[Show abstract][Hide abstract]ABSTRACT: In contrast to high rates of oral human papillomavirus (HPV) found in human immunodeficiency virus (HIV)-infected adults, only 2% of 209 perinatally HIV-infected youth had oral HPV. This rate was similar in HIV-exposed but uninfected youth. No association was found with sexual activity; however, low CD4 counts were associated with oral HPV.
[Show abstract][Hide abstract]ABSTRACT: Objective:
To compare oral health parameters in perinatally HIV-infected (PHIV) and perinatally HIV-exposed but uninfected youth (PHEU).
In a cross-sectional substudy within the Pediatric HIV/AIDS Cohort Study, participants were examined for number of decayed teeth (DT), Decayed, Missing, and Filled Teeth (DMFT), oral mucosal disease, and periodontal disease (PD). Covariates for oral health parameters were examined using zero-inflated negative binomial regression and ordinal logistic regression models.
Eleven sites enrolled 209 PHIV and 126 PHEU. Higher DT scores were observed in participants who were PHIV [Adjusted Mean Ratio (aMR) = 1.7 (95% CI 1.2-2.5)], female [aMR = 1.4 (1.0-1.9)], had no source of regular dental care [aMR = 2.3 (1.5-3.4)], and had a high frequency of meals/snacks [≥5 /day vs 0-3, aMR = 1.9 (1.1-3.1)] and juice/soda [≥5 /day vs 0-3, aMR = 1.6 (1.1-2.4)]. Higher DMFT scores were observed in participants who were older [≥19, aMR = 1.9 (1.2-2.9)], had biological parent as caregiver [aMR = 1.2 (1.0-1.3)], had a high frequency of juice/soda [≥5 /day vs 0-3, aMR = 1.4 (1.1-1.7)] and a low saliva flow rate [mL/min, aMR = 0.8 per unit higher (0.6-1.0)]. Eighty percent had PD; no differences were seen by HIV status using the patient-based classifications of health, gingivitis or mild, moderate, or severe periodontitis. No associations were observed of CD4 count and viral load with oral health outcomes after adjustment.
Oral health was poor in PHIV and PHEU youth. This was dismaying since most HIV infected children in the U.S. are carefully followed at medical health care clinics. This data underscore the need for regular dental care. As PHIV youth were at higher risk for cavities, it will be important to better understand this relationship in order to develop targeted interventions.
[Show abstract][Hide abstract]ABSTRACT: Multivariable zero-inflated negative binomial models of decayed-missing-filled-teeth (DMFT) and decayed teeth (DT) among HIV positive participants, adjusted for covariates in the core multivariable models.
[Show abstract][Hide abstract]ABSTRACT: Introduction The first generation of adolescents born with HIV infection has reached young adulthood due to advances in treatment. It is important to continue follow-up of these individuals to assess their long-term medical, behavioural and mental health and ability to successfully transition to adulthood while coping with a chronic, potentially stigmatising condition. To accomplish this, and to maintain their interest in long-term research participation, we need to accommodate the changing lifestyles and interests of young adult study participants while ensuring valid data collection. We report the protocol for Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP) Up, a prospective cohort study enrolling young adult participants for long-term follow-up.
Methods and analysis AMP Up is recruiting 850 young men and women 18 years of age and older—600 perinatally HIV-infected and a comparison group of 250 perinatally HIV-exposed, uninfected—at 14 clinical research sites in the USA and Puerto Rico. Recruitment began in April 2014 and is ongoing, with 305 participants currently enrolled. Planned follow-up is ≥6 years. Data are collected with a flexible hybrid of online and in-person methods. Outcomes include: transition to adult clinical care and retention in care; end-organ diseases; malignancies; metabolic complications; sexually transmitted infections; reproductive health; mental health and neurocognitive functioning; adherence to antiretroviral treatment; sexual behaviour and substance use; hearing and language impairments; and employment and educational achievement.
Ethics and dissemination The study received ethical approval from the Harvard T.H. Chan School of Public Health's institutional review board (IRB), and from the IRBs of each clinical research site. All participants provide written informed consent; for cognitively impaired individuals with legally authorised representatives, legal guardian permission and participant assent is obtained. Findings will be disseminated through peer-reviewed journals, conference presentations and participant summaries.
