Association of genetic variants in RAB23 and ANXA11 with uveitis in sarcoidosis.

Purpose: Uveitis occurs in a subset of patients with sarcoidosis. The purpose of this study was to determine whether genetic variants that have been associated previously with overall sarcoidosis are associated with increased risk of developing uveitis. Methods: Seventy-seven subjects were enrolled, including 45 patients diagnosed with sarcoidosis-related uveitis as cases and 32 patients with systemic sarcoidosis without ocular involvement as controls. Thirty-eight single nucleotide polymorphisms (SNPs) previously associated with sarcoidosis, sarcoidosis severity, or other organ-specific sarcoidosis involvement were identified. Allele frequencies in ocular sarcoidosis cases versus controls were compared using the chi-square test, and p values were corrected for multiple hypotheses testing using permutation. All analyses were conducted with PLINK. Results: SNPs rs1040461 and rs61860052, in ras-related protein RAS23 (RAB23) and annexin A11 (ANXA11) genes, respectively, were associated with sarcoidosis-associated uveitis. The T allele of rs1040461 and the A allele of rs61860052 were found to be more prevalent in ocular sarcoidosis cases. These associations remained after correction for the multiple hypotheses tested (p=0.01 and p=0.02). In a subanalysis of Caucasian Americans only, two additional variants within the major histocompatibility complex (MHC) genes on chromosome 6, in HLA-DRB5 and HLA-DRB1, were associated with uveitis as well (p=0.009 and p=0.04). Conclusions: Genetic variants in RAB23 and ANXA11 genes were associated with an increased risk of sarcoidosis-associated uveitis. These loci have previously been associated with overall sarcoidosis risk.

NOD2 genetic variants and sarcoidosis-associated uveitis.

PURPOSE: Identifying genetic risk factors for developing sarcoidosis-associated uveitis could provide insights into its pathogenesis which is poorly understood.We determine if variants in NOD2 confer an increased risk of developing uveitis in adults with sarcoidosis. METHODS: In this genetic case-control study, 51 total subjects were enrolled: 39 patients diagnosed with sarcoid-related uveitis and 12 patients with systemic sarcoidosis without ocular involvement as controls. Sanger sequencing of the eleven exons of the NOD2 gene was performed on DNA obtained from whole blood. Sanger sequencing data were aligned against the NOD2 NCBI-RefSeq reference sequence to identify novel mutations in uveitis patients. For common variants, allele frequencies in cases versus controls were compared using the chi-square test. RESULTS: There were no significant differences in NOD2 common variant allele frequencies between sarcoidosis patients with and without uveitis, and none of the pathogenic NOD2 mutations associated with Blau syndrome were found in this cohort. However, four rare, non-synonymous variants were identified in four patients with ocular sarcoidosis and none of the controls. Variants rs149071116, rs35285618, and 16:g.50745164T > C have never been previously reported to be associated with any disease and may be pathogenic. The fourth variant, rs2066845, is associated with Crohn's disease and psoriatic arthritis. CONCLUSIONS: Despite the phenotypic overlap between sarcoidosis and Blau syndrome, none of the established pathogenic NOD2 variants were present in adults with sarcoidosis. However, four novel, rare, non-synonymous variants were identified in four cases with ocular sarcoidosis. Further investigation is needed to explore the potential clinical significance of these polymorphisms.

Knowledge and perceptions of HIV-infected patients regarding HIV transmission and treatment in Ho Chi Minh City, Vietnam.

Patient education concerning HIV and antiretroviral (ARV) medications is important for optimal outcomes. The authors assessed the knowledge and perceptions of HIV-infected patients in an ARV education program in Ho Chi Minh City, Vietnam. Of 185 patients, 64 (35%) receiving ARV medications, nearly 80% correctly answered questions regarding HIV. Correct responses were associated with higher education (P < .05) and longer duration of HIV diagnosis (P < .05). A lack of knowledge was observed in 40% of respondents who believed HIV and AIDS were the same and 70% of respondents who believed ARV medications cured HIV. Greater embarrassment of living with HIV was associated with female gender (P < .05) and lower education (P < .05). Patients were concerned over ARV medication use (27%) and its side effects (38%). The study population's knowledge of HIV/AIDS and ARV medications, perceived stigmatization, and areas of knowledge deficits underscore the need for effective patient education programs addressing poorly understood issues around HIV/AIDS.

Association between risk behaviors and antiretroviral resistance in HIV-infected patients receiving opioid agonist treatment.

