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Director's Report to the National Advisory Council on Drug Abuse - May, 2010

Research Findings - Research on Medical Consequences of Drug Abuse and Co-Occurring Infections (HIV/AIDS, HCV)

No Excess Risk of Follicular Lymphoma in Kidney Transplant and HIV-Related Immune Deficiency

Subtype-specific incidence patterns in populations at high-risk of lymphoma offer insight into lymphomagenesis. The incidence profiles for the two most common non-Hodgkin lymphoma subtypes were compared for two immune-deficient populations, adults receiving a kidney transplant 1982-2003 (n=7,730) or diagnosed with HIV infection 1982-2004 (n=17,175). National population-based registries were linked and standardized incidence ratios (SIRs) were computed for each cohort and lymphoma subtype. Risk of diffuse large B-cell lymphoma was significantly increased after transplantation (SIR 17.83, 95%CI 13.61-22.95) and after HIV infection (SIR 58.81, 95%CI 52.59-65.56). Rates of follicular lymphoma were neither significantly increased nor decreased in transplant recipients (SIR 0.82, 95%CI 0.10-2.96) and in people with HIV (SIR 1.25, 95%CI 0.41-2.91). The findings argue against an infectious or other immune-deficiency- related aetiology for follicular lymphoma, and clearly differentiate it from diffuse large B-cell lymphoma. Vajdic CM, van Leeuwen MT, Turner JJ, McDonald AM, Webster AC, McDonald SP, Chapman JR, Kaldor JM, Grulich AE. Int J Cancer. No excess risk of follicular lymphoma in kidney transplant and HIV-related immune deficiency. Int J Cancer. 2010 Feb 22. [Epub ahead of print].

Effect of Reduced Immunosuppression After Kidney Transplant Failure on Risk of Cancer: Population Based Retrospective Cohort Study

The objective of this study was to compare cancer incidence in kidney transplant recipients during periods of transplant function (and immuno-suppression) and after transplant failure (when immunosuppression is ceased or reduced). This study used a population based retrospective cohort of 8173 Australian kidney transplant recipients registered on the Australia and New Zealand Dialysis and Transplant Registry who first received a transplant during 1982-2003. Incident cancers were ascertained using linkage with national cancer registry records. The main outcome measures were cancer-specific standardized incidence ratios for periods of transplant function and for dialysis after transplant failure. Incidence was compared between periods using multivariate incidence rate ratios adjusted for current age, sex, and duration of transplantation. All cases of Kaposi's sarcoma occurred during transplant function. Standardized incidence ratios were significantly elevated during transplant function, but not during dialysis after transplant failure, for non-Hodgkin's lymphoma, lip cancer, and melanoma. For each of these cancers, incidence was significantly lower during dialysis after transplant failure in multivariate analysis (incidence rate ratios 0.20 (95% CI 0.06 to 0.65) for non-Hodgkin's Lymphoma, 0.04 (0.01 to 0.31) for lip cancer, and 0.16 (0.04 to 0.64) for melanoma). In contrast, standardized incidence ratios during dialysis after transplant failure remained significantly elevated for leukaemia and lung cancer, and cancers related to end stage kidney disease (kidney, urinary tract, and thyroid cancers), with thyroid cancer incidence significantly higher during dialysis after transplant failure (incidence rate ratio 6.77 (2.64 to 17.39)). There was no significant difference in incidence by transplant function for other cancers. The effect of immunosuppression on cancer risk is rapidly reversible for some, but not all, cancer types. Risk reversal was mainly observed for cancers with a confirmed infectious cause. Risk of other cancers, especially those related to end stage kidney disease, remained significantly increased after reduction of immunosuppression. van Leeuwen MT, Webster AC, McCredie MR, Stewart JH, McDonald SP, Amin J, Kaldor JM, Chapman JR, Vajdic CM, Grulich AE. Effect of reduced immunosuppression after kidney transplant failure on risk of cancer: population based retrospective cohort study. BMJ. 2010 Feb 11; 340: c570.

