Health-related quality of life (HRQOL) is an important consideration in chronic illness management, particularly in the context of life-long therapy and management of complex comorbidities. HRQOL is increasingly viewed as an essential patient-rated outcome for developing patient-centered treatment interventions for chronic illnesses.1 HIV infection and substance-use disorders are chronic illnesses that frequently co-occur. Approximately half of HIV-infected patients report past or current use of illicit drugs or hazardous alcohol use2,3 and injection drug use accounted for 14% of new US HIV/AIDS diagnoses in 2007.4 HIV disease and substance-use disorders interact in complex ways to adversely impact HRQOL.
HIV disease decreases HRQOL.5-8 In a nationally representative sample of HIV-infected persons in the United States, physical HRQOL for those with symptomatic HIV infection was lower than general population norms. Patients with all stages of HIV experienced lower mental HRQOL. Both physical and mental HRQOL were poorer compared with persons with other chronic conditions.6 Mental and physical HRQOL decrease with more advanced stages of HIV disease5,6 and with an increasing number of HIV symptoms.9,10 Although HRQOL may improve with treatment of HIV infection and symptoms,9,11-13 HIV-infected patients with low HRQOL experience decreased survival.14-16 Improvements in the HRQOL of HIV-infected persons increase survival.16
Substance-use disorders are associated with worse HRQOL for both HIV-infected17-19 and HIV-uninfected individuals.20-22 In a multicenter study of HIV-infected patients in care, current illicit drug users reported lower physical and mental HRQOL compared with nonusers, but HRQOL of illicit drug users who had not used in at least 6 months was comparable to nonusers, suggesting that facilitating sobriety may improve HRQOL for these individuals.17 Yet access to substance-abuse treatment remains limited for many HIV-infected patients.3,23 The approval of buprenorphine/naloxone (bup/nx) for treatment of opioid dependence can expand access to treatment for opioid-dependent patients engaged in HIV care.24 Bup/nx is preferred to methadone maintenance by some HIV-infected patients.25
Few studies of patients engaged in opioid agonist treatment assess changes in HRQOL over time.26 Studies in non-HIV-infected opioid-dependent patients receiving bup/nx or methadone maintenance from specialty addiction treatment centers in Europe and Israel suggest that treatment with methadone or bup/nx maintenance can improve HRQOL.27-30 To our knowledge, no prior studies have assessed the capacity of clinic-based bup/nx therapy to improve HRQOL in HIV-infected populations meeting DSM-IV criteria for opioid dependence. Treatment of opioid dependence in HIV-infected populations may have additional potential to benefit HRQOL by decreasing depressive symptoms31 and improving cognitive impairment32 and adherence to antiretroviral treatment, cellular immunity, and HIV-1 virologic suppression.33,34
The objective of this study was to assess the effect of clinic-based bup/nx on HRQOL in a cohort of opioid-dependent HIV-infected persons receiving outpatient HIV care. We hypothesized that (1) mental and physical HRQOL before initiating bup/nx treatment would be lower than general population norms, and that (2) patients with greater exposure to clinic-based bup/nx over time would experience greater improvements in HRQOL compared with those with less exposure.
As described in detail elsewhere,24,35 from 2004 to 2009, the HIV/AIDS Bureau of the Health Resources and Services Administration (HRSA) funded, through its Special Projects of National Significance (SPNS), the development of demonstration programs that integrated HIV care and bup/nx treatment for opioid dependence at 10 HIV clinic sites across the US. HRSA also funded an Evaluation and Technical Assistance Center (Center) to coordinate the multisite evaluation, provide clinical and evaluation support and technical assistance, and promote dissemination of findings. Data from 9 of the 10 sites were included in the current analysis. One site was excluded due to a limited number of patients prescribed clinic-based bup/nx. Each site and the Center obtained institutional review board approval for conducting this evaluation.
