Search

Introduction Obstructive sleep apnea (OSA) has been associated with low grade systemic inflammation and greater cardiovascular risk, but the specific pathways mediating these effects are unclear. Monocyte activation is implicated in the development of cardiovascular disease in people with treated HIV infection. We sought to evaluate the impact of OSA on monocyte activation in people living with human immunodeficiency virus (HIV) infection. Methods Ten HIV seropositive participants with undetectable ( Results Participants had a mean ± SD age of 61 ± 4.7 years, were 50% female, 80% Black race and had well-constituted CD4+ counts (mean ± SD: 934 ± 283 cells/ml). The mean AHI4% among participants with OSA (n=4) was 21.8 ± 4.4 events/hour whereas controls (n=6) had an AHI4% of 2.4 ± 2.0 events/hour (p-value = 0.001). There was no difference in the proportion of classical monocytes between groups (mean ± SD 83.8% ± 11.5% in participants with OSA vs. 84.9% ± 7.5% in controls, p=0.86). Intracellular TNFα was greater in monocytes from participants with OSA vs. controls (log-transformed MFI 3.49±0.20 au vs. 3.00±0.35 au, p=0.03). Additionally, there was a trend toward greater intracellular concentrations of IL-1β (mean log-transformed MFI 3.24±0.15 au vs. 2.95±0.48 au, p=0.22) and IL-6 (log-transformed MFI 3.28±0.16 au vs. 2.91±0.64 au, p=0.23), in participants with OSA vs. controls. Conclusion Pro-inflammatory cytokine levels are greater in monocytes obtained from people with treated HIV infection with OSA compared to those without OSA. Our findings suggest OSA may exacerbate chronic inflammation and cardiovascular risk in chronic HIV infection. Support (If Any) HL082610 and American Thoracic Society ASPIRE Fellowship

People living with HIV (PLWH) have a higher prevalence of respiratory symptoms than people without human immunodeficiency virus (HIV). Antiretroviral therapy has been associated with worsened airflow limitation. This cross-sectional study assessed respiratory health impairment among PLWH and its association with protease inhibitor use using data from Multicenter AIDS Cohort Study visits between April 1, 2017 and March 31, 2018. Participants completed the St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnea scale, spirometry, and diffusion capacity measurement. Visit data were compared among PI users, non-PI users, and men without HIV. Binary and ordinal logistic models were used to determine the associations between HIV status, PI use, and covariates with primary outcomes of dichotomized SGRQ and mMRC dyspnea scores. Of PI users, 57/177 (32.2%) self-reported pulmonary disease compared with 132/501 (26.4%) of non-PI users and 105/547 (19.2%) men without HIV. Of PI users, 77/177 (45.3%) had SGRQ scores ≥10, while 171/501 (34.7%) of non-PI users and 162/549 (29.9%) of people living without HIV had SGRQ scores ≥10 (p = .001). Adjusted models found an association between PI use and SGRQ score ≥10 [odds ratio (OR) 1.91 (95% confidence interval [CI] 1.29–2.82), ref: HIV negative and OR 1.50 (95% CI 1.01–2.22) ref: non-PI users]. A similar association was found with mMRC scores and PI use [OR 1.79 (95% CI 1.21–2.64), ref: HIV negative and OR 1.53 (95% CI 1.04–2.25), ref: non-PI users]. PI use is associated with worse respiratory health status, increased dyspnea, and an increased prevalence of self-reported pulmonary disease.

Introduction While inadequate sleep is known to increase inflammation in immunocompetent individuals, it is unknown if poor sleep worsens inflammation in people living with HIV. The ratio of CD4+/CD8+ T cells is a readily derived measure of chronic inflammation in people living with HIV. We sought to investigate the association between lymphocyte subsets and actigraphy-derived sleep measures in a cohort of HIV seropositive men. Methods HIV seropositive men on antiretroviral therapy for > 1 year and with undetectable (< 20 copies/mL) plasma HIV-1 RNA participating in the Multicenter AIDS Cohort Study underwent a sleep evaluation with 1 week of wrist actigraphy. Data from 287 participants with ≥ 5 days of actigraphy were analyzed. We evaluated three dimensions of sleep: mean nocturnal sleep duration, sleep onset latency, and sleep maintenance efficiency. Linear regression was used to assess the association between each sleep dimension with CD4+ and CD8+ T-cell counts. Because of a U-shaped association, nocturnal sleep duration was also modelled dichotomously as a normal (6-8 hrs) vs. abnormal duration (8 hrs). Results Participants had a mean (±SD) age of 55 ± 12 years, mean CD4+ count of 723 ± 293 cells/ml, and 7.0 ± 1.7 days of actigraphy data. None of the sleep measures were associated with CD4+ counts. However, participants with abnormal sleep duration had 129 ± 31 cells/mL higher CD8+ counts compared to those with normal sleep duration (p=0.01). There were also nonsignificant trends whereby every 30-minute increase in sleep latency was associated with a 138 cells/ml increase in CD8+ count (p=0.07) while every 10% reduction in sleep efficiency was associated with a 56 cells/ml increase in CD8+ count (p=0.12). These findings were unchanged after adjusting for age and body mass index. Conclusion Among men with treated HIV infection, abnormal sleep duration (both short and long) is associated with increased circulating CD8+ T cell count, suggesting increased chronic inflammation. Support (If Any) NIH AI0355041, HL082610 and American Thoracic Society ASPIRE Fellowship

