ISSN 1472-4863. Published by i-Base.
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Injection drug use represents the second most common route of transmission of HIV in the United States. Although treatment of HIV disease in this population can be successful, injection drug users (IDUs) with HIV disease present special treatment challenges. These include the existence of an array of complicating comorbid conditions, limited access to HIV care, inadequate adherence to therapy, medication side effects and toxicities, need for substance abuse treatment, and the presence of treatment-complicating drug interactions [311-313].
Underlying health problems among this population result in increased morbidity and mortality, either independent of or accentuated by HIV disease. Many of these problems are the consequence of prior poverty-related infectious disease exposures and the added effects of non-sterile needle and syringe use.
These include tuberculosis, skin and soft tissue infections, recurrent bacterial pneumonia, endocarditis, hepatitis B and C, and neurologic and renal disease. Furthermore, the high prevalence of underlying mental illness in this population, antedating and/or exacerbated by substance use, results in both morbidity and difficulties in provision of clinical care and treatment [311-313]. Successful HIV therapy for injection drug users often rests upon acquiring familiarity with and providing care for these comorbid conditions.
IDUs often have decreased access to HIV care and are less likely to receive antiretroviral therapy than other populations [314, 315]. Factors associated with lack of use of antiretroviral therapy among drug users have included active drug use, younger age, female gender, suboptimal health care, not being in a drug treatment program, recent incarceration, and lack of health care provider expertise [314, 315]. The chaotic lifestyle ofmany drug users, the powerful pull of addictive substances and a series of beliefs about the dangers of antiretroviral therapy among this population impact on and blunt the benefit of antiretroviral therapy and contribute to decreased adherence to antiretroviral therapy [316]. The chronic and relapsing nature of substance abuse and lack of appreciation of substance abuse as a biologic and medical disease, compounded by the high rate of coexisting mental illness, further complicates the relationship between health care workers and IDUs.
Efficacy of HIV treatment in IDUs
Although underrepresented in clinical trials of HIV therapies, available data indicate that, when not actively using drugs, efficacy of antiretroviral therapies among IDUs is similar to other populations.
Further, therapeutic failure in this population is generally the degree to which drug use results in disruption of organized daily activities, rather than drug use per se. Whereas many drug users can control their drug use sufficiently and over sustained periods of time to engage in care successfully, treatment of substance abuse is often a prerequisite for successful antiretroviral therapy. Close collaboration with substance abuse treatment programs, and proper support and attention to the special needs of this population, is often a critical component of successful treatment for HIV disease. Essential to this end as well are flexible, community-based HIV care sites characterized by familiarity with, and non-judgmental expertise in, managing the wide array of needs of substance abusers, and the development and use of effective strategies for promoting medication adherence [312, 313]. Foremost among these is the provision of substance abuse treatment. In addition, other support mechanisms for adherence are of value, and the use of drug treatment and community-based outreach sites for modified directly observed therapy has shown promise in this population [317].
IDU/HIV drug toxicities and interactions
IDUs are more likely to experience an increased frequency of side effects and toxicities of antiretroviral therapies. Although not systematically studied, this is likely because of the high prevalence of underlying hepatic, renal, neurologic, psychiatric, gastrointestinal, and hematologic disease among IDUs. The selection of initial and continuing antiretroviral agents in this population should be made based upon the presence of these conditions and risks.
Methadone and antiretroviral therapy
Methadone, an orally administered long-acting opiate agonist, is the most common pharmacologic treatment for opiate addiction. Its use is associated with decreased heroin use, improved quality of life, and decreased needle sharing. Methadone exists in two racemic forms, R (active) and S (inactive). As a consequence of its opiate-induced effects on gastric emptying and metabolism by cytochrome P450 (CYP) isoenzymes 3A4 and 2D6, pharmacologic effects and interactions with antiretrovirals may commonly occur [318]. These may diminish the effectiveness of either or both therapies by causing opiate withdrawal, opiate overdose, or increased toxicity or decreased efficacy of antiretrovirals.
• Methadone and NRTIs. Most of the currently available antiretrovirals have been examined in terms of potential pharmacokinetic interactions of significance with methadone. (See Table 21.)
Among the NRTIs, none appear to have a clinically significant effect on methadone metabolism. Conversely, important effects of methadone on NRTIs have been well documented. Methadone is known to increase the area under the curve of zidovudine by 40% [318], with a possible increase in zidovudine-related side effects. Methadone decreases levels of stavudine and the buffered tablet didanosine formulation (no longer available) by 18% and 63%, respectively [319]. This marked reduction in didanosine levels is not observed with the EC formulation. Recent data indicate lack of significant interaction between abacavir and tenofovir and methadone.
