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Published online before print October 17, 2007, 10.1097/PSY.0b013e318157b142
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Psychosomatic Medicine 69:785-792 (2007)
© 2007 American Psychosomatic Society

ORIGINAL ARTICLES

Affect Regulation, Stimulant Use, and Viral Load Among HIV-Positive Persons on Anti-Retroviral Therapy

Adam W. Carrico, PhD, Mallory O. Johnson, PhD, Judith T. Moskowitz, PhD, MPH, Torsten B. Neilands, PhD, Stephen F. Morin, PhD, Edwin D. Charlebois, PhD, MPH, Wayne T. Steward, PhD, MPH, Robert H. Remien, PhD, F. Lennie Wong, PhD, Mary Jane Rotheram-Borus, PhD, Marguerita A. Lightfoot, PhD, Margaret A. Chesney, PhD and The NIMH Healthy Living Project Team

From the Department of Psychiatry (A.W.C.), University of California, San Francisco, San Francisco, California; Center for AIDS Prevention Studies (M.O.J., T.B.N., S.F.M., E.D.C., W.T.S., NIMH Healthy Living Project Team), University of California, San Francisco, San Francisco, California; Osher Center for Integrative Medicine (J.T.M.), University of California, San Francisco, San Francisco, California; New York State Psychiatric Institute/Columbia University (R.H.R., NIMH Healthy Living Project Team), New York, New York; Center for Community Health (F.L.W., M.J.R.-B., M.A.L., NIMH Healthy Living Project Team), University of California, Los Angeles, Los Angeles, California; National Institutes of Health Center for Complementary and Alternative Medicine (M.A.C.); Medical College of Wisconsin (NIMH Healthy Living Project Team), Milwaukee, Wisconsin.

Address correspondence and reprint requests to Adam W. Carrico, University of California, San Francisco, Health Psychology Program, 3333 California St., Suite 465, Box 0848, San Francisco, CA 94143-0848. E-mail: adam.carrico{at}ucsf.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Objective: A substantial minority of HIV-positive individuals have comorbid affective or substance use disorders, which can interfere with effective medical management. The present study examined the associations among affect regulation, substance use, non-adherence to anti-retroviral therapy (ART), and immune status in a diverse sample of HIV-positive persons.

Methods: A total of 858 HIV-positive participants self-reporting risk of transmitting HIV were enrolled in a randomized behavioral prevention trial and provided baseline blood samples to measure T-helper (CD4+) counts and HIV viral load.

Results: Among individuals on ART, regular stimulant users had a five-fold (0.70 log10) higher HIV viral load than those who denied regular stimulant use. The association between regular stimulant use and elevated HIV viral load remained after accounting for demographics, differences in CD4+ counts, and polysubstance use. In the final model, 1 unit increase in affect regulation (decreased severity of depressive symptoms as well as enhanced positive states of mind) was associated with a 23% decrease in the likelihood of reporting regular stimulant use and 15% decrease in the likelihood of being classified as nonadherent to ART. Regular stimulant users, in turn, were more than twice as likely to be nonadherent to ART. Even after accounting for the effects of nonadherence and CD4+ counts, regular stimulant use was independently associated with 50% higher HIV viral load.

Conclusions: Increased mental health treatment as well as more intensive referrals to substance abuse treatment or 12-step self-help groups may be crucial to assist stimulant users with more effectively managing treatment for HIV/AIDS.

