""""""""When to start"""""""" antiretroviral therapy (ART) and """"""""what to start"""""""" represent key ongoing issues in HIV care. While these questions have been asked for the outcomes of AIDS and all-cause mortality, they now need to be extended to other serious outcomes, including cancer, which has endured as a major cause of morbidity and mortality for HIV-infected patients. The overarching goal of the current proposal is to formulate evidence-based recommendations about the preferred CD4 T-cell count at which to initiate ART, and the preferred initial ART regimen, that would minimize cancer incidence among HIV-infected persons. We will conduct this research within the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), which includes 22 diverse HIV cohorts in the U.S. and Canada with more than 100,000 HIV-infected patients, validated cancer diagnoses, and up to 15 years of follow-up. We will focus on three cancer groups as primary outcomes: AIDS- defining cancers, virus-related non-AIDS-defining cancers (NADC), and virus-unrelated NADC. We propose these grouped primary endpoints because their large Ns provide good statistical power and because clinical decisions about when and what to start might be based more on effects on cancer incidence for aggregated related cancers than on effects on incidence of individual cancer types. We also will consider 14 specific cancer types/groups as secondary outcomes. We propose to achieve two complementary and interrelated specific aims.
The first aim will use a restricted sample of NA-ACCORD to emulate randomized controlled trials of ART for reducing cancer risk using causal statistical methodologies.
This aim will evaluate the effect of the timing and composition of the initial ART regimen on the incidence of our primary and secondary cancer outcomes and includes two sub-aims:
Aim 1 a will evaluate whether initiation of ART at higher CD4 thresholds is associated with reduced incidence compared with initiation of ART at lower CD4 thresholds;
Aim 1 b will determine whether cancer incidence varies for the major ART classes and more common individual ART medications.
The second aim will use the entire NA-ACCORD sample to elucidate the underlying relationships between patterns of immune suppression, HIV virus replication and incidence of our primary and secondary cancer outcomes and also has two sub-aims:
Aim 2 a will examine relationships between cancer risk and cumulative and current CD4 count and HIV RNA;
Aim 2 b will evaluate whether ART use, specific ART classes, or more common individual ART medications have an effect on cancer risk independent of the effect mediated by measures of CD4 count and HIV RNA found to be key predictors of cancer risk in Aim 2a. NA-ACCORD provides an ideal platform for conducting this study, with its diverse cohorts, large sample size, validated cancer diagnoses, longitudinal data on CD4 count, HIV RNA, and ART use, data on traditional cancer risk factors, efficient structure for harmonization of data, and high level of multidisciplinary expertise of collaborating investigators.
Cancer has endured as a major cause of morbidity and mortality for HIV-infected patients during the antiretroviral therapy (ART) era. The overarching goal of the proposed research is to formulate evidence-based recommendations about the preferred CD4 T-cell count at which to initiate ART, and the preferred initial ART regimen, that would minimize cancer incidence among HIV-infected persons.
|AIDS-defining Cancer Project Working Group of IeDEA, COHERE in EuroCoord (2018) Non-Hodgkin lymphoma risk in adults living with HIV across five continents. AIDS 32:2777-2786|
|Elion, Richard A; Althoff, Keri N; Zhang, Jinbing et al. (2018) Recent Abacavir Use Increases Risk of Type 1 and Type 2 Myocardial Infarctions Among Adults With HIV. J Acquir Immune Defic Syndr 78:62-72|
|Desir, Fidel A; Lesko, Catherine R; Moore, Richard D et al. (2018) One Size Fits (n)One: The Influence of Sex, Age, and Sexual Human Immunodeficiency Virus (HIV) Acquisition Risk on Racial/Ethnic Disparities in the HIV Care Continuum in the United States. Clin Infect Dis :|
|Grover, Surbhi; Desir, Fidel; Jing, Yuezhou et al. (2018) Reduced Cancer Survival Among Adults With HIV and AIDS-Defining Illnesses Despite No Difference in Cancer Stage at Diagnosis. J Acquir Immune Defic Syndr 79:421-429|
|Burger, Emily A; Dyer, Michael A; Sy, Stephen et al. (2018) Development and Calibration of a Mathematical Model of Anal Carcinogenesis for High-Risk HIV-Infected Men. J Acquir Immune Defic Syndr 79:10-19|
|Yanik, Elizabeth L; Hernández-Ramírez, Raúl U; Qin, Li et al. (2018) Brief Report: Cutaneous Melanoma Risk Among People With HIV in the United States and Canada. J Acquir Immune Defic Syndr 78:499-504|
|Altekruse, Sean F; Shiels, Meredith S; Modur, Sharada P et al. (2018) Cancer burden attributable to cigarette smoking among HIV-infected people in North America. AIDS 32:513-521|
|Wong, Cherise; Gange, Stephen J; Moore, Richard D et al. (2018) Multimorbidity Among Persons Living with Human Immunodeficiency Virus in the United States. Clin Infect Dis 66:1230-1238|
|Farhadian, Shelli; Jalbert, Emilie; Deng, Yanhong et al. (2018) HIV and Age Do Not Synergistically Affect Age-Related T-Cell Markers. J Acquir Immune Defic Syndr 77:337-344|
|Wong, Cherise; Gange, Stephen J; Buchacz, Kate et al. (2017) First Occurrence of Diabetes, Chronic Kidney Disease, and Hypertension Among North American HIV-Infected Adults, 2000-2013. Clin Infect Dis 64:459-467|
Showing the most recent 10 out of 41 publications