• Methadone and NNRTIs. Pharmacokinetic interactions between NNRTIs and methadone are well known and clinically problematic [320]. Both efavirenz and nevirapine, potent inducers of CYP isoenzymes, have been associated with significant decreases in methadone levels. Methadone levels are decreased by 43% and 46% in those receiving efavirenz and nevirapine, respectively, with corresponding clinical opiate withdrawal. It is necessary to inform patients and substance abuse treatment facilities of the likelihood of occurrence of this interaction if either drug is prescribed to those receiving methadone. The clinical effect is usually seen after 7 days of coadministration and is treated with increase in methadone dosage, usually at 5-10mg daily until the patient is comfortable.
Delavirdine, an inhibitor of CYP isoenzymes, increases methadone levels moderately and without clinical significance.
• Methadone and PIs. Limited information indicates that PI levels are generally not affected by methadone, except for amprenavir, which appears to be reduced by 30%. However, many PIs have significant effects on methadone metabolism.
Saquinavir does not affect free, unbound methadone levels. However, amprenavir, nelfinavir, and lopinavir administration each results in a significant decrease in methadone levels [321, 322]. Whereas fosamprenavir may result in mild opiate withdrawal, decrease in methadone concentration from nelfinavir was not associated with opiate withdrawal. This is likely because of lack of effect on free, rather than total, methadone levels.
Lopinavir/ritonavir combination has been associated with significant reductions in methadone levels and opiate withdrawal symptoms. This is because of the lopinavir, not ritonavir, component [323]. Another study indicates a lack of pharmacokinetic interaction among atazanavir and methadone [324].
Buprenorphine
Buprenorphine, a partial μ-opiate agonist, is increasingly being used for opiate abuse treatment. Its decreased risk of respiratory depression and overdose enables use in physician’s offices for the treatment of opioid dependence. This flexible treatment setting could be of significant value to drug-abusing opiateaddicted HIV-infected patients requiring antiretroviral therapy, as it would enable one physician or program to provide needed medical and substance abuse services.
Only limited information is currently available about interactions between buprenorphine and antiretroviral agents. In contrast to methadone, buprenorphine does not appear to raise zidovudine levels. Pilot data indicate that buprenorphine levels do not appear to be reduced and opiate withdrawal does not occur during coadministration with efavirenz.
Summary
Provision of successful antiretroviral therapy for injection drug users is possible. It is enhanced by supportive clinical care sites and provision of drug treatment, awareness of interactions with methadone, and the increased risk of side effects and toxicities and the need for simple regimens to enhance medication adherence. These are important considerations in selection of regimens and provision of appropriate patient monitoring in this population. Preference should be given to antiretroviral agents with lower risk for hepatic and neuropsychiatric side effects, simple dosing schedules, and lack of interaction with methadone.
Extract from US Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, January 2008.
References
311. Tindall B, Cooper DA. Primary HIV infection: host responses and intervention strategies. AIDS, 1991. 5(1):1-14.
312. Niu MT, Stein DS, Schnittman SM. Primary human immunodeficiency virus type 1 infection: review of pathogenesis and early treatment intervention in humans and animal retrovirus infections. J Infect Dis, 1993. 168(6):1490-501.
313. Kinloch-De Loes S et al. Symptomatic primary infection due to human immunodeficiency virus type 1: Review of 31 cases. Clin Infect Dis, 1993. 17(1):59-65.
314. Schacker T et al. Clinical and epidemiologic features of primary HIV infection. Ann Intern Med, 1996. 125(4):257-64.
315. Daar ES et al. Diagnosis of primary HIV-1 infection. Los Angeles County Primary HIV Infection Recruitment Network. Ann Intern Med, 2001. 134(1):25-9.
316. Hecht FM et al. Use of laboratory tests and clinical symptoms for identification of primary HIV infection. AIDS, 2002. 16(8):1119-29.
318. Hoen B et al. Highly active antiretroviral treatment initiated early in the course of symptomatic primary HIV-1 infection: Results of the ANRS 053 trial. J Infect Dis, 1999. 180(4):1342-6.
319. Lafeuillade A et al. Effects of a combination of zidovudine, didanosine, and lamivudine on primary human immunodeficiency virus type 1 infection. J Infect Dis, 1997, 175(5).1051-5.
320. Lillo FB et al. Viral load and burden modification following early antiretroviral therapy of primary HIV-1 infection. AIDS, 1999. 13(7):791-6.
321. Malhotra U et al. Effect of combination antiretroviral therapy on T-cell immunity in acute human immunodeficiency virus type 1 infection. J Infect Dis, 2000. 181(1):121-31.
322. Smith DE et al. Is antiretroviral treatment of primary HIV infection clinically justified on the basis of current evidence? AIDS, 2004. 18(5):709-18.
323. Mehandru S et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med, 2004. 200(6):761-70.
324. Guadalupe M et al. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol, 2003. 77(21):11708-17.
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