Multiple data sources suggest that patients infected with human immunodeficiency virus (HIV) experience chronic lung inflammation, rapid lung function decline, and an increased risk of chronic obstructive pulmonary disease (COPD). Although newer and more potent antiretroviral treatment (ART) appears to nearly eliminate lung inflammation, ART's effects on the rate of lung function decline and other important clinical outcomes remain unknown. Our proposal is designed to address this knowledge gap, while providing a better understanding of the mechanisms for the rapid lung function decline observed in patients with HIV infection. We will accomplish these general aims through longitudinal measurements of pulmonary function and respiratory health status in a subsample of 1,000 participants enrolled in a large, international, randomized, controlled trial - the Strategic Timing of Antiretroviral Treatment (START) trial. START is scheduled to begin in early 2009. The parent trial will enroll 4,000 HIV-1 (subsequently referred to as HIV) infected persons who are na?ve to antiretroviral treatment, with a CD4+ count >500 cells/mm3. Participants will be randomized to either immediate initiation of potent ART or deferral of ART until the CD4+ count declines to <350 cells/mm3. This permits an appropriately controlled, randomized experimental evaluation of the relative effects of early ART treatment (vs. deferred treatment) on pulmonary status in patients with HIV infection. Much of the infrastructure for the START trial is supported by the National Institute of Allergy and Infectious Diseases (NIAID) through a Leadership Group grant award to the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT). Our proposal seeks support to include the measurement of pulmonary function and respiratory health status in an ancillary study to START. With the data being collected by the main START protocol and the additional data we propose to collect as part of this application, respiratory parameters will be reliably quantified in HIV-infected patients treated with immediate and deferred ART, with control of multiple confounding factors through randomization. The extensive biological specimen repository, including genetic data and other data collected as part of the main START protocol, will provide opportunities for multiple future investigations of biomarkers, proteomics, and genomics related to the development of COPD in patients infected with HIV. Our study will advance understanding of the pathogenesis and course of rapid lung function decline and subsequent COPD in the presence of HIV infection.
Patients with HIV infection appear to lose lung function at a faster rate than expected and may be at long-term risk for significant lung health problems. This study will determine if early treatment of HIV might reduce this risk. (End of Abstract)
|Fitzpatrick, Meghan E; Kunisaki, Ken M; Morris, Alison (2018) Pulmonary disease in HIV-infected adults in the era of antiretroviral therapy. AIDS 32:277-292|
|Hodgson, Shane; Griffin, Timothy J; Reilly, Cavan et al. (2017) Plasma sphingolipids in HIV-associated chronic obstructive pulmonary disease. BMJ Open Respir Res 4:e000180|
|Kunisaki, Ken M; Niewoehner, Dennis E; Collins, Gary et al. (2016) Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial. Lancet Respir Med 4:980-989|
|Drummond, M Bradley; Kunisaki, Ken M; Huang, Laurence (2016) Obstructive Lung Diseases in HIV: A Clinical Review and Identification of Key Future Research Needs. Semin Respir Crit Care Med 37:277-88|
|Kunisaki, K M; Niewoehner, D E; Collins, G et al. (2015) Pulmonary function in an international sample of HIV-positive, treatment-naïve adults with CD4 counts >?500 cells/?L: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med 16 Suppl 1:119-28|
|Kunisaki, Ken M (2014) Will expanded ART use reduce the burden of HIV-associated chronic lung disease? Curr Opin HIV AIDS 9:27-33|