Interventions targeting HIV-infected risky drinkers: drops in the bottle.
Article Type: Clinical report
Subject: HIV patients (Sexual behavior)
HIV patients (Research)
HIV patients (Care and treatment)
HIV infection (Research)
HIV infection (Development and progression)
HIV infection (Care and treatment)
Alcoholism (Research)
Alcoholism (Complications and side effects)
Disease transmission (Research)
Authors: Samet, Jeffrey H.
Walley, Alexander Y.
Pub Date: 09/22/2010
Publication: Name: Alcohol Research & Health Publisher: U.S. Government Printing Office Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2010 U.S. Government Printing Office ISSN: 1535-7414
Issue: Date: Fall, 2010 Source Volume: 33 Source Issue: 3
Topic: Event Code: 310 Science & research
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 243042498
Full Text: In the United States, people infected with the human immunodeficiency virus (HIV) drink more alcohol than people in the general population. Specifically, a higher proportion drink risky amounts (1) or have an alcohol use disorder (i.e., abuse or dependence) (Conigliaro et al. 2003; Galvan et al. 2002; Lefevre et al. 1995; Samet et al. 2003a,b, 2004). Risky alcohol use in HIV-infected people has been associated with the following range of adverse effects:

* Reduced adherence to medication regimens for treatment of HIV infection (Chander et al. 2006; Conen et al. 2009; Cook et al. 2001; Golin et al. 2002; Halkitis et al. 2003; Samet et al. 2004);

* Lack of a health care provider for the HIV infection (Metsch et al. 2009);

* Delayed linkage to HIV medical care (Samet et al. 1998);

* Increase in risky sexual behaviors (Kalichman et al. 2002; Metsch et al. 2009);

* Increased transmission of sexually transmitted infections (Kalichman et al. 2000); and

* Progression of HIV disease (Conigliaro et al. 2003; Miguez et al. 2003; Samet et al. 2007).

Given the spectrum of problems associated with such alcohol use among HIV-infected patients, one important avenue to improving the health of this population is to develop interventions that target alcohol use and its associated consequences. Accordingly, interventions have been designed to both decrease alcohol consumption and address the specific adverse health consequences.

The concept that negative consequences of alcohol use can be reduced in patients with HIV infection is based on research demonstrating the impact of clinical interventions on alcohol consumption and associated negative consequences in patients without HIV infection (Institute of Medicine 1990; Kristenson et al. 1983). Alcohol research over the past three decades has demonstrated that behavioral interventions can be effective, with benefits varying based on setting, severity of alcohol problems, and patient characteristics. For example, meta-analyses of randomized controlled trials (RCTs) (2) of interventions to reduce risky alcohol use demonstrated decreased drinking for patients in primary care settings (Beich et al. 2003; Kaner et al. 2007). However, no such effects were found in meta-analyses of interventions delivered in hospital settings (Emmen et al. 2004), possibly because inpatients typically have greater severity of alcohol problems (i.e., most are alcohol dependent) (Saitz et al. 2007, 2008). Several high-quality RCTs of brief interventions delivered in emergency departments also detected no or limited benefit (D'Onofrio and Degutis 2002; Daeppen et al. 2007; Longabaugh et al. 2001; Monti et al. 1999). The influence of the patient's consumption levels also was demonstrated in several studies. For example, in two separate RCTs in the primary-care setting (Fleming et al. 1997; Ockene et al. 1999), where patients were seeking medical care but not necessarily for an alcohol problem, implementation of a 5- to 15-minute discussion reduced alcohol consumption in patients who met the criteria for risky drinking. Studies of such brief interventions among patients who met the criteria for alcohol dependence, however, have shown no benefit (Kaner et al. 2007; Whitlock et al. 2004; Wutzke et al. 2002).

For alcohol-dependent patients, more extensive behavioral interventions (e.g., cognitive-behavioral coping skills, motivational enhancement, 12-step facilitation) can be effective (Project MATCH Research Group 1997). In addition, several medications (i.e., disulfiram, naltrexone, and acamprosate) are approved for the treatment of alcohol dependence, and other medications (e.g., topiramate) are being further evaluated (Anton et al. 2006; Garbutt et al. 2005; Kranzler and Van Kirk 2001; Olmsted and Kockler 2008; Rubio et al. 2001).

Given the strong evidence that alcohol consumption is an important health issue for many people with HIV infection, efforts to potentially ameliorate these problems by addressing alcohol use are of great interest. The studies in non-HIV-infected people reviewed above suggest that interventions among HIV-infected people with alcohol problems could be beneficial. However, the wide range of results in these intervention studies based on setting and disease severity argues for the need to carefully assess efforts to mitigate alcohol's deleterious impact on health in HIV-infected patients. As an important step in this direction, this article summarizes the findings of a review of the clinical trial literature on interventions addressing alcohol consumption and its consequences among HIV-infected patients. After describing the design of the literature search and evaluation, the article reviews the findings of the studies identified and discusses the implications of those findings.

DESIGN OF THE LITERATURE REVIEW

The literature review sought to identify clinical trials of interventions among ' HIV-infected people with past or current unhealthy alcohol use (i.e., the spectrum from risky drinking to alcohol dependence [Saitz 2005]) that reported effects on any of the following outcomes:

* HIV disease progression;

* Receipt of HIV treatment;

* HIV medication adherence;

* HIV risk behaviors;

* Acquisition of sexually transmitted infections; and

* Alcohol use.

To be included in the review, the studies had to report alcohol-specific outcomes. Beyond that, the studies were classified into three categories of specificity. The most specific category comprised clinical trials that included only HIV-infected people with past or current unhealthy alcohol use. The second category comprised clinical trials that included only HIV-infected people but in which not all of the participants exhibited unhealthy alcohol use. For a study to be included in this category, at least 10 percent of participants had to report current alcohol use. The third category of studies comprised trials that were aimed at preventing alcohol use and sexual behaviors that put people at risk of HIV infection among alcohol-using people. Although these studies did not include HIV-infected participants or did not report the HIV status of the participants, they were reviewed because they may inform future research on people at risk of HIV transmission in the setting of alcohol use.

Initially, the review intended to include only RCTs. However, very few studies were identified that met this criterion in the first two categories. Therefore, the search was expanded to include nonrandomized and non-controlled clinical intervention trials in categories 1 and 2.