Key Words: adherence • affect • cocaine • depression • methamphetamine • HIV

Abbreviations: ACASI = audio-computer-assisted self-interviewing; AIDS = acquired immune deficiency syndrome; ART = anti-retroviral therapy; BDI = Beck Depression Inventory I; CFI = comparative fit index; HIV = human immunodeficiency virus; PSOM = positive states of mind; RMSEA = root mean square error of approximation; CD4+ = T-helper; WRMR = weighted root mean square residual.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Depression is associated with functional impairment, higher mortality rates, and increased medical costs for persons managing a variety of chronic medical conditions, even after controlling for objective markers of disease status (1). Because human immunodeficiency virus (HIV)-positive individuals are at elevated risk for developing an affective or adjustment disorder across the disease spectrum (2), effectively managing depressive symptoms may be an especially relevant task for this population. This is supported by observations that depressive symptoms predict more rapid T-helper (CD4+) cell count decline, faster progression to acquired immune deficiency syndrome (AIDS), and hastened mortality (3). Even among HIV-positive individuals treated with anti-retroviral therapy (ART), depressive symptoms and depressed mood predict decrements in CD4+ cell counts and increases in HIV viral load after controlling for adherence to these potent regimens (4,5).

The absence of clinically significant symptoms of depression is often characterized by the ability to achieve and maintain positive psychological states of mind (6). Consequently, there is increasing recognition that positive psychological resources may facilitate engagement across a number of domains to assist individuals with managing the multiple chronic, uncontrollable stressors inherent in living with HIV/AIDS (7,8). These psychological resources, which include positive affect and finding meaning in living with HIV/AIDS, predict less rapid CD4+ cell decline and longevity (9,10) even after accounting for the effect of depressive symptoms (11). Although it seems that both positive psychological states and depressive symptoms predict immune status and health outcomes among HIV-positive persons, relatively little is known about the biobehavioral mechanism(s) for these effects (3,12).

The relationship between poor affect regulation and HIV disease progression may be partially attributable to the effects of comorbid substance use disorders (2). Although a variety of theoretical models have been proposed to explain the dynamic processes involved in the development and maintenance of substance use disorders (13,14), one core feature seems to be difficulties with awareness or tolerance of internal experiences that can serve as triggers for continued substance use (15–17). Thus, it may be that individuals use a variety of substances as a means of managing negative mood states and to provide a temporary respite from intrusive thoughts about their HIV serostatus (18,19). Although substance use may be an effective method of coping in the short term, increases in depressive symptoms are commonly observed over time (18). Elevated depressive symptoms, in turn, predict continued substance use as well as relapse to substance use across a variety of populations (18). These cyclic impairments in the ability of individuals to regulate negative affect without turning to substance use may result in suboptimal management of HIV disease (20).

Investigations with diverse samples of HIV-positive persons indicate that those who use stimulants such as cocaine and methamphetamine are substantially more likely to be nonadherent to ART (21,22) and to display poor or incomplete suppression of HIV viral load (21,23). However, elevated HIV viral load among stimulant users on ART may be only partially attributable to nonadherence (23). Because use of stimulants such as cocaine and methamphetamine has been associated with higher rates of sexual risk-taking behavior and greater risk of HIV seroconversion (23,24), acquisition of nonnucleoside reverse transcriptase inhibitor resistance as well as comorbid sexually transmitted infections such as syphilis may directly increase HIV viral load (25–27). In addition, the direct physiologic effects of stimulants seem to be mediated by sympathetic nervous system activation, which results in the release of norepinephrine (28). By binding with ß2 receptors on the lymphocyte membrane, norepinephrine activates the G protein linked adenyl cyclase-cAMP-protein kinase A signaling cascade (29). Cellular changes of this nature are associated with in vitro decrements in interferon-{gamma} and interleukin-10 which, in turn, predict elevations in HIV viral load over time (30). Lending further support to the role of sympathetic nervous system activation in HIV disease progression, individuals who displayed higher autonomic nervous system activity at rest before beginning ART subsequently displayed poorer suppression of HIV viral load and decreased CD4+ cell reconstitution over time (31). Taken together, there is emerging evidence that stimulants may increase HIV replication through both behavioral and biological pathways.

