SUBSTANCE USE

Adherence to ART Among Substance Users Guideline

Introduction

Substance Use Guidelines Committee, June 2005

RECOMMENDATION
  • Clinicians should consider substance users candidates for ARV therapy if they meet the medical eligibility criteria for ARV therapy and demonstrate readiness to begin therapy by attending the majority of their appointments and expressing interest in ARV treatment.

A significant portion of people with HIV use drugs. Injection drug users (IDUs) accounted for 13.63% of people living with HIV in New York State in 2006, and 26.7% of people living with AIDS. In New York City, more than half of all reported AIDS cases are directly or indirectly due to injection drug use. HIV-infected substance users have benefited less than other patients from advances in HIV treatment because of the challenges involved in navigating and sustaining engagement with the often complex system of medical care delivery. However, numerous studies have shown that current and former substance users can adhere to complex ARV regimens.

KEY POINT
  • History of substance use or current substance use should not be the sole factor in withholding ARV therapy from eligible patients. Decisions about when to prescribe ARV therapy for eligible drug-using patients should be made on a case-by-case basis.

Potent ARV combinations have provided opportunities for effectively treating HIV-infected persons and have led to a dramatic decline in HIV morbidity and mortality. ARV therapy can inhibit viral replication and markedly delay disease progression; however, achieving this potential often requires careful adherence to regimens that may be complex and/or cause unpleasant side effects. Non-adherence to ARV therapy may result not only in reduced treatment efficacy but also in the selection of drug-resistant HIV strains [1,2]. Because the exact level of adherence that is necessary to prevent the emergence of drug-resistant virus or to delay disease progression and death is unknown, near-perfect adherence (>90-95%) remains the goal for all HIV-infected patients, regardless of whether the patient is a past or current substance user [3,4].

This chapter discusses the general importance of adherence for all HIV-infected persons and presents specific issues that are unique to substance users or that may affect their treatment.

References:
  1. Bangsberg DR, Hecht FM, Charlebois ED, et al. Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent population. AIDS 2000;14:357-366.
  2. Montaner JSG, Reiss P, Cooper D, et al. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients. JAMA 1998;279:930-937.
  3. Bangsberg DR, Perry S, Charlebois ED, et al. Non-adherence to highly active antiretroviral therapy predicts progressions to AIDS. AIDS2001;15:1181-1183.
  4. Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large urban clinic: Risk factors for virologic failure and adverse drug reactions. Ann Intern Med 1999;131:81-87.

Predictors

June 2005

Studies of adherence to ARV therapy have identified few stable predictors of adherence. Lack of adherence to treatment recommendations in general is so widespread that no grouping of sociodemographic or psychosocial characteristics can reliably predict it [1]. Nonetheless, particular emphasis has been given to defining correlates of poor adherence among substance users for the following reasons:

  1. Substance users account for a large proportion of prevalent AIDS cases in many US cities [2].
  2. Substance users are traditionally thought to be less capable of adhering to medical treatments [3].
  3. Concern that poor adherence among persons engaged in high-risk behaviors will foster development and transmission of resistant virus [4].

Active substance or alcohol use is one of the few relatively consistent predictors of poor adherence but past history of drug or alcohol abuse is not [5,6]. Studies have shown that past users who do not currently use drugs, as well as some active users, are able to adhere to ARV treatments with success comparable to that of non-substance users [7,8].

Active mental illness, in particular depression, is consistently associated with poor adherence [9]. Other common reasons for non-adherence include difficulty remembering to take medications, inconvenient dosing, and medication side effects [10,11].

KEY POINT
  • A strong patient-provider relationship, including trust and engagement with the provider, has been associated with improved ARV adherence.

Predictors of adherence that have been consistently identified among both substance-using and non-substance-using persons with HIV infection include the following:

  • Social stability and support
  • Beliefs and knowledge about medications
  • Confidence in the ability to take HIV medications, including both self-efficacy and how well the regimen works (“fits”) with daily activities [12-14]
  • A strong and trusting patient-provider relationship

In addition to patient-related factors, several provider- and system-level characteristics have been associated with ARV adherence. These factors may be particularly important for substance users, who often lack access to reliable primary care. Participation in substance use treatment has been associated with adherence to preventive healthcare services in substance users, although the effect of engagement in substance use treatment on ARV adherence has not been formally studied. A strong patient-provider relationship, including trust and engagement with the provider, has been associated with improved ARV adherence [15]. To build trust, clinicians should be aware of their own personal perspectives and explore and respect the patient’s perspective.