To identify relevant studies, the literature database MEDLINE was searched through September 30, 2009, using the search terms "HIV alcohol, hazardous drinking, risky drinking, problem drinking, counseling, brief intervention, 12 step, pharmacotherapy, naltrexone, acamprosate, disulfiram, topiramate, and clinical trial." For all articles identified using this approach, the reference lists also were scanned, as were related articles identified by the search engine for the MEDLINE data base to look for additional studies. Reference lists for articles that were closely related, but did not meet the criteria, also were reviewed. Finally, articles referenced in relevant review articles were examined. Titles of all articles were reviewed to determine if the articles met the selection criteria. If the nature of the study could not be discerned through the title, the abstract and/or full text of the article was retrieved and reviewed.

For all studies that met the criteria for one of the three categories, information on the setting, study design, methodological quality, type of intervention, outcomes reported, period of follow-up, and results was extracted. The following sections summarize the findings of these analyses. They are presented as a descriptive narrative synthesis because studies were too few and heterogeneous to perform a standard meta-analysis.

RESULTS OF THE LITERATURE REVIEW

The search strategy described above identified 241 potentially relevant studies that were evaluated further. Of these, four studies including a total of 578 patients (Aharonovich et al. 2006; Parsons et al. 2007; Samet et al. 2005; Velasquez et al. 2009) met the selection criteria for the first category (see table 1). Another five clinical trials that included 1,311 patients (Gilbert et al. 2008; Naar-King et al. 2006, 2008; Rotheram-Borus et al. 2001, 2009; Sorensen et al. 2003) fell into the second category. In addition, two informative studies of interventions among people at high-risk for HIV reported outcomes specific to alcohol use (Kalichman et al. 2008; Morgenstern et al. 2007). All of these studies are reviewed below. Some other studies that involved alcohol-using, HIV-infected patients, but were excluded from this discussion because of serious design or methodological limitations, are listed in Table 2 because they may inform additional research. Interestingly, no controlled trials of the four medications recommended by NIAAA (2007) for the treatment of alcohol dependence (i.e., disulfiram, naltrexone, acamprosate, and topiramate) have been conducted in HIV-infected patients.

CLINICAL TRIALS AMONG HIV-INFECTED PEOPLE WITH PAST OR CURRENT UNHEALTHY ALCOHOL USE

Velasquez and Colleagues (2009) Study. These investigators conducted an RCT among 253 HIV-infected men who had had sex with men in the previous 3 months and who scored more than eight points on the AUDIT questionnaire (Babor et al. 2001). The intervention group received four manual-guided individual sessions and four manual-guided peer education and support group sessions that utilized motivational interviewing (MI) counseling strategies (Miller and Rollnick 2002) to guide participants through the stages of change of Prochaska and DiClemente's Trans-Theoretical Model (3) (Prochaska and DiClemente 1982). In contrast, the control group received educational materials on HIV and alcohol, referral information, and advice to stop or cut back on their alcohol use. At the 12-month follow-up, the investigators determined some benefits of the intervention on some of the measures evaluated. For example, the control group had 1.4 times the number of drinks per 30 days and 1.5 times the number of heavy-drinking days per 30 days compared with the intervention group. For other measures (e.g., having anal sex without a condom, number of drinking days, or number of days on which both drinking and sex occurred), however, no significant difference existed between the two groups. Only when the analysis of same-day drinking and sex was restricted to participants who had shown this behavior at baseline, did those in the control group have significantly (i.e., 2.19 times) more days on which drinking and sex occurred than the intervention group. The interpretation of these findings is limited by the fact that there was differential loss to follow-up--that is, the analyses included only 81 percent of participants randomized to the intervention group and 90 percent of subjects randomized to the control group. Thus, one cannot exclude the possibility that particularly in the intervention group, participants with worse outcomes were not included in the analysis.

Aharonovich and Colleagues (2006) Study In this pilot study, 31 HIV-infected primary-care patients with heavy alcohol use received one session of MI from a trained counselor, followed by daily telephone-based interactive voice response (IVR) assessments of drinking amounts and graphic feedback of changes in drinking at 30 and 60 days. This intervention resulted in a decrease in the number of drinks per day at 30 and 60 days (from 3.2 drinks per day at baseline to 1.7 drinks at 30 days and 1.2 drinks at 60 days). The IVR system was utilized; 77 percent of all possible daily calls were completed at 30 days. However, these improvements can not be attributed to the intervention with confidence because there was no control group.

Parsons and Colleagues (2007) Study. These investigators conducted an RCT among 143 HIV-infected people with "hazardous drinking" (defined as more than 16 standard drinks per week for men or more than 12 standard drinks per week for women), assessing treatment effects on HIV medication adherence and alcohol outcomes. The intervention involved eight 1-hour individual sessions of MI and cognitive behavioral skills training over 3 months and was compared with a time- and content-equivalent control. (4) Over the follow-up period (3 and 6 months), both groups exhibited substantial improvement for both total alcohol drinks over 14 days or drinks per drinking day, although no significant differences existed between the intervention and the control group. However, compared with the control group, the intervention did improve medication adherence, number of virus particles detectable in the blood (i.e., viral load), and CD4 cell (5) counts at 3 months. These statistically significant improvements were not sustained at 6 months.

Samet and Colleagues (2005) Study. This RCT included 151 HIV-infected patients on antiretroviral therapy (ART) who had a history of alcohol problems. The participants received either four nurse-delivered, 30- to 60-minute sessions focusing on HIV medication adherence and alcohol counseling, both in a clinic and at home, or no intervention. The study found no significant differences between groups upon examination of the following outcomes: 3-day medication adherence, 30-day adherence, CD4 cell count, viral load, drinks per day, percent reporting drinking, or percent reporting hazardous drinking. Study limitations were that not all participants were non-adherent to their HIV medication at baseline and a substantial percentage were not in the risky-drinking range of unhealthy alcohol use, the group most amenable to brief interventions.