Per-Contact Probability of HIV Transmission in Homosexual Men in Sydney in the Era of HAART

The objective of this study is to estimate per-contact probability of HIV transmission in homosexual men due to unprotected anal intercourse (UAI) in the era of HAART. Data were collected from a longitudinal cohort study of community-based HIV-negative homosexual men in Sydney, Australia. A total of 1427 participants were recruited from June 2001 to December 2004. They were followed up with 6-monthly detailed behavioral interviews and annual testing for HIV till June 2007. Data were used in a bootstrapping method, coupled with a statistical analysis that optimized a likelihood function for estimating the per-exposure risks of HIV transmission due to various forms of UAI. During the study, 53 HIV seroconversion cases were identified. The estimated per-contact probability of HIV transmission for receptive UAI was 1.43% [95% confidence interval (CI) 0.48-2.85] if ejaculation occurred inside the rectum, and it was 0.65% (95% CI 0.15-1.53) if withdrawal prior to ejaculation was involved. The estimated transmission rate for insertive UAI in participants who were circumcised was 0.11% (95% CI 0.02-0.24), and it was 0.62% (95% CI 0.07-1.68) in uncircumcised men. Thus, receptive UAI with ejaculation was found to be approximately twice as risky as receptive UAI with withdrawal or insertive UAI for uncircumcised men and over 10 times as risky as insertive UAI for circumcised men. Despite the fact that a high proportion of HIV-infected men are on antiretroviral treatment and have undetectable viral load, the per-contact probability of HIV transmission due to UAI is similar to estimates reported from developed country settings in the pre-HAART era. Jin F, Jansson J, Law M, Prestage GP, Zablotska I, Imrie JC, Kippax SC, Kaldor JM, Grulich AE, Wilson DP. Per-contact probability of HIV transmission in homosexual men in Sydney in the era of HAART. AIDS. 2010 Mar 27; 24(6): 907-913.

Protease Polymorphisms in HIV-1 Subtype CRF01_AE Represent Selection by Antiretroviral Therapy and Host Immune Pressure

Most of our knowledge about how antiretrovirals and host immune responses influence the HIV-1 protease gene is derived from studies of subtype B virus. The effect of protease resistance-associated mutations (PRAMs) and population-based HLA haplotype frequencies on polymorphisms found in CRF01_AE pro was investigated. CRF01_AE protease sequences retrieved from the LANL database were used and regional HLA frequencies from the dbMHC database were obtained. Polymorphisms and major PRAMs in the sequences were identified using the Stanford Resistance Database, and phylogenetic and selection analyses was performed using HyPhy. HLA binding affinities were estimated using the Immune Epitope Database and Analysis. Overall, 99% of CRF01_AE sequences had at least 1 polymorphism and 10% had at least 1 major PRAM. Three polymorphisms (L10 V, K20RMI and I62 V) were associated with the presence of a major PRAM (P < 0.05). Compared to the subtype B consensus, six additional polymorphisms (I13 V, E35D, M36I, R41K, H69K, L89M) were identified in the CRF01_AE consensus; all but L89M were located within epitopes recognized by HLA class I alleles. Of the predominant HLA haplotypes in the Asian regions of CRF01_AE origin, 80% were positively associated with the observed polymorphisms, and estimated HLA binding affinity was estimated to decrease 19-40 fold with the observed polymorphisms at positions 35, 36 and 41. Polymorphisms in CRF01_AE protease gene were common, and polymorphisms at residues 10, 20 and 62 most likely represent selection by use of protease inhibitors, whereas R41K and H69K were more likely attributable to recognition of epitopes by the HLA haplotypes of the host population. Manosuthi W, Butler DM, Pérez-Santiago J, Poon AF, Pillai SK, Mehta SR, Pacold ME, Richman DD, Pond SK, Smith DM. Protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure. AIDS. 2010 Jan 28; 24(3): 411-416.

Large-Scale Candidate Gene Analysis of Spontaneous Clearance of Hepatitis C Virus