References:
  1. Haynes RB, McKibbon KA, Kanani R. Systematic review of randomised trials of interventions to assist patients to follow prescriptions for medications. Lancet 1996;348:383-386.
  2. Holmberg SD. The estimated prevalence and incidence of HIV in 96 large U.S. metropolitan areas. Am J Public Health 1996;86:642-654.
  3. Sherer R. Adherence and antiretroviral therapy in injection drug users. JAMA 1998;280:567-568.
  4. Hecht FM, Grant RM, Petropoulos CJ, et al. Sexual transmission of an HIV-1 variant resistant to multiple reverse-transcriptase and protease inhibitors. N Engl J Med 1998;339:307-311.
  5. Haubrich RH, Little SJ, Currier JS, et al. The value of patient-reported adherence to antiretroviral therapy in predicting virologic and immunologic response. AIDS 1999;13:1099-1107.
  6. Arnsten JH, Demas PA, Grant RW, et al. Impact of active drug use on antiretroviral therapy adherence and viral suppression in HIV-infected drug users. J Gen Intern Med 2002;17:377-381.
  7. Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000;133:21-30.
  8. Catz SL, Kelly JA, Bogart LM, et al. Patterns, correlates, and barriers to medication adherence among persons prescribed new treatments for HIV disease. Health Psychol 2000;19:124-133.
  9. Avants SK, Margolin A, Warburton LA, et al. Predictors of nonadherence to HIV-related medication regimens during methadone stabilization. Am J Addict 2001;10:69-78.
  10. Gifford AL, Bormann JE, Shively MJ, et al. Predictors of self-reported adherence and plasma HIV concentrations in patients on multidrug antiretroviral regimens. J Acquir Immun Defic Syndr 2000;23:386-395.
  11. Roberts KJ, Mann T. Barriers to antiretroviral medication adherence in HIV-infected women. AIDS Care 2000;12:377-386.
  12. Chesney MA, Ickovics JR, Chambers DB, et al. Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: The AACTG adherence instruments. AIDS Care 2000;12:255-266.
  13. Safren SA, Otto MW, Worth JL, et al. Two strategies to increase adherence to HIV antiretroviral medication: Life-steps and medication monitoring. Behav Res Ther 2001;39:1151-1162.
  14. Kalichman SC, Ramachandran B, Catz S. Adherence to combination antiretroviral therapies in HIV patients of low health literacy. J Gen Intern Med 1999;14:267-273.
  15. Bakken S, Holzemer WL, Brown MA, et al. Relationships between perception of engagement with health care provider and demographic characteristics, health status, and adherence to therapeutic regimen in persons with HIV/AIDS. AIDS Patient Care STDs 2000;14:189-197.

Addressing Potential Barriers

June 2005

RECOMMENDATIONS
  • Clinicians should identify and address potential barriers to adherence before initiating ARV therapy in HIV-infected substance users (see below) . If clinicians elect to defer prescribing ARV therapy while addressing potentially modifiable barriers to adherence, they should discuss this decision with the patient.
  • Clinicians should reassess potential barriers to adherence at least every 3 to 4 months and whenever adherence problems are identified.
  • Clinicians should discuss with patients the known interactions between prescribed medications and illicit substances.
  • Clinicians should educate patients who receive concurrent opioid pharmacotherapy and ARV therapy about the safety and efficacy of methadone and buprenorphine because these patients may have misconceptions regarding the safety of concurrent opioid pharmacotherapy and ARV therapy.
  • Clinicians should assess potential interactions between ARV therapy and methadone before and  during therapy by inquiring about oversedation and opioid withdrawal symptoms. If withdrawal symptoms are present, the primary care clinician should conduct a detailed history and facilitate a dose increase by educatingthe patient and communicating with the methadone provider.

Identifying and addressing potential barriers to adherence before initiating ARV therapy in HIV-infected substance users is critical (see below). Clinicians may choose to defer ARV therapy while addressing potentially modifiable barriers to adherence. In patients with advanced AIDS, it may be appropriate to initiate ARV therapy even if barriers to adherence are present. In these cases, referrals should be made for intensified adherence support.

