HIV is recognized as a devastating infection that leads to severe morbidity and earlier death. It is known that HIV infection is associated not only with disruptions in immune function but also in sleep with daytime fatigue, somnolence and impaired quality of life. Highly Active Anti-Retroviral Therapy (HAART) is now extending the life expectancy of those infected with HIV either allowing or producing chronic medical conditions and significant associated medical comorbidity. Our preliminary data indicate that both HIV infection and HAART are associated with substantial daytime fatigue. Moreover, HAART is also associated with sleep apnea, a known cause of sleep disruption and daytime somnolence. Our major hypothesis is that HIV infection, HAART, and associated alterations in humoral factors and cellular immunity lead to sleep disruption and sleep apnea, which both cause daytime dysfunction.
In Specific Aim 1, we will elucidate the effects of HIV and HAART on nocturnal sleep architecture and daytime function. We hypothesize that HIV infection will be associated with sleep disruption and alterations in measures of daytime sleepiness, neurocognitive and neurobehavioral function, and quality of life.
In Specific Aim 2, we will delineate the effects of HIV and HAART on the severity of upper airway obstruction and sleep. We hypothesize that HAART, but not HIV infection, is associated with an increased susceptibility for sleep apnea due to alterations in regional fat distribution and leptin.
In Specific Aim 3, we will elucidate specific humoral and molecular pathways involved in the pathogenesis of upper airway, ventilatory and sleep/wake dysregulation. In this proposal, we capitalize on the well-established Baltimore site or the Multicenter Aids Cohort Study (MACS), a longitudinal study of HIV infection in gay men, to determine the impact of these factors on sleep quality, sleep apnea and daytime function. In a series of complementary murine studies, we further probe causal pathways involved in the pathogenesis of upper airway, respiratory and sleep/wake dysfunction. Conventional methods will be employed to assess sleep architecture, cellular immunity, humoral factors and daytime function, while novel analytic approaches will be used to quantify effects of HIV infection and therapy on sleep structure and upper airway function.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL079554-02
Application #
6954650
Study Section
Special Emphasis Panel (ZHL1-CSR-P (S1))
Program Officer
Twery, Michael
Project Start
2004-09-30
Project End
2008-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
2
Fiscal Year
2005
Total Cost
$595,908
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Brigham, Emily P; Patil, Susheel P; Jacobson, Lisa P et al. (2014) Association between systemic inflammation and obstructive sleep apnea in men with or at risk for HIV infection. Antivir Ther 19:725-33
Brown, Todd T; Patil, Susheel P; Jacobson, Lisa P et al. (2010) Anthropometry in the prediction of sleep disordered breathing in HIV-positive and HIV-negative men. Antivir Ther 15:651-9
Jun, Jonathan; Savransky, Vladimir; Nanayakkara, Ashika et al. (2008) Intermittent hypoxia has organ-specific effects on oxidative stress. Am J Physiol Regul Integr Comp Physiol 295:R1274-81
Savransky, Vladimir; Bevans, Shannon; Nanayakkara, Ashika et al. (2007) Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver. Am J Physiol Gastrointest Liver Physiol 293:G871-7
Savransky, Vladimir; Nanayakkara, Ashika; Li, Jianguo et al. (2007) Chronic intermittent hypoxia induces atherosclerosis. Am J Respir Crit Care Med 175:1290-7
Savransky, Vladimir; Nanayakkara, Ashika; Vivero, Angelica et al. (2007) Chronic intermittent hypoxia predisposes to liver injury. Hepatology 45:1007-13