Jackie White, MPH Presenting on behalf of: Matthew J. Mimiaga, ScD, MPH

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Negative affect moderates the association between atrisk sexual behaviors and substance use during sex: Findings from a large cohort study of HIV-infected males engaged in primary care in the United States Jackie White, MPH Presenting on behalf of: Matthew J. Mimiaga, ScD, MPH

Background HIV infection is associated with a number of psychosocial co-morbidities, such as substance use and negative affect Alcohol use and illicit drug use prevalence is high among HIVinfected men and predicts unprotected sex in this population (Morin et al. 2007; Shuper et al. 2009) Recent review articles suggest that substance use may synergistically interact with negative affect to increase the risk of unprotected sex (Kalichman 2000; Stall et al. 2003; Sikkema et al. 2010; Mayer & Mimiaga, 2011)

Background However There are inconsistent findings regarding the association of at-risk sexual behaviors and substance use during sex Studies with HIV-infected patients typically treat depression and anxiety diagnoses, as well as depressive and anxious symptoms, as separate or discrete constructs or conditions Negative affect may impact the association between substance use and sexual risk in the context of sexual encounters Not been evaluated in large cohort studies of HIV-infected men

Methods Participants and Procedures Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort is a longitudinal observational study of HIV-infected patients A clinical assessment was integrated into clinical care between 2005 and 2008 at four participating CNICS sites: University of California San Diego (UCSD) HIV Clinic Fenway Health/Harvard-Mass General Hospital, Boston University of Alabama at Birmingham (UAB) 1917 HIV/AIDS Clinic University of Washington (UW) Harborview Medical Center HIV Clinic, Seattle

Methods Participants and Procedures Inclusion Criteria: HIV Infected male patients 18 years of age or older Completed a clinical assessment of patient reported outcomes (PROs) as part of a routine clinical care visit before April 2010 Patients completed the PRO assessment using touch screen tablets or personal computers Approved by Institutional Review Boards at each participating site

Methods: Measures Outcome: Alcohol and/or Drug Use During Sex, Last 6 Months Participants were queried as to whether or not they had used alcohol and/or drugs during sex in the last 6 months (yes/no) Independent Variable 1: Internalizing Symptoms of Negative Affect Self-reported depressive and anxious symptoms PHQ-9 and PHQ-5 A summary score of general negative affect was created by summing participants scores on PHQ-9 and PHQ-5 (14 items total) 6

Independent Variable 2: Sexual Behavior, Last 6 Months Participants were queried about their sexual behaviors in the last 6 months Four variables were operationalized across two domains: (1) Anal Sex: Any unprotected anal sex with another man in last 6 months Number of distinct men engaged in anal sex with in last 6 months (2) Vaginal Sex: Any unprotected vaginal sex last 6 months Number of distinct women engaged in vaginal sex with in the last 6 months Covariates Geographic location Age Race/ethnicity Methods: Measures 7

Methods: Statistical Analysis SAS version 9.1.3 Generalized estimating equations (GEE) were used for all statistical procedures PROC GENMOD (logit link function) with study site as a design covariate A complete case analysis (listwise deletion) All models were adjusted for: HIV disease characteristics HIV medication use Accessed substance abuse treatment services in past year 8

Model 1 = all participants who reported engaging in anal sex with a man in the past 6 months (N=1,232) Model 2 = all participants who reported engaging in vaginal sex in the past 6 months (N=390) Two interaction terms were included to test whether the relationship between unprotected anal sex (UAS) / vaginal sex (UVS) and substance use during sex was moderated by negative affect Anal Sex: Negative Affect x UAS Negative Affect x Number Anal Sex Partners Vaginal Sex: Methods: Statistical Analysis Negative Affect x UVS Negative Affect x Number Vaginal Sex Partners 9

GEE Models Examining Associations between Demographics/Covariates and Substance Use During Sex* Total Sample Substance Use During Sex 10 * Substance use during sex = Alcohol and/or Drug Use in Past 6 Months. No Substance Use During Sex Bivariate, Unadjusted Comparisons+ N=2868 (100%) N=739 (26%) N=2129 (74%) N (%) N (%) N (%) Crude OR (95% CI) p-value GEOGRAPHIC LOCATION San Diego, CA 622 (21.69) 199 (26.93) 423 (19.87) Ref ---- Seattle, WA 873 (30.44) 191 (25.85) 682 (32.03) 0.60 (0.47, 0.75) <0.0001 Birmingham, AL 1064 (37.10) 218 (29.50) 846 (39.74) 0.55 (0.44, 0.69) <0.0001 Boston, MA 309 (10.77) 131 (17.73) 178 (8.36) 1.56 (1.18, 2.07) 0.002 SOCIODEMOGRAPHICS Mean (SD) Age (in years) 44.60 (9.78) 41.83 (9.48) 45.57 (9.71) 0.96 (0.95, 0.97) <0.0001 Race/Ethnicity White 1650 (57.53) 446 (60.35) 1204 (56.55) Ref ---- Hispanic/Latino 340 (11.85) 93 (12.58) 247 (11.60) 0.86 (0.71, 1.05) 0.141 Black/African American 735 (25.63) 165 (22.33) 570 (26.77) 0.97 (0.80, 1.16) 0.732 Other Race/Ethnicity 143 (4.99) 35 (4.74) 108 (5.07) 0.78 (0.45, 1.36) 0.385 VIRAL LOAD, MEDICATION, & SUBSTANCE USE SERVICES Detectable Viral Load 1309 (82.33) 356 (48.17) 953 (44.76) 1.28 (1.16, 1.42) <0.0001 Currently Taking HIV Medications 2239 (85.52) 543 (73.48) 1696 (79.66) 0.71 (0.57, 0.87) 0.001 Substance Abuse Treatment, Past 280 (9.76) 125 (16.91) 155 (7.28) 2.45 (1.89, 3.19) <0.0001 + Year Unadjusted estimates are presented for geographic location/study site. All other bivariate statistics were estimated using generalized estimating equation (GEE) models to adjust standard errors for clustering induced by study design (study site included as a design covariate).