Potential barriers to adherence:

  • Active substance use
  • Inadequate substance use treatment
  • Lack of social stability (e.g., housing problems, legal issues) or social support (e.g., disrupted family and community ties, unstable relationships)
  • Lack of belief in medications or denial about being HIV-infected
  • Poor self-efficacy
  • Regimen does not “fit” with patient’s daily routine
  • Untreated mental illness, particularly depression
  • Side effects
  • Drug-drug interactions

Patients receiving concurrent opioid pharmacotherapy: A unique barrier to ARV therapy adherence among many substance users in substance use treatment is the interaction between ARV medications and methadone [1]. Clinicians should educate patients about drug interactions, especially when initiating a new drug. It is critical that such interactions are identified in clinical practice because  precipitation of narcotic withdrawal by an ARV agent that induces methadone metabolism may result in resumption of heroin use or in non-adherence to ARV medications. Most significantly, the non-nucleoside reverse transcriptase  inhibitors (NNRTIs) efavirenz and nevirapine substantially induce methadone metabolism and may precipitate  significant narcotic withdrawal symptoms and reduce methadone blood levels [2,3].

References:
  1. Gourevitch MN, Friedland GH. Interactions between methadone and medications used to treat HIV infection: A review. Mt Sinai J Med 2000;67:429-436.
  2. Clarke SM, Mulcahy FM, Tjia J, et al. The pharmacokinetics of methadone in HIV-positive patients receiving the non-nucleoside reverse transcriptase inhibitor efavirenz. Br J Clin Pharmacol 2001;51:213-217.
  3. McCance-Katz EF, Gourevitch MN, Arnsten J, et al. Modified directly observed therapy (MDOT) for injection drug users with HIV disease. Am J Addict 2002;11:271-278.

Adherence and ARV Resistance

June 2005

RECOMMENDATIONS
  • Clinicians should counsel patients before initiating ARV therapy and at routine monitoring visits during therapy concerning the need for strict adherence and the risk of viral drug resistance when adherence is compromised.
  • Clinicians should perform a thorough adherence assessment and obtain antiretroviral resistance assays prior to changing regimens in patients who are receiving a failing regimen (failure to demonstrate ≥1.5-log drop in viral load within 3 months of initiating treatment and, more importantly, failure to achieve a viral load <50 copies/mL within 6 months of initiating treatment).

Any discussion of adherence to ARV therapy must take into account the issue of drug resistance. Although the belief that low levels of adherence promote drug resistance is often cited as a reason to withhold ARV therapy from active substance users, there is little empirical evidence to support this decision. Evidence is beginning to accumulate demonstrating that the selection of drug resistance occurs most readily in patients with higher levels of adherence and incomplete viral suppression [1]. Studies have shown that among patients with low adherence (<50-60%), lack of viral suppression is more likely due to inadequate drug exposure than to the presumed development of drug resistance. Sustained low levels of adherence are not automatically or even generally associated with development of high levels of drug-resistant virus [1]. Rather, the documented close relationship between poor adherence and both disease progression and death is most likely associated with inadequate drug exposure and resulting high levels of viral replication [2,3]. Higher levels of adherence are associated with improved clinical outcome, although they may also be associated with an increased risk of developing drug-resistant virus. Therefore, the decision to withhold ARV therapy should not be based solely on the potential of developing drug resistance, but rather efforts should be directed toward a regimen that is pharmacologically and behaviorally appropriate to the individual.

References:
  1. Bangsberg DR, Moss AR, Deeks SG. Paradoxes of adherence and drug resistance to HIV antiretroviral therapy. J Antimicrob Chemother2004;53:696-699.
  2. Bangsberg DR, Perry S, Charlebois ED, et al. Non-adherence to highly active antiretroviral therapy predicts progressions to AIDS. AIDS2001;15:1181-1183.
  3. Low-Beer S, Yip B, O’Shaughnessy MV, et al. Adherence to triple therapy and viral load response. AIDS 2000;23:360-361.

Measuring Adherence

June 2005

RECOMMENDATIONS
  • Clinicians should assess adherence at every routine monitoring visit.
  • Clinicians should use finite time intervals when inquiring about and quantifying the patient’s self-report. Clinicians should average responses across visits to obtain a more accurate estimate of adherence.

When assessing adherence, clinicians should use precise language that the patient can understand. In addition, clinicians should verify that patients are taking the medications as prescribed, specifically, correct medications, correct number of pills per dose, and correct number of doses per day.

KEY POINTS
  • Adherence measurements averaged from repeated adherence assessments will yield a more accurate calculation of adherence than one-time assessments.
  • Clinicians’ estimates of patient adherence have been shown to be inaccurate and should not be substituted for a thorough adherence assessment [1].

