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Over the past two decades, the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) has made major contributions to progress in substance use treatment research. However, contributions to research addressing the considerable medical and mental health comorbidities of substance use, which can impede treatment efficacy and compromise health, have been emphasized less. In this Commentary, we review the contributions of CTN studies focused on medical comorbidities, initially centered on the HIV epidemic in people who use drugs, and subsequently broadening to address hepatitis C and life-threatening bacterial infections; as well as mental health comorbidities, especially post-traumatic stress disorder, attention-deficit/hyperactivity disorder, and suicidality. These studies demonstrate that comorbidities assessments and treatment can be feasibly implemented in substance use treatment programs and, conversely, that substance use assessments and treatments can be feasibly implemented in clinical care sites. We highlight the NIDA CTN Data Share as an invaluable resource for secondary analyses of comorbidities using data from CTN substance use treatment protocols and provide examples of its use. We describe the work of the CTN Comorbidities of Substance Use Special Interest Group (SIG), formerly known as the HIV SIG, as an example of the role that SIGs can play in facilitating CTN research in areas of emerging significance. We emphasize the importance of implementing a “whole person” approach—one that integrates both substance use and comorbidities outcomes. We identify promising opportunities for conducting this research by studying strategies for integrating prevention, screening, linkage, treatment, adherence, and retention support for comorbidities into substance use disorder (SUD) treatment venues; as well as strategies for integrating SUD treatment into primary care venues, hospitals, and other non-SUD clinical settings.

Men who have sex with men who use substances (SU-MSM) can benefit from pre-exposure prophylaxis (PrEP) for HIV prevention, especially in Southern US cities where HIV incidence is high; however, uptake remains low. Identifying barriers and facilitators is crucial for developing and implementing strategies to enhance uptake. Few studies of PrEP barriers and facilitators have focused on Southern SU-MSM, and most existing studies have not robustly measured such barriers and facilitators. In this study, 225 SU-MSM were recruited from community STI clinics, syringe services programs, or substance use treatment programs in eight Southern cities. Using structural equation modeling, we examined latent variable constructs of barriers and facilitators (i.e., affordability, burden, risk compensation, side effects, and stigma) and their associations with both willingness to take PrEP and length of PrEP use. Greater concern over affordability was robustly associated with more willingness to take PrEP under a variety of conditions. Risk compensation was associated with greater length of PrEP use, suggesting a major motivator to remain on PrEP was the perceived freedom to forego condoms during sex. Findings advance research on measurement of barriers and facilitators of PrEP willingness and uptake and highlight the importance of addressing affordability in PrEP implementation.

Related protocols: CTN-0082

Background: Methamphetamine (MA) use has been linked to engaging in sexual risk behaviors (SRBs) that are associated with HIV/STIs, particularly among men who have sex with men (MSM) and men who have sex with men and women (MSMW; hereafter MSM/W). The objectives of this analysis were to determine whether reduced MA is associated with decreases in SRBs in a sample of MSM/W.

Method: Data came from the ADAPT-2 trial, a randomized, double-blind, two-stage sequential parallel design trial evaluating extended-release injectable naltrexone (NTX) and oral bupropion (BUP) vs. placebo for MA use disorder. In the first 6 weeks of the trial (stage 1), participants were randomized to receive NTX-BUP or placebo. In the second 6 weeks, participants in the placebo group who did not have a treatment response were rerandomized (stage 2). For this secondary analysis, the independent variable was the number of MA-negative urine drug screens (UDS). The dependent variables included three different types of SRBs. Regression models of the independent and dependent variables were adjusted for age, race/ethnicity status, marital status, treatment assignment, and baseline SRBs.

Results: Of the 151 participants, median age was 40 years and majority were non-Hispanic white (52%) and completed more than high school education (82%). Each additional MA-negative UDS was associated with a 7% (adjusted rate ratio (aRR) =0.93; 95% CI, 0.87, 0.99) reduction in total number of sex partners in stage 2 only. Each additional MA-negative UDS was associated with a 13% (aRR =0.87 95%; confidence interval (CI), (0.76, 0.98)) and 9% (aRR =0.91; 95% CI, 0.84, 0.99) reduction in number of condomless sexual encounters in stage 1 and stage 2, respectively. Lastly, each additional MA-negative UDS was associated with a 16% (aRR =0.84; 95% (CI), 0.75, 0.94)) and 27% (aRR =0.73; 95% CI, 0.64, 0.84) reduction in number of sexual encounters when high on MA.

