Page 128 - HIV/AIDS Guidelines

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populations. Furthermore, therapeutic failure in this population generally correlates with the degree that
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drug use disrupts daily activities rather than with drug use per se. Providers need to remain attentive to the
possible impact of disruptions caused by drug use on the patient both before and while receiving ART.
Although many illicit drug users can sufficiently control their drug use for long enough time to benefit from
care, substance abuse treatment is often necessary for successful HIV management.
Close collaboration with substance abuse treatment programs and proper support and attention to this
population’s special multidisciplinary needs are critical components of successful HIV treatment. Essential to
this end are accommodating, flexible, community-based HIV care sites that are characterized by familiarity
with and nonjudgmental expertise in management of drug users’ wide array of needs and in development of
effective strategies to promote medication adherence. These strategies should include, if available, the use of
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adherence support mechanisms such as modified directly observed therapy (mDOT), which has shown
promise in this population. 12

Antiretroviral Agents and Opioid Substitution Therapy
Compared with noninjection drug users receiving ART, injection drug users (IDUs) receiving ART are more
likely to experience an increased frequency of side effects and toxicities of ART. Although not systematically
studied, this is likely because underlying hepatic, renal, neurologic, psychiatric, gastrointestinal (GI), and
hematologic disorders are highly prevalent among IDUs. These comorbid conditions should be considered
when selecting antiretroviral (ARV) agents in this population. Opioid substitution therapies such as
methadone and buprenorphine/naloxone and extended-release naltrexone are commonly used for
management of opioid dependence in HIV-infected patients.

Methadone and Antiretroviral Therapy. Methadone, an orally administered, long-acting opioid agonist, is
the most common pharmacologic treatment for opioid addiction. Its use is associated with decreased heroin
use, decreased needle sharing, and improved quality of life. Because of its opioid-induced effects on gastric
emptying and the metabolism of cytochrome P (CYP) 450 isoenzymes 2B6, 3A4, and 2D6, pharmacologic
effects and interactions with ARV agents may commonly occur. These may diminish the effectiveness of
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either or both therapies by causing opioid withdrawal or overdose, increased methadone toxicity, and/or
decreased ARV efficacy. Efavirenz (EFV), nevirapine (NVP), and lopinavir/ritonavir (LPV/r) have been
associated with significant decreases in methadone levels. Patients and substance abuse treatment facilities
should be informed of the likelihood of this interaction. The clinical effect is usually seen after 7 days of
coadministration and may be managed by increasing the methadone dosage, usually in 5-mg to 10-mg
increments daily until the desired effect is achieved.
Buprenorphine and Antiretroviral Therapy. Buprenorphine, a partial μ-opioid agonist, is administrated
sublingually and is often coformulated with naloxone. It is increasingly used for opioid dependence
treatment. Compared with methadone, buprenorphine has a lower risk of respiratory depression and
overdose. This allows physicians in primary care to prescribe buprenorphine for the treatment of opioid
dependency. The flexibility of the primary care setting can be of significant value to opioid-addicted HIV-
infected patients who require ART because it enables one physician or program to provide both medical and
substance abuse services. Limited information is currently available about interactions between
buprenorphine and ARV agents. 13-14 Findings from available studies show that the drug interaction profile of
buprenorphine is more favorable than that of methadone.

Naltrexone and Antiretroviral Therapy. A once-monthly extended-release intramuscular formulation of
naltrexone was recently approved for prevention of relapse in patients who have undergone an opioid
detoxification program. Naltrexone is also indicated for treatment of alcohol dependency. Naltrexone is not
metabolized via the CYP450 enzyme system and is not expected to interact with protease inhibitors (PIs) or
non-nucleoside reverse transcriptase inhibitors (NNRTIs). 15

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents I-12

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