Measurement of adherence is challenging in both clinical and research settings and usually relies on any one of the following methods or a combination:

  • Self-report
  • Pill counts
  • Pharmacy records
  • Electronic pill bottle monitors
  • Therapeutic drug monitoring
  • Directly observed therapy (DOT)
  • Modified directly observed therapy (MDOT)
  • Computer-assisted self interview (CASI) assessment

The advantages and disadvantages of each method are discussed in the appendix Advantages and Disadvantages of Adherence Measures.

Despite its tendency to overestimate adherence, self-report remains the most practical measure in most clinical settings and is most likely to facilitate discussion between patients and providers about the reasons for non-adherence. Many studies, including those in substance-using populations, have demonstrated a strong correlation between actual medication intake and viral load [2-4]. Self-report is most valid when patients are asked about the number of missed doses within a short time frame (1-7 days), but some studies have found that asking about adherence within the past month is also valid [5,6]. In either case, finite time intervals should be used. For example, the clinician should ask about the number of doses taken and missed in the past day or past week.

Clinicians should acknowledge the difficulty of adhering to ARV medications and ask about missed doses in the immediate past. For example:

  • Taking all of these pills must be very hard. How many pills did you miss yesterday?
  • How many pills did you miss the day before yesterday? What about 2 days ago?
  • Sometimes the weekends can be a hard time to take medications. Did you miss any pills last weekend?

Therapeutic drug monitoring may become a useful adjunct measure in the future, but because plasma drug levels reflect only recent adherence, its usefulness will be limited.

References:
  1. Miller LG, Liu H, Hays RD, et al. How well do clinicians estimate patients’ adherence to combination antiretroviral therapy? J Gen Intern Med 2002;17:1-12
  2. Bangsberg DR, Hecht FM, Charlebois ED, et al. Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent population. AIDS 2000;14:357-366.
  3. Haubrich RH, Little SJ, Currier JS, et al. The value of patient-reported adherence to antiretroviral therapy in predicting virologic and immunologic response. AIDS 1999;13:1099-1107.
  4. Arnsten JH, Demas PA, Farzadegan H, et al. Antiretroviral therapy adherence and viral suppression in HIV-infected drug users: Comparison of self-report and electronic monitoring. Clin Infect Dis 2001;33:1417-1423.
  5. Walsh JC. Responses to a 1 month self-report on adherence to antiretroviral therapy are consistent with electronic data and virological treatment outcome. AIDS 2002;16:269-277.
  6. Giordano TP, Guzman D, Clark R, et al. Measuring adherence to antiretroviral therapy in a diverse population using a visual analogue scale. HIV Clin Trials 2004;5:74-79.

Interventions to Improve Adherence

June 2005

RECOMMENDATION
  • Clinicians should refer patients to substance use treatment programs to optimize patients’ ability to successfully utilize and adhere to ARV therapy and other medical therapies [1,2].

Adherence intervention strategies should include the following elements:

  • Education and motivation, including treatment readiness, should be part of every visit
  • If medically feasible, simplifying the regimen and tailoring it to the patient’s lifestyle
  • Preparation for and management of side effects
  • Identification and treatment of depression and other psychiatric conditions
  • Substance use treatment
  • Involving an adherence team or monitor
  • Referring the patient to social services and mental health providers for assistance in dealing with (or resolving) issues that are barriers to adherence

Clinicians and substance-using patients should work together to develop a plan to decrease or stabilize substance use in preparation for initiating ARV therapy.

KEY POINT
  • Behavioral skills and motivation are crucial factors for promoting behavior change.

Few reliable adherence-enhancing interventions have been described among HIV-infected substance users, and almost none of these interventions have been evaluated using randomized designs [3]. Many adherence intervention programs have relied on the information-motivation-behavior skills (IMB) model of behavior change. This model asserts that information is necessary but insufficient to alter behavior, and that motivation and behavioral skills are critical determinants in promoting behavior change [4]. Table 1 describes several techniques that may improve adherence.