In the present investigation, we examined the relationships among affect regulation, regular stimulant use, nonadherence to ART, and immune status in a diverse sample of 858 HIV-positive persons considered to be at risk of transmitting HIV. Bearing in mind previous findings (23), we hypothesized that regular stimulant use would be independently associated with elevated HIV viral load among individuals currently on ART. Then, as shown in Figure 1, we hypothesized the following: a) enhanced affect regulation would be associated with a decreased likelihood of regular stimulant use and nonadherence to ART; b) regular stimulant users would be more likely to be nonadherent to their ART regimens; c) regular stimulant use and nonadherence would be independently associated with higher HIV viral load after controlling for CD4+ cells; and d) a decreased likelihood of regular stimulant use and nonadherence to ART would account for the relationship between affect regulation and lower HIV viral load.


Figure 112
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  		Figure 1. Proposed Model of the associations among affective regulation, regular stimulant use, ART nonadherence, and HIV viral load.

 


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Procedures
HIV-positive individuals in four US cities (San Francisco, Los Angeles, Milwaukee, and New York City) were screened between July 2000 and January 2002 for a randomized behavioral prevention trial of an intervention designed to reduce HIV transmission risk (32,33). Institutional Review Board approval was received at each of the four sites. Participants were required to be at least 18 years of age and provide written informed consent and medical documentation of their HIV serostatus. Individuals were excluded if they did not complete the screening interview for any reason. Such reasons included evidence of psychosis or severe neuropsychological impairment, fatigue, and voluntary withdrawal from the interview. Participants were eligible for inclusion in the randomized controlled trial if they reported at least one act of unprotected vaginal or anal intercourse in the previous 3 months with any partner of HIV-negative or unknown serostatus. In addition, individuals were eligible for the trial if they reported unprotected intercourse with at least one HIV-positive individual who was not their primary partner. Of the 3818 individuals screened, 2746 (71.9%) were not eligible. Of those who were eligible (n = 1072), 136 (12.6%) chose not to enroll in the trial. For the 936 individuals who were randomized, 858 (91.7%) had a CD4+ cell count or HIV viral load available for analysis.

Interviews were conducted in private settings using laptop computers (32). Procedures involved a combination of audio-computer-assisted self-interviewing (ACASI) and computer-assisted personal interviewing using the Questionnaire Development System (Nova Research Company, Bethesda, Maryland). ACASI has been shown to be an effective method of decreasing social desirability bias and thereby enhancing the veracity of self-report of sensitive behaviors, including sexual and substance use risk acts (34). If participants were determined to be eligible for the trial, they were randomized and peripheral venous blood samples were taken. Peripheral venous blood samples were collected a median of 21 days after the baseline psychosocial and behavioral assessment.

Measures
Demographics
Age, race/ethnicity, gender, education, sexual orientation, relationship status, and stability of housing during the past year were assessed by questionnaire.

Affect Regulation
Affect regulation describes the degree to which individuals effectively manage depressive symptoms as well as the capacity of individuals to achieve and maintain positive psychological states that promote resilience in the face of negative life events (6). In the present investigation, we measured affect regulation using separate measures of positive psychological states and depressive symptoms.

Positive States of Mind
The 6-item Positive States of Mind (PSOM) scale was developed to examine the degree to which individuals are able to achieve and maintain a variety of desirable cognitive and interpersonal states (i.e., focused attention, productivity, responsible caretaking, restful repose, sensuous nonsexual pleasure, and sharing) during the past week (Cronbach’s {alpha} = 0.80). Even in the absence of clinically significant levels of depressive symptoms, impairments in PSOM may provide an index of the degree to which individuals are vulnerable to experiencing sustained negative affect in response to life events (6,35). Thus, relative decrements in PSOM may confer increased risk for a recurrence of clinically significant depressive symptoms.

Depressive Symptoms
The 21-item Beck Depression Inventory I (BDI) assesses the severity of somatic, affective, cognitive, and behavioral symptoms of depression during the past week (36). The BDI is reliable and has demonstrated good concurrent validity with the Hamilton Rating Scale for Depression (0.78–0.80 for nonpsychiatric patients). To control for confounds between HIV-related symptoms and somatic symptoms of depression, we utilized the 13-item BDI-Affective subscale (Cronbach’s {alpha} = 0.86) for the present investigation (37).

