Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methadone maintenance patients infected with human immunodeficiency virus (HIV) currently receiving antiretroviral therapy had HIV RNA testing and were surveyed regarding their adherence to their treatment regimens. Adherence was measured using self-report on four questions relating to medication use in the last day and last month and whether the patient took "drug holidays." Of the patients (N = 42), 52% were receiving two-drug antiretroviral therapy and 48% were receiving triple therapy that included a protease inhibitor. Persons on triple therapy reported higher rates of adherence on all measures and were more likely to have undetectable HIV RNA levels than persons on dual therapy (60% vs. 50%). Ongoing illicit drug injection was the only factor significantly associated (p < .05) with multiple measure nonadherence; however, it was not associated with undetectable HIV RNA level. Levels of nonadherence were comparable to estimates from other chronic diseases, but this finding has important implications for patients receiving highly active antiretroviral therapy.
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PMID:Adherence to antiretroviral therapy among HIV-infected methadone patients: effect of ongoing illicit drug use. 1085 56

Methadone, a regimen for the treatment of opioid dependency, was found to induce the expression of CCR5, a co-receptor for human immunodeficiency virus (HIV)/simian form of HIV (SIV) entry, on human CEM x174 lymphocytes. Both CCR5 mRNA and protein were elevated in methadone-treated cells. A concomitant increase of mu opioid receptors was also observed. Upon methadone exposure, SIVmac239-infected CEM x174 cells released greater amounts of virus particles as revealed by both the number of syncytia formation and reverse transcriptase activities. Similar methadone effect was not observed on CEM x174 cells infected with other simian retroviruses that do not depend on CCR5 for cellular entry. These studies raise concerns considering methadone as an innocuous morphine substitute.
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PMID:Methadone induces CCR5 and promotes AIDS virus infection. 1202 39

Adherence is a primary determinant of treatment effectiveness; thus, poor adherence attenuates optimum clinical benefit. A bibliographic review was conducted to evaluate the impact of adherence to heroin dependence treatment on human immunodeficiency virus (HIV) transmission and to identify interventions proven to be effective in improving adherence. The best adherence rates were achieved by methadone and diacetylmorphine, both of which are comparable in promoting significant reduction in heroin use. Methadone adjusted-dose studies with daily doses ranging from 100 to 200 mg and multiple support interventions achieved the highest adherence rates. Studies of methadone maintenance that examined changes in HIV prevalence of infection have found that higher treatment adherence is correlated with a reduction in HIV transmission. These data suggest that patients who adhere continuously to methadone treatment are less likely to continue injecting illicit drugs and sharing contaminated injection equipment than are those who interrupt treatment, thus preventing the spread of HIV via drug injection.
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PMID:Adherence to heroin dependence therapies and human immunodeficiency virus/acquired immunodeficiency syndrome infection rates among drug abusers. 1464 65

The objective of this prospective, observational clinical study was to evaluate the safety and efficacy of once-daily and twice-daily directly observed therapy (DOT) in human immunodeficiency virus (HIV)-infected patients undergoing methadone treatment. Methadone and highly active antiretroviral therapy (HAART) were dispensed daily as DOT, with patients in the twice-daily HAART group self-administering the second dose. Clinical and laboratory end points were monitored, along with the impact of ongoing cocaine use. We studied 54 patients coinfected with HIV and hepatitis C virus. At baseline, the median virus load was 111,000 copies/mL, and the median CD4+ cell count was 165 cells/mm3. After a median of 24 months, 17 of 29 patients in the once-daily HAART group and 18 of 25 in the twice-daily HAART group had virus loads of <400 copies/mL, regardless of ongoing cocaine use. Thirty-two patients required methadone dose adjustment, which was managed without modification of HAART. Treatment-limiting hepatic toxicity was rare. A DOT program of coadministered methadone and HAART can be implemented with good results, even for patients who continue to use cocaine.
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PMID:Directly observed therapy for the management of HIV-infected patients in a methadone program. 1515 30