[Show abstract][Hide abstract]ABSTRACT: The Surveillance Monitoring for ART Toxicities (SMARTT) cohort of the Pediatric HIV/AIDS Cohort Study (PHACS) includes over 3500 HIV-exposed but uninfected (HEU) infants and children at 22 sites in the U.S. including Puerto Rico. The goal of the study is to determine the safety of in utero exposure to antiretrovirals (ARV) and to estimate the incidence of adverse events. Domains being assessed include metabolic, growth and development, cardiac, neurological, neurodevelopmental, behavior, language, and hearing. SMARTT employs an innovative trigger-based design as an efficient means to identify and evaluate adverse events. Participants who met a predefined clinical or laboratory threshold (trigger) undergo additional evaluations to define their case status. After adjusting for birth cohort and other factors, there was no significant increase in the likelihood of meeting overall case status (case in any domain) with exposure to combination ARVs (cARV), any ARV class, or any specific ARV. However, several individual ARVs were significantly associated with case status in individual domains, including zidovudine for a metabolic case, first trimester stavudine for a language case, and didanosine plus stavudine for a neurodevelopmental case. We found an increased rate of preterm birth with first trimester exposure to protease inhibitor-based cARV. Although there was no overall increase in congenital anomalies with first trimester cARV, a significant increase was seen with exposure to atazanavir, ritonavir, and didanosine plus stavudine. Tenofovir exposure was associated with significantly lower mean whole-body bone mineral content in the newborn period and a lower length and head circumference at 1 year of age. With neurodevelopmental testing at 1 year of age, specific ARVs (atazanavir, ritonavir-boosted lopinavir, nelfinavir, and tenofovir) were associated with lower performance, although all groups were within the normal range. No ARVs or classes were associated with lower performance between 5 and 13 years of age. Atazanavir and saquinavir exposure were associated with late language emergence at 1 year but not 2 years of age. The results of the SMARTT study are generally reassuring, with little evidence for serious adverse events resulting from in utero ARV exposure. However, several findings of concern warrant further evaluation and new ARVs used in
[Show abstract][Hide abstract]ABSTRACT: Background:
Rilpivirine (RPV), a recently developed, once daily HIV non-nucleoside reverse transcriptase inhibitor (NNRTI), is not currently approved for pediatric patients, but is sometimes prescribed for adolescents with multiple treatment failures, for regimen simplification or to minimize toxicity. Darunavir/ritonavir (DRV/r) administered once daily is also increasingly used in adolescents and may alter RPV pharmacokinetics (PK). We evaluated the pharmacokinetic interactions between RPV and DRV/r once daily in adolescents and young adults.
HIV-infected subjects 12 to <24 years old receiving a stable background therapy including RPV 25 mg once-daily without or combined with DRV/r 800/100 mg once-daily were enrolled. Intensive 24-hour blood sampling was performed and pharmacokinetics indices were determined using non-compartmental analysis. Protocol-defined target drug exposure ranges based on adult data were used to assess the adequacy of each regimen.
Fifteen subjects receiving RPV without, and 14 subjects with, DRV/r were enrolled. When dosed without DRV/r the rilpivirine geometric mean (90% confidence interval (CI)) for RPV AUC0-24, Cmax and C24h were 2.38 µg.hr/mL (1.92-2.94), 0.14 µg/mL (0.12-0.18), and 0.07 µg/mL (0.03-0.10), respectively, similar to adult values. RPV concentrations were significantly increased with concomitant DRV/r use: RPV AUC24, Cmax and C24h were 6.74 µg.hr/mL (4.89-9.28), 0.39 µg/mL (0.27-0.57), and 0.23 µg/mL (0.17-0.32), respectively, well above the target ranges based on adult data. DRV/r pharmacokinetics were not affected by co-administration of RPV.
Rilpivirine pharmacokinetics in this adolescent population were similar to adults when dosed without DRV/r. Darunavir/ritonavir co-administration increased rilpivirine exposure 2-3 fold indicating that drug-related side effects should be closely monitored.
Article · May 2016 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract]ABSTRACT: Data on the combination of darunavir/ritonavir and etravirine both given twice daily in adolescents/young adults are lacking.
In this study, we assessed the pharmacokinetics of darunavir/ritonavir 600/100 mg with etravirine 200 mg twice daily in 36
treatment-experienced human immunodeficiency virus-infected adolescents and young adults and found that exposures were comparable
to those reported in adults.
Article · Apr 2016 · Journal of the Pediatric Infectious Diseases Society
[Show abstract][Hide abstract]ABSTRACT: Among 234 U.S. youth with perinatal HIV, 75% had antiretroviral resistance, substantially higher than that of the reference
laboratory overall (36-44%). Resistance to newer antiretrovirals (ARV) and to all ARVs in a class was uncommon. The only factor
independently associated with future resistance was a higher peak viral load.