Alcohol and Substance Use
Participants rated the frequency of alcohol and substance use during the past 3 months using the following responses: never, less than once a month, once a month, two to three times a month, once a week, two to three times per week, four to six times per week, once a day, more than once a day. Participants who used stimulants (i.e., cocaine, crack, or amphetamines) two to three times per week or more were considered regular users. Using a similar coding strategy, regular use of alcohol and heroin were also examined. Other illicit substances (e.g., gamma hydroxy butyrate or gamma hydroxybutyric acid and ketamine) were not examined in the present study because the prevalence of regular use was negligible (i.e., less than one-tenth of one percent). Finally, we examined whether individuals reported any injection drug use in the past year.

Adherence to ART
Self-reported adherence was assessed over the previous 3 days to calculate percent adherence by dividing the number of pills taken by the total number of pills prescribed (38). Previous investigations lend support to the validity of brief self-report measures of ART adherence in relationship to immune status (39). However, the nature of the relationship between adherence and immune status seems to be variable across different classes of medications (40,41). Consistent with prior investigations of adherence to ART (32), participants who reported <90% adherence were considered nonadherent.

Immune Status
HIV Viral Load
HIV-1 viral load was determined using the AMPLICOR ultrasensitive method for the in vitro reverse transcriptase polymerase chain reaction assay (# 83088, Roche Laboratories, Nutley, New Jersey), which has a valid range of 50 to 750,000 copies/ml. In total, viral loads from 763 participants were available.

CD4+ Cell Counts
CD3+CD4+ lymphocyte counts were determined by whole blood using direct immunofluorescence. In total, CD4+ cell counts from 842 participants were available.

Statistical Analyses
We began with a two-way analysis of variance to examine the interaction effects between regular stimulant use and ART status on HIV viral load. Next, we conducted a multiple linear regression only among individuals who were currently prescribed ART in order to examine whether regular stimulant use was independently associated with HIV viral load after accounting for differences by site, demographics, CD4+ cell counts, and other forms of alcohol-substance use. Finally, we utilized structural equation modeling to examine whether regular stimulant use and ART nonadherence accounted for the relationship between affect regulation and HIV viral load after controlling for CD4+ cell counts (Figure 1). Structural equation modeling analyses were conducted only with the subsample of participants who were currently prescribed ART. For all analyses, we utilized a log10 transformation for HIV viral load and a square root transformation for CD4+ cell count.

By using structural equation modeling, we were able to develop a latent variable of affect regulation that included both the PSOM and BDI as indicators. Using this latent variable enabled us to examine the common variance in these indicators while partialing out the effects of measurement error. Additional strengths of utilizing structural equation modeling were that we were able to examine the associations among multiple independent and dependent variables in the model simultaneously as well as obtain indices of global model fit. Because the proposed model examined the degree to which two categorical mediators (i.e., stimulant use and ART nonadherence) accounted for the relationship between affect regulation and HIV viral load, we estimated probit regression weights via the weighted least squares mean and variance-adjusted estimator with the theta parameterization in MPlus (42). For the present investigation, we utilized multiple indices of model fit: comparative fit index (CFI) values >0.95, root mean square error of approximation (RMSEA) values <0.06, and weighted root mean square residual (WRMR) values <0.90 (42,43). Although a nonsignificant {chi}2 is also generally indicative of better model fit, this statistic may not be as reliable given the large sample size for the present investigation. Thus, we examined if the ratio of the {chi}2 to degrees of freedom ({chi}2/df) was <3 (44). After obtaining satisfactory global model fit, we refit the model using a maximum likelihood logit link function to obtain odds ratios and their 95% confidence intervals for categorical endogenous variables. Finally, we converted the unstandardized parameter estimates using a simple formula [100 (10B – 1)] to examine the percent increase in HIV viral load that was independently associated with regular stimulant use and ART nonadherence.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 NOTES
 REFERENCES
 