CLINICAL TRIALS AMONG HIV-INFECTED PEOPLE OF WHOM AT LEAST 10 PERCENT CURRENTLY USE ALCOHOL

Five studies identified in the literature review fell into this category, and only one of these (Rotheram-Borus et al. 2009) demonstrated significant treatment effects on alcohol use (see table 1). This study was a subanalysis of a parent RCT among 936 HIV-infected people who were sexually active without a condom with at least one HIV-negative partner or two HIV-infected partners (Wong et al. 2008). The participants received either 15 90-minute individual sessions of cognitive-behavioral therapy (CBT) delivered over 15 months or usual care. The subanalysis by Rotheram-Borus and colleagues (2009) was limited to 270 HIV-infected participants who were homeless or without stable housing. In this group, the intervention was found to reduce alcohol or marijuana use from 36 to 28 days in the prior 90 days, whereas in the control group the frequency of alcohol or marijuana use was unchanged at 35 of the last 90 days. However, this study had substantial methodological limitations, some of which pertain to the parent study. For example, in the parent study, random assignment of participants to the groups resulted in an imbalance between the groups with respect to baseline HIV risk behaviors or demographics. Moreover, the sub analysis was limited to participants who completed four follow-ups and were homeless or without stable housing. Finally, the outcome was alcohol or marijuana use in the last 3 months with no alcohol-specific results provided.

The four other studies in this category did not demonstrate any significant effects of the interventions tested on alcohol use:

* In a preliminary analysis of 3-month outcomes among 51 subjects randomized to four 1-hour motivational enhancement therapy sessions in an adolescent clinic, Naar-King and colleagues (2006) observed a trend, but no statistically significant reduction, in the number of drinks per week during the week with the maximum number of drinks. Moreover, in the final analysis of the study, which included 65 subjects, 39 percent of whom used alcohol, this difference was not sustained at 6 or 9 months (Naar-King et al. 2008).

* Gilbert and colleagues (2008) randomized 476 HIV-infected patients, 38 percent of whom reported risky drinking, to an MI-based "Video Doctor" intervention via laptop computer or a control group receiving usual care. The intervention resulted in decreased 30-day illicit drug use, lower mean number of drug use days, and a modest reduction of unprotected sex at 3 and 6 months. However, no differences in alcohol use existed between the intervention and control groups.

* Sorensen and colleagues (2003) randomly assigned HIV-infected patients with drug dependence, 61 percent of whom reported current alcohol use, to 1 year of continuous case management or to a brief contact (i.e., one HIV risk education session and printed information). No differences were noted in alcohol outcomes at 6, 12, or 18 months.

* A study among HIV-infected youths compared the effects of 23 2-hour group sessions and usual care on risk behaviors (Rotheram-Borus et al. 2001). The investigators found no changes from baseline on a measure reflecting alcohol and marijuana use and no difference between the intervention and control groups.

RCTS AMONG ALCOHOL USERS AT HIGH-RISK FOR HIV INFECTION

Two informative RCTs have been conducted among alcohol drinkers at high risk for HIV infection. Morgenstern and colleagues (2007) performed a study with 198 high-risk, HIV-negative men who had sex with men and who were diagnosed with alcohol abuse or dependence but were seeking to moderate their alcohol use. The investigators compared the effects of 12 weekly MI sessions augmented with CBT with 4 sessions of MI alone. Unexpectedly, the investigators found that the nonaugmented MI group had less drinking and fewer alcohol-related drinking problems than the MI-plus-CBT group during the 12 weeks of the intervention and that there were no significant differences at 12-month follow-up. Thus, the addition of CBT to MI techniques provided no additional benefit regarding alcohol outcomes and potentially even diminished effects in this population. Subgroup analyses demonstrated that the detrimental effect of augmentation occurred particularly in participants with a concomitant drug use disorder.

Another RCT (Kalichman et al. 2008) compared a 3-hour, skills-based HIV and alcohol risk reduction group session with a 1-hour HIV/alcohol information group session among 342 South Africans frequenting drinking establishments. In this study, the extended session resulted in decreases in alcohol use before sex and unprotected intercourse at 3 month but not at 6 month follow-up. Moreover, intervention effects were stronger in participants drinking less at baseline.

DISCUSSION

Given the high prevalence of unhealthy alcohol use among HIV-infected people and its associated adverse health consequences, development of clinical and public health interventions that seek to address alcohol use and improve health outcomes in this population is a priority. In recognition of this, NIAAA, as early as 1996, issued a request for applications entitled "Developing Alcohol-Related HIV Preventive Interventions (AA-97 -03)." Since then, several studies have been published that describe clinical outcomes of interventions in this population. However, as this article has demonstrated, the literature on this important topic still is not extensive. A literature search revealed only four clinical intervention studies focusing exclusively on HIV-infected patients with current or past unhealthy alcohol use; five other clinical trials included and documented the alcohol use of some of their HIV-infected participants. Overall, the current state of research strongly suggests that although the problems related to alcohol in HIV-infected people are abundant, effective interventions are few and new ones are urgently needed. Hence, addressing alcohol problems remains an important issue in HIV research.

Not only are studies among alcohol-abusing, HIV-infected patients scarce, but the existing studies also yielded mixed results. Two of the four studies that specifically targeted HIV-infected people with alcohol problems showed improvement in drinking outcomes. Velasquez and colleagues (2009) demonstrated reduced drinking levels over 12 months after an intervention that included both MI and peer support. The intervention was particularly strong in reducing same-day drinking and sex, which compels further research on interventions targeting alcohol use at the time of HIV risk behaviors (Velasquez et al. 2009). Although the intervention types used in the study only were shown to be effective in a sample of men who have sex with men, they warrant study among other populations. In the other study, Aharanovich and colleagues (2006) demonstrated the feasibility of ongoing telephone-based interactive voice response and graphic feedback, which should inspire the inclusion of automated, tailored, ongoing intervention boosting as part of behavioral interventions. It is important to note, however, that both these studies had methodological limitations (e.g., substantial or differential loss to follow-up, incomplete assessments) and their findings therefore are not definitive. Nevertheless, they provide some guidance for future more rigorous clinical trials.

