The impact of COVID-19 and its response on the psychosocial wellbeing and medical care among persons living with HIV and COPD
I Konstantinidis1, M Lu2, V Petraglia1, C Kessinger1, FC Sciurba1, A Morris1
1Division of Pulmonary, Allergy and Critical Care, University of Pittsburgh; 2Department of Medicine, University of Pittsburgh
Aims: People with COPD and persons with HIV have been recognized as medically and socially vulnerable populations during the COVID-19 pandemic. Data on the impact of the pandemic and its response on the psychosocial wellbeing and medical care of persons living with HIV and COPD is lacking. We evaluated the mental health and health-care utilization consequences during the pandemic in this population.
Methods: We surveyed Pittsburgh HIV Lung Cohort participants from May through July 2020. Demographic and clinical data included age, sex, race and smoking history. Anxiety, depression and insomnia during the pandemic were evaluated using the General Anxiety Disorder-7 scale, Patient Health Questionnaire-9 and Insomnia Severity Index. The survey assessed for COVID-19 symptoms, health-care access/ utilization and risk/protective behaviours. Continuous variables were compared between participants with and without COPD using t-test and Mann–Whitney test as appropriate and categorical variables were compared using Fisher's exact test. Multiple and ordinal logistic regression was used to evaluate the association of COPD and any interaction effect by HIV status with anxiety, depression, insomnia, general health status, health-care utilization and risk/protective behaviours. All statistical tests were two-sided.
Results: 136 individuals were included: age 57.9 ±9.5 years; 76.5% male; 60.3% Caucasian and 39% Black; 47% current or former smokers. Forty-two (30.9%) respondents screened positive for anxiety disorders, 35 (25.7%) had major depressive disorder and 7 (5.1%) reported insomnia. Median scores and proportions across categories by severity of symptoms did not differ by COPD status. Of 22 participants with new or worsening symptoms that could be related to COVID-19, only 10 sought medical care. Participants with COPD reported similar levels of concern about seeking care due to potential COVID-19 exposures (50.0% versus 42.9%; P=0.64), interruptions in medical care (30.4% versus 27.4%; P=0.801) and a trend to less delay in diagnostic testing as those without COPD (8.7% versus 20.4%; P=0.247). Individuals with COPD were more likely to have sought emergent or urgent care since March (30.4% versus 8.0%; P=0.007). Although all respondents reported practicing social-distancing and masking, the majority (119; 87.5%) had in fact continued interacting with people outside the household and 38 (27.9%) joined large gatherings. Those with COPD reported similar risk behaviour as those without. There was no interaction effect by HIV status. See Table 1.
(Abstract O09)
All Participants (n=136)
Participants with COPD(n=23)
Participants without COPD (n=113)
p-value
Used telemedicine since March 1st
79 (58.1%)
13 (56.5%)
66 (58.4%)
0.875
Had an ED/urgent care visit since March 1st
16(11.8%)
7 (30.4%)
9 (8.0%)
0.007
Experienced interruptions of medical care
38 (27.9%)
7 (30.4%)
31 (27.4%)
0.801
Experienced delay in diagnostic testing
25 (18.4%)
2 (8.7%)
23 (20.4%)
0.247
Experienced difficulty obtaining medications
2 (1.5%)
0
2 (1.8%)
1
Worried about seeking care that is not related to coronavirus symptoms due to concern for COVID-19 exposure
59 (43.4%)
11 (50.0%)
48 (42.9%)
0.640
Delayed seeking care due to concerns for COVID-19 exposure
9 (6.6%)
2 (8.7%)
7 (6.2%)
0.648
Visited a gym, restaurant, bar, or movie theater
53 (39.0%)
7 (30.4%)
46 (40.7%)
0.483
Interacted with people outside the household
119 (87.5%)
19 (82.6%)
100 (88.5%)
0.489
Visited an event or gathering with >10 people
38 (27.9%)
8 (34.8%
30 (26.6%)
0.450
Traveled on an airplane since March 1st
5 (3.7%)
1 (4.4%)
4 (3.5%)
0.363
Conclusions: Anxiety, depression and concern of COVID-19 exposure were prevalent among persons with and without COPD or HIV. Many respondents experienced interruptions in medical care and diagnostic testing and concern about health-care-associated COVID-19 exposure, but this was not more severe in those with COPD or HIV. Despite likely higher risk of poor outcome in those with COPD, individuals with COPD were not more likely to curtail social interactions than those without COPD. HIV status also did not seem to modify the impact of COVID-19 on behaviours in this group.
