Egrifta Replacement and Sleep Disordered Breathing

Sleep-disordered breathing is characterized primarily by partial or total upper airway
obstruction during sleep. The most common form of sleep-disordered breathing is obstructive
sleep apnea (OSA) due to recurrent collapse of the upper airway with the onset of sleep
state. The major risk factors associated with the development of sleep apnea are obesity and
male sex. The investigators have also found a high prevalence of OSA in HIV infected men and
women, particularly among those with central lipohypertrophy, which is a common finding in
HIV-infected persons receiving antiretroviral therapy. Currently, our overall hypothesis is
that visceral adiposity, as seen in HIV-infected persons with central lipohypertrophy,
alters both mechanical properties and compensatory neuromuscular responses leading to upper
airway obstruction. Based on our most recent findings in the non-HIV population, the
investigators demonstrate that obesity is associated with elevations in the upper airway
load (passive Pcrit) that are counterbalanced by compensatory upper airway neural responses.
Moreover, the investigators have found that female sex, peripheral adiposity, and younger
age are associated with increased compensatory neuromuscular responses, while male sex,
central adiposity, and older age are associated with blunted compensatory responses. The
loss of the compensatory neuromuscular responses leads to obstructive sleep apnea. Among
HIV-infected patients with central lipohypertrophy, tesamorelin (Egrifta), a growth hormone
releasing hormone (GHRH) analogue, is approved for the reduction of visceral adipose tissue.
The investigators hypothesize that tesamorelin therapy will reverse both the mechanical and
neurocompensatory alterations associated with increased central obesity. In this project the
investigators will determine whether tesamorelin affects sleep apnea severity and
compensatory neuromuscular responses of the upper airway on sleep and breathing in men and
women with HIV infection. The proposed studies are designed to elucidate the
pathophysiologic basis for the development of obstructive sleep apnea in this population.
The studies also provide insights into the neurohumoral regulation of upper airway function,
and potentially new approaches to the treatment for sleep-disordered breathing.