Figure 1. Mean change in CD4+ cell count from baseline (* P < .01; ** P < .001 compared with baseline).

Figure 2. Proportion of patients with HIV RNA levels below the limit of detection (< 50 copies/mL)

[AIDS Read 12(7):305-316, 2002. © 2002 Cliggott Publishing, Division of SCP Communications ]

Table 1. Baseline Patient Characteristics in San Francisco AIDS Clinic Study

Table 2. Significant Interactions Between Methadone and Other Medications

CYP-450, cytochrome P-450; PK, pharmacokinetic.
*No alteration in the pharmacokinetics of methadone, but an interaction with the intracellular pharmacokinetics of the nucleoside analogue.

1. Clinton DD, Valhi D, Cohn S, et al. Self-reported antiretroviral therapy in injection drug users. JAMA. 1998;280:544-546.
2. Deeks SG, Loftus R, Beatty G, et al. Incidence and predictors of virological failure of indinavir or ritonavir in an urban AIDS clinic. In: Program and abstracts of the 37th International Conference on Antimicrobial Agents and Chemotherapy; September 8-October 1, 1997; Toronto. Abstract 88.
3. Iseman MD, Cohen DL, Sbarbaro JA. Directly observed treatment of tuberculosis: we can't afford not to do it. N Engl J Med. 1993;328:576-578.
4. Bayer R, Wilkinson D. Directly observed therapy for tuberculosis: history of an idea. Lancet. 1995;345: 1545-1548.
5. Dye C, Garnett GP, Sleeman K, Williams BG. Prospects for worldwide tuberculosis control under the WHO DOTS strategy: directly observed short-course therapy. Lancet. 1998;352:1886-1891.
6. Joint Tuberculosis Committee of the British Thoracic Society. Chemotherapy and management of tuberculosis in the UK: recommendations, 1998. Thorax. 1998;53:536-548.
7. Centers for Disease Control and Prevention. Initial therapy for tuberculosis in the era of multidrug resistance: recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR. 1993;42(RR-7):1-8.
8. Fischl M, Rodriguez A, Scerpella E, et al. Impact of directly observed therapy on outcomes in HIV clinical trials. In: Program and abstracts of the 7th Conference on Retroviruses and Opportunistic Infections; January 30-February 2, 2000; San Francisco. Abstract 71.
9. Haberl FL. Combination didanosine, lamivudine, and nevirapine for injection drug users with HIV infection. In: Program and abstracts of the World AIDS Conference; June 28-July 3, 1998; Geneva. Abstract 156.
10. Ward J, Hall W, Mattick RP. Role of maintenance treatment in opioid dependence. Lancet. 1999;353:221-225.
11. Stenzel MS, McKenzie M, Mitty JA, Flanagan T. Enhancing adherence to HAART: modified directly observed therapy. AIDS Reader. 2001;11:317-328.
12. Ahluwalia G, Cooney DA, Hartman NR, et al. Anomalous accumulation and decay of 29,39-dideoxyadenosine-59-triphosphate in human T-cell cultures exposed to the anti-HIV drug 29,39-dideoxyinosine. Drug Metab Dispos. 1993;21:369-376.
13. Hoetelmans RM, van Fleeswijk RP, Profijt M, et al. Comparison of the plasma pharmacokinetics and renal clearance of didanosine during once and twice daily dosing in HIV infected individuals. AIDS. 1998,12:F211-F216.
14. Cammack N, Rouse P, Marr CL, et al. Cellular metabolism of (2) enantiomeric 29-deoxy-39-thiacytidine. Biochem Pharmacol. 1992;43:2059-2064.
15. Murphy RL, Montaner J. Nevirapine: a review of its development, pharmacological profile and potential for clinical use. Exp Opin Invest Drugs. 1996;5:1183-1199.
16. Havlir D, Cheeseman SH, McLaughlin M, et al. High dose nevirapine: safety, pharmacokinetics, and antiviral effect in patients with HIV infection. J Infect Dis. 1995;171:537-545.
17. van Heeswijk RP, Veldkamp AI, Mulder JW, et al. The steady-state pharmacokinetics of nevirapine during once daily and twice daily dosing in HIV-1-infected individuals. AIDS. 2000;14:F77-F82.
18. Adkins JC, Noble S. Efavirenz. Drugs. 1998;56:1055-1064.
19. Clarke SM, Mulcahy FM, Tjia J, et al. Pharmacokinetic interactions of nevirapine and methadone and guidelines for use of nevirapine to treat injection drug users. Clin Infect Dis. 2001;33:1595-1597.
20. 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.
21. Tong TG, Pond SM, Kreek MJ. Phenytoin-induced methadone withdrawal. Ann Intern Med. 1981;94:349-351.
22. Nation RL, Evans AM, Milne RW. Pharmacokinetic drug interactions with phenytoin. Clin Pharmacokinet. 1990;18:37-60.