Potential study participants identified through provider referral, word of mouth, and community outreach were enrolled from 2005 through 2007. Eligible participants were HIV infected, at least 18 years old, met DSM-IV criteria for opioid dependence, and spoke English or Spanish. Potential participants were excluded if they had unstable alcohol or benzodiazepine dependence or other severe medical or psychiatric conditions that constituted an imminent threat to participant safety, aspartate aminotransferase or alanine aminotransferase levels >5 times normal, or were pregnant. All participants completed written informed consent before enrollment.
Data Collection Methods
Study participants completed baseline assessments that recorded demographic, social, substance use, and quality of life measures; research personnel conducted medical record abstraction to confirm substance abuse and medical treatment at baseline, 3, 6, 9, and 12 months follow-up. Data were entered electronically at participating sites and uploaded to the Center for collation and analysis.35
The primary independent variable for this analysis was persistence on bup/nx from baseline over the course of a year, as a measure of exposure to clinic-based bup/nx. After bup/nx induction, maintenance doses ranged from 2mg to 24mg per day, according to site dosing protocols. A bup/nx clinical coordinator facilitated bup/nx treatment in HIV clinics. Participants were considered as being on bup/nx if quarterly chart abstraction demonstrated receipt of at least 1 prescription for bup/nx during that quarter. Participants were categorized according to the progressive number of quarters they continued being prescribed bup/nx in the year after baseline induction (persistent at quarter 1, quarters 1 and 2, quarters 1-3, and quarters 1-4).
Health Related Quality of Life
The main dependent variable of interest was HRQOL. HRQOL was assessed using the Medical Outcomes Study Short Form Health Survey (SF-12), version 2 that generates a physical composite summary score (composed of general health, physical functioning, physical role functioning, and bodily pain domains) and a mental composite summary score (composed of mental health, vitality, social functioning, and emotional role functioning).36 We used standard norm-based scoring procedures that transform raw scores for comparison with the general US population mean score of 50 and standard deviation of 10 (possible range 0-100).37 The SF-12 has been previously validated in HIV-infected populations,15,38,39 and in persons with current substance-use disorders and other serious mental disorders,40 low socioeconomic status,39 homelessness,41 and minority racial/ethnic groups42,43-similar to the current study population.
We examined potential covariates including gender (male, female), race/ethnicity (white, black, Hispanic, other), age in years at time of baseline survey, education level (<high school, high school graduate or General Educational Development test (GED), and at least some college), employment status (employed vs. not employed), housing status (homeless vs. not), Hepatitis C antibody status (positive/negative), and incarceration in the 30 days before baseline (yes/no). We used Addiction Severity Index (ASI)-lite drug and alcohol composite scores to assess addiction severity,44,45 and assessed self-reported time since HIV diagnosis (years), self-reported CD4 nadir before baseline (≤200 cells/mL3, >200 cell mL3), and whether or not participants were prescribed highly active antiretroviral therapy (HAART) in each quarter (yes/no) as measures of HIV severity.
We used descriptive statistics to describe patient characteristics at baseline. We compared mean normalized mental and physical composite scores and their subcomponent scores across 4 quarters using generalized estimating equation models. We developed mixed effects regression models to test our hypothesis that clinic-based bup/nx prescription was associated with change from baseline in quality of life mental and physical composite summary scores over time. Site was included as a random effect and time was included as a repeated effect in all models. We considered covariates for inclusion in multivariate models if important in bivariate analysis (P < 0.10) or of a priori importance.
A total of 303 patients received bup/nx as part of the study. Of these, 289 had HRQOL scores at baseline and at least 1 subsequent quarter and were included in the current analysis. Table 1 shows baseline participant characteristics. Participants were primarily male (67.5%), Black (52.3%), heterosexual (81.1%), unemployed (74.4%), prescribed HAART (59.9%), Hepatitis C coinfected (77.3%) and had a mean age of 45.2 years (SD 8.2). At baseline, a quarter of participants were homeless and 13.5% had been incarcerated in the previous 30 days. Baseline addiction severity scores were comparable to normative data for opiate-dependent populations46 for both drug use (ASI-drug score 0.321, SD 0.129) and alcohol use (ASI-alcohol score 0.088, SD 0.121).