The other two clinical trials (Parsons et al. 2007; Samet et al. 2005) among alcohol-abusing HIV-infected people attempted to improve ART adherence. This is an appropriate target of alcohol intervention studies in this population because medication adherence is of utmost importance for achieving good HIV disease outcomes, and alcohol-using patients have been documented to exhibit suboptimal ART adherence (Braithwaite et al. 2005; Chander et al. 2006; Conen et al. 2009; Samet et al. 2004). The results of both of these trials are discouraging, however, because although they explicitly addressed both alcohol use and medication adherence, one study (Samet et al. 2005) found no impact on adherence, alcohol consumption, or any HIV outcome, and the other (Parsons et al. 2007) only detected short-lived improvements (i.e., they were evident at 3 months, but not at 6 months). Thus, these two high-quality studies suggest that achieving clinically beneficial outcomes in HIV-infected people with alcohol problems is more difficult than has been the case with populations of HIV-infected without diagnosed unhealthy alcohol use (Amico et al. 2006; Simoni et al. 2006). Among the latter group, RCTs to improve adherence that used interventions with a range of intensities did reveal improvements in adherence which were sustained for up to 12 months, as well as in HIV viral load and CD4 counts (Tuldra et al. 2000). The difficulty of achieving positive benefits (e.g., improved ART adherence) through interventions among HIV-infected people who have alcohol problems also is evidenced by the study by Kalichman and colleagues (2008) among drinkers who were not infected with HIV. The findings of that study suggest that, as in brief intervention studies, intervention effectiveness varies by severity of alcohol use, with less improvement noted in dependent than in nondependent drinkers. Thus, levels of alcohol consumption, alcohol use disorder severity, and alcohol-related consequences are important covariates to be assessed and reported in HIV intervention studies.

A notable finding of this literature review was that as of 2009, no study of pharmacotherapy for alcohol dependence in HIV-infected patients had been published. This is surprising given that pharmacotherapy plays a major role in addressing the AIDS epidemic by improving outcomes of HIV-infected subjects. Moreover, some preclinical research has demonstrated that naltrexone, an effective medication for alcohol dependence, inhibits alcohol-mediated enhancement of HIV infection (Wang et al. 2006) and may potentiate the anti-HIV effects of antiretroviral medications (Gekker et al. 2001). Therefore, testing the effectiveness of naltrexone and other medications in alcohol-dependent HIV-infected patients is an important current research direction.

Two of the studies reviewed here that included HIV-infected patients among whom at least 10 percent currently used alcohol, targeted risky sexual behaviors rather than alcohol consumption. Assessing treatment effects on sex risk factors is appropriate for studies among HIV-infected drinkers because several studies have demonstrated an association between alcohol use and risky sex (Purcell et al. 2001; Stein et al. 2009). In both the study by Gilbert and colleagues (2008) and the study by Naar-King and colleagues (2006, 2008), sex risk behaviors were decreased in the group randomized to the intervention at 3 and 6 months, but there were no or only transient effects on alcohol use. These findings suggest that behavioral interventions which are not specifically tailored to address alcohol use are unlikely to impact alcohol problems in a sustained fashion.

The dearth of studies focusing on alcohol consumption among HIV-infected people is understandable. Although the spectrum of unhealthy alcohol use ranging from risky use to alcohol dependence occurs in this population, other pressing health concerns (e.g., ART adherence, risky sexual behaviors, or engagement in HIV care) appropriately become the main focus of clinical trials that also may address alcohol consumption in their intervention arms. Developing interventions that target a specific behavior (e.g., sex) at the time of alcohol use is a worthy pursuit, and understanding the importance of decreasing alcohol use in order to successfully achieve behavior change is crucial for developing future interventions.

One interesting development noted in the studies reviewed here was the use of new technology (e.g., interactive voice-response systems) in two of the studies (Aharonovich et al. 2006; Gilbert et al. 2008). These approaches to delivering a behavioral intervention merit further exploration because they have the potential for providing scalable, ongoing delivery of tailored automated messages that may boost a more intensive directly administered intervention.

When assessing the relevance of the studies reviewed here, particularly those conducted among HIV-infected patients with past or current unhealthy alcohol use, it is important to consider the methodological quality of the work (i.e., the potential for bias, design limitations, and outcome measures). The report by Velasquez and colleagues (2009) is the only controlled study demonstrating a sustained clinically significant treatment effect on an alcohol-specific outcome, making publication bias (i.e., the preferential publication of studies that find significant differences) unlikely.

Regarding their design, most, but not all, of these studies met important design criteria, such as random allocation of participants to treatment groups and intention-to-treat analyses (6) in the presentation of results. As with all behavioral intervention studies, keeping participants in the dark about which treatment they receive (i.e., blinding of participants to their treatment) is not possible. However, both Parsons and colleagues (2007) and Gilbert and colleagues (2008) utilized time- and content-equivalent controls to allow for the detection of effects specific to the counseling method studied.

The outcome measures reported were not consistent across studies and not always meaningful, limiting the comparability of study outcomes. For example, Naar-King and colleagues (2006) used an alcohol-specific measure--the number of drinks per week during the week with the maximum number of drinks at 3 months--that is not widely used and of questionable clinical meaning. Sorensen and colleagues (2003) only report a measure called the Addiction Severity Index Alcohol Composite Score, without any explanation or reporting of the individual components, complicating judgment of its clinical meaning. Finally, Samet and colleagues (2005) focused on ART adherence as an outcome, yet this study may underestimate the effectiveness of the intervention because the criteria for eligibility to participate in the study did not exclude patients with already good adherence. Thus, participants with good adherence at baseline provided little opportunity for an intervention to reveal a clinically meaningful impact.

In summary, as of 2009 the medical literature on clinical trials focused on people with HIV infection and unhealthy alcohol use is limited (i.e., "drops in a bottle"). Few of these studies were able to document improved outcomes, and any effects observed generally were modest and transitory. Based on these findings and current knowledge, the following questions need to be addressed:

* What are the characteristics of interventions that mitigate the health consequences of alcohol use in HIV-infected people?

* How does the treatment setting impact the effectiveness of behavioral interventions?

* How can technology best be used to extend and enhance intervention effects?

* What characteristics of HIV infected drinkers suggest greater challenges when attempting to improve clinical outcomes?

* How can individual, network, or community interventions in people with multiple overlapping problems, including alcohol use, optimally reduce unhealthy behaviors?

* How might combined pharmacotherapy and behavioral therapy be utilized to address the spectrum of clinical consequences that accompany heavy alcohol consumption?

Obtaining answers to these questions is the key next step in the successful development of clinical and public health interventions to mitigate the adverse outcomes from alcohol use in HIV-infected patients.

