CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

701 START OR SWITCH OF INTEGRASE INHIBITORS ON DEPRESSIVE SYMPTOMS IN WOMEN WITH HIV Jane A. O'Halloran 1 , Kunbo Wang 2 , Dionna W. Williams 3 , Raha Dastgheyb 3 , Kathryn Fitzgerald 3 , Asante R. Kamkwalala 3 , Amanda B. Spence 4 , Anjali Sharma 5 , Deborah Gustafson 6 , Pauline M. Maki 7 , Kathleen M. Weber 8 , Adaora Adimora 9 , Margaret Fischl 10 , Yanxun Xu 3 , Leah H. Rubin 3 1 Washington University in St Louis, St Louis, MO, USA, 2 Johns Hopkins University, Baltimore, MD, USA, 3 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4 Georgetown University, Washington, DC, USA, 5 Albert Einstein College of Medicine, Bronx, NY, USA, 6 SUNY Downstate Medical Center, Brooklyn, NY, USA, 7 University of Illinois at Chicago, Chicago, IL, USA, 8 Cook County Health & Hospitals System, Chicago, IL, USA, 9 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 10 University of Miami, Miami, FL, USA Background: Depressive symptoms are associated with use of some antiretroviral therapy (ART) agents. Recently, concerns regarding neuropsychiatric symptoms with integrase strand transfer inhibitor (INSTI) use have been raised. We examined INSTI-associated changes on the profile of depressive symptoms in women with HIV (WWH). Methods: Women’s Interagency HIV Study (WIHS) participants who started or switched to INSTI-based ART and had two consecutive records (one before and one after the start/switch) with a completed Center for Epidemiologic Studies Depression Scale (CES-D) were included in the present analysis. We examined the adverse effects of INSTI start or first switch as a drug class on subscale-level (interpersonal, somatic, negative and positive affect) CES-D symptoms using linear mixed effects models adjusting for relevant covariates (e.g., age, race, substance use, body mass index, HIV RNA). Subsequent models examined each of the INSTIs separately. Results: 1036 WWH, median age 48 (interquartile range 36, 60) years, 697 (67%) black, non-Hispanic were included in the analysis. Twenty-one percent were INSTI starts (30% raltegravir [RAL]; 29% elvitegravir [EVG]; 41% dolutegravir [DTG]) and the remainder of observations were switches to INSTI- based regimens (35% RAL; 27% EVG; 38% DTG). The majority of switches were from a protease inhibitor (PI) (56%) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) (34%) based regimen. Overall, INSTI use was not associated with subscale changes in depressive symptoms after start/switch. Similarly, start/switch to individual INSTIs did not affect depressive symptoms. When analysis was restricted to those who switched to INSTIs from any ART, again no effects on depressive symptoms were observed. Similarly, switch from a NNRTI- based or PI-based regimen to any INSTI or individual INSTIs did not impact depressive symptoms. Starting any INSTI on the other hand improved positive affect, when stratified by INSTI type EVG but not RAL or DTG improved positive affect (p=0.004). Conclusion: Among WWH, switching to INSTI based therapy did not have an impact of depressive symptoms. Initiation of INSTIs did result in improvement in positive affect symptoms and this was predominantly driven by EVG use. 702 PTSD SYMPTOMS AND HYPERAROUSAL INFLUENCED BY CHILDHOOD TRAUMA IN WOMEN WITH HIV Gretchen Neigh 1 , Vasiliki Michopoulos 2 , Rebecca Hinrichs 2 , Sierra Carter 2 , Igho Ofotokun 2 , Tanja Jovanovic 3 1 Virginia Commonwealth University, Richmond, VA, USA, 2 Emory University, Atlanta, GA, USA, 3 Wayne State University, Detroit, MI, USA Background: Lack of knowledge about HIV interactions with posttraumatic stress disorder (PTSD) may limit generalizability of treatment strategies for patients with HIV and PTSD. In addition, childhood trauma is a risk factor for PTSD. Methods: African American women (18-65 yrs) recruited fromWomen’s Interagency HIV Study (WIHS) in Atlanta, GA (n=91, 30 without HIV, 61 with HIV (WWH)), provided informed consent, and underwent interviews to capture trauma exposure and PTSD symptoms for DSM-5. Psychophysiological hyperarousal was assessed by skin conductance (SC) at baseline and during CAPS-5 using mobile eSense SC Level App. ANOVAs controlled for income and HIV viral load. Results: Rates of adult and childhood trauma did not differ by HIV serostatus (p’s>0.05). Sociodemographic variables were similar among groups: age (p=0.19); education (p=0.24); employment (p=0.84). Income level was greater in WWH (p=0.02). Within WWH, the median CD4 count was 652 and 82% had undetectable viral loads. PTSD symptom severity was influenced by interaction of HIV serostatus and childhood trauma (p=0.018; eta2=0.07; Fig 1). HIV was associated with greater PTSD symptoms only with low childhood trauma