Methadone-maintenance treatment clinics are strategically appealing sites for provision of directly administered antiretroviral therapy (DAART) to human immunodeficiency virus type 1 (HIV-1)-infected injection drug users (IDUs). We initiated an ongoing DAART protocol at a university-associated methadone clinic in April 2001, which continues to enroll participants. Participants ingested antiretroviral medications under direct supervision on days they attended the clinic; evening doses and doses on "methadone take-home days" were self-administered. Comparison IDUs receiving either standard care or treatment-adherence support were randomly selected from the population of the HIV-1 clinic where DAART participants received their primary care for HIV-1 infection, with frequency matching by sex, prior antiretroviral exposure, and receipt of methadone therapy. In an intention-to-treat analysis, 79% of DAART participants achieved HIV-1 RNA levels of <400 copies/mL by month 6 of therapy, compared with 54% in the standard care group (P=.035) and 48% in the adherence support group (P=.008). The preliminary results of this study both suggest that DAART can be feasible and acceptable to patients in a methadone clinic setting and provide impetus for further study of this treatment strategy in randomized controlled trials.
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PMID:Directly administered antiretroviral therapy in an urban methadone maintenance clinic: a nonrandomized comparative study. 1515 31

Methadone is metabolized by various isoforms of the cytochrome P450 family, which can be induced by many drugs, including nevirapine. The objective of the present study was to determine the effects of coadministration of nevirapine and methadone on the dose-adjusted areas under the concentration-time curves (AUCs) of racemic and (R)-methadone. Twenty-five human immunodeficiency virus-infected subjects taking stable single daily doses of racemic methadone or (R)-methadone were included in this prospective, single-crossover trial. At the baseline, nevirapine was either started as part of a new regimen containing two nucleoside reverse transcriptase inhibitors (NRTIs) or added to an ongoing NRTI regimen. Patients could increase their methadone doses if withdrawal symptoms developed. Twelve-hour pharmacokinetic profiles were obtained before and 28 days after the start of nevirapine treatment. The total concentrations of methadone and its inactive metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), in serum were determined by liquid chromatography-tandem mass spectrometry. Among the 20 evaluable patients, coadministration of nevirapine significantly decreased the mean dose-adjusted AUC of methadone by 41%. AUC reductions were similar for patients taking racemic methadone (37%; n = 11) and (R)-methadone (44%; n = 9). AUC changes ranged from mild increases in three patients to decreases of up to 70%. Fourteen of 20 patients required additional methadone due to withdrawal symptoms. However, the median dose increase was only 15%, which was less than that which would have been expected from the pharmacokinetic data. The AUC of EDDP increased significantly, by 35%. Methadone dose adjustments are justified when methadone is coadministered with nevirapine. Due to extensive variability, the adjustments must be tailored to the individual patient's needs.
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PMID:Nevirapine significantly reduces the levels of racemic methadone and (R)-methadone in human immunodeficiency virus-infected patients. 1550 34

The occurrence of human immunodeficiency virus (HIV) disease and hepatitis C is common in injection drug users, most of whom are opioid dependent. Methadone pharmacotherapy has been the most widely used treatment for opioid addiction in this population. Methadone has significant, adverse drug-drug interactions with many antiretroviral therapeutic agents that can contribute to nonadherence and poor clinical outcomes in this high-risk population. The present article summarizes current knowledge about interactions between methadone and antiretroviral medications. Buprenorphine is the newest agent available for the treatment of opioid dependence and may have fewer adverse interactions with antiretroviral agents. Buprenorphine has a significant pharmacokinetic interaction with efavirenz but no pharmacodynamic interaction; therefore, simultaneous administration of these drugs is not associated with opioid withdrawal, as has been observed with methadone. This promising finding may simplify the treatment of opioid-dependent patients with HIV disease and should also improve clinical outcomes for persons coinfected with HIV and hepatitis C virus.
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PMID:Treatment of opioid dependence and coinfection with HIV and hepatitis C virus in opioid-dependent patients: the importance of drug interactions between opioids and antiretroviral agents. 1626 22