Health-Related Quality of Life
Table 2 presents normalized mean physical and mental composite HRQOL scores for each domain over time. Normed scores were lower than those observed for the general US population (mean 50, SD 10) at baseline for all domains. The average composite mental HRQOL score improved by more than 5 points during the follow-up period (β 1.13; 95% CI: 0.72 to 1.54). Average scores improved for all mental HRQOL subcomponents [mental health β 0.96 (95% CI: 0.55 to 1.37); vitality β 0.81 (95% CI: 0.44 to 1.17); social functioning β 1.03 (95% CI: 0.60 to 1.47); and emotional role β 0.84 (95% CI 0.41 to 1.28)]. Although the average composite physical HRQOL score did not significantly improve over time, patients experienced improved general health [β 0.71 (95% CI: 0.30 to 1.12)] and physical role functioning [β 0.60 (95% CI: 0.23 to 0.97)]. The majority of improvement for all HRQOL composite and component scores occurred during the first quarter of clinic-based bup/nx and then persisted throughout the follow-up period.
Participant Characteristics Associated With Quality of Life
Table 3 reports multivariate associations between patient characteristics and mental composite quality of life score. Persistence on bup/nx through all 4 quarters was associated with improved mental HRQOL [β 2.51 (95% CI: 0.42 to 4.60)], or a mean adjusted increase in mental HRQOL score of 2.51 points compared with baseline. This was comparable to the independent effect of taking HAART [β 2.81 (95% CI: 1.20 to 4.41)]. Several baseline patient characteristics were associated with lower mental HRQOL, including female gender, white and Hispanic race/ethnicity (compared with blacks), homelessness, incarceration in the 30 days before baseline and higher drug use severity. Increased age at baseline was also associated with higher mental HRQOL.
Table 4 reports multivariate associations between patient characteristics and physical composite quality of life score. Persistence on bup/nx through 3 quarters [β 2.72 (95% CI: 0.31 to 5.14)], or 4 quarters [β 2.38 (95% CI: 0.63 to 4.12)] was associated with improved physical HRQOL. Being employed at baseline was associated with greater physical HRQOL. Patient characteristics at baseline predicting lower physical HRQOL included increased age, female gender, white, Hispanic and other race/ethnicity (compared with blacks), and homelessness.
The mental and physical HRQOL of HIV-infected study participants with opioid dependence improved over time with clinic-based bup/nx. Those continuing to receive bup/nx through all 4 quarters of follow-up experienced greater gains in both physical and mental HRQOL. Our findings suggest that clinic-based bup/nx maintenance therapy may potentially be effective in ameliorating some of the adverse effects of opioid dependence on HRQOL for HIV-infected populations.
Improvements in composite and all component mental HRQOL scores are consistent with findings from studies evaluating the effect of bup/nx treatment on HRQOL among HIV-uninfected patients receiving bup/nx maintenance from specialized addiction treatment centers.27-30 Improvements were also observed for the general health and role physical component scores. Using different quality of life measures, Giacomuzzi et al28 and Ponizovsky et al30 both reported similar improvements in the physical health subdomains of their instruments for heroin-dependent patients receiving bup/nx maintenance from addiction treatment centers. Though observed increases in HRQOL were numerically small in this and other studies, they correspond to potentially dramatic improvements in outcomes. In one study of patients with advanced HIV disease, a 1-point increase in the baseline composite physical or mental HRQOL score corresponded to a 4% decrease in risk of death.16 This suggests the 5-point improvement in composite mental HRQOL observed in our data could potentially reflect improvements associated with decreased mortality.