[Show abstract][Hide abstract]ABSTRACT: APOL1 renal risk alleles are associated with chronic kidney disease (CKD) in adults, with the strongest effect being for HIV-associated nephropathy. Their role in youth with perinatal HIV infection (PHIV) has not been studied. In a nested case-control study of 451 PHIV participants in the Pediatric HIV/AIDS Cohort Study, we found a 3.5-fold increase odds of CKD in those carrying high-risk APOL1 genotypes using a recessive model (95% confidence interval [CI]: 1.2-10.0). We report an unadjusted incidence of 1.2 CKD cases/100 person-years (95% CI: 0.5, 2.5) in PHIV youth carrying APOL1 high-risk genotypes, with important implications for sub-Saharan Africa.
Full-text Article · Mar 2016 · JAIDS Journal of Acquired Immune Deficiency Syndromes
[Show abstract][Hide abstract]ABSTRACT: To evaluate antiretroviral (ARV) drug exposure and other factors during pregnancy that may increase the risk of neurologic conditions (NC) in HIV-exposed/uninfected (HEU) infants. Prospective cohort study conducted at 24 clinical sites in Latin America and the Caribbean. Maternal demographics, health, HIV disease status, and ARV use during pregnancy were collected. Infant data included measurement of head circumference after birth and reported medical diagnoses at birth, 6-12 weeks and 6 months. Only infants with maternal exposure to combination ARV therapy (cART) (≥3 drugs from ≥2 drug classes) during pregnancy were included. Microcephaly, defined as head-circumference for age z-score less than -2, and NC were evaluated for their association with covariates, including individual ARVs, using bivariable and logistic regression analyses. From 2002-2009, 1400 HEU infants met study inclusion criteria. At least one NC was reported in 134 (9.6%; 95% confidence interval [CI]: 8.1-11.2%), microcephaly in 105 (7.5%; 95% CI: 6.2-9.0%), and specific neurologic diagnoses in 33 (2.4%; 95% CI: 1.6-3.3%). Microcephaly and NC were not significantly associated with any specific ARV analyzed (p>0.05). Covariates associated with increased odds of NC included male sex (odds ratio [OR]=1.9; 95% CI: 1.3-2.8), birth weight <2.5 kg (OR=3.1; 95% CI: 2.1-4.8), 1-minute Apgar score <7 (OR=2.5; 95% CI: 1.4-4.4), and infant infections (OR=2.5; 95% CI: 1.5-4.1). No ARV investigated was associated with adverse neurologic outcomes. Continued investigation of such associations may be warranted as new ARVs are used during pregnancy and cART exposure during the first trimester becomes increasingly common.
Article · Feb 2016 · AIDS research and human retroviruses
[Show abstract][Hide abstract]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.
Article · Jan 2016 · AIDS Research and Human Retroviruses
[Show abstract][Hide abstract]ABSTRACT: Introduction: The number of children less than 15 years estimated to be living with HIV globally approximated 3.2 million in 2013. Young people aged 15 to 24 years living with HIV approximated 4 million. The survival of these children and adolescents into adulthood poses new and urgent challenges of transition from the paediatric to adolescent to adult healthcare settings due to emerging developmental, psychosocial and comorbid issues. In order to achieve treatment targets of 90 90 90 across the continuum of care for paediatric HIV by 2020, focused efforts on the implementation of appropriate healthcare transition plans across the lifespan, with a focus on adolescence, should be prioritized. Discussion: Published data or empirical evidence examining implementation of transition models and association with clinical outcomes are limited. While some guidelines do exist that offer recommendations about how to promote seamless transitions, very few data are available to assess the adequacy of these guidelines and whether they are effectively adhered to in clinical care settings globally. Furthermore, paediatric and adolescent HIV infection, either acquired perinatally or behaviourally, is set apart from other chronic illnesses as a highly stigmatizing disease that disproportionately affects poor, minority and often marginalized populations. Focused efforts on adolescence as the touchstone for transition practices and policies need to be implemented. Conclusions: Optimal healthcare for these vulnerable populations, particularly in resource-limited settings, will require HIV-specific transitional care services and programmes that are coordinated, collaborative, integrated and, importantly, evidence-based.
Article · Dec 2015 · Journal of the International AIDS Society