(p=0.016; eta2=0.07). There was no impact of HIV status on PTSD symptoms in women with high childhood trauma (p=0.46). HIV serostatus interacted with childhood trauma to impact baseline arousal (p=0.05; eta2=0.17) and reactivity to trauma reminders (p=0.015; eta2=0.25). Higher childhood trauma in uninfected women associated with greater baseline SC compared to uninfected women with low childhood trauma (p=0.05; eta2=0.15). Childhood trauma did not impact baseline SC in WWH (p=0.69). HIV associated with lower baseline SC in women with high childhood trauma (p=0.08; eta2=0.14). In women with low levels of childhood trauma, psychophysiological response to trauma reminders was lower in WWH compared to uninfected women (p=0.06; eta2=0.15). In women exposed to high childhood trauma, HIV associated with augmented reactivity to trauma reminders (p=0.06; eta2=0.15). Conclusion: Taken together, these findings suggest HIV impacts PTSD symptoms and hyperarousal in women dependent on childhood trauma. Given that HIV status impacts PTSD symptoms as well as baseline and trauma reminder-evoked SC response, the current data have high clinical relevance for treating PTSD in WWH.

Poster Abstracts

703 DYSREGULATED SYNTHESIS OF NEUROTRANSMITTERS IN METHAMPHETAMINE USERS LIVING WITH HIV

Antonio Chahine 1 , Tulay Koru-Sengul 1 , Daniel J. Feaster 1 , Nichole Klatt 1 , Margaret Roach 1 , Suresh Pallikkuth 1 , Mark Sharkey 1 , Jessica Salinas 1 , Mario Stevenson 1 , Savita Pahwa 1 , Dietmar Fuchs 2 , AdamW. Carrico 1 1 University of Miami, Miami, FL, USA, 2 Innsbruck Medical University, Innsbrusk, Austria Background: Elevations in the kynurenine/tryptophan (K/T) ratio are only partially reversed by effective treatment, linked to neuropsychiatric disorders, and predict faster clinical HIV progression. However, relatively less is known about the mechanisms of HIV-associated increases in the phenylalanine/ tyrosine (P/T) ratio, which disrupts catecholamine synthesis (e.g., dopamine). This 15-month longitudinal study examined whether co-occurring stimulant use and HIV-associated pathophysiologic processes predict greater K/T and P/T ratios even after adjusting for detectable HIV viral load. Methods: In total, 110 sexual minority men (i.e., gay, bisexual, and other men who have sex with men) living with HIV were enrolled in a randomized controlled trial. All participants had biologically confirmed, recent methamphetamine use via urine or hair toxicology screening. Peripheral venous blood samples were collected at baseline, 6, 12, and 15 months. Marginal, generalized linear mixed models were constructed to identify predictors of the time-varying K/T and P/T ratios. Generalized Estimating Equations were used to test the predictors of screening positive for clinical depression using the Centers the Epidemiologic Study of Depression scale (scores > 16). Results: The majority of participants were racial/ethnic minorities (57%) and middle-aged (mean = 43.2 years; SD = 8.9). At baseline, the median baseline CD4+ T-cell count was 646 cells/mm 3 (Interquartile Range = 428 – 816) and 26% had a detectable HIV viral load (> 40 copies/mL). As shown in the Table, greater time-varying sCD14 and detectable viral load were independent predictors of a higher K/T ratio in adjusted analyses. On the other hand, greater proviral HIV DNA at baseline and time-varying sCD14 as well as time-varying reactive urine toxicology results for stimulants (i.e., methamphetamine or cocaine) independently predicted an increased P/T ratio. Time-varying reactive urine toxicology results for stimulants (Adjusted Odds Ratio = 2.26, 95% CI: 1.06-4.80, p = 0.043) but not the time-varying K/T or P/T ratios were significantly associated with screening positive for clinical depression. Conclusion: HIV persistence and stimulant use are independent risk factors for dysregulated catecholamine synthesis. Findings support the need for targeted pharmacologic treatments to mitigate dysregulated catecholamine synthesis in those who co-occurring HIV and stimulant use.

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