Conclusions: Our analysis showed that reductions in MA use was associated with reductions in several sexual risk behaviors associated with HIV/STI. These findings provide further support for exploring reductions in sexual risk behaviors as a clinical endpoint in future treatment interventions for MA use.

Related protocols: CTN-0068

This is one of the primary outcomes articles for CTN-0082.

In Southern U.S. states with high HIV incidence and low HIV Pre-Exposure Prophylaxis (PrEP) uptake, enhanced efforts to increase interest in and willingness to use PrEP are needed. This implementation survey examined the associations of sociodemographic background, substance use, and sexual risk behaviors with willingness to use daily oral and long-acting injectable (LAI) PrEP among substance using men who have sex with men (SU-MSM). Participants were 225 SU-MSM recruited from sexually transmitted infection (STI) clinics, syringe services programs (SSPs), and substance use treatment programs (SUTPs) in eight Southern U.S. cities. Rates of willingness were high for both daily oral PrEP (78%) and LAI PrEP (66%). In multivariable analyses, distinct factors were associated with willingness towards each. For daily oral PrEP, greater willingness was associated with condomless anal sex, less frequent non-injection opioid use, prior PrEP awareness, and past use of PrEP. For LAI PrEP, greater willingness was associated with Black race, identifying as gay, being single, and higher injection drug use frequency. Lower willingness to use LAI PrEP was associated with higher non-injection opioid use frequency. Findings about willingness to use LAI PrEP, as a relatively newer modality, and greater willingness among Black SU-MSM as a disproportionately HIV-impacted population, are especially important.

Conclusions: These findings argue for the necessity to enhance PrEP promotion efforts that distinguish between oral and LAI PrEP and that are specifically tailored to major SU-MSM subgroups in the Southern U.S.

Related protocols: CTN-0082

This poster reports on an initiative to implement HIV rapid testing in substance abuse treatment programs in the state of South Carolina. A multi-agency collaboration between the Single State Authority, the state Health Department, the regional Addiction Technology Transfer Center (ATTC), and one substance abuse treatment program (Lexington-Richland Alcohol and Drug Abuse Council (LRADAC)), facilitated state-wide implementation. LRADAC, a community-based treatment program, was one of twelve sites that participated in the CTN trial on HIV rapid testing (protocol CTN-0032). Upon completion of the trial, LRADAC implemented a rapid HIV testing and counseling program as a clinical service. South Carolina’s previous efforts to implement on-site rapid HIV testing in 10 pilot agencies had less than optimal success due to the absence of a successful model on which agencies could base their implementation plan. With support from the collaborating agencies, staff developed and presented a 2 1/2 day HIV testing and counseling curriculum at the annual SC School of Alcohol and Drug Studies in 2010. Following the successful completion of the course, participants were fully certified to conduct testing and counseling in their local programs. Course participants had the opportunity to learn the counseling and testing procedures that LRADAC staff found successful in implementing their program. Although challenging, implementing HIV testing program in substance abuse treatment programs is feasible for agencies. The multi-agency collaboration in South Carolina supported the development of an HIV testing and counseling course that was team taught and showcased a successful model on which implementation could be based. Consequently, this effort increased the likelihood that additional substance abuse agencies within the state would move forward with implementation.

Related protocols: CTN-0032

This poster discusses the results of a survey done as part of protocol CTN-0012 (“Characteristics of Screening, Evaluation, and Treatment of HIV/AIDS, Hepatitis C Viral Infections, and Sexually Transmitted Infections in Substance Abuse Treatment Programs”), emphasizing the perspective of state substance abuse and health departments in relationship to the treatment programs within their jurisdiction for three infection groups: HIV/AIDS, Hepatitis C virus, and sexually transmitted infections. State substance abuse and health departments were compared regarding priorities, written guidelines and availability of funding for 8 selected services for the 3 infections (24 comparisons). In addition, clarity of guidelines and availability of funding for the 8 services, as reported by administrators and clinicians at treatment programs offering these services were compared with guidelines and funding as reported by the states. Surveys were received from 48 states and DC (96%) representing 46 substance abuse and 42 health departments. The response rate from treatment program administrators and clinicians was 269 (84%) and 1723 (78%), respectively. There was general agreement between states and the two departments within the states regarding priorities and availability of funding (19 of 24 comparisons). While most states had guidelines for infection-related services, clarity of guidelines as expressed by treatment program administrators and clinicians was less than optimal. For funding, treatment program administrators indicated less availability than the states for all 24 comparisons, 19 of which were statistically significant. While states appear generally to have their priorities, guidelines and funding in place, the mosaic that constitutes the healthcare delivery system may be too complex for the treatment programs to access most efficiently.