ACKNOWLEDGEMENTS

The authors acknowledge Victoria Churchill, M.P.H, for her thoughtful assistance in the preparation of this manuscript and Carly Bridden, M.A., M.P.H. for reviewing the manuscript.

FINANCIAL DISCLOSURE

The authors declare that they have no competing financial interests.

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LONGABAUGH, R.; WOOLARD, R.E.; NIRENBERG, T.D.; ET AL. Evaluating the effects of a brief motivational intervention for injured drinkers in the emergency department. Journal of Studies on Alcohol 62:806-816, 2001. PMID: 11838918

METSCH, L.R.; BELL, C.; PEREYRA, M.; ET AL. Hospitalized HIV-infected patients in the era of highly active antiretroviral therapy. American Journal of Public Health 99:1045-1049, 2009. PMID: 19372520

MIGUEZ, M.J.; SHOR-POSNER, G.; MORALES, G.; ET AL. HIV treatment in drug abusers: Impact of alcohol use. Addiction Biology 8:33-37, 2003. PMID: 12745413

MILLER, W.R., AND ROLLNICK, S. Motivational Interviewing: Preparing People to Change. New York: Guilford Press, 2002.

MONTI, P.M.; COLBY, S.M.; BARNETT, N.P.; ET AL. Brief intervention for harm reduction with alcohol-positive older adolescents in a hospital emergency department. Journal of Consulting and Clinical Psychology 67:989-994, 1999. PMID: 10596521

MORGENSTERN, J.; IRWIN, T.W.; WAINBERG, M.L.; ET AL. A randomized controlled trial of goal choice interventions for alcohol use disorders among men who have sex with men. Journal of Consulting and Clinical Psychology 75:72-84, 2007. PMID: 17295566

NAAR-KING, S.; LAM, P.; WANG, B.; ET AL. Brief report: Maintenance of effects of motivational enhancement therapy to improve risk behaviors and HIV-related health in a randomized controlled trial of youth living with HIV. Journal of Pediatric Psychology 33:441-445, 2008. PMID: 17905800

NAAR-KING, S.; WRIGHT, K.; PARSONS, J.T.; ET AL. Healthy choices: Motivational enhancement therapy for health risk behaviors in HIV-positive youth. AIDS Education and Prevention 18:1-11, 2006. PMID: 16539572

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OLMSTED, C.L., AND KOCKLER, D.R. Topiramate for alcohol dependence. Annals of Pharmacotherapy 42:1475-1480, 2008. PMID: 18698008

PARSONS, J.T.; GOLUB, S.A.; ROSOF, E.; AND HOLDER, C. Motivational interviewing and cognitive-behavioral intervention to improve HIV medication adherence among hazardous drinkers: A randomized controlled trial. Journal of Acquired Immune Deficiency Syndromes 46:443-450, 2007. PMID: 18077833

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PURCELL, D.W.; PARSONS, J.T.; HALKITIS, P.N.; ET AL. Substance use and sexual transmission risk behavior of HIV-positive men who have sex with men. Journal of Substance Abuse 13:185-200, 2001. PMID: 11547619

ROTHERAM-BORUS, M.J.; DESMOND, K.; COMULADA, W.S.; ET AL. Reducing risky sexual behavior and substance use among currently and formerly homeless adults living with HIV. American Journal of Public Health 99:1100-1107, 2009. PMID: 18799777

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SAITZ, R.; HORTON, N.J.; CHENG, D.M.; AND SAMET, J.H. Alcohol counseling reflects higher quality of primary care. Journal of General Internal Medicine 23:1482-1486, 2008. PMID: 18618204

SAITZ, R.; PALFAI, T.P.; CHENG, D.M.; ET AL. Brief intervention for medical inpatients with unhealthy alcohol use: A randomized, controlled trial. Annals of Internal Medicine 146:167-176, 2007. PMID: 17283347

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SAMET, J.H.; HORTON, N.J.; MELI, S.; ET AL. Alcohol consumption and antiretroviral adherence among HIV-infected persons with alcohol problems. Alcoholism: Clinical and Experimental Research 28:572-577, 2004. PMID: 15100608

SAMET, J.H.; HORTON, N.J.; TRAPHAGEN, E.T.; ET AL. Alcohol consumption and HIV disease progression: Are they related? Alcoholism: Clinical and Experimental Research 27:862-867, 2003a. PMID: 12766632

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WUTZKE, S.E.; CONIGRAVE, K.M.; SAUNDERS, J.B.; AND HALL, W.D. The long-term effectiveness of brief interventions for unsafe alcohol consumption: A 10-year follow-up. Addiction 97:665-675, 2002. PMID: 12084136

JEFFREY H. SAMET, M.D., M.A., M.P.H., AND ALEXANDER Y. WALLEY, M.D., M.SC.

(1) According to the National Institute on Alcohol Abuse and Alcoholism (2007), women who drink more than 3 drinks per day or more than 7 drinks per week and men who drink more than 4 drinks per day or more than 14 drinks per week are at increased risk for alcohol-related problems. Alcohol consumption levels above these limits are considered risky drinking.

(2) RCTs are clinical studies in which patients randomly are assigned to either one or more groups receiving the treatment under investigation or to a control group receiving no treatment or a treatment of known efficacy.

(3) The transtheoretical model (TTM) is a health behavior theory that assesses the individual's readiness to change a particular behavior in order to facilitate the desired behavior change. The stages of change are: precontemplation, contemplation, preparation, action, and maintenance.

(4) With a time- and content-equivalent control group, participants in that group spend the same amount of time with a health care provider/therapist as the intervention group, and they receive the same type of information. The only difference between the intervention and control groups is the method used to deliver the information, allowing researchers to determine whether one approach is more effective than the other.

(5) CD4 cells are a type of white blood cell that is the main target of the HIV virus; accordingly, levels of these cells in the blood decline with progressing HIV infection and are a marker for disease progression.

(6) An intention-to-treat analysis is based on the initial treatment intent, not on the treatment actually administered. Thus, every participant who begins the treatment is considered to be part of the trial, whether they finish it or not. This is done to avoid various misleading artifacts that can arise in a study. For example, if participants who have a more serious problem tend to drop out at a higher rate, even an ineffective treatment may appear to provide benefits if one only compares the condition before and after the treatment among participants who finish the treatment and ignores participants who were enrolled originally but did not finish the treatment.

