (50,000 IU every four weeks) or placebo (PL). We measured FGF23 and VDBP and calculated free 1,25-OH(2)D at baseline and week 12, and compared changes by TDF treatment and VITD randomized group. At baseline, serum FGF23 concentration showed a quadratic relationship with 1,25-OH(2)D most pronounced in the TDF group. At week 12, total and free 1,25-OH(2)D increased in the VITD but not PL groups, independent of TDF use. FGF23 increased in the TDF group receiving VITD, but there was no FGF23 change in the no-TDF group receiving VITD or the PL groups. The adjusted mean change in FGF23 from baseline to week 12 was +7.7 pg/mL in the TDF/VITD group, compared to -1.7 (no-TDF/VITD, p=0.010); -1.3 (TDF/PL, p=0.006); and +1.1 (no-TDF/PL, p=0.035). These results suggest that TDF-containing cART may alter the FGF23 response to vitamin D supplementation in HIV-infected youth.
    Antiviral therapy 02/2014; DOI:10.3851/IMP2755 · 3.14 Impact Factor
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    ABSTRACT: To examine the relationship between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected (PHIV+) and perinatally HIV-exposed but uninfected (PHEU) youth. Cross-sectional design within a prospective, 15-site US-based cohort study. Neurodevelopmental outcomes were evaluated in relation to nine selected vascular biomarkers in 342 youth (212 PHIV+, 130 PHEU). Serum levels were assessed for adiponectin, C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), monocyte chemoattractant protein (sMCP-1), intercellular adhesion molecule-1 (sICAM-1), and P-selectin (sP-selectin). The Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) was administered at entry, yielding a Full-Scale IQ score, and four index scores. Factor analysis was conducted to reduce the biomarkers to fewer factors with related biological roles. Structural equation models (SEMs) were used to measure associations between resulting factors and WISC-IV scores. Mean participant age was 11.4 years, 54% were female, 70% black. The nine biomarkers were clustered into three factor groups: F1 (fibrinogen, CRP, and IL-6); F2 (sICAM-1 and sVCAM-1); and F3 (MCP-1, sP-selectin, and sE-selectin). Adiponectin showed little correlation with any factor. SEMs revealed significant negative association of F1 with WISC-IV processing speed score in the total cohort. This effect remained significant after adjusting for HIV status and other potential confounders. A similar association was observed when restricted to PHIV+ participants in both unadjusted and adjusted SEMs. Aggregate measures of fibrinogen, CRP, and IL-6 may serve as a latent biomarker associated with relatively decreased processing speed in both PHIV+ and PHEU youth.
    AIDS (London, England) 01/2014; 28(3):355-64. DOI:10.1097/QAD.0000000000000072 · 6.56 Impact Factor
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    ABSTRACT: Background: P1093 is an ongoing Phase I/II multicenter open-label PK, safety, dose finding study of DTG plus optimized background regimen (OBR) in children and adolescents in age defined cohorts. The pediatric weight band dosing of ~1 mg/kg once a day achieved PK exposure in adolescents comparable to those observed at 50 mg once daily in adults. Methods: HIV infected treatment experienced children >12 to < 18 yrs on a failing antiretroviral (ARV) regimen with an HIV RNA of ≥1000 copies/mL (c/mL) were enrolled in Stage 1 (intensive PK) or Stage 2 (extended follow up). DTG was added to a stable, failing ARV regimen in Stage 1, with an OBR added after intensive PK (~Day5-10), or DTG was started with an OBR in Stage 2. Safety, tolerability, CD4 cell count and HIV-1 RNA were evaluated at Week 24. Virologic