Abstract O10
Antiviral Therapy 2020; 25 Suppl 1:A23
Faster decline in lung function in treated HIV-positive versus HIV-negative AGEhIV cohort participants independent of smoking behaviour
SO Verboeket1,2, A Boyd3,4, FW Wit1,2,3, E Verheij1,2, MF Schim van der Loeff1,4, N Kootstra5, M van der Valk1, RP van Steenwijk6, MB Drummond7, GD Kirk8, P Reiss1,2,3, the AGEHIV Cohort Study
1Amsterdam UMC, University of Amsterdam, Department of Internal Medicine, Amsterdam Infection and Immunity Institute and Amsterdam Public Health Research Institute, Amsterdam, the Netherlands; 2Amsterdam UMC, University of Amsterdam, Department of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands; 3HIV Monitoring Foundation, Amsterdam, the Netherlands; 4Public Health Service of Amsterdam, Department of Infectious Diseases, Amsterdam, the Netherlands; 5Amsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam, the Netherlands; 6Amsterdam UMC, University of Amsterdam, Department of Pulmonary Medicine, Amsterdam, the Netherlands; 7University of North Carolina, Division of Pulmonary and Critical Care Medicine, Chapel Hill, United States; 8Johns Hopkins University, Department of Epidemiology, Bloomberg School of Public Health, Baltimore, United States
Objectives/aim: We previously reported forced vital capacity (FVC) to be lower in HIV-positive versus HIV-negative participants with limited smoking exposure at time of enrolment in the AGEhIV cohort study. We now evaluate longitudinal changes in spirometry indices, accounting for smoking and other risk factors.
Methods: Pre-bronchodilator spirometry measurements from biennial AGEhIV cohort study visits over a median 6 years were analysed. Adjusted declines in 1-second forced expiratory volume (FEV1), FVC and FEV1/FVC were modelled using linear mixed-effects models and compared between HIV and smoking categories. Rates of FEV1 and FVC decline were evaluated in relation to CD4 and CD8 T-cell counts, C-reactive protein (CRP), interleukin-6, soluble CD14, soluble CD163 and intestinal fatty acid-binding protein levels in separate models.
Results: 500 HIV-positive and 481 HIV-negative participants were included, with median baseline age 53.2 versus 52.5 years (P=0.2), 89% versus 85% male (P=0.04), 89% versus 94% White (P<0.001), and 159 (32%) HIV-positive and 183 (38%) HIV-negative participants never smoked. HIV-positive participants were virally suppressed during 95% of study visits. Adjusted yearly declines in FEV1 as well as FVC, but not FEV1/FVC, were greater in HIV-positive than HIV-negative participants. This was the case both for participants who smoked and for those who did not smoke during follow-up (Figure 1). Compared with HIV-negative participants, HIV-positive participants had an overall adjusted additional decline in FEV1 of 10.4 ml/year, P=0.0005 and FVC of 11.5 ml/year, P=0.01 (FEV1/FVC 0.07 %/year, P=0.3), with a similar trend for never smokers (FEV1 6.0 ml/year, P=0.1; FVC 9.1 ml/year, P=0.1; FEV1/FVC 0.00 %/year, P=0.9). Higher CRP levels during follow-up were associated with accelerated declines in FEV1 and FVC among HIV-positive participants.
Mean predicted declines in spirometry indices by HIV status and smoking status during follow-up (Abstract O10)
Conclusion(s)/discussion: Treated HIV infection was associated with faster declines in both FEV1 and FVC, but not FEV1/FVC. These changes were not only dependent of smoking and may be partly driven by ongoing interstitial or (small-)airway damage, potentially related to increased inflammation.
Abstract O11
Antiviral Therapy 2020; 25 Suppl 1:A25
Gp120/CXCR4 axis promotes uncoupling of NOS3 in HIV smokers
S Aggarwal1,2, S Malik1, SV Raju3, JM Wells4,5,6, SL Heath7
1Department of Anesthesiology and Perioperative Medicine, Division of Molecular and Translational Biomedicine; 2Pulmonary Injury and Repair Center; 3Gregory Fleming James Cystic Fibrosis Research Center; 4Division of Pulmonary, Allergy and Critical Care Medicine; 5UAB Lung Health Center; 6Birmingham Veterans Administration Medical Center; 7Divisions of General Internal Medicine and Infectious Diseases, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
Purpose: Human immunodeficiency virus (HIV)-associated pulmonary artery hypertension (HIV-PAH) occurs approximately in 1 out of every 200 people with HIV (PWH), which is 100–1,000 times higher than the rate of PAH in general population. Further, disproportionately higher number of PWH are current smokers than the general population. However, the role of cigarette smoking (CS) in the pathogenesis of HIV-PAH is still elusive. The current hypothesis was that CS increases the interaction between the HIV protein, envelope glycoprotein 120 (gp120) and the host chemokine receptor, C-X-C motif chemokine receptor 4 (CXCR4), which disproportionately impairs the vasodilatory function of pulmonary artery endothelial cell (PAEC) in HIV and therefore increases the risk of HIV-PAH.
Methods: Smokers and non-smokers with and without HIV-1 infection were recruited at the University of Alabama at Birmingham 1917 clinic. All HIV-positive patients were on ART and had low blood viral load. Endothelial function in the participants was recorded by evaluating flow mediated dilation (FMD) and measuring in plasma, the key readouts of the endothelial nitric oxide synthase (NOS3) signalling, a crucial enzyme involved in vascular dilation. To determine the role of CS and gp120/CXCR4 axis in endothelial dysfunction, rat pulmonary artery endothelial cells (RPAEC) were exposed to 2% cigarette smoke extract (CSE), 50 ng/ml gp120, in the presence or absence of the CXCR4 antagonist, 25 μM AMD3100 (Plerixafor). Subsequently, NOS3 expression and function was assessed in these cells.