JEFFREY H. SAMET, M.D., M.A., M.P.H., is a professor in the Clinical Addiction Research and Education (CARE) Unit, Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, and in the Department of Social and Behavioral Sciences, Boston University School of Public Health, both in Boston, Massachusetts.

ALEXANDER Y. WALLEY, M.D., M.SC., is an assistant professor in the CARE Unit, Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
Table 1 Studies Identified During a Literature
Search on Interventions to Decrease Alcohol Use
and Related Behaviors among HIV-Infected People
and Alcohol Users at High Risk for Infection

Study          Population/Setting

Category 1: Clinical trials among HIV-infected people with
past or current unhealthy alcohol use

Velasquez      Population: 253
et al. 2009    HIV-infected men
               who had sex with men
               (MSM) in the previous 3
               months and an AUDIT
               score of more than 8.
               Setting: Recruited from
               HIV organizations,
               advertising, and
               social venues
               between 1999 and
               2003.

Aharonovich    Population: 31
et al. 2006    HIV-infected men and
               women engaged in
               HIV primary care.
               Alcohol use: All had
               four or more drinks
               at least once in the
               past 30 days, 55%
               had five or more
               drinks in the last
               week.
               Setting: HIV primary
               care clinic.

Parsons        Population: 143
et al. 2007    HIV-infected subjects
               on antiretroviral therapy
               (ART) with hazardous
               drinking (more than 16
               drinks per week for
               men, more than 12
               drinks per week for
               women) recruited
               through HIV clinics and
               advertising from 2002
               to 2005.
               Setting: Behavioral
               research center.

Samet          Population: 151
et al. 2005    HIV-infected patients
               on ART, with current
               or lifetime alcohol
               problems, determined
               by two or more
               positive responses on
               CAGE questionnaire
               or clinical diagnosis of
               alcohol disorder
               recruited from 1997
               to 2000.
               Setting: Hospital
               (patients receiving
               HIV medical care).

Category 2: Clinical trials among HIV-infected people of
whom at least 10% have current alcohol use

Rotheram-      Population: 270
Borus et al.   HIV-infected people
2009           sexually active without
               a condom with at least
               one HIV-negative
               partner or two
               HIV-infected partners
               who were marginally
               housed and had four
               or more assessments;
               recruited from 2000
               to 2002.
               Alcohol use: Mean
               number of days using
               alcohol or marijuana
               in the last 90 was 37.
               Setting: Recruited from
               community agencies,
               medical clinics, and
               advertisements.

Naar-King      Population: 65
et al. 2006,   HIV-infected patients,
2008           aged 16-25 regardless
               of alcohol use or risk
               behaviors.
               Alcohol use: 77%
               lifetime, 39% had used
               alcohol in last 30 days
               at study entry.
               Setting: Adolescent
               HIV care clinic within
               a tertiary care children's
               hospital.

Gilbert        Population: 476
et al.         patients with alcohol
2008           risk (38%), defined
               as exceeding NIAAA
               safe drinking limits
               or drug risk (42%),
               or sex risk (60%),
               were recruited
               between 2003 and
               2006.
               Setting: Outpatient
               HIV clinics.

Sorensen       Population: 190
et al. 2003    HIV-infected patients
               with substance
               dependence; recruited
               from inpatient medical
               wards, detoxification
               clinic, and the
               emergency department
               from 1994 to 1996.
               Alcohol use: 61% in
               the last 30 days.
               Setting: Public general
               hospital.

Study          Population/Setting

Rotheram-      Population: 310
Borus et al.   HIV-infected patients
2001           (age 13-24) from nine
               adolescent clinics
               recruited from 1994
               to 1996.
               Alcohol use: 67%
               nonabstinent at
               baseline.
               Setting: Adolescent
               clinics.

Category 3: Randomized controlled trials among alcohol
users at high risk for HIV infection

Morgenstern    Population: 198 MSM
et al. 2007    with current alcohol
               user disorder.
               Alcohol use: 88% with
               alcohol dependence.
               Mean drinks per
               drinking day was 10.4.
               Setting: Subjects
               recruited through
               advertisements in gay
               media, internet chat
               rooms, outreach to
               gay bars and clubs.

Kalichman      Population: 342 men
et al. 2008    and women who drink
               in South African
               shebeens.
               Setting: Informal
               alcohol establishments
               (shebeens).

Study          Design

Category 1: Clinical trials among HIV-infected people with
past or current unhealthy alcohol use

Velasquez      Intervention: Randomized
et al. 2009    Controlled Trial (RCT) of four
               sessions of motivational
               interviewing (MI)-based
               individual counseling and
               four sessions of transtheoretical
               model-based peer-group
               education/support.
               Control: HIV and alcohol
               educational materials,
               resource referrals, and advice
               to stop or reduce drinking.
               Assessment: Baseline, 3,
               6, 9, and 12 months.

Aharonovich    Intervention: 30-minute MI
et al. 2006    session on reducing alcohol
               use by counselor trained in
               MI plus an automated daily
               telephone self-monitoring
               interactive voice response
               (IVR) system with graphical
               feedback at 30-day follow-up
               meetings.
               Control: No control group.
               Assessment: Baseline, 30,
               60, and 90 days.

Parsons        Intervention: RCT of eight
et al. 2007    60-minute MI plus cognitive
               behavioral skills training (CBST)
               session by Masters-level
               counselors.
               Control: Eight 60-minute
               time and content-equivalent
               education sessions by health
               educators.

               All sessions delivered
               individually in private office
               over 12 weeks.
               Assessment: Baseline, 3
               and 6 months.

Samet          Intervention: RCT of four 15-
et al. 2005    to 60-minute sessions over
               3 months with MI-trained
               nurse who (1) addressed
               alcohol problems, (2) educated
               about ART efficacy, and
               (3) delivered tailored
               adherence advice including a
               reminder watch and a home visit.
               Control: Standard care
               Assessment: Baseline, 6,
               and 12 months.

Category 2: Clinical trials among HIV-infected people of
whom at least 10% have current alcohol use

Rotheram-      Intervention: RCT of 15
Borus et al.   90-minute individual counseling
2009           sessions, organized in three
               modules ("Coping" at 0-5
               months, "Act Safe" at 5-10
               months, and "Stay Healthy"
               at 10-15 months).
               Control: No intervention, only
               assessments
               Assessment: Baseline, 15, 20,
               and 25 months.