Approximately 7 million people in the United States are in jail, in prison, or on probation or parole, many as a result of drug-related offenses. Individuals who use opiates account for a significant minority of this population. Methadone maintenance treatment (MMT) of opiate addiction is highly effective in reducing drug use, drug-related criminal activity, and risk of human immunodeficiency virus transmission. Recently released inmates are at particularly high risk for overdose and disease transmission. Project MOD (Managing Opioid Dependency) provides services to eliminate logistical and financial barriers to MMT entry immediately on release from incarceration. Such programs provide a promising opportunity to facilitate reentry into the community, combat disease transmission, and reduce recidivism.
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PMID:Opiate replacement therapy at time of release from incarceration: Project MOD, a pilot program. 1731 18

Methadone maintenance therapy (MMT) has been increasingly implemented as the treatment of choice for opiate-addicted individuals and has been associated with reduced harm related to opiate addiction. Barriers to MMT uptake still exist, however, and many opiate-addicted individuals do not access this form of treatment. We examined barriers to and facilitators of MMT access among opiate users enrolled in a prospective cohort study of injection drug users (IDUs). We identified individuals who had initiated MMT during follow-up interviews and used generalized estimating equations to identify sociodemographic and drug-related variables associated with MMT access. Of the 1,587 participants recruited into the Vancouver Injection Drug User Study, 1,463 individuals were eligible for the present analysis. Factors negatively associated with MMT use included male gender (odds ratio [OR] = 0.41; 95 percent confidence interval [CI], 0.32 to 0.52), Aboriginal ethnicity (OR = 0.37; 95 percent CI, 0.29 to 0.48), recent incarceration (OR = 0.82; 95 percent CI, 0.72 to 0.93), Downtown Eastside residence (OR = 0.86; 95 percent CI, 0.75 to 0.97), sex-trade involvement (OR = 0.80; 95 percent CI, 0.67 to 0.95), syringe lending (OR = 0.76; 95 percent CI, 0.66 to 0.89), denied addiction treatment (OR = 0.81; 95 percent CI, 0.68 to 0.96), heroin injection (OR = 0.51; 95 percent CI, 0.44 to 0.59), nonfatal overdose (OR = 0.59; 95 percent CI, 0.51 to 0.68), and infecting in public (OR = 0.75; 95 percent CI, 0.63 to 0.89). Older age (OR = 1.03; 95 percent CI, 1.01 to 1.04), human immunodeficiency virus (HJV) positivity (OR = 1.89; 95 percent CI, 1.52 to 2.2.3), and crack cocaine smoking (OR = 1.41; 95 percent CI, 1.22 to 1.62) were positively associated with MMT use. Our study identified a large number of barriers to and facilitators of MMT use among IDUs. While some populations such as HIV-positive individuals are frequently accessing MMT, identified barriers among men and Aboriginal lDUs are of great concern. These findings indicate the need for additional interventions aimed at maximizing coverage of MMT and other treatments for opiate-addicted individuals.
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PMID:Barriers and facilitators to methadone maintenance therapy use among illicit opiate injection drug users in Vancouver. 1731 16

Methadone treatment reduces human immunodeficiency virus (HIV) risk, but the effects of primary-care-based buprenorphine/naloxone on HIV risk are unknown. The purpose of this study was to determine whether primary-care-based buprenorphine/naloxone was associated with decreased HIV risk behavior. We conducted a longitudinal analysis of 166 opioid-dependent persons (129 men and 37 women) receiving buprenorphine/naloxone treatment in a primary care clinic. We compared baseline and 12- and 24-week overall, drug-related, and sex-related HIV risk behaviors using the AIDS/HIV Risk Inventory (ARI). Buprenorphine/naloxone treatment was associated with significant reductions in overall and drug-related ARI scores from baseline to 12 and 24 weeks. Intravenous drug use in the past 3 months was endorsed by 37%, 12%, and 7% of patients at baseline and at 12 and 24 weeks, respectively (p< .001). Sex while you or your partner were "high" was endorsed by 64%, 13%, and 15% of patients at baseline and at 12 and 24 weeks, respectively (p< .001). Inconsistent condom use during sex with a steady partner was high at baseline and did not change over time. We conclude that primary-care-based buprenorphine/naloxone treatment is associated with decreased drug-related HIV risk, but additional efforts may be needed to address sex-related HIV risk when present.
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PMID:Buprenorphine/naloxone treatment in primary care is associated with decreased human immunodeficiency virus risk behaviors. 1793 86


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