Model 1: Adjusted GEE Model Examining Associations between Anal Sex and Substance Use During Sex Outcome: Substance Use During Sex N=739 (26%) ANAL SEX, LAST 6 MONTHS Adj OR (95% CI) p-value Unprotected Anal Sex (UAS) 2.79 (1.79, 4.37) <0.0001 Number Anal Sex Partners 1.34 (1.04, 1.72) 0.023 Interaction Terms: Negative Affect x UAS 0.97 (0.94, 0.99) 0.032 Negative Affect x Number Anal Sex Partners 0.99 (0.98, 1.01) 0.712 + Model adjusted for detectable viral load, current use of HIV medications, and accessing substance abuse treatment services in the past year. Also significant were the following covariates: age (OR=0.98; 95% CI=0.97, 0.99; p=0.0005); Latino race (OR= 0.69 ; 95% CI=0.59, 0.82; p=0.0001); and substance abuse treatment, past year (OR= 1.72; 95% CI=1.44, 2.06; p<0.0001). Moderation: Fitted Model Anal Sex (N= 1,232) Fitted Probability of Substance Use During Sex 11 No UAS UAS + Negative affect: low=quartile 1 scores, moderate=median scores, high=quartile 3 scores).

Model 2: Adjusted GEE Model Examining Associations between Vaginal Sex and Substance Use During Sex Outcome: Substance Use During Sex N=739 (26%) VAGINAL SEX, LAST 6 MONTHS Adj OR (95% CI) p-value Unprotected Vaginal Sex (UVS) 1.60 (1.14, 2.26) 0.007 Number Vaginal Sex Partners 1.77 (0.94, 3.35) 0.077 Interaction Terms: Negative Affect x UVS 0.98 (0.97, 0.99) <0.0001 Negative Affect x Number Vaginal Sex Partners 0.98 (0.96, 1.01) 0.109 + Model adjusted for detectable viral load, current use of HIV medications, and accessing substance abuse treatment services in the past year. Also significant were the following covariates: age (OR=0.99; 95% CI=0.97, 0.99; p=0.0004); and Latino race (OR= 0.44; 95% CI=0.23, 0.85; p=0.014). Moderation: Fitted Model Vaginal Sex (N=390) Fitted Probability of Substance Use During Sex 12 No UVS UVS + Negative affect: low=quartile 1 scores, moderate=median scores, high=quartile 3 scores).

Summary The relationship between sexual risk and substance use behaviors at the time of sex was moderated by negative affect Higher levels of negative affect increase the strength of the relationship between UAS and substance use during sex, yet inverse is true for UVS Findings appear reasonable given research suggesting a curvilinear relation between negative affect and sexual risk behaviors (Kalichman & Weinhardt 2001; Koblin et al. 2006) Behavioral health HIV prevention interventions may benefit from: Considering depressive and anxious symptoms as symptom clusters that share internalizing properties Addressing underlying mental health conditions and behavioral outcomes simultaneously to maximize intervention effects 13

Limitations and Strengths Limitations: Cross-sectional data from baseline assessment Lack of temporal ordering Need longitudinal prospective data No indicators of: Sexual identity (gay/bisexual/heterosexual) Partner serostatus Partner type (primary vs. casual partners) Strengths: Large, multi-site clinical cohort of HIV-infected men First study to examine and demonstrate the moderating effect of negative affect on the association of sexual risk and substance use during sex among HIV-Infected MSM 14

Coauthors: Sari L. Reisner, MA Heidi M. Crane MD, MPH Johannes Wilson, BA Chris Grasso, MPH Steven A. Safren, PhD Mari M. Kitahata, MD, MPH, Wm. Christopher Mathews, MD, MSPH Kenneth H. Mayer, MD This work was supported in part by (R34 DA031028, Mimiaga) and the CNICS grant (R24 AI067039, Saag). Patient Reported Outcome (PRO) collection in CNICS is also supported in part by the PROMIS HIV grant (U01 AR057954, Crane). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Matthew Mimiaga, ScD, MPH: MMimiaga@FenwayHealth.org