Naar-King      Intervention: RCT of four
et al. 2006,   60-minute sessions of
2008           motivational enhancement.
               Therapy focused on two of
               three areas: substance use,
               sexual risk, or medication
               adherence over 10 weeks.
               Control: Wait list and standard
               care.
               Assessment: Baseline, 3, 6,
               and 9 months.

Gilbert        Intervention: RCT of two
et al.         sessions of tailored risk-
2008           reduction counseling at study
               entry and 3 months using a
               MI "Video Doctor" via laptop
               computer, printed educational
               worksheet, and delivery of
               a cueing sheet on reported
               risks to clinic care providers.
               Control: Standard care.
               Assessment: Baseline, 3,
               and 6 months.

Sorensen       Intervention: RCT of 12
et al. 2003    months of case management
               by certified substance
               counselors in the community
               with caseload of 1:20
               Control: Single brief contact
               with education about
               reducing HIV risk, information
               on HIV services, referrals to
               addiction treatment, social
               services.
               Assessment: Baseline, 6,
               12, and 18 months.

Study          Design

Rotheram-      Intervention: 23 group
Borus et al.   sessions of two modules
2001           ("Stay Healthy" and "Act
               Safe").
               Control: Standard care.
               Eligible for receiving the
               intervention at the
               conclusion of the study.
               Assessment: Baseline, 9,
               and 15 months.

Category 3: Randomized controlled trials among alcohol
users at high risk for HIV infection

Morgenstern    Intervention: 12 sessions of
et al. 2007    combined MI and coping
               skills training (MI+CBT) over
               12 weeks (n = 47).
               Control: Four sessions of
               MI over 12 weeks (n = 42).
               Non-help-seeking (NHS)
               control group (n = 109).
               Assessment: Baseline, 12
               weeks, and 12 months.

Kalichman      Intervention: 3-hour skills-
et al. 2008    based HIV-alcohol risk-
               reduction group session.
               Control: 1-hour HIV-alcohol
               information group session.
               Assessment: Baseline, 3,
               and 6 months.

Study          Outcomes/Results

Category 1: Clinical trials among HIV-infected people with
past or current unhealthy alcohol use

Velasquez      Alcohol use: Control group
et al. 2009    had 1.38 times the number
               of drinks per 30 days and
               1.50 times the number of
               heavy drinking days per 30
               days compared with the
               intervention group.
               Sex risk: No significant
               effect was demonstrated
               for anal sex without a
               condom or number of days
               on which drinking and sex
               occurred.

Aharonovich    Drinks per day: Using 7-day
et al. 2006    recall, mean drinks per
               day was 3.2 at baseline,
               1.7 at 30 days, and 1.2 at
               60 days. Mean highest
               drinks per day was 8.4, 4.1,
               and 3.8, respectively.
               Cocaine use: Decreased
               significantly at 60 days.

Parsons        Alcohol use: No significant
et al. 2007    effects on total drinks over
               14 days or drinks per drinking
               day. Decreases in both
               groups from baseline to 3
               and 6 months for these two
               drinking outcomes.
               Medication adherence:
               Significant improvement in
               dose and day adherence
               at 3 months, but difference
               not retained at 6 months.
               HIV viral load/CD4 cell
               count: Significant
               improvement at 3 months
               but not at 6 months.

Samet          Alcohol use: No significant
et al. 2005    effects on drinks per day,
               percent reporting any
               drinking, percent reporting
               hazardous drinking.
               Medication adherence:
               No significant effects on
               3-day or 30-day adherence.
               HIV viral load/ CD4 cell
               count: No significant
               effects on mean CD4 cell
               count or mean log HIV RNA.

Category 2: Clinical trials among HIV-infected people of
whom at least 10% have current alcohol use

Rotheram-      Alcohol or marijuana use
Borus et al.   in the last 3 months: At 25
2009           months, the intervention
               group reduced its use
               from 36 to 28 days in the
               prior 90 days, whereas
               the control group was
               unchanged at 35 days of
               the last 90.

               Number of HIV negative
               partners and risky sexual
               acts also was reduced.

Naar-King      No significant effects at
et al. 2006,   9-month follow-up.
2008           Alcohol use: Borderline
               significant reduction in
               number of drinks in the
               week containing the
               maximum number of drinks
               (-9.65 vs. -1.3) at 3 months
               (n = 51).
               Marijuana use: Borderline
               significant reduction in
               number of times marijuana
               was used (n = 65).
               Sexual risk: Borderline
               significant reduction in total
               number of intercourse acts
               without a condom at 6
               months (n = 65).
               HIV viral load: Significant
               reduction in log viral load at
               6 months (n = 65).

Gilbert        Alcohol use: No significant
et al.         effects on any risky drinking
2008           or number of drinks per
               week.
               Drug use: Significantly
               decreased 30-day illicit
               drug use at 3 and 6 months
               and fewer days of illicit
               drug use at 6 months.
               Sex risk: Significantly
               decreased 3-month
               unprotected sex at 3 and
               6 months and fewer casual
               sex partners at 6 months.
               No effects on condom use.

Sorensen       No outcomes showed
et al. 2003    significant change between
               study groups at any time
               points, except decreased
               sex risk index.
               Outcomes measured:
               Addiction severity index
               composite scores, AIDS risk
               assessment scores, Beck
               depression inventory, health
               status questionnaire, and
               support evaluation list.

Study          Outcomes/Results

Rotheram-      Alcohol/marijuana use:
Borus et al.   63% for attendees vs. 67%
2001           for control vs. 84% for
               nonattendees at 15 months.

Category 3: Randomized controlled trials among alcohol
users at high risk for HIV infection

Morgenstern    Drinks per day : At 12
et al. 2007    weeks, the MI group had
               greater decreases in drinks
               per day than the MI+CBT
               group. This difference was
               not sustained at 12 months.
               Both intervention groups
               had greater decreases then
               the NHS group, but the
               NHS group also had
               substantial decreases in
               drinking.

Kalichman      The following behaviors
et al. 2008    were improved significantly
               at 3 months among the
               intervention group:
               * alcohol use before sex
               * unprotected intercourse
               * percent of sex with condoms
               * number of sex partners.