success was defined as achieving an HIV-1 RNA < 400 c/mL by Week 24 based on the FDA snapshot algorithm, with an additional secondary endpoint of HIV-1 RNA <50 c/mL. Results: Twenty three adolescents (Stage 1, n=10; Stage 2, n=13) were enrolled and completed the 24 week study visit. Demographics were as follows: 78% (18/23) female, 52% (12/23) African American, 35% (8/23) Caucasian, 26% (6/23) were of Hispanic ethnicity. Mean (SD) age 14 yrs (±1.8) and weight= 55.1 kg (±15.6). Median (IQR) baseline CD4+ cell count and % were 466 cells/µL (297, 771) and 22% (18.4, 29.2) respectively. Median (IQR) baseline HIV-1 RNA log10 was 4.3 log10 c/mL (3.9, 4.6). Virologic success with an HIV RNA < 400 c/mL was achieved in 82.6 % (19/23 ; 95% CI: 61.2 % to 95%) at Week 24. Additionally, 69.6% (16/23 ; 95% CI: 47.1% to 86.8%) had an HIV RNA load < 50 c/mL at Week 24. Median (IQR) gain in CD4 cell count and % at Week 24 was 63 cells/µL (-56, 180) and 4.9% (1, 8) respectively. DTG was well tolerated, with 2 subjects experiencing Grade 3 laboratory abnormalities; one developed unconjugated bilirubin elevation while on atazanavir as part of the OBR, and another subject developed asymptomatic lipase elevation, which was deemed treatment unrelated. There were no Grade 4 AEs, SAEs or discontinuations due to AEs. Conclusion: DTG plus OBR was safe and well tolerated in HIV infected adolescents. In addition, DTG treatment as part of an OBR provided high virologic efficacy through Week 24.
    IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013
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    ABSTRACT: Background:Tenofovir disoproxil fumarate (TDF) causes bone, endocrine and renal changes, by unknown mechanism(s). Data are limited on tenofovir pharmacokinetics and these effects.Methods:Using baseline data from a multicenter study in HIV-infected youth on stable treatment with regimens containing TDF (N=118) or no TDF (N=85), we measured cross-sectional associations of TDF use with markers of renal function, vitamin D-calcium-parathyroid hormone balance, phosphate metabolism (tubular reabsorption of phosphate and fibroblast growth factor 23 (FGF23)), and bone turnover. Pharmacokinetic-pharmacodynamic associations with plasma tenofovir and intracellular tenofovir diphosphate concentrations were explored among those receiving TDF.Results:Mean age was 20.9 (SD 2.0) years; 63% were male; and 52% African American. Compared to the noTDF group, the TDF group showed lower mean estimated glomerular filtration rate and tubular reabsorption of phosphate; and higher parathyroid hormone and 1,25-dihydroxy vitamin D (1,25-OH(2)D). The highest quintile of plasma tenofovir concentrations was associated with higher vitamin D binding protein, lower free 1,25-OH (2)D, higher 25-OH vitamin D and higher serum calcium. The highest quintile of intracellular tenofovir diphosphate concentration was associated with lower FGF23.Conclusion:Higher plasma tenofovir concentrations were associated with higher vitamin D binding protein and lower free 1,25-OH (2)D, suggesting a functional vitamin D deficiency possibly explaining TDF-associated increased parathyroid hormone. The finding of lower FGF-23 accompanying higher intracellular tenofovir diphosphate suggests different mechanisms mediate TDF-associated changes in phosphate handling. Separate pharmacokinetic properties may be associated with distinct TDF toxicities: tenofovir with parathyroid hormone and altered calcium balance, and tenofovir diphosphate with hypophosphatemia and FGF23 regulation.The clinical trials registration number for this study is NCT00490412, available online at http://clinicaltrials.gov/ct2/show/NCT00490412.