BACKGROUND Antiretroviral therapy (ART) regimens changes occur frequently among HIV-infected persons. Duration and type of initial highly active antiretroviral therapy (HAART) and factors associated with regimen switching were evaluated in the Multicenter AIDS Cohort Study. METHODS Participants were classified according to the calendar period of HAART initiation: T1 (1996-2001), T2 (2002-2005), and T3 (2006-2009). Kaplan-Meier curves depicted time from HAART initiation to first regimen changes within 5.5 years. Cox proportional hazards regression models were used to examine factors associated with time to switching. RESULTS Of 1009 participants, 796 changed regimen within 5.5 years after HAART initiation. The percentage of participants who switched declined from 85% during T1 to 49% in T3. The likelihood of switching in T3 decreased by 50% (P < 0.01) compared with T1 after adjustment for pre-HAART ART use, age, race, and CD4 count. Incomplete HIV suppression decreased over time (P < 0.01) but predicted switching across all time periods. Lower HAART adherence (≤95% of prescribed doses) was predictive of switching only in T1. In T2, central nervous system symptoms predicted switching [relative hazard (RH) = 1.7; P = 0.012]. Older age at HAART initiation was associated with increased switching in T1 (RH = 1.03 per year increase) and decreased switching in T2 (RH = 0.97 per year increase). CONCLUSIONS During the first 15 years of the HAART era, initial HAART regimen duration lengthened and regimen discontinuation rates diminished. Both HIV RNA nonsuppression and poor adherence predicted switching before 2001 while side effects that were possibly ART related were more prominent during T2.

Adenosine (ADO) is associated with immunosuppression in multiple diseases, yet its role in modulating immune activation/inflammation (IA/INFL) in HIV-1/SIV infection is unclear. We compared changes in ADO pathway-associated markers between African green monkeys (AGMs) that control SIV-related IA/INFL and pigtailed macaques (PTMs) that exhibit IA/INFL associated with AIDS progression. CD39/CD73 and CD26 (which promote ADO production or breakdown to inosine) were assessed by flow cytometry on T cells from blood, lymph nodes (LNs) and intestine of AGMs and PTMs pre and post SIV infection. ADO was measured by mass spectrometry in frozen tissues. Baseline CD39/CD73 expression on Tregs from LNs and intestine were intrinsically high in AGMs and remained high throughout SIV infection. CD26 and inosine did not change in AGMs. In the gut, basal ADO was high in AGMs and further increased early after infection. Conversely, in PTMs, CD26 expression dramatically increased in the gut early in infection, a change associated with increased inosine. CD39/CD73 only increased during late infection in PTMs. Our results suggest a key role for ADO in the control of IA/INFL in nonprogressive SIV infections and that ADO production may be counteracted by the early increase of CD26 in pathogenic HIV/SIV. Furthermore, changes of ADO levels predominately occur in the gut rather than in blood or LNs, suggesting that future studies of the ADO pathway should focus on mucosal sites of viral replication.

Ectonucleotidases CD39 and CD73 are expressed on the surface of regulatory T cells (Treg) and cleave ATP to immunosuppressive adenosine. CD39 could potentially serve as a new functional marker for Treg isolation. The frequency and absolute numbers of CD4+CD39+ T cells were determined in 32 HIV+ patients and in 10 healthy donors (HD). CD4+ T cells were negatively selected by magnetic beads PBMC. CD39+ Treg cells were then isolated by biotin-conjugated anti-CD39 Abs and anti-biotin magnetic beads. T cells were phenotyped by flow cytometry for CD39+, CD73+, FOXP3+, CCR4+, CD127neg, CD49dneg, and CD121a+. CFSE-based proliferation assays and ATP hydrolysis were used to measure Treg functions. Cytokine expression in CD4+CD39+ T cells was determined by Luminex. HIV-patients on and off anti-retroviral regimen had a significantly lower absolute number of CD39+CD25+ Treg and CD39+CD25neg T cells (p