Table 1: Interventions to Improve Adherence
Determinant Actions
Beliefs and knowledge (of HIV medications)
  • Educate patient
  • Provide information
Self-efficacy and adherence Enhance motivation
Memory (difficulty remembering doses)
  • Offer patient visual aids to help remember daily regimen
  • Use beepers, pillboxes, and other reminders

One randomized trial demonstrated that a single-session intervention that used cognitive-behavioral, problem-solving, and motivational interviewing techniques resulted in significant improvements in adherence after 12 weeks [5]. Another study demonstrated that a brief medication counseling and behavioral intervention (20 minutes per month for 5 months) for substance-using men improved adherence and decreased subsequent hospitalizations [6]. Other non-controlled studies have suggested that prompt, frequent, and intensive follow-up is essential to adherence to ARV therapy [7]. Despite limited published data, it is well-accepted that behavioral counseling coupled with information enhances adherence [8].

Strategies to educate patients about adherence include the following:

  • Providing information in an organized manner, both orally and in written form, with easy to understand, brief statements that include common examples.
  • Using educational tools, such as pamphlets and information cards; however, these should complement and enhance the direct communication and not replace it.
  • Providing culturally competent, patient-centered care by tailoring educational efforts to the individual patient through language interpretation, including services for the hearing impaired, translation, health literacy, avoiding cultural categorization, and identifying and addressing areas of cross-cultural sensitivity.

Because twice- and even once-daily dosing of HIV medication regimens have become common, the concept of directly observing pill ingestion has received increased attention. DOT relies on the visual observation of pill taking to ensure adherence. Although shown to be effective in several non-randomized trials [9,10], published data are limited that compare the efficacy of DOT with other modalities for successful treatment of HIV disease. However, preliminary data from several pilot programs suggest that modified DOT strategies (for example, daily observation of morning doses with self-administration of evening doses, or observation of a once-daily regimen on 4 days of the week with self-administration on the other 3 days) might be appropriate for adoption in substance use treatment settings where patients are seen daily or several times per week [11].

References:
  1. Samet JH, Friedmann P, Saitz R. Benefits of linking primary medical care and substance abuse services: Patient, provider, and societal perspectives.Arch Intern Med 2001;161:85-89.
  2. Sorenson JL, Mascovich A, Wall TL, et al. Medication adherence strategies for drug abusers with HIV/AIDS. AIDS Care 1998;10:297-312.
  3. Malow RM, McPherson S, Klimas N, et al. Adherence to complex combination antiretroviral therapies by HIV-positive drug abusers. Psychiatr Serv1998;49:1021-1023.
  4. Fisher JDF, Fisher WAF, Bryan ADF, et al. Information-motivation-behavioral skills model-based HIV risk behavior change intervention for inner-city high school youth. Health Psychol 2002;21:177-186.
  5. Safren SA, Otto MW, Worth JL, et al. Two strategies to increase adherence to HIV antiretroviral medication: Life-steps and medication monitoring.Behav Res Ther 2001;39:1151-1162.
  6. McPherson-Baker S, Malow RM, Penedo F, et al. Enhancing adherence to combination antiretroviral therapy in non-adherent HIV-positive men.AIDS Care 2000;12:399-404.
  7. Chesney MA. Factors affecting adherence to antiretroviral therapy. Clin Infect Dis 2000;30(Suppl):S171-S176.
  8. Stone VE. Strategies for optimizing adherence to highly active antiretroviral therapy: Lessons from research and clinical practice. Clin Infect Dis2001;33:865-872.
  9. Stenzel MS, McKenzie M, Adelson-Mitty J, et al. Enhancing adherence to HAART: A pilot program of modified directly observed therapy. AIDS Reader 2001;11:317-328.
  10. Babudieri S, Aceti A, D’Offizi GP, et al. Directly observed therapy to treat HIV infection in prisoners. JAMA 2000;284:179-180.
  11. Altice FL, Mezger JA, Hodges J, et al. Developing a directly administered antiretroviral therapy intervention for HIV-infected drug users: Implications for program replication. Clin Infect Dis 2004;38(Suppl):S376-S387.