Participant Demographics
At baseline, the mean age of the 858 participants who enrolled in the trial and had immune measures available for analysis was 40 years (range 19–67 years). Most participants were male (79%), and approximately 83% of these were men who have sex with men. Forty-five percent of participants were African American, 33% were White, 14% were Hispanic, and 8% were of multicultural heritage. Eighty-two percent had education less than a college degree. During the past 3 months, 26% reported regular alcohol use, 15% reported regular stimulant use, and approximately 2% reported regular heroin use. Approximately 14% of participants reported injection drug use in the past year. Finally, we determined that approximately 37% individuals on ART reported that they were nonadherent (i.e., <90% of prescribed pills were taken) during the past 3 days.

Stimulant Use and Immune Status
As shown in Figure 2, we observed a significant interaction of stimulant use and current ART status (F(1,762) = 6.41, p = .012). Among individuals currently prescribed an ART regimen, regular stimulant users had a five-fold higher (0.70 log10; 2238 versus 447 copies/mL) HIV viral load than those who denied regular stimulant use (t (527) = –4.07, p < .001). Examining regular stimulant users only (n = 114), those on ART (n = 64) had a 0.62 log10 lower HIV viral load when compared with individuals who were not currently treated with ART (n = 50; t (112) = 2.70, p < .01). However, among individuals who did not report regular stimulant use (n = 648), the magnitude of the decrease in HIV viral load when comparing the ART-treated (n = 465) and untreated (n = 183) groups was two times (1.27 log10) as large (t (646) = 12.77, p < .001). The relationship between regular stimulant use and CD4+ counts did not vary as a function of current ART status (F(1,841) = 2.76, p = .097) and there was no main effect of stimulant use on CD4+ counts (F(1,841) = 1.44, p = .231). Finally, we examined if regular stimulant use was independently associated with higher HIV viral load among individuals currently prescribed an ART regimen after accounting for site differences, demographics, CD4+ counts, regular alcohol use, regular heroin use, and any injection drug use in the past year. As shown in Table 1, regular stimulant use was independently associated with elevated HIV viral load (ß = 0.11, t = 2.30, p < .05).


Figure 212
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  		Figure 2. Planned pairwise comparisons indicated that a) among individuals currently prescribed ART, regular stimulant users (n = 64) had a five-fold higher HIV viral load (0.70 log10) than those who denied regular stimulant use (n = 465; 2238 versus 447 copies/mL); b) regular stimulant users on ART (n = 64) had significantly lower HIV viral load (0.62 log10) when compared with regular stimulant users who were not prescribed ART (n = 50); and c) among individuals who denied regular stimulant use, individuals currently prescribed ART (n = 465) had significantly lower HIV viral load (1.27 log10) when compared with those not currently treated with ART (n = 183).

 

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  		TABLE 1. Association Between Regular Stimulant Use and Higher HIV Viral Load

 

Affect Regulation, Health-Related Behaviors, HIV Viral Load
We began by testing the hypothesized model (Figure 1) with the subgroup of participants who were currently prescribed ART and had HIV viral load measures available for analysis (n = 529). The {chi}2 test was statistically significant ({chi}2 (4) = 10.79, p = .029), but the {chi}2/df ratio was <3 (2.70). Other fit indices (CFI = 0.969, RMSEA = 0.058, WRMR = 0.836) also provided consistent evidence that the model was a good fit for the data. Examining the standardized parameter estimates for the model, we observed that all were significant (p < .05) with the exception of the direct effect of affect regulation on HIV viral load (ß = 0.04, t = 0.81, p > .10). For the sake of clarity, this nonsignificant path is not shown in the final model (Figure 3).


Figure 312
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  		Figure 3. Final model of the associations among affect regulation, regular stimulant use, ART nonadherence and immune status in the subsample of participants who were currently prescribed ART and had a valid HIV viral load measure (n = 529). This model accounted for 12% of the variance in regular stimulant use, 14% of the variance in ART nonadherence, and 23% of the variance in HIV viral load.