Although substance abuse treatment programs are an important point of contact to provide health services to diagnose, treat and prevent transmission of hepatitis B (HBV) and hepatitis C (HCV) viral infection, little is known about the availability of these services in substance abuse programs. This presentation reports on a study that evaluated the prevalence and spectrum of HBV and HCV services offered by drug treatment programs in the U.S. A questionnaire-based survey of drug treatment programs within the National Drug Abuse Treatment Clinical Trials Network was conducted as part of protocol CTN-0012 (“Characteristics of Screening, Evaluation, and Treatment of HIV/AIDS, Hepatitis C Viral Infections, and Sexually Transmitted Infections in Substance Abuse Treatment Programs”). Completed questionnaires were received from 269 (84.3%) of the 319 program administrators. Although 78.7% of programs reported that they offered ongoing hepatitis training for clinical staff, only a minority of programs offered testing for HBsAg (37.7%), HBsAb (36.7%), HBcAb (27.7%), HBV DNA (7.8%), HCV antibodies (52.9%), HCV qualitative (10.1%) or quantitative (8.9%) PCR, and HCV genotyping (11.6%). Hepatitis A and B vaccinations were offered by 68.3% of programs, either on site (19.3%) or via referral (49.1%). Programs having clear guidelines for hepatitis testing were significantly more likely to offer each of the hepatitis tests as compared with those that did not have clear guidelines. Only 28.9% of programs offered HCV treatment either on-site or via referral.

Despite the importance of substance abuse in sustaining the hepatitis epidemics in the U.S., many substance abuse treatment programs do not offer comprehensive HBV, HCV and hepatitis vaccination services. Public health interventions to improve access to hepatitis testing, treatment and prevention for substance abusers are needed.

In addition to the studies underway, CTN participants are planning multi-site clinical trials with emerging results that address HIV/AIDS. The CTN has a HIV/AIDS Special Interest Group (SIG) that meets regularly to discuss study ideas and policy approaches. The SIG provides a supportive place to discuss HIV research related to the CTN, share information with each other about opportunities and developments, promote AIDS ideas and research in the CTN, and link CTN research with the AIDS Research Office of NIDA. The SIG periodically reviews and prioritizes study ideas before they work their way up the organizational hierarchy, and, in the latest CTN Call for Concepts, had developed approximately ten suggestions for HIV-related research studies.

Several studies using the CTN ?platform? have also been fielded with external resources. The term ?platform study? describes extramurally funded research that builds on the CTN infrastructure. Studies can add a dimension to a CTN trial, test an intervention by using the infrastructure of the CTN, focus on CTN programs to understand an issue, include CTN programs in data collection, or provide training or career development in the CTN. Extramurally funded platform studies are addressing such issues as models of care for HIV and hepatitis, integrating medical treatment with addiction treatment, and improving adherence to HIV medications.

Current HIV testing guidelines recommend that all adolescents and adults aged 13–64 be routinely screened for HIV in healthcare settings. Sexually transmitted disease (STD) clinic patients represent a population at increased risk for HIV, justifying more frequent risk assessment and testing. This analysis describes missed opportunities for HIV testing among a sample of STD clinic patients to identify areas where HIV testing services may be improved. Secondary analysis was conducted using data from Project AWARE, a randomized trial of 5012 adult patients from 9 STD clinics in the United States, enrolled April–December 2010. HIV testing history, healthcare service utilization, and behavioral risks were obtained through audio computer-assisted self-interview. Missed opportunities for HIV testing, defined as having a healthcare visit but no HIV test in the last 12 months, were characterized by location and frequency. Of 2315 (46.2%) participants not tested for HIV in the last 12 months, 1715 (74.1%) had a missed opportunity for HIV testing. These missed opportunities occurred in both traditional (54.9% at family doctor, 20.3% at other medical doctor visits) and non-traditional (28.5% at dental, 19.0% at eye doctor, 13.9% at correctional facility, and 13.3% at psychology visits) testing settings. Of 53 participants positive for HIV at baseline, 16 (30.2%) had a missed testing opportunity. Missed opportunities for HIV testing were common in this population of STD clinic patients. There is a need to increase routinized HIV screening and expand testing services to a broader range of healthcare settings.