Human genetic variation is a determinant of recovery from acute hepatitis C virus (HCV) infection; however, to date, single-nucleotide polymorphisms (SNPs) in only a limited number of genes have been studied with respect to HCV clearance. The authors determined whether SNPs in 112 selected immune response genes are important for HCV clearance, by genotyping 1536 SNPs in a cohort of 343 persons with natural HCV clearance and 547 persons with HCV persistence. PLINK (version 1.05) and Haploview (version 4.1) software packages were used to perform association, permutation, and haplotype analyses stratified by African American and European American race. Of the 1536 SNPs tested, 1426 (92.8%) were successfully genotyped. In African Americans, 18 SNPs located in 11 gene regions associated with HCV infection outcome (empirical P value, < .01) were identified. In European Americans, there were 20 SNPs located in 8 gene regions associated with HCV infection outcome. Four of the gene regions studied (TNFSF18, TANK, HAVCR1, and IL18BP) contained SNPs for which the empirical P value was <.01 in both of the race groups. In this large-scale analysis of 1426 genotyped SNPs in 112 candidate genes, the investigators identified 4 gene regions that are likely candidates for a role in HCV clearance or persistence in both African Americans and European Americans. Mosbruger TL, Duggal P, Goedert JJ, Kirk GD, Hoots WK, Tobler LH, Busch M, Peters MG, Rosen HR, Thomas DL, Thio CL. Large-Scale Candidate Gene Analysis of Spontaneous Clearance of Hepatitis C Virus. J Infect Dis. 2010 Mar 5. [Epub ahead of print].

Hepatic Steatosis Associated with Increased Central Body Fat By Dual-Energy X-Ray Absorptiometry and Uncontrolled HIV In HIV/Hepatitis C Co-Infected Persons

The objective was to evaluate the relationship between regional body composition and liver disease (fibrosis or steatosis) in HIV/HCV co-infected individuals. Whole body dual-energy X-ray absorptiometry (DXA) was performed in 173 HIV/HCV co-infected persons within 12 months of a liver biopsy. Significant fibrosis was defined as a METAVIR stage greater than 1. Steatosis was graded as: 0, none; 1, steatosis involving less than 5% of hepatocytes; 2, 5-29%; 3, 30-60%; 4 greater than 60%, and was defined as more than 0. Poisson regression with robust variance was used to estimate prevalence ratios of the outcome measures. The population was 62% male and 84% black with a median body mass index of 25.2 kg/m (interquartile range 22.5, 29.3 kg/m). No differences in regional body fat or fat distribution were observed in 42 patients with significant fibrosis compared to others with less fibrosis. However, the 77 individuals (45%) with steatosis had greater central fat than those without steatosis [prevalence ratio 1.04 per kg trunk fat; 95% confidence interval (CI) 1.04, 1.11], after adjusting for hepatic fibrosis (prevalence ratio 1.77; 95% CI 1.29, 2.42), uncontrolled HIV replication (viral load >400 copies/ml) (prevalence ratio 1.57; 95% CI 1.12, 2.22), age, sex, race and diabetes mellitus. In HIV/HCV co-infected individuals, measures of regional body fat or fat distribution were not associated with hepatic fibrosis. In contrast, increased central adiposity by DXA, as well as concomitant fibrosis and uncontrolled HIV, were associated with hepatic steatosis. The extent to which weight loss and effective antiretroviral therapy can reduce the risk of steatosis deserves further investigation. Brown TT, Mehta SH, Sutcliffe C, Higgins Y, Torbenson MS, Moore RD, Thomas DL, Sulkowski MS. Hepatic steatosis associated with increased central body fat by dual-energy X-ray absorptiometry and uncontrolled HIV in HIV/hepatitis C co-infected persons. AIDS. 2010 Mar 27; 24(6): 811-817.

Lack of Clinically Significant Drug Interactions Between Nevirapine and Buprenorphine

This study was conducted to determine whether drug interactions of clinical importance occur between buprenorphine, an opioid partial agonist medication used in treatment of opioid dependence, and the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine. Opioid-dependent, buprenorphine/naloxone-maintained, HIV-negative volunteers (n = 7) participated in 24-hour sessions to determine the pharmacokinetics of buprenorphine alone and of buprenorphine and nevirapine following administration of 200 mg nevirapine daily for 15 days. Opiate withdrawal symptoms, cognitive effects, and adverse events were determined prior to and following nevirapine administration. Modest decreases were observed for AUC for buprenorphine and its metabolites. There was a trend for more rapid clearance of both buprenorphine (p = .08) and buprenorphine-3-glucuronide (p = .08). While no single effect reached statistical significance, the joint probability that the consistent declines in all measures of exposure were due to chance was extremely low, indicating that nevirapine significantly reduces overall exposure to buprenorphine and buprenorphine metabolites. Clinically significant consequences of the interaction were not observed. Buprenorphine did not alter nevirapine pharmacokinetics. Dose adjustments of either buprenorphine or nevirapine are not likely to be necessary when these drugs are coadministered for the treatment of opiate dependence and HIV disease. McCance-Katz EF, Moody DE, Morse GD, Ma Q, Rainey PM. Lack of Clinically Significant Drug Interactions between Nevirapine and Buprenorphine. Am J Addict. 2010 Jan 1; 19(1): 30-37.