    Antimicrobial Agents and Chemotherapy 09/2013; DOI:10.1128/AAC.01096-13 · 4.57 Impact Factor
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    ABSTRACT: Perinatally HIV-infected (PHIV) children may be at risk of undervaccination. Vaccination coverage rates among PHIV and HIV-exposed uninfected (HEU) children in Latin America and the Caribbean were compared. All PHIV and HEU children born from 2002 to 2007 who were enrolled in a multisite observational study conducted in Latin America and the Caribbean were included in this analysis. Children were classified as up to date if they had received the recommended number of doses of each vaccine at the appropriate intervals by 12 and 24 months of age. Fisher's exact test was used to analyze the data. Covariates potentially associated with a child's HIV status were considered in multivariable logistic regression modeling. Of 1156 eligible children, 768 (66.4%) were HEU and 388 (33.6%) were PHIV. HEU children were significantly (P < 0.01) more likely to be up to date by 12 and 24 months of age for all vaccines examined. Statistically significant differences persisted when the analyses were limited to children enrolled before 12 months of age. Controlling for birth weight, sex, primary caregiver education and any use of tobacco, alcohol or illegal drugs during pregnancy did not contribute significantly to the logistic regression models. PHIV children were significantly less likely than HEU children to be up to date for their childhood vaccinations at 12 and 24 months of age, even when limited to children enrolled before 12 months of age. Strategies to increase vaccination rates in PHIV are needed.
    The Pediatric Infectious Disease Journal 08/2013; 32(8):845-850. DOI:10.1097/INF.0b013e31828bbe68 · 3.14 Impact Factor
  • Annette H Sohn, Rohan Hazra
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    ABSTRACT: The global paediatric HIV epidemic is shifting into a new phase as children on antiretroviral therapy (ART) move into adolescence and adulthood, and face new challenges of living with HIV. UNAIDS reports that 3.4 million children aged below 15 years and 2 million adolescents aged between 10 and 19 years have HIV. Although the vast majority of children were perinatally infected, older children are combined with behaviourally infected adolescents and youth in global reporting, making it difficult to keep track of their outcomes. Perinatally HIV-infected adolescents (PHIVA) are a highly unique patient sub-population, having been infected before development of their immune systems, been subject to suboptimal ART options and formulations, and now face transition from complete dependence on adult caregivers to becoming their own caregivers. As we are unable to track long-term complications and survival of PHIVA through national and global reporting systems, local and regional cohorts are the main sources for surveillance and research among PHIVA. This global review will utilize those data to highlight the epidemiology of PHIVA infection, treatment challenges and chronic disease risks. Unless mechanisms are created to count and separate out PHIVA outcomes, we will have few opportunities to characterize the negative consequences of life-long HIV infection in order to find ways to prevent them.
    Journal of the International AIDS Society 06/2013; 16(1):18555. DOI:10.7448/IAS.16.1.18555 · 4.21 Impact Factor
    This article is viewable in ResearchGate's enriched format
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    ABSTRACT: IMPORTANCE Prior to contemporary antiretroviral therapies (ARTs), children infected with human immunodeficiency virus (HIV) were more likely to have heart failure. This study suggests that highly active ART (HAART) does not appear to impair heart function. OBJECTIVE To determine the cardiac effects of prolonged exposure to HAART on HIV-infected children. DESIGN In the National Institutes of Health-funded Pediatric HIV/AIDS Cohort Study's Adolescent Master Protocol (AMP), we used linear regression models to compare echocardiographic measures. SETTING A total of 14 US pediatric HIV clinics. PARTICIPANTS Perinatally HIV-infected children receiving HAART (n = 325), HIV-exposed but uninfected children (n = 189), and HIV-infected (mostly HAART-unexposed) historical pediatric controls from the National Institutes of Health-funded Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2-HIV) Study (n = 70). EXPOSURE Long-term HAART. MAIN OUTCOMES AND MEASURES Echocardiographic measures of left ventricular (LV) function and structure. RESULTS The 325 AMP HIV-infected children had lower viral loads, higher CD4 counts, and longer durations of ART than did the 70 HIV-infected children from the P2C2-HIV Study (all P < .001). The z scores for LV fractional shortening (a measure of cardiac function) were significantly lower among HIV-infected children from the P2C2-HIV Study than among the AMP HIV-infected group or the 189 AMP HIV-exposed but uninfected controls (P < .05). For HIV-infected children, a lower nadir CD4 percentage and a higher current viral load were associated with significantly lower cardiac function (LV contractility and LV fractional shortening z scores; all P = .001) and an increased LV end-systolic dimension z score (all P < .03). In an interaction analysis by HIV-infected cohort, the HIV-infected children from the P2C2-HIV Study with a longer ART exposure or a lower nadir CD4 percentage had lower mean LV fractional shortening z scores, whereas the mean z scores were relatively constant among AMP HIV-infected children (P < .05 for all interactions). CONCLUSIONS AND RELEVANCE Long-term HAART appears to be cardioprotective for HIV-infected children and adolescents.