Related protocols: CTN-0032, Project AWARE

The extent to which behavioral drug abuse treatments affect sexual risk behaviors is largely unknown. This study examined the impact of behavioral drug abuse treatments on sexual risk behaviors using an integrative data analysis approach across eight trials conducted within the NIDA Clinical Trials Network (CTN-0004, 0005, 0006, 0007, 0009, 0013, 0015, and 0021). Participants (N=1305) from eight randomized controlled trials who were sexually active at baseline were included in the pooled dataset; 48.7% were female, 64.1% self-identified as a racial/ethnic minority, with M (SD) age of 34.9 (9.6). Longitudinal logistic regression estimated the probability of risky sexual behavior (i.e., inconsistent condom use and/or > 1 sexual partner in past 30 days) post-intervention with an indicator variable (1 for post-intervention), study condition (control, intervention), and their interaction as predictors; the analysis employed random effects for each trial and included relevant control variables. Time-varying differences in effects based on weeks post-intervention were incorporated using interacted linear and quadratic terms with condition status. Approximately 84.2% reported risky sexual behaviors at baseline. The control and intervention conditions were 18.5 and 17.3 percentage points less likely to report risky sexual behavior post-intervention, respectively.

Conclusions: Results suggest decreasing rates of risky sex engagement until 8 weeks (control) or 9 weeks (intervention post-intervention; risky sexual behavior subsequently increased. Behavioral CTN trial participation was associated with decreased sexual risk behaviors in both the intervention and control trial conditions. Given the heterogeneity of treatment approaches employed across the 8 CTN trials, these results point to the effectiveness of behavioral drug abuse treatment to reduce sexual risk behaviors. To bolster further reductions in sexual risk behavior engagement, there is a need to identify HIV risk reduction interventions that can best be integrated within existing resource-limited substance use disorder treatment programs.

Related protocols: CTN-0004, CTN-0005, CTN-0006, CTN-0007, CTN-0009, CTN-0013, CTN-0015, CTN-0021

Sex risk behaviors and substance use are intertwined. Many men continue to engage in high-risk sexual behaviors even when enrolled in substance use disorder (SUD) treatment. We hypothesized that changes in sex risk behaviors would coincide with changes in drug/alcohol use severity among men in SUD treatment. During an HIV risk-reduction trial, CTN-0018, men in methadone maintenance and outpatient drug-free treatment (N=359) completed assessments at baseline and six months after. Changes in sex risk and substance use severity were assessed using the Addiction Severity Index-Lite (ASI-Lite), controlling for treatment condition.

In multinomial logistic regressions, decreased alcohol severity was significantly associated with decreases in reported sex partners, and increased alcohol severity was significantly associated with increases in reported sex partners. Increasing drug use severity was significantly associated with maintaining and initiating sex with a high-risk partner, while decreasing alcohol use severity was significantly associated with discontinuing sex under the influence. However, changes in drug/alcohol use severity were not associated with changes in unprotected sex.

Conclusions: Substance use reductions may decrease HIV risk behaviors among male substance users. Our findings highlight the importance of integrating interventions in SUD treatment settings that address the intersection of sex risk behaviors and substance use.

Related protocols: CTN-0018

Sexual risk behavior is now the primary vector of HIV transmission among substance users in the United States with gender as a crucial moderator of risk behavior. This study examined gender differences in factors (age, race/ethnicity, education) that predict main-partner unprotected sexual occasions (USO) using the unique platform of two parallel NIDA Clinical Trials Network gender-specific safer sex intervention trials. Baseline assessments of male (N=430) and female (N=377) participants included demographic characteristics; past 3-month sexual activity; and a diagnostic assessment for alcohol, cocaine/stimulant, and opioid use disorders. Using mixed effects generalized linear modeling of the main outcome USO, two-way interactions of gender with age, race/ethnicity, and education were evaluated and adjusted by alcohol, cocaine/stimulant, or opioid use disorder.

When adjusted for alcohol use disorder, the interaction of education and gender was significant. For men, a high school or greater education was significantly associated with more USO compared to men with less than high school. For women, greater than high school education was significantly associated with less USO compared to women with a high school education. None of the other interactions were significant when adjusted for cocaine/stimulant or opioid use disorder.