Interactions between Buprenorphine and Antiretrovirals: Nucleos(t)ide Reverse Transcriptase Inhibitors (NRTI) Didanosine, Lamivudine, and Tenofovir

To improve outcomes among injection drug users with HIV and/or chronic hepatitis B, it is important to identify drug interactions between antiretroviral and opiate therapies. The investigators report the results of a study designed to examine the interaction between buprenorphine and the nucleos(t)ide reverse transcriptase inhibitors (NRTI) didanosine (ddI), lamivudine (3TC), and tenofovir (TDF). Opioid-dependent, buprenorphine/naloxone-maintained, HIV-negative volunteers (n = 27) participated in two 24-hour sessions to determine (1) pharmacokinetics of buprenorphine alone and (2) pharmacokinetics of both buprenorphine and either ddI, 3TC, or TDF. Among buprenorphine/ naloxone-maintained study participants, no significant changes in buprenorphine pharmacokinetics were observed following ddI, 3TC, or TDF administration. Buprenorphine had no significant effect on NRTI concentrations. Concomitant use of buprenorphine with ddI, 3TC, or TDF results in neither a significant pharmacokinetic nor pharmacodynamic interaction. Baker J, Rainey PM, Moody DE, Morse GD, Ma Q, McCance-Katz EF. Interactions between Buprenorphine and Antiretrovirals: Nucleos(t)ide Reverse Transcriptase Inhibitors (NRTI) Didanosine, Lamivudine, and Tenofovir. Am J Addict. 2010 Jan 1; 19(1): 17-29.

Pharmacokinetic Interactions Between Buprenorphine/Naloxone and Tipranavir/Ritonavir in HIV-Negative Subjects Chronically Receiving Buprenorphine/Naloxone

HIV-infected patients with opioid dependence often require opioid replacement therapy. Pharmacokinetic interactions between HIV therapy and opioid dependence treatment medications can occur. HIV-seronegative subjects stabilized on at least 3 weeks of buprenorphine/naloxone (BUP/NLX) therapy sequentially underwent baseline and steady-state pharmacokinetic evaluation of open-label, twice daily tipranavir 500 mg co-administered with ritonavir 200 mg (TPV/r). Twelve subjects were enrolled and 10 completed the study. Prior to starting TPV/r, the geometric mean BUP AUC(0-24h) and C(max) were 43.9 ng h/mL and 5.61 ng/mL, respectively. After achieving steady-state with TPV/r (> or = 7 days), these values were similar at 43.7 ng h/mL and 4.84 ng/mL, respectively. Similar analyses for norBUP, the primary metabolite of BUP, demonstrated a reduction in geometric mean for AUC(0-24h) [68.7-14.7 ng h/mL; ratio=0.21 (90% CI 0.19-0.25)] and C(max) [4.75-0.94 ng/mL; ratio=0.20 (90% CI 0.17-0.23)]. The last measurable NLX concentration (C(last)) in the concentration-time profile, never measured in previous BUP/NLX interaction studies with antiretroviral medications, was decreased by 20%. Despite these pharmacokinetic effects on BUP metabolites and NLX, no clinical opioid withdrawal symptoms were noted. TPV steady-state AUC(0-12h) and C(max) decreased 19% and 25%, respectively, and C(min) was relatively unchanged when compared to historical control subjects receiving TPV/r alone. No dosage modification of BUP/NLX is required when co-administered with TPV/r. Though mechanistically unclear, it is likely that decreased plasma RTV levels while on BUP/NLX contributed substantially to the decrease in TPV levels. BUP/NLX and TPV/r should therefore be used cautiously to avoid decreased efficacy of TPV in patients taking these agents concomitantly. Bruce RD, Altice FL, Moody DE, Lin SN, Fang WB, Sabo JP, Wruck JM, Piliero PJ, Conner C, Andrews L, Friedland GH. Drug Alcohol Depend. 2009 Dec 1; 105(3): 234-239.