 

As hypothesized, affect regulation was comprised of increased positive states of mind ({lambda} = 0.76) and decreased severity of affective symptoms of depression ({lambda} = –0.81). Higher levels of affect regulation were significantly associated with a decreased likelihood of regular stimulant use (ß = –0.35) and a decreased likelihood of ART nonadherence (ß = –0.21). We also determined that regular stimulant use was associated with an increased likelihood of ART nonadherence (ß = 0.24). Regular stimulant use (ß = 0.15) and ART nonadherence (ß = 0.20) were each, in turn, independently associated with higher HIV viral load after accounting for CD4+ cell counts. The total indirect effect of affect regulation on lower HIV viral load via a decreased likelihood of regular stimulant use and ART nonadherence was also significant (ß = –0.11, t = –3.45, p < .01).

We refit the model using a maximum likelihood logit link function to obtain odds ratios and their 95% confidence intervals for endogenous categorical variables. As shown in Table 2, for every 1 unit increase in affect regulation individuals were 23% less likely to report regular stimulant use and 15% less likely to report ART nonadherence. We also determined that regular stimulant users were more than twice as likely to report <90% adherence to ART. Finally, we determined that individuals who were classified as nonadherent to their ART regimen had 72% higher HIV viral load. Independent of this effect, regular stimulant users had 50% higher HIV viral load.


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  		TABLE 2. Odds Ratios for Categorical Endogenous Variables

 


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
NOTES
 REFERENCES
 
Among individuals on ART, regular stimulant users had a five-fold (0.70 log10) higher HIV viral load than those who denied regular stimulant use. This observation is consistent with prior findings that stimulant users displayed poor or incomplete suppression of HIV viral load (21,23). Results of the present investigation also lend support to previous studies, which observed that HIV-positive stimulant users are more likely to be nonadherent to ART (21,22). We determined that regular stimulant users were more than twice as likely to report taking <90% of ART medications in the past 3 days. Although it seems that regular stimulant users on ART did achieve some degree of viral suppression in comparison with their untreated peers, ART was two times more effective in suppressing HIV viral load among individuals who did not report regular stimulant use in this cross-sectional investigation. This association between regular stimulant use and elevated HIV viral load among individuals on ART was independent of demographics, differences in CD4+ cell counts, and regular use of alcohol or other substances. Although provocative, these findings should be confirmed in future longitudinal investigations with more representative samples of HIV-positive persons. Individuals were selected for the present study because they reported HIV transmission risk behavior and chose to participate in a randomized controlled trial of a behavioral intervention. Thus, it is likely that individuals in the present investigation may have reported increased rates of a variety of risk-taking behaviors than would have been observed in more representative samples of HIV-positive persons. Future investigations conducted in clinical settings should also examine whether stimulant users, as compared with nonusers, are more likely to be prescribed different ART regimens at later stages of disease progression.

In the present investigation, we also observed that elevated viral load among stimulant users was not exclusively attributable to increased rates of nonadherence to ART. After accounting for the effects of ART nonadherence, regular stimulant use was associated with a 50% higher viral load. Bearing in mind the relationship between stimulant use and increased sexual risk-taking behavior (45), individuals may be more likely to acquire strains of HIV that are resistant to some classes of antiretroviral medications as well as comorbid sexually transmitted infections that increase HIV viral load (25,26). It is also possible that the direct, physiologic effects of stimulants on sympathetic nervous system arousal increase rates of HIV replication (30,31), but we only observed elevated HIV viral load among regular stimulant users on ART. Substantially elevated blood concentrations of stimulants have been reported among individuals on some antiretroviral medications (46), and this may result in intense, protracted sympathetic nervous system activation that is sufficient to increase rates of HIV replication in a clinically meaningful manner. Despite the fact that all stimulants produce increases in mesolimbic dopamine levels, there are important distinctions regarding the specific neurobiologic mechanisms of action and metabolism of different types of stimulants (46,47). For example, methamphetamine has a much longer half-life and is metabolized by the cytochrome P450 2D6 pathway, which also metabolizes commonly prescribed protease inhibitors such as Ritonavir (46). This may result in more prolonged effects of methamphetamine as well as potentially increased toxicity among patients on some anti-retroviral medications. Thus, future longitudinal investigations should examine the plausible biobehavioral mechanisms whereby regular use of specific stimulants such as methamphetamine may increase HIV viral load. Plausible mechanisms that should be examined include genotypic resistance, sexually transmitted infections, sleep dysregulation, poor nutrition, and sympathetic nervous system activation. One limitation of the present study is the use of a self-report measure of adherence, and as a result rates of nonadherence may be an underestimate. Future investigations should also include electronic monitoring and urine toxicology screening to better characterize the nature and patterns of nonadherence among stimulant users (22,48).