Conclusions: This study demonstrates gender differences in the relationship of education, alcohol use disorder, and main-partner USO in individuals in substance abuse treatment. This underscores the importance of considering demographic and substance use factors in HIV sexual risk behavior and in crafting prevention messages for this population.

Related protocols: CTN-0018, CTN-0019

This study examined differences in sexual risk behaviors by gender and over time among 1281 patients (777 males and 504 females) from 12 community-based substance use disorder treatment programs throughout the United States participating in CTN-0032, a randomized controlled trial conducted within the NIDA Clinical Trials Network. Zero-inflated negative binomial and negative binomial models were used in the statistical analysis. Results indicated significant reductions in most types of sexual risk behaviors among substance users regardless of the intervention arms. There were also significant gender differences in sexual risk behaviors. Men (compared with women) reported more condomless sex acts with their non-primary partners (IRR=1.80, 95% CI 1.21–2.69) and condomless anal sex acts (IRR=1.74, 95% CI 1.11–2.72), but fewer condomless sex partners (IRR=0.87, 95% CI 0.77–0.99), condomless vaginal sex acts (IRR=0.83, 95%CI 0.69–1.00), and condomless sex acts within 2 hours of using drugs or alcohol (IRR=0.70, 95%CI 0.53–0.90).

Conclusions: Significant reductions in most types of sexual risk behaviors were observed among participants in substance use disorder treatment, in the forms of increased abstinence and decreased number of condomless sex acts. These findings provide evidence that substance use disorder treatment may lead to HIV risk reduction. For the most part, gender differences showed women to have higher levels of risk than men, having more unprotected sex with primary partners and partners of unknown HIV status than men. Women also reported 30% more condomless sex acts within two hours of using drugs or alcohol compared to men in the study group. Gender-specific intervention approaches are called for in substance use disorder treatment.

Related protocols: CTN-0032

Receptive anal sex has high human immunodeficiency virus (HIV) transmission risk, and heterosexual substance-abusing individuals report higher anal sex rates compared to their counterparts in the general population. This secondary analysis of two NIDA Clinical Trials Network studies (CTN-0018 and CTN-0019) evaluated the effectiveness of two gender-specific, evidence-based HIV prevention interventions (Real Men are Safe, or REMAS, for men; Safer Sex Skill Building, or SSSB, for women) against an HIV education (HIV-Ed) control condition on decreasing unprotected heterosexual anal sex (HAS) among substance abuse treatment-seeking men (n=171) and women (n=105). Two variables, engagement in any HAS and engagement in unprotected HAS, were assessed at baseline and three months post-intervention.

Compared to the control group, women in the gender-specific intervention did not differ on rates of any HAS at follow-up but significantly decreased their rates of unprotected HAS. Men in both the gender-specific and the control interventions reported less HAS and unprotected HAS at three-month follow-up compared to baseline, with no treatment condition effect.

Conclusions: Women and men showed different patterns when it came to unprotected HAS. For men, rates of unprotected HAS decreased overall in the sample, and patterns suggest the reduction may, at least partly, reflect their decreased rates of engaging in any HAS. On the other hand, SSSB women did show a decrease in unprotected HAS compared to controls despite no significant difference in overall HAS rates. For them, the results suggest the SSSB intervention did produce intentional action toward risk reduction. The mechanism of action for SSSB compared to REMAS in decreasing unprotected HAS is unclear. More attention to HAS in HIV-prevention interventions for heterosexual men and women in substance abuse treatment is warranted.

Related protocols: CTN-0018, CTN-0019

Sexually transmitted infections (STIs) are significant public health and financial burdens in the United States. This manuscript examines the relationship between substance use and prevalent and incident STIs in HIV-negative adult patients at STI clinics.

A secondary analysis of Project AWARE was performed based on 5012 patients from 9 STI clinics. STIs were assessed by laboratory assay and substance use by self-report. Patterns of substance use were assessed using latent class analysis. The relationship of latent class to STI rates was investigated using Poisson regression by population groups at high risk for STIs defined by participant’s and partner’s gender.

Drug use patterns differed by risk group and substance use was related to STI rates with the relationships varying by risk behavior group. Substance use treatment participation was associated with increased STI rates.

Conclusion: Substance use focused interventions may be useful in STI clinics to reduce morbidity associated with substance use. Conversely, gender-specific sexual health interventions may be useful in substance use treatment.

Related protocols: CTN-0032, Project AWARE