23. Knoll B, Haefeli WE, Ladewig D, Stohler R. Early recurrence of withdrawal symptoms under phenytoin and chronic alcohol use. Pharmacopsychiatry. 1997;30:72-73.
24. Saxon AJ, Whittacker S, Hawker S. Valproic acid, unlike other anticonvulsants, has no effect on methadone metabolism: two cases. J Clin Psychiatry. 1989;50:228-229.
25. Liu SJ, Wang RI. Case report of barbiturate-induced enhancement of methadone metabolism and withdrawal syndrome. Am J Psychiatry. 1984;10:1287-1288.
26. Bertschy G, Baumann P, Eap CB, Baettig D. Probable metabolic interaction between methadone and fluvoxamine in addict patients. Ther Drug Monit. 1994;16:42-45.
27. DeMaria PA Jr, Serota RD. A therapeutic use for the methadone fluvoxamine drug interaction. J Addict Dis. 1999;18(4):5-12.
28. Petrais I, Carroll KM, Nich C, et al. Fluoxetine treatment of depressive disorders in methadone-maintained opioid addicts. Drug Alcohol Depend. 1998;50:221-226.
29. Bertschy G, Eap CB, Powell K, Baumann P. Fluoxetine addition to methadone in addicts: pharmacokinetic aspects. Ther Drug Monit. 1996;18:570-572.
30. Sorkin EM, Ogawa GS. Cimetidine potentiation of narcotic action. Drug Intell Clin Pharm. 1983;17:60-61.
31. Dawson GW, Vestal RE. Cimetidine inhibits the in-vitro N-demethylation of methadone. Res Commun Chem Pathol Pharmacol. 1984;46:301-304.
32. Cobb MN, Desai J, Brown LS, et al. The effects of fluconazole on the clinical pharmacokinetics of methadone. Clin Pharmacol Ther. 1998;63:655-662.
33. Kreek MJ, Garfield JW, Gutjahr CL, Giusti LM. Rifampicin-induced methadone withdrawal. N Engl J Med. 1976;294:1104-1106.
34. Baciewicz AM, Self TH. Rifampin drug interactions. Arch Intern Med. 1984;144:1667-1671.
35. Raistrick D, Hay A, Wolff K. Methadone maintenance and tuberculosis treatment. BMJ. 1996;313:925-926.
36. Holmes VF. Rifampicin-induced methadone in AIDS. J Clin Psychopharmacol. 1990;10:443-444.
37. Otero MJ, Fuertes A, Sanchez R, Luna G. Nevirapine induced withdrawal symptoms in HIV patients on methadone maintenance programme: an alert. AIDS. 1999;13:1004-1005.
38. Altice FL, Friedland GH, Cooney EL. Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone. AIDS. 1999;13:957-962.
39. Staszewski S, Haberl A, Gute P, et al. Nevirapine/didanosine/lamivudine once daily in HIV-1 infected intravenous drug users. Antivir Ther. 1998;3(suppl 4):55-56.
40. Pinzani V, Faucherre V, Peyriere H, Blayac JP. Methadone withdrawal symptoms with nevirapine and efavirenz. Ann Pharmacother. 2000;34:405-407.
41. Iribarne C, Berthou F, Carlhant D, et al. Inhibition of methadone and buprenorphine N-dealkylations by three HIV-1 protease inhibitors. Drug Metab Dispos. 1998;26:257-260.
42. Hsu A, Granneman GR, Carothers L, et al. Ritonavir does not increase methadone exposure in healthy volunteers. In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago. Abstract 342.
43. Beauverie P, Taburet AM, Dessalles MC, et al. Therapeutic drug monitoring of methadone in HIV infected patients receiving protease inhibitors. AIDS. 1998;12:2510-2511.
44. Hsyu PH, Lillibridge JH, Maroldo L, et al. Pharmacokinetic (PK) and pharmacodynamic (PD) interactions between nelfinavir and methadone. In: Program and abstracts of the 7th Conference on Retroviruses and Opportunistic Infections; January 30-February 2, 2000; San Francisco. Abstract 87.
45. Clarke S, Mulcahy F, Bergin C, et al. Absence of opioid withdrawal symptoms in patients receiving methadone and the protease inhibitor lopinavir-ritonavir. Clin Infect Dis. 2002;34:1143-1145.
46. Schwartz EL, Brechbuhl AB, Kahl P, et al. Pharmacokinetic interactions of ZDV and methadone in intravenous drug-using patients with HIV infection. J Acquir Immune Defic Syndr. 1992;5:619-626.
47. McCance-Katz E, Rainey PM, Jatlow P, Friedland G. Methadone effects on zidovudine disposition. (ACTG 262). J Acquir Immune Defic Syndr. 1998;18:435-443.
48. Rainey PM, Friedland G, McCance-Katz EF, et al. Interaction of methadone with didanosine and stavudine. J Acquir Immune Defic Syndr. 2000;24:241-248.
49. Barry M, Feely J. Enzyme induction and inhibition. Pharmacol Ther. 1990;48:71-94.
50. John M, Flexman J, French MA. Hepatitis C virus-associated hepatitis following treatment of HIV-infected patients with HIV protease inhibitors: an immune restoration disease? AIDS. 1998;12:2289-2293.