Previous studies have focused largely on the role of depressive symptoms and other forms of negative affect in continued substance use and relapse (18). Whereas this represents one important component of affect regulation, findings of the present investigation highlight the importance of achieving and maintaining positive psychological states. Positive states of mind may result in increased engagement across a variety of life domains, which could promote continued abstinence from substance use as well as sustained remission of clinically significant symptoms of depression. This is supported by findings that affect regulation was associated with a decreased likelihood of regular stimulant use and nonadherence to ART. Consequently, regular stimulant use and ART nonadherence may be two potent behavioral pathways whereby affect regulation influences HIV disease progression. However, it is also possible that elevations in HIV viral load produce concurrent increases in proinflammatory cytokines, which leads to decreases in cognitive functioning and decrements in affect regulation (47). The potentially causal relationships among affect regulation, stimulant use, ART nonadherence, and HIV disease progression should be examined in future longitudinal investigations and randomized controlled trials of interventions designed to improve affect regulation and decrease stimulant use among HIV-positive persons.

Taken together, findings from the current study have important implications for the medical care of stimulant users who are HIV-positive. Incomplete viral suppression associated with ART nonadherence may result in more rapid HIV disease progression and could contribute to the emergence of medication-resistant strains of HIV (49). As a result, mental health treatment as well as more intensive referrals to substance abuse treatment or 12-step self-help groups may be crucial to assist stimulant users with successfully initiating ART, to improve adherence among those who are currently prescribed ART, and to reduce the transmission of HIV to their sexual partners (25,33). Including pharmacologic and cognitive-behavioral interventions to assist HIV-positive stimulant users with improving affect regulation may also substantially enhance the efficacy of adherence interventions for HIV-positive substance users that have been developed to date (50,51). Although a number of innovative psychological interventions have been designed to assist HIV-positive persons with improving affect regulation and disease management, individuals with substance use disorders have commonly been excluded from the well-controlled trials examining the efficacy of these treatments (4,52). Future trials with HIV-positive stimulant users should examine whether interventions designed to improve both affect regulation and ART adherence demonstrate superior efficacy when compared with more problem-focused ART adherence interventions.

The authors thank those at NIMH: Ellen Stover, PhD, and Willo Pequegnat, PhD, for their technical assistance in developing the study and Christopher M. Gordon, PhD, and Dianne Rausch, PhD, for their support of this research. Gratitude is also given to Susan Tross, PhD, and Gary Dowsett, PhD, for methodological guidance; to the assessors in each city who conducted the interviews, to our clinic and community-based organization collaborators, to all other support staff involved in the project, and to the men and women who participated in the interviews.