Methadone Maintenance Patients' Knowledge, Attitudes, Beliefs, and Experiences Concerning Treatment For Hepatitis C Virus Infection

Hepatitis C virus (HCV) knowledge, attitudes, beliefs, and experiences (KABE) of 64 HCV antibody positive methadone maintenance treatment (MMT) patients were assessed in conjunction with acceptability of an on-site semi-structured HCV education session, HCV RNA diagnostic testing, HCV treatment motivational assessment, and initiation of HCV treatment. The KABE interviews were conducted in 2006 and 2007 in an urban New York State MMT clinic in affiliation with a NIDA-funded HCV research project. The majority had basic knowledge of HCV disease, but poor understanding of HCV testing and treatment. While the majority of participants expressed fear of HCV treatment side effects, 88% accepted HCV RNA testing and 78% expressed willingness to start HCV treatment with the majority of chronically infected choosing to start HCV treatment medications. Study limitations and implications are discussed. Canfield KM, Smyth E, Batki SL. Methadone maintenance patients' knowledge, attitudes, beliefs, and experiences concerning treatment for hepatitis C virus infection. Subst Use Misuse. 2010 Mar; 45(4): 496-451.

Acceleration of HCV Envelope Evolution in Humans is Consistent with Progressive Humoral Immune Selection During the Transition from Acute to Chronic Infection

During the transition from acute to chronic infection in HCV persistently infected individuals, cellular responses initiate within the first 6 months of primary infection and collapse thereafter whereas humoral responses activate later during the chronic phase. Whether and how this deviation of immune responses specifically influences HCV evolution is unknown. To determine the pattern of HCV evolution during this critical period, the authors conducted extensive sequence analysis on annual clonal hemigenomic sequences up to three years in six well-characterized subjects, using statistical methods that accounted for repeated measures. Significantly different evolutionary rates were observed in envelope versus non-envelope genes, with increasing rate of non-synonymous change (dN) in envelope and stable dN in non-envelope genes (p=0.006). The ratio of envelope to non-envelope non-synonymous rate increased from 2 in year 1 to 5 in years 2 and 3. Centripetal changes (reversions toward matching of worldwide subtype 1a consensus sequence) were frequently observed during the three year transition from acute infection to chronicity, even in the presence of nAb pressure. Remarkably, HVR1 sequences remained stable for up to 21 months in the absence of nAb pressure in one subject, followed by rapid changes that were temporally associated with the detection of nAb responses, strongly suggesting that HVR1 evolution is shaped by nAb pressure. These data provide the first systematic estimates of HCV evolutionary rates in multiple genes during early infection in vivo, and provide additional evidence for deterministic, rather than random, evolution of HCV. Liu L, Fisher BE, Dowd KA, Astemborski J, Cox AL, Ray SC. Acceleration of HCV envelope evolution in humans is consistent with progressive humoral immune selection during the transition from acute to chronic infection. J Virol. 2010 Mar 3. [Epub ahead of print].

Risk Behaviors after Hepatitis C Virus Seroconversion in Young Injection Drug Users In San Francisco

The rationale for screening populations at risk for hepatitis C virus infection (HCV) includes the possibility of altering risk behaviors that impact disease progression and transmission. This study prospectively examined young injection drug users (IDU) to determine if behaviors changed after they were made aware of HCV seroconversion. The authors estimated the effects of HCV seroconversion coupled with post-test counseling on risk behaviors (alcohol use, non-injection and injection drug use, lending and sharing injecting equipment, and having sex without a condom) and depression symptoms using conditional logistic regression, fitting odds-ratios for immediately after disclosure and 6 and 12 months later, and adjusting for secular effects. 112 participants met inclusion criteria, i.e. they were documented HCV seronegative at study onset and subsequently seroconverted during the follow-up period, with infection confirmed by HCV RNA testing. HCV seroconversion was independently associated with a decreased likelihood of consuming alcohol (OR=0.52; 95% CI: 0.27-1.00, p=0.05) and using non-injection drugs (OR=0.40; 95% CI: 0.20-0.81, p=0.01) immediately after disclosure, however, results were not sustained over time. There were significant (p<0.05) declines in the use of alcohol, injection and non-injection drugs, and sharing equipment associated with time that were independent from the effect of seroconversion. Making young IDU aware of their HCV seroconversion may have a modest effect on alcohol and non-injection drug use that is not sustained over time. Tsui JI, Vittinghoff E, Hahn JA, Evans JL, Davidson PJ, Page K. Risk behaviors after hepatitis C virus seroconversion in young injection drug users in San Francisco. Drug Alcohol Depend. 2009 Nov 1; 105(1-2): 160-163.