    04/2013; 167(6):1-8. DOI:10.1001/jamapediatrics.2013.1206
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    ABSTRACT: Background: Perinatally HIV-infected children (PHIV) may be at risk of undervaccination. Vaccination coverage rates among PHIV and HIV-exposed uninfected children (HEU) in Latin America and the Caribbean were compared. Methods: All PHIV and HEU children born from 2002-2007 that were enrolled in a multi-site observational study conducted in Latin America and the Caribbean were included in this analysis. Children were classified as up to date (UTD) if they had received the recommended number of doses of each vaccine at the appropriate intervals by 12 and 24 months of age. Fisher's exact test was used to analyze the data. Covariates potentially associated with a child's HIV status were considered in multivariable logistic regression modeling. Results: Of 1156 eligible children, 768 (66.4%) were HEU and 388 (33.6%) were PHIV. HEU children were significantly (p<0.01) more likely to be UTD by 12 and 24 months of age for all vaccines examined. Statistically significant differences persisted when the analyses were limited to children enrolled prior to 12 months of age. Controlling for birth weight, sex, primary caregiver education and any use of tobacco, alcohol or illegal drugs during pregnancy did not contribute significantly to the logistic regression models. Conclusions: PHIV children were significantly less likely than HEU children to be UTD for their childhood vaccinations at 12 and 24 months of age, even when limited to children enrolled before 12 months of age. Strategies to increase vaccination rates in PHIV are needed.xs (C) 2013 Lippincott Williams & Wilkins, Inc.
    The Pediatric Infectious Disease Journal 02/2013; · 3.14 Impact Factor
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    ABSTRACT: We measured glucose, insulin, and lipids in 249 perinatally HIV-infected Latin American children. Only one subject had impaired fasting glucose; 6.8% had insulin resistance. Abnormalities in total, LDL and HDL cholesterol, and triglycerides were reported for 13%, 13%, 21%, and 34%, respectively. Continued follow up of this population is necessary to characterize the evolution and clinical consequences of these findings.
    The Pediatric Infectious Disease Journal 01/2013; 32(7). DOI:10.1097/INF.0b013e318286c774 · 3.14 Impact Factor

Publication Stats

905 Citations
312.07 Total Impact Points

Institutions

  • 2008–2014
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development
      Maryland, United States
  • 2013
    • National Institute of Child Health and Human Development
      Maryland, United States
    • Children's Hospital of Wisconsin
      Madison, Wisconsin, United States
  • 2012
    • University of Illinois at Chicago
      • Department of Pediatrics (Peoria)
      Chicago, Illinois, United States
  • 2005–2012
    • National Institutes of Health
      • Branch of HIV and AIDS Malignancy
      Maryland, United States
  • 2011
    • National University of San Marcos
      • Instituto de Medicina Tropical "Daniel A. Carrión"
      Λίμα, Lima, Peru
  • 2004–2011
    • National Cancer Institute (USA)
      • • Pediatric Oncology Branch
      • • HIV and AIDS Malignancy Branch
      Maryland, United States
  • 2010
    • Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
      Tlalpam, The Federal District, Mexico
  • 2009
    • University of São Paulo
      San Paulo, São Paulo, Brazil
  • 2006
    • George Washington University
      Washington, Washington, D.C., United States
    • Children's National Medical Center
      Washington, Washington, D.C., United States