This study was conducted by the NIMH Healthy Living Trial Group. Research Steering Committee (site principal investigators and NIMH staff collaborator): Margaret A. Chesney, PhD, University of California, San Francisco; Anke A. Ehrhardt, PhD, New York State Psychiatric Institute/Columbia University, New York; Jeffrey A. Kelly, PhD, Medical College of Wisconsin, Milwaukee; Willo Pequegnat, PhD, National Institute of Mental Health, Bethesda, Maryland; Mary Jane Rotheram-Borus, PhD, University of California, Los Angeles. Collaborating Scientists, Co-Principal Investigators, and Investigators: Eric G. Benotsch, PhD, Medical College of Wisconsin, Milwaukee; Michael J. Brondino, PhD, Medical College of Wisconsin, Milwaukee; Sheryl L. Catz, PhD, Medical College of Wisconsin, Milwaukee; Edwin D. Charlebois, PhD, MPH, University of California, San Francisco; Don C. DesJarlais, PhD, Beth Israel Medical Center, New York; Naihua Duan, PhD, University of California, Los Angeles; Theresa M. Exner, PhD, New York State Psychiatric Institute/Columbia University, New York; Rise B. Goldstein, PhD, MPH, University of California, Los Angeles; Cheryl Gore-Felton, PhD, Medical College of Wisconsin, Milwaukee; A. Elizabeth Hirky, PhD, New York State Psychiatric Institute/Columbia University, New York; Mallory O. Johnson, PhD, University of California, San Francisco; Robert M. Kertzner, MD, New York State Psychiatric Institute/Columbia University, New York; Sheri B. Kirshenbaum, PhD, New York State Psychiatric Institute/Columbia University, New York; Lauren E. Kittel, PsyD, New York State Psychiatric Institute/Columbia University, New York; Robert Klitzman, MD, New York State Psychiatric Institute/Columbia University, New York; Martha Lee, PhD, University of California, Los Angeles; Bruce Levin, PhD, New York State Psychiatric Institute/Columbia University, New York; Marguerita Lightfoot, PhD, University of California, Los Angeles; Stephen F. Morin, PhD, University of California, San Francisco; Steven D. Pinkerton, PhD, Medical College of Wisconsin, Milwaukee; Robert H. Remien, PhD, New York State Psychiatric Institute/Columbia University, New York; Fen Rhodes, PhD, University of California, Los Angeles; Susan Tross, PhD, New York State Psychiatric Institute/Columbia University, New York; Lance S. Weinhardt, PhD, Medical College of Wisconsin, Milwaukee; Robert Weiss, PhD, University of California, Los Angeles; Hannah Wolfe, PhD, St. Luke’s-Roosevelt Medical Center, New York; Rachel Wolfe, PhD, St. Luke’s-Roosevelt Medical Center, New York; Lennie Wong, PhD, University of California, Los Angeles. Data Management and Analytic Support: Philip Batterham, MA, University of California, Los Angeles; Tyson Rogers, MA, University of California, Los Angeles. Site Project Coordinators: Kristin Hackl, MSW, Medical College of Wisconsin, Milwaukee; Daniel Hong, MA, University of California, Los Angeles; Karen Huchting, BA, University of California, Los Angeles; Joanne D. Mickalian, MA, University of California, San Francisco; Margaret Peterson, MSW, Medical College of Wisconsin, Milwaukee. NIMH: Christopher M. Gordon, PhD, National Institute of Mental Health, Bethesda, Maryland; Dianne Rausch, PhD, National Institute of Mental Health, Bethesda, Maryland; Ellen Stover, PhD, National Institute of Mental Health, Bethesda, Maryland.


   NOTES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
REFERENCES
 
Received for publication April 2, 2007; revision received July 13, 2007.

This research was funded by National Institute of Mental Health Grants U10-MH57636, U10-MH57631, U10-MH57616, and U10-MH57615; and NIMH Center Grants P30-MH058107 (M.J.R.-B., Principal Investigator), P30-MH57226 (J.A.K., Principal Investigator), P30-MH43520 (A.A.E., Principal Investigator), and P30-MH062246 (T.J.C., Principal Investigator). Additional support was provided by a Ruth L. Kirschstein National Research Service Award (T32-MH019391).

DOI:10.1097/PSY.0b013e318157b142


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 

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