Methadone and Buprenorphine Toxicity in Children

Recent years have seen very large increases in the prescribing of methadone and buprenorphine formulations for treatment of opioid addiction as well as the increasing utilization of methadone for the treatment of chronic pain. Coincident with the rise in the prescribing of these drugs has been a substantial increase in pediatric opioid toxicities and adverse events. This review will address the current state of methadone- and buprenorphine-related adverse events in children in the United States. The authors also discuss treatment of opioid toxicity in pediatric populations and make recommendations aimed at reducing these occurrences. Boyer EW, McCance-Katz EF, Marcus S. Methadone and buprenorphine toxicity in children. Am J Addict. 2010 Jan 1; 19(1): 89-95.

Indicators of Buprenorphine and Methadone Use and Abuse: What Do We Know?

Abuse of prescription opioids is a growing problem. The number of methadone pain pills distributed now exceeds liquid methadone used in opioid treatment, and the increases in buprenorphine indicators provide evidence of the need to monitor and intervene to decrease the abuse of this drug. The need for additional and improved data to track trends is discussed, along with findings as to the characteristics of the users and combinations of drugs. Data on toxicities related to methadone or buprenorphine, particularly in combination with other prescribed drugs, are presented and clinical implications and considerations are offered. These findings underscore the need for physicians to be aware of potential toxicities and to educate their patients regarding these issues. Maxwell JC, McCance-Katz EF. Indicators of buprenorphine and methadone use and abuse: what do we know? Am J Addict. 2010 Jan 1; 19(1): 73-88.

Effect of Cocaine Use on Methadone Pharmacokinetics in Humans

Chronic cocaine use has been shown to significantly decrease buprenorphine concentrations in the blood with potential for adverse events and poor treatment response. In this study, the authors investigated whether a similar drug interaction occurred between cocaine and methadone. In a retrospective analysis, methadone pharmacokinetics were compared for those who were either regular cocaine users (N = 16) or with intermittent or no cocaine use (N = 23). Participants who used cocaine regularly showed a significant decrease in C(min) (p = .04) and a trend for decreased AUC (p = .09) and more rapid methadone clearance (p = .08). Regular cocaine use may adversely impact treatment outcomes for opioid dependence in those receiving methadone maintenance by decreasing methadone exposure. McCance-Katz EF, Jatlow P, Rainey PM. Effect of cocaine use on methadone pharmacokinetics in humans. Am J Addict. 2010 Jan 1; 19(1): 47-52.

Effect of Cocaine Use on Buprenorphine Pharmacokinetics in Humans

The effect of chronic cocaine use on buprenorphine pharmacokinetics was investigated to identify drug interactions and potential toxicities. In a retrospective analysis, pharmacokinetics were compared for 16 studies completed on subjects who were regular cocaine users and 74 studies on subjects who used cocaine only occasionally or not at all. All participants were stably maintained on buprenorphine/naloxone 16/4 mg daily. Participants who used cocaine regularly had lower buprenorphine exposure (AUC 34% lower; C(max) 27% lower and C(24) 37% lower; p <= .001 for all comparisons. Regular cocaine users were younger (p = .0007), and used more heroin (p = .004) and cocaine (p < .0001). Regular cocaine use may result in lower buprenorphine plasma concentrations with potential for adverse clinical outcomes. McCance-Katz EF, Rainey PM, Moody DE. Effect of cocaine use on buprenorphine pharmacokinetics in humans. Am J Addict. 2010 Jan 1; 19: 38-46.

