IntroductionThe 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 analysisAMP 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 disseminationThe 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.
Purpose Exposure to violence in childhood has been linked to adverse health outcomes. Little is known about the prevalence and relationship of youth and caregiver violence exposure to clinical outcomes among youth with perinatal HIV infection (PHIV). We evaluated associations of youth and caregiver violence exposure with unsuppressed viral load (VL) (HIV RNA>400 copies/ml) and CD4%<25% among 8-15 year-old participants with PHIV in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP). Methods Annual clinical examination, record abstraction and interview data were collected, including youth report of recent exposure to violence and caregivers' self-report of being assaulted/abused in adulthood. Multivariable logistic regression methods were used to calculate adjusted odds ratios (OR) for unsuppressed VL and CD4%<25%, controlling for socio-demographic characteristics. Results Among 268 youth with PHIV (53% girls, mean age 12.8 years, 21% white, 42% with household income<$20,000/year), 34% reported past year violence exposure; 30% had a caregiver who reported being assaulted in adulthood. One quarter of youth (24%) had unsuppressed VL, and 22% had CD4%<25%. Youth who were exposed to violence in the past year vs. those who were not had elevated odds of unsuppressed VL. Youth with indirect exposure to violence in the past year vs. those without had elevated odds of unsuppressed VL and CD4%<25% in adjusted models. Conclusion Youth with PHIV report a high prevalence of recent violence exposure, which was associated with poor virologic and immunologic outcomes. Reducing violence and providing support to youth with violence exposure and PHIV may improve health outcomes.
Introduction Previously, we demonstrated that inhibition of poly(ADP-ribose) polymerase (PARP) exerts protective effects against high-fat (HF) diet-induced atherogenesis, in part, by increasing tissue inhibitor of metalloproteinase (TIMP)-2 expression. Given that characteristics of dilated cardiomyopathy closely associate with atherosclerosis and are mediated by an imbalance between matrix metalloproteinases (MMPs) and TIMPs, we hypothesized that PARP-1 gene deletion may protect against HF-induced cardiac hypertrophy and dilatations by altering TIMP-2/MMPs balance in favor of a maintenance of tissue homeostasis. Methods and Results Hemodynamic parameters determined by echocardiography were similar in ApoE−/− mice and PARP-1-deficient ApoE−/− mice (DKO) fed a regular-diet (RD). However, histological analysis revealed that cardiomyocytes of ApoE−/− mice on RD were hypertrophied displaying an enlarged cell body and nucleus, traits that were absent in DKO animals. HF diet-fed ApoE−/− mice exhibited increased interventricular septum, left ventricular (LV) internal dimension, LV volume, and LV mass in addition to a separation of myocardial fibers suggestive of dilated cardiomyopathy. PARP-1 gene deletion protected against these degenerative changes. MMP activity was dramatically increased in hearts of ApoE−/− mice on HF diet and was accompanied by increased collagen degradation, mast cell degranulation and increased myocyte cell death. PARP-1 gene-knockout was associated with increased TIMP-2 expression antagonizing, as a result, the damaging effects of active MMPs. Conclusions The present study demonstrates that PARP-1 gene deletion exerts protective effects against HF diet-induced dilated cardiomyopathy by maintaining increased expression of TIMP-2. With additional protective effects against cell death and inflammation, PARP-1 deficiency preserves cardiac tissue homeostasis.
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