Pathogenesis of obstructive sleep apnea in people living with HIV

Abstract

Obstructive sleep apnea (OSA) is highly prevalent in people living with human immunodeficiency virus (HIV) (PLWH), and it might contribute to frequently reported symptoms and comorbidities. Traditional risk factors for OSA are often absent in PLWH, suggesting that HIV or HIV medications might predispose to OSA. Therefore, we measured the anatomical and nonanatomical traits important for OSA pathogenesis in those with and without HIV. We recruited virally suppressed PLWH who had been previously diagnosed with OSA (PLWH + OSA) adherent to positive airway pressure (PAP) therapy, along with age-, sex-, and body mass index (BMI)-matched OSA controls. All participants underwent a baseline polysomnogram to assess OSA severity and a second overnight research sleep study during which the airway pressure was adjusted slowly or rapidly to measure the OSA traits. Seventeen PLWH + OSA and 17 OSA control participants were studied [median age = 58 (IQR = 54-65) yr, BMI = 30.7 (28.4-31.8) kg/m², apnea-hypopnea index = 46 (24-74)/h]. The groups were similar, although PLWH + OSA demonstrated greater sleepiness (despite PAP) and worse sleep efficiency on baseline polysomnography. On physiological testing during sleep, there were no statistically significant differences in OSA traits (including V_eupnea, V_arousal, V_passive, V_active, and loop gain) between PLWH + OSA and OSA controls, using mixed-effects modeling to account for age, sex, and BMI and incorporating each repeated measurement (range = 72-334 measures/trait). Our data suggest that well-treated HIV does not substantially impact the pathogenesis of OSA. Given similar underlying physiology, existing available therapeutic approaches are likely to be adequate to manage OSA in PLWH, which might improve symptoms and comorbidities.NEW & NOTEWORTHY Clinical data suggest an increased risk of obstructive sleep apnea (OSA) in people living with HIV (PLWH), while OSA might account for chronic health issues in this population. We characterized the anatomical and nonanatomical OSA traits in PLWH + OSA compared with OSA controls, using detailed physiological measurements obtained during sleep. Our data suggest against a major impact of HIV on OSA pathogenesis. Available OSA management strategies should be effective to address this potentially important comorbidity in PLWH.

Keywords: HIV; fatigue; obstructive sleep apnea.

Graphical abstract

Figure 1.

Measurement of OSA traits via airway pressure manipulation. OSA traits are measured by manipulating CPAP (A) during supine nonrapid eye movement (NREM) sleep and measuring the resultant changes in ventilation (B). i: minute ventilation is taken over 30–60 s while on optimal CPAP settings (i.e., holding pressure) to measure V_eupnea; ii: the pressure is rapidly dropped to sequentially lower pressures. Minute ventilation (for V_passive) and peak inspiratory flow (for P_crit) are taken from the 3rd through 5th breaths following a drop. Regression is used to determine ventilation at atmospheric pressure for V_passive and CPAP level at onset of zero peak inspiratory flow for P_crit. iii: CPAP is then gradually lowered until flow limitation starts and arousals occur intermittently. Ventilation just before arousal is defined as V_arousal. During stable breathing between arousals under this maximally increased respiratory drive, CPAP is dialed down or up from this level to obtain V_active (iv) and loop gain (v), respectively. For V_active, minute ventilation was estimated from the 2nd and 3rd breaths following a rapid drop from the minimum tolerable CPAP level, using regression to determine ventilation at atmospheric pressure for V_active. Loop gain is the ventilatory response (first breath overshoot in ventilation above V_eupnea) divided by the ventilatory disturbance (preceding 5-breath reduction in ventilation below V_eupnea). CPAP, continuous positive airway pressure; OSA, obstructive sleep apnea.

Figure 2.

Measured OSA traits in HIV-positive individuals with OSA compared with matched HIV-negative controls with OSA. Dots are each individual’s mean value from repeated measurements taken during sleep. The bar plot represents each group’s estimated marginal mean and associated 95% confidence interval determined by mixed-effects modeling adjusted for age and BMI, as described in methods. A: V_eupnea (17 male PLWH + OSA, 17 male OSA controls) was not significantly different (P = 0.31). B: V_arousal (17 male PLWH + OSA, 17 male OSA controls) was not significantly different (P = 0.17). C: V_passive (14 male PLWH + OSA, 17 male OSA controls) was not significantly different (P = 0.73). D: V_active (16 male PLWH + OSA, 16 male OSA controls) was not significantly different (P = 0.51). E: loop gain (12 male PLWH + OSA, 15 male OSA controls) was not significantly different (P = 0.32). BMI, body mass index; HIV, human immunodeficiency virus; OSA, obstructive sleep apnea; PLWH, people living with HIV.