Methamphetamine Use is Associated with Increased Dental Disease

Methamphetamine (MA) use has been anecdotally linked to rampant dental disease. UCLA based researchers sought to determine the relative prevalence of dental comorbidities in MA users, verify whether MA users have quantifiably more dental disease and report more dental problems than non-users, and establish the influence of mode of MA administration on oral health outcomes. MA-dependent adults (N = 301) underwent comprehensive medical and oral assessments by participating physicians. Patient self-reports on oral health and substance use behaviors were collected. Propensity score matching from the National Health and Nutrition Examination Survey (NHANES) showed Dental/oral disease was one of the most prevalent medical comorbidities in MA users (41.3%) although they were generally healthy. On average, MA users had significantly more missing teeth than matched NHANES controls (4.58 vs. 1.96, p < .001) and were more likely to report poor oral health (p < .001). Significant subsets of subjects expressed concerns with their dental appearance (28.6%), problems with broken/loose teeth (23.3%) and tooth grinding/erosion (22.3%). The intravenous (IV) use of MA was more likely to be associated with missing teeth than smoking MA (OR=2.47., 95% C.I., 1.3 - 4.8). The investigators conclude that overt dental disease is a key distinguishing comorbidity in MA use. Contrary to common perception, MA users who inject have higher rates of disease than those who smoke or inhale. The investigators conclude that dental disease may provide a temporally stable MA-specific medical marker with discriminant utility in many ways for identifying MA users. Concerns about "dental self-image" could be used as a trigger for targeted behavioral interventions in dental office or for referral to substance use treatment programs. Given the relative prominence of dental comorbidities, dentists can play a crucial role in the early detection of MA use and participate as integral members of a collaborative care team tending to the MA user. Shetty V, Mooney LJ, Zigler CM, Belin TR, Murphy D, Rawson R. The relationship between methamphetamine use and increased dental disease. J Am Dent Assoc. 2010 Mar; 141(3): 307-318.

Effects of Buprenorphine and Hepatitis C on Liver Enzymes in Adolescents and Young Adults

This study explored changes in transaminase values associated with buprenorphine treatment and hepatitis C status among opioid-dependent subjects aged 15 to 21 years. One hundred fifty-two subjects were randomized to 2-week detoxification with buprenorphine/naloxone (DETOX) or 12 weeks with buprenorphine/naloxone (BUP). Liver chemistries were obtained at baseline and at 4, 8, and 12 weeks. One hundred eleven patients had at least one set of transaminases during treatment and were included in analyses of treatment effects. Overall, 8 of the 60 BUP participants versus 12 of the 51 DETOX participants had ≥ one elevated alanine aminotransferase value during follow-up ([chi]2 = ns). Five of the 60 BUP participants versus 11 of the 51 DETOX participants had ≥ one elevated aspartate aminotransferase value (P = 0.048). Twenty eight of the 152 participants were hepatitis C (HCV) positive at baseline and 4 seroconverted within 12 weeks, 2 in each group. HCV status was significantly associated with transaminase abnormalities (P = 0.009 and 0.006 for alanine aminotransferase and aspartate aminotransferase, respectively). HCV status had a strong effect on transaminase abnormalities among participants assigned to DETOX, but not among those assigned to BUP. No evidence was found for hepatotoxicity of buprenorphine in this exploratory analysis. HCV was present in a significant minority of participants and was a significant predictor of transaminase elevation. Results suggest that stabilization on buprenorphine may be associated with a decrease in the frequency of transaminase abnormalities associated with HCV in opioid-dependent young people. The high rate of seroconversion underscores the importance of effective treatment and prevention. Bogenschutz MP, Abbott PJ, Kushner R, Tonigan JS, Woody GE. J Addict Med. Published Ahead of Print January 22, 2010.

Sex Under the Influence of Drugs or Alcohol: Common for Men in Substance Abuse Treatment and Associated with High-risk Sexual Behavior

Sex under the influence of drugs or alcohol is associated with high-risk sexual behavior. Heterosexual men (n = 505) in substance abuse treatment completed a computer-administered interview assessing sexual risk behaviors. Most men (73.3%) endorsed sex under the influence in the prior 90 days, and 39.1% endorsed sex under the influence during their most recent sexual event. Sex under the influence at the most recent event was more likely to involve anal intercourse, sex with a casual partner, and less condom use. Patients might benefit from interventions targeting sexual behavior and substance use as mutual triggers. Calsyn DA, Cousins SJ, Hatch-Maillette MA, Forcehimes A, Mandler R, Doyle SR, Woody G. Am J Addict. 2010 Mar 1; 19(2): 119-127.


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