Dr. Peck is board certified in Internal Medicine and Pediatrics and has received postdoctoral training in tropical medicine and epidemiology. He has demonstrated a longstanding commitment to patient- oriented research in resource-poor countries. He has lived in Tanzania for the past seven years, where he has become fluent in Kiswahili, developed collaborations with Tanzanian scientists, trained a local study team, and authored 15 first or senior author peer-reviewed publications. The candidate's work has focused on the epidemiology and of HIV, hypertension, and kidney disease which forms the basis for the proposed research. Career Development Plan: The candidate's long-term goal is to become an independent physician investigator focused on the prevention and treatment of chronic non-communicable diseases in Africa. To achieve this goal, the candidate will pursue the following objectives during his K01 training: 1) To gain experience conducting a large clinical study on hypertension in HIV infected adults in Tanzania with rigorous follow-up and data collection. This will require Dr Peck to direct a multidisciplinary team including nurses, physicians, data managers, and laboratory technicians; 2) To better understand translational immunology through coursework and mentored laboratory experience; 3) To gain training and experience in advanced epidemiological and statistical methods through coursework and analysis of his own research data. Environment: The proposed research and training will take place at the Mwanza Intervention Trials Unit (Mwanza, Tanzania) and Weill Cornell Medical College (NY, NY). The partnerships between these institutions provides a unique collaborative environment with the infrastructure for both large clinical studies and translational research. Both institutions are whole-heartedly committed to the career development of Dr. Peck and have made significant financial commitments to him. The candidate has assembled an outstanding mentorship team with expertise in clinical epidemiology, infectious diseases, hypertension, nephrology, immunology, and biostatistics. Research: The proposed research builds upon Dr. Peck's prior work in Tanzania on HIV, hypertension, and renal disease.
In Aim 1, he hypothesizes that HIV-1 immune suppression decreases the risk of hypertension and that ART-related immune reconstitution of CD4+ T cells increases hypertension rates. There are animal studies suggesting that CD4+ T cells play an important role in the development of hypertension. The proposed study would provide critical human data to support this novel hypothesis.
In Aim 2, he proposes that renal damage as evidenced by albuminuria at the time of ART initiation will predict future onset of hypertension in HIV-infected adults. This is based upon the candidate's prior research showing that 44% of HIV infected adults in Tanzania have albuminuria, as well as international cohort studies showing an association between albuminuria and new onset hypertension.
Aim 1 : To prospectively determine the incidence and predictors of hypertension in a cohort study of 500 recently diagnosed HIV-infected adults and 300 matched HIV-negative controls during 4 years of follow-up. We estimate that 300 (60%) of the HIV-infected patients will initiate ART within one month of HIV diagnosis and study enrollment. Two hundred (40%) will not be ART eligible and will be followed for a median of two years prior to starting ART.
The Aim 1 hypothesis is that the incidence of new-onset hypertension will be 6% per year after ART initiation in HIV-infected patients and this will be at least 3-times higher than the incidence in either the HIV-negative controls or the HIV-infected patients prior to ART initiation. Further, hypertension onset after ART initiation will be preceded by persistently elevated serum markers of inflammation (hsCRP and IL-6) and rising CD4+ T-cell counts. Cox proportional-hazards models will be used to determine the independent contribution of systemic inflammation, ART drugs, adiposity, diet, and exercise to incident hypertension.
Aim 2 : To determine the association and temporal relationship between renal damage and incident hypertension in HIV-infected adults after ART initiation in a nested case-control study. From the cohort described in Aim 1, we will study the first 60 HIV-infected patients who develop hypertension after ART initiation and 120 matched HIV-infected controls who initiate ART, but do not develop hypertension. The hypothesis is that pre-ART urine albumin-to-creatinine ratios will be 2-times higher among cases than controls. We will quantitate other measures of renal disease including estimated glomerular filtration rates (eGFR) and T-cell mediated renal inflammation (by measuring urine-cellular mRNA). We will also examine the temporal relationship between renal disease, CD4+ T-cell counts, and serum markers of inflammation. Controls will be matched to cases by age, sex and duration of ART.
Dr. Peck has documented that the prevalence of hypertension in HIV-infected persons receiving antiretroviral therapy (ART) is nearly twice as high as the prevalence in HIV-negative persons (29% vs. 16%). The lowest prevalence of hypertension was in HIV-infected persons who were not receiving ART (4%). These studies will determine the incidence of hypertension in these three populations and seek predictors and immunologic correlates which may elucidate the pathogenesis of hypertension and lead to the design of novel interventions.
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