Improvements in both mental and physical HRQOL in patients with longer retention in clinic-based bup/nx were observed even after adjusting for other significant determinants of HRQOL, suggesting that longer-term prescription of bup/nx maintenance may lead to greater improvements in HRQOL. Clinical trials of bup/nx maintenance versus short-term bup/nx (supervised opioid withdrawal) demonstrate improved substance-abuse treatment outcomes for long-term maintenance.47,48 Independent improvements in mental HRQOL due to remaining on bup/nx over time were comparable to the observed effect of remaining on HAART in multivariate models. Remaining on HAART over time is associated with decreased depressive symptoms, which may contribute to improved mental HRQOL.31 Although these data cannot address this issue, successful and sustained integration of treatment for HIV and opioid dependence may further benefit patients' HRQOL by improving convenience, streamlining treatment decisions, increasing engagement in substance abuse and HIV treatment,49 decreasing stigma, and providing a more patient-centered care experience.25
The current study contributes to calls for evaluation of more patient-centered approaches to treatment of substance-use disorders50 by directly evaluating HRQOL. US federal agencies are increasingly prioritizing patient-rated HRQOL as a key patient-centered outcome.1,51 Clinic-based bup/nx may be a tool for achieving better patient-centered outcomes for persons with opioid dependence and HIV infection.25
Baseline patient characteristics, including age, gender, race/ethnicity, homelessness, incarceration, and HIV and drug-use severity were important contributors to mental and physical HRQOL, as has been reported previously in similar populations.6,19,52-54 Despite the importance of and adjustment for these factors, persistence on bup/nx throughout 4 quarters of follow-up was associated with improvements in both mental and physical HRQOL. This is consistent with prior observations that substance-use disorders likely eclipse other factors that contribute to HRQOL.52 Our data suggest that addressing opioid dependence with clinic-based bup/nx treatment may mitigate these adverse baseline effects on HRQOL.
Our findings should be interpreted in the context of several potential limitations. First, we were unable to assess participant adherence to bup/nx, potentially biasing our findings toward the null hypothesis. Second, we did not consider substance abuse outcomes (eg, urine drug screens), which may mediate observed improvements in HRQOL. Third, the number of participants with HRQOL data decreased from baseline through follow-up, potentially resulting in retention bias. An alternative explanation for observed improvements in HRQOL is that participants feeling well were more likely to continue on bup/nx. Fourth, participating HIV clinic providers and staff received substantial training and expert support in implementation of clinic-based bup/nx and patients benefited from a grant-supported bup/nx clinical coordinator. Observed improvements in HRQOL may not be generalizable to HIV practice settings lacking such resources. Fifth, HIV clinic sites varied in their development of models for bup/nx integration.55 Bup/nx was, however, typically administered by providers using standard bup/nx guidelines.56 Finally, we relied on a single measure, the SF-12, to estimate HRQOL. Though the SF-12 has been well validated in HIV-infected and substance-abusing populations previously,15,38-40 it does not include HIV or opioid dependence specific domains and is susceptible to “floor” effects (ie, limited sensitivity in measuring lower levels of HRQOL).57-59 Consequently, our results potentially underestimate the true effect of clinic-based bup/nx on HRQOL in this population with highly prevalent physical and mental health disorders.
In summary, the results of this observational cohort study suggest that clinic-based bup/nx maintenance therapy is potentially effective in improving HRQOL for HIV-infected patients with concurrent opioid dependence. Given the adverse impact of opioid dependence on HRQOL and often limited access to treatment, interventions that promote more widespread adoption of clinic-based bup/nx in HIV clinical care settings may contribute to substantial quality of life improvements for this highly vulnerable population.
The authors wish to thank Ms Sarann Bielavitz for assistance with article preparation and David Feeny, PhD, for assistance in identifying key HRQOL references.
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APPENDIX 1: BHIVES COLLABORATIVE
The CORE Center, Chicago, IL; El Rio Santa Cruz Neighborhood Health Center, Tucson, AZ; Johns Hopkins University, Baltimore, MD; Miriam Hospital, Providence, RI; Montefiore Medical Center, Bronx, NY; OASIS, Oakland, CA; Oregon Health Sciences University, Portland, OR; University of California San Francisco Positive Health Program at San Francisco General Hospital, San Francisco, CA; University of Miami Medical School, Miami, FL; Yale University School of Medicine, New Haven, CT; and The New York Academy of Medicine, New York, NY.