CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

impaired mitochondrial fuel oxidation (MFO), but underlying mechanisms are unknown and interventions lacking. We investigated deficiency of the intracellular antioxidant glutathione, GSH) and impaired MFO as metabolic and mitochondrial mechanisms contributing to accelerated aging and functional decline in HIV patients. Methods: An open-label clinical trial (NCT02348775) in 8 older GSH-deficient HIV-infected patients of both genders (aged 50-64y), compared to 8 age, gender and BMI-matched non-HIV controls. HIV subjects were studied before and after 12-weeks of oral supplementation with N-acetylcysteine plus glycine (NAC-Gly, provided as GSH precursors), and again 8-weeks after stopping supplementation. Controls were not supplemented. All subjects underwent muscle biopsy, calorimetry, physical function measures (gait speed, chair-rise test, 6-min walk, grip strength), DEXA scan, anthropometry, and infusion of 2H3-3-methylhistidine tracer to measure the following: glutathione levels in muscle and red-cells, MFO, muscle strength, exercise capacity, body composition, waist-circumference and rate of muscle protein breakdown. Results: Compared to non-HIV controls, ‘older’ HIV patients had significantly lower intracellular GSH, impaired MFO, lower gait speed, grip strength and 6-min walk times, higher fat mass and waist circumference, and increased muscle protein breakdown. Molecular analyses indicate a post-translational defect in genes regulating mitochondrial fuel oxidation. With NAC-Gly supplementation over 12weeks all these defects improved significantly; GSH, MFO and gait speed normalized to levels seen in non-HIV controls. Benefits began to recede on stopping supplementation. Results are summarized in attached table. Conclusion: In HIV patients, deficiency of GSH and impaired mitochondrial fuel oxidation contribute to accelerated aging with decreased muscle strength and exercise capacity, increased muscle breakdown and fat accumulation. Supplementing NAC-Gly fully corrected intracellular GSH deficiency, impaired MFO and gait speed, and also improved strength, exercise capacity, fat mass, waist circumference and muscle loss. These findings suggest a key role for NAC-Gly supplementation and GSH on reversing accelerated aging in HIV, and warrants further investigation.

756 THE ASSOCIATION OF PAIN AND LONG-TERM OPIOID THERAPY WITH HIV TREATMENT OUTCOMES Jessica Merlin 1 , Dustin M. Long 1 , William Becker 2 , Edward R. Cachay 3 , Katerina A. Christopoulos 4 , Heidi M. Crane 5 , E. J. Edelman 2 , Richard Harding 6 , Jane Liebschutz 7 , W. C. Mathews 3 , Michael J. Mugavero 1 , Sonia Napravnik 8 , Michael Saag 1 , Joanna Starrels 9 , Robert Gross 10 1 University of Alabama at Birmingham, Birmingham, AL, USA, 2 Yale University, New Haven, CT, USA, 3 University of California San Diego, San Diego, CA, USA, 4 University of California San Francisco, San Francisco, CA, USA, 5 University of Washington, Seattle, WA, USA, 6 King’s College Hospital, London, UK, 7 University of Pittsburgh, Pittsburgh, PA, USA, 8 University of North Carolina Chapel Hill, Chapel Hill, NC, USA, 9 Albert Einstein College of Medicine, Bronx, NY, USA, 10 University of Pennsylvania, Philadelphia, PA, USA Background: Chronic pain is common in persons living with HIV (PLWH) and is associated with impaired function and high care utilization. Few studies have investigated the impact of this important comorbidity on HIV outcomes. Long- term opioid therapy (LTOT) is commonly prescribed for chronic pain despite lack of evidence of benefit and known risks of misuse and addiction, but may keep patients in care due to the need for regular visits to obtain refills. We aimed to determine the impact of chronic pain and LTOT on HIV outcomes. Methods: Between 7/2015-7/2016, we assessed pain in PLWH followed at 5 Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites using the Brief Chronic Pain Questionnaire (BCPQ) and the Pain and pain’s impact on Enjoyment of life and General activity (PEG) questionnaire (scored 1-10). Chronic pain was defined as both ≥moderate pain for ≥ 3 months on the BCPQ and ≥ 4/10 on the PEG. We used logistic regression to assess the relationship between chronic pain at an index visit and HIV outcomes over the subsequent year: plasma HIV RNA > 1000 copies/mL that did not suppress within a month (virologic failure) and no-shows without another visit within the next month (a measure of suboptimal retention). We also assessed the interaction between chronic pain and LTOT, defined as ≥ 90 consecutive days of prescribed opioids, for both outcomes. Results: Among 2334 participants, 44%were ≥ 50 years old, 16%were female, 12% had virologic failure, 25% had chronic pain, and 19%were on LTOT. Chronic pain was associated with virologic failure (aOR 1.64, 95% CI 1.21-2.21, p=0.0014) and no-shows (aOR 1.45, 95% CI 1.15, 1.82, OR p=0.0016). Among PLWH with chronic pain, LTOT was not protective against no-shows (aOR 1.01, 95% CI 0.7-1.45, p=0.98), but was protective against virologic failure (aOR 0.53, 95% CI 0.33-0.88, p=0.013). Conclusion: We found chronic pain to be associated with virologic failure. While virologic failure could lead to chronic pain, we hypothesize that chronic pain leads to virologic failure, as has been shown with similar comorbidities such as depression. If future studies confirm this hypothesis, potential next steps include developing chronic pain treatments in PLWH, and if effective, investigating whether they improve HIV-related outcomes. The protective association of LTOT on virologic failure warrants further research into the patient’s lived experience and doctor-patient relationship to identify potential mechanisms of this effect. 757 REVERSING ACCELERATED AGING IN HIV PATIENTS: METABOLIC AND MITOCHONDRIAL MECHANISMS Rajagopal V. Sekhar , Jean W. Hsu, James Suliburk, Ruya Liu, Charles G. Minard, Vijay K. Yechoor, Farook Jahoor, Chun Liu Baylor College of Medicine, Houston, TX, USA Background: HIV-infected patients are reported to have ‘accelerated aging’ based on rapid physical and functional decline. Such patients have muscle weakness, decreased exercise capacity, fat accumulation, muscle loss and

Poster Abstracts

758 BLOOD TELOMERE LENGTH CHANGES AFTER DRV/R + EITHER RAL OR TDF/FTC AS FIRST-LINE ART Natalia Stella-Ascariz 1 , Rocio Montejano 1 , Javier Rodriguez-Centeno 1 , Belen Alejos 2 , Christine Schwimmer 3 , Jose I. Bernardino 1 , Berta Rodes 1 , Clotilde Allavena 4 , Christian Hoffmann 5 , Magnus Gisslén 6 , Rosa de Miguel 1 , Cédrick Wallet 7 , François Raffi 8 , Jose R. Arribas 1 1 Hospital La Paz Institute for Health Research, Madrid, Spain, 2 Institute of Health Carlos III, Madrid, Spain, 3 INSERM, Bordeaux, France, 4 CHU Hôtel-Dieu, Nantes, France, 5 ICH Study Center, Hamburg, Germany, 6 Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden, 7 CHU de Bordeaux, Bordeaux, France, 8 CHU de Nantes, Nantes, France Background: In vitro tenofovir is a potent inhibitor of human telomerase. The in vivo relevance of this inhibition is unknown.

CROI 2018 283