Appendix: Advantages and Disadvantages of Adherence Measures

June 2005

Method Advantages Disadvantages
Self-report
  • Easily obtained using patient interview or questionnaire (report of non-adherence is more reliable than report of adherence)
  • Inexpensive
  • Overestimates adherence
  • Correlation is dependent on patient’s relationship with staff
  • Individuals may give providers what they perceive as socially desirable, “right” responses
Pill counts
  • Useful adjunct to self-report
  • Unannounced pill counts may be more accurate
  • Direct costs minimal
  • Tends to overestimate adherence because of “pill dumping” before visit
  • Casts provider in the role of medication monitor and not ally or advocate
  • Indirect costs may be a concern due to time constraints
  • Does not prove that patient actually took medication
Electronic monitoring
  • Best correlation with virologic outcomes
  • Allows more detailed view of non-adherence patterns
  • Most accurate measure
  • Expensive and generally reserved for clinical trials
  • Precludes use of pillbox
  • Fails if multiple medications are kept in a single bottle or if multiple doses are taken out at one time
  • Requires carrying the container
  • Subject to “pocket doses” (removing more than one dose at a time)
  • Does not guarantee that the patient took the medication
Pharmacy refill monitoring
  • Easy, minimal time commitment
  • Timely refilling of prescriptions correlates well with adherence
  • Most successful when limited to patient using one pharmacist
  • Is a useful adjunct to self-report
  • Effective in understanding adherence behavior in large populations
  • Patients may use more than one pharmacy
  • Does not equate with medication-taking
Therapeutic drug monitoring  Low drug levels confirm non-adherence, but therapeutic drug levels do not confirm adherence
  • Pharmacokinetic levels for most drugs have not been well established
  • Only confirms the pre-measurement adherence, long-term adherence still unknown
Hematologic monitoring (using either complete blood count or expanded chemistry panel) Confirms patient reporting
  • Only effective for certain drugs: zidovudine, stavudine (increased MCV); indinavir (increased bilirubin)
  • Not always reliable
Directly observed therapy
  • 100% adherence, in theory
  • Ideal method for institutional settings (prisons, nursing homes, residential treatment programs, etc.)
  • Labor intensive
  • Not practical for complex regimens with multiple doses and/or dietary restrictions
  • May compromise confidentiality
Modified directly observed therapy (observation of most but not all medication doses)
  • 100% adherence, in theory
  • Ideal method for ambulatory settings
  • Labor intensive
  • Concern for development of resistance if plan not followed
Viral load Can correlate with adherence
  • Does not necessarily indicate non-adherence; not all individuals with virologic failure will be poor adherers
  • May overestimate adherence
  • Virologic failure can be indicative of drug resistance
Provider estimation  None Most poorly correlated with actual adherence

All Recommendations

Substance Use Guidelines Committee, June 2005

ALL RECOMMENDATIONS: ADHERENCE TO ART AMONG SUBSTANCE USERS
Introduction 
  • Clinicians should consider substance users candidates for ARV therapy if they meet the medical eligibility criteria for ARV therapy and demonstrate readiness to begin therapy by attending the majority of their appointments and expressing interest in ARV treatment.
Addressing Potential Barriers 
  • Clinicians should identify and address potential barriers to adherence before initiating ARV therapy in HIV-infected substance users (see below) . If clinicians elect to defer prescribing ARV therapy while addressing potentially modifiable barriers to adherence, they should discuss this decision with the patient.
  • Clinicians should reassess potential barriers to adherence at least every 3 to 4 months and whenever adherence problems are identified.
  • Clinicians should discuss with patients the known interactions between prescribed medications and illicit substances.
  • Clinicians should educate patients who receive concurrent opioid pharmacotherapy and ARV therapy about the safety and efficacy of methadone and buprenorphine because these patients may have misconceptions regarding the safety of concurrent opioid pharmacotherapy and ARV therapy.
  • Clinicians should assess potential interactions between ARV therapy and methadone before and during therapy by inquiring about oversedation and opioid withdrawal symptoms. If withdrawal symptoms are present, the primary care clinician should conduct a detailed history and facilitate a dose increase by educatingthe patient and communicating with the methadone provider.
Adherence and ARV Resistance 
  • Clinicians should counsel patients before initiating ARV therapy and at routine monitoring visits during therapy concerning the need for strict adherence and the risk of viral drug resistance when adherence is compromised.
  • Clinicians should perform a thorough adherence assessment and obtain antiretroviral resistance assays prior to changing regimens in patients who are receiving a failing regimen (failure to demonstrate ≥1.5-log drop in viral load within 3 months of initiating treatment and, more importantly, failure to achieve a viral load <50 copies/mL within 6 months of initiating treatment).
Measuring Adherence 
  • Clinicians should assess adherence at every routine monitoring visit.
  • Clinicians should use finite time intervals when inquiring about and quantifying the patient’s self-report. Clinicians should average responses across visits to obtain a more accurate estimate of adherence.
  • Clinicians should refer patients to substance use treatment programs to optimize patients’ ability to successfully utilize and adhere to ARV therapy and other medical therapies.