Results: Compared with non-smokers or HIV-negative smokers, PWH who smoke (HIV-smokers) had attenuated response to FMD. The plasma levels of nitrates/ nitrites and cyclic guanosine monophosphate (cGMP), a readout of NOS-derived vasodilator, nitric oxide, were low, while the levels of peroxynitrite (highly reactive oxidant formed from nitrite and hydrogen peroxide) were elevated in HIV-smokers. In vitro, exposure to CSE increased the expression of CXCR4 in RPAEC. The RPAECs challenged with gp120 in the presence of CSE, had reduced nitrite/nitrate and cGMP, and instead had increased production of NOS3-derived superoxide and peroxynitrite. This uncoupling of NOS3 activity from producing nitric oxide to superoxide and peroxynitrite was mediated by gp120+CSE dependent decrease in the phosphorylation of NOS3 at Ser1177 and increase in the phosphorylation at Thr495 (two key post-translational modifications that control NOS3 activity). The effects of gp120+CSE on NOS3 were inhibited by treating the RPAECs with the CXCR4 inhibitor, AMD3100.
Conclusions: Together, the study demonstrated that CS dependent gp120/CXCR4 signalling cascade is an important driver of endothelial dysfunction in HIV and the inhibition of CXCR4 by AMD3100 can be a potential therapeutic target for HIV-PAH.
Abstract O12
Antiviral Therapy 2020; 25 Suppl 1:A26
Anti-inflammatory effects of arabinoxylan rice bran supplementation in participants with treated, suppressed HIV infection and inadequate immune reconstitution: a randomized, double-blind trial
JJ Cadden1, KA Loomis1, R Kallia1, S Louie2, MP Dubé1
1University of Southern California Keck School of Medicine; 2School of Pharmacy, Los Angeles, CA, USA
Objectives/aims: Arabinoxylan rice bran (MGN-3/ Biobran, Daiwa Pharmaceutical) has shown immu-nomodulatory effects, including augmentation of NK cell activity, inhibition of HIV replication in vitro in mononuclear cells, enhancement cytotoxic CD8 T-cell activity in HIV-infected patients, reduced exercise- and lipopolysaccharide-induced inflammation in an animal model, and reduced high sensitivity C-reactive protein (hsCRP) in irritable bowel syndrome. We evaluated the anti-inflammatory effects of arabinoxylan rice bran supplementation in virologically suppressed participants with HIV who had incomplete immune reconstitution. Markers of inflammation, microbial translocation and monocyte/macrophage activation were measured including soluble CD14 (sCD14), soluble CD163 (sCD163), lipopolysaccharide binding protein (LBP), high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). Our primary hypothesis was that arabinoxylan rice bran supplementation would reduce sCD14 levels.
Methods: We conducted a randomized, double-blind, placebo-controlled trial of 27 adults with HIV on antiretroviral therapy (ART) with CD4+ cell counts of 100–350 cells/mm3, who had been on ART with HIV-1 RNA ≤50 copies/ml for at least 24 weeks prior to entry. Participants were randomized to receive two 500 mg capsules of arabinoxylan rice bran three times daily (n=13) or two placebo capsules three times daily (n=14) for 12 weeks. Fasting blood samples were obtained in the morning at entry and week 12. Soluble CD14, sCD163, LBP and IL-6 were measured by ELISA (R&D Systems).
A total sample of 24 participants (12 per arm) would detect a clinically relevant difference of 0.07 log10 in sCD14 (and other biomarkers) between treatment versus placebo arms with 90% power and a 0.05 two-sided type I error rate, assuming the sd of the changes in log10 sCD14 from baseline to week 12 is 0.05 for both groups.
Absolute change in sCD14 (and other biomarkers) from baseline to week 12 was compared between the treatment arm and the placebo arm by a two-sided, two-sample t-test. The primary efficacy analysis was a modified intent-to-treat analysis, which included all randomized participants for whom baseline and week 12 samples were available for assays.
Results: A total of 24 participants were included in our analyses (12 rice bran and 12 placebo). Three participants were lost to follow-up. Those included had chronic HIV infection, with a median ART duration of 144 months (range 24–444). The median baseline CD4 cell count was 244 cells/mm3 (range 117–354). There was no statistically significant difference in the change in sCD14, sCD163, IL-6, hsCRP or LBP levels from baseline to 12 weeks between the treatment and placebo group (Table 1). Treatment was well tolerated with no withdrawals due to side effects.
Discussion: We found no evidence of a beneficial effect of 12 weeks of arabinoxylan rice bran supplementation on markers of inflammation and monocyte/macrophage activation in virologically suppressed participants with HIV who had inadequate immune reconstitution.