               Intervention effects were
               significantly stronger in
               those drinking less and
               dissipated at 6 months.

Study          Comments

Category 1: Clinical trials among HIV-infected people with
past or current unhealthy alcohol use

Velasquez      Alcohol measures:
et al. 2009    AUDIT, 90-day timeline
               follow-back (TLFB) at
               follow-up assessments.

               Differential loss to follow-
               up at 12 months (34%
               in intervention group and
               26% in control group). Only
               95 of 118 (81%) of the
               intervention group and
               121 of 135 (90%) of the
               control group were included
               in the analyses.

Aharonovich    Alcohol measures:
et al. 2006    Quantity and frequency in
               past week and past month.

               Qualitative assessment of
               the program demonstrated
               satisfaction with daily
               calling and the feedback
               graph.

               Not a randomized
               controlled trial.

Parsons        Alcohol measure:
et al. 2007    Self-report 14-day TLFB
               to calculate total drinks
               and drinks per drinking day.
               Adherence measures:
               Self-report dose
               adherence = number of
               doses taken/number of
               doses scheduled over 14
               days. Self-report day
               adherence = number of
               days with perfect
               adherence/14 days.

Samet          Alcohol measures:
et al. 2005    Self-report 30-day alcohol
               use from the Addiction
               Severity Index.
               Adherence measures:
               Self-reported AIDS Clinical
               Trial Group scale with
               100% and 95% or more
               thresholds at 3-day and
               30-day adherence,
               respectively.

Category 2: Clinical trials among HIV-infected people of
whom at least 10% have current alcohol use

Rotheram-      Subanalysis of a clinical
Borus et al.   trial (Wong et al. 2008):
2009           5% used alcohol/
               marijuana in the parent
               study. Proportion of
               alcohol users at baseline
               not presented in this study.

               Parent study reported only
               transmission act outcomes
               and demonstrated an
               effect that was not
               maintained at 25 months.

               Imbalance in transmission
               risk acts at baseline
               resulted in ineffective
               randomization, thus
               propensity scores were
               used to adjust for imbalances.

Naar-King      Alcohol and drug
et al. 2006,   measures: Timeline
2008           follow-back, though time
               window is not stated.
               Sex risk measure:
               Total number of
               unprotected intercourse
               acts without a condom.

               Note: 3-month outcomes
               on 51 subjects were
               published in 2006 and 6-
               and 9-month outcomes
               on 65 subjects published
               in 2008.

Gilbert        Alcohol measures:
et al.         Self-reported NIAAA risky
2008           drinking over 3 months.
               Drug use measures:
               Self-reported drug use
               over 30 days included any
               cocaine, methamphetamine,
               or heroin or 3 or more days
               of barbiturates, prescription
               opiates, hallucinogens,
               inhalants, or methylene-
               dioxymethamphetamine
               (MDMA).

Sorensen       Summary/index
et al. 2003    score is shown without
               explanation of the raw
               measure.

Study          Comments

Rotheram-      Sequential assignment of
Borus et al.   15 youths to intervention
2001           versus control groups (not
               randomized).

               The reported comparisons
               were attendees versus
               non-attendees versus
               control subjects. No
               intention-to-treat analysis
               was reported.
               Differential loss to
               follow-up. No alcohol-
               specific outcome was
               reported.

Category 3: Randomized controlled trials among alcohol
users at high risk for HIV infection

Morgenstern    Alcohol measures:
et al. 2007    CIDI at baseline.
               TLFB and short
               inventory of problems
               at followup.

               Potential subjects with
               drug use more severe
               than alcohol use disorder
               were excluded. Less than
               10% HIV infected.

               Subjects lost to follow-up
               not included in the
               analysis.
Kalichman
et al. 2008    Alcohol measures: AUDIT,
               frequency of drinking
               before sex in previous
               month. Change in AUDIT
               scores not reported.

               7% HIV infected in
               intervention group. 4% HIV
               infected in control group.

Table 2 Studies Identified but not Selected for the Literature Review

Citation       Population                  Reason Excluded

Golin et       140 HIV-infected            No data on the proportion
al. 2003       patients. Setting:          of drinkers at baseline.
               Hospital HIV clinic.

Goujard et     326 HIV-infected            No specific alcohol
al. 2003       patients.                   outcomes; alcohol group
               Setting: Hospital--and      not analyzed
               university-based centers.   independently.

Jones et       174 women with AIDS from    No alcohol-specific
al. 2003       three U.S. cities           outcomes reported.
               recruited in 1997 from
               outpatient clinics,
               community health centers
               and agencies, and
               participant referrals.

               Alcohol use: 32% with
               history of alcohol.

               Setting: Primarily
               recruited from outpatient
               clinics, community health
               centers, and participant
               referrals.

Pradier et     244 HAART-treated           No specific alcohol
al. 2003       patients.                   outcomes; alcohol group

               Setting: Hospital           not analyzed
                                           independently.

Samet et       181 Russian men and women   No alcohol-specific
al. 2008       who reported any alcohol    outcomes reported.
               or drug dependence and      Although both HIV-
               who reported at least one   infected and alcohol-
               incidence of unprotected    dependent patients were
               sex in the past 6 months.   included in this study,
                                           the HIV-infected patients
               Setting: Narcology          were not the alcohol-
               hospitals                   dependent patients.

Sampaio-       107 HIV-infected,           Alcohol-specific outcomes
Saet al.       antiretroviral-naive        not reported.
2008           patients at an Brazilian
               HIV clinic for whom
               antiretrovirals were
               indicated were recruited
               from 2003 to 2004. 45%
               with alcohol use in the
               last 3 months.

Simoni et      136 HIV-infected men and    No information on current
al. 2007       women.                      use; no specific alcohol
                                           outcomes.
               Setting: Outpatient
               clinic

Wong et        936 HIV-infected from       Alcohol-specific outcomes
al. 2008       four U.S. cities            not reported; absolute
               recruited between 2000      numbers for outcome not
               and 2002.                   presented.

               Setting: Community
               agencies, AIDS service
               organizations, and
               medical clinics

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randomized, controlled trial of a motivational interviewing-
based intervention to improve adherence to antiretroviral
therapy (ART) among patients failing or initiating ART.
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a patient education program on adherence to HIV medication:
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