OBJECTIVES: Antiretroviral (ARV) resistance is of concern. Opioid agonist treatment (ie, methadone or buprenorphine) is effective and decreases HIV transmission risk behaviors and HIV seroconversion. Despite prevention efforts, injection drug use (IDU) and risky sexual behaviors remain prevalent in patients receiving opioid agonist treatment. The purpose of this study is to determine in HIV-infected patients receiving opioid agonist treatment, the prevalence of HIV transmission risk behaviors, the prevalence of ARV resistance, and the prevalence of ARV resistance among those with risk behaviors. METHODS: The design was a cross-sectional study of patients recruited from opioid treatment programs and outpatient practices. We measured demographic, drug treatment, and HIV clinical information (including ARV adherence), self-reported HIV risk behaviors and drug use, urine toxicologies, and genotype testing for ARV resistance (with both standard assays and ultradeep sequencing). Data analysis included descriptive statistics. RESULTS: Fifty-nine subjects were enrolled, 64% were male, 24% were white, and mean age was 46 years. Fifty-three percent were receiving methadone, 47% were receiving buprenorphine, and 80% were receiving opioid agonist treatment for 12 weeks or more. Fourteen percent reported unprotected sex, 7% reported sharing needles or works, and 60% had positive urine toxicology for illicit drug use. Fifteen percent had evidence of HIV resistance by standard genotyping; 7% with single class resistance, 3% with double class resistance, and 5% with triple class resistance. Ultradeep sequencing found additional class resistance in 5 subjects. Twenty-two percent of subjects with evidence of transmission risk behaviors versus 14% of subjects without risk behaviors had evidence of ARV resistance. CONCLUSIONS: Improved prevention and treatment efforts may be needed for HIV-infected, opioid dependent individuals receiving opioid agonist treatment to decrease transmission of ARV resistant virus, especially in resource limited settings.

A randomized trial of cognitive behavioral therapy in primary care-based buprenorphine.

OBJECTIVE: To determine the impact of cognitive behavioral therapy on outcomes in primary care, office-based buprenorphine/naloxone treatment of opioid dependence. METHODS: We conducted a 24-week randomized clinical trial in 141 opioid-dependent patients in a primary care clinic. Patients were randomized to physician management or physician management plus cognitive behavioral therapy. Physician management was brief, manual guided, and medically focused; cognitive behavioral therapy was manual guided and provided for the first 12 weeks of treatment. The primary outcome measures were self-reported frequency of illicit opioid use and the maximum number of consecutive weeks of abstinence from illicit opioids, as documented by urine toxicology and self-report. RESULTS: The 2 treatments had similar effectiveness with respect to reduction in the mean self-reported frequency of opioid use, from 5.3 days per week (95% confidence interval, 5.1-5.5) at baseline to 0.4 (95% confidence interval, 0.1-0.6) for the second half of maintenance (P<.001 for the comparisons of induction and maintenance with baseline), with no differences between the 2 groups (P=.96) or between the treatments over time (P=.44). For the maximum consecutive weeks of opioid abstinence there was a significant main effect of time (P<.001), but the interaction (P=.11) and main effect of group (P=.84) were not significant. No differences were observed on the basis of treatment assignment with respect to cocaine use or study completion. CONCLUSIONS: Among patients receiving buprenorphine/naloxone in primary care for opioid dependence, the effectiveness of physician management did not differ significantly from that of physician management plus cognitive behavioral therapy.

Counseling and directly observed medication for primary care buprenorphine maintenance: a pilot study.

OBJECTIVES: Counseling and medication adherence can affect opioid agonist treatment outcomes. We investigated the impact of 2 counseling intensities and 2 medication-dispensing methods in patients receiving buprenorphine in primary care. METHODS: In a 12-week trial, patients were assigned to physician management (PM) with weekly buprenorphine dispensing (n = 28) versus PM and directly observed, thrice-weekly buprenorphine (DOT) and cognitive-behavioral therapy (CBT) (PM+DOT/CBT; n = 27) based on therapist availability. Fifteen-minute PM visits were provided at entry, after induction, and then monthly. Cognitive-behavioral therapy was weekly 45-minute sessions provided by trained therapists. RESULTS: Treatment groups differed on baseline characteristics of years of opioid use, history of detoxification from opioids, and opioid negative urines during induction. Analyses adjusting for baseline characteristics showed no significant differences between groups on retention or drug use based on self-report or urines. Patient satisfaction was high across conditions, indicating acceptability of CBT counseling with observed medication. The number of CBT sessions attended was significantly associated with improved outcome, and session attendance was associated with a greater abstinence the following week. CONCLUSIONS: Although the current findings were nonsignificant, DOT and individual CBT sessions were feasible and acceptable to patients. Additional research evaluating the independent effect of directly observed medication and CBT counseling is needed.

Human immunodeficiency virus testing practices among buprenorphine-prescribing physicians.

BACKGROUND: Despite the Centers for Disease Control and Prevention recommendations for annual HIV testing of at-risk populations, including those with substance use disorders, there are no data on the human immunodeficiency virus (HIV) testing practices of buprenorphine-prescribing physicians. OBJECTIVE: To describe HIV testing practices among buprenorphine-prescribing physicians. METHODS: We conducted a cross-sectional survey of physicians enrolled in a national system to support buprenorphine prescribing between July and August 2008. The electronic survey included questions on demographics; clinical training and experience; clinical practice; patient characteristics; and physician screening practices, including HIV testing. RESULTS: Only 46% of 382 respondent physicians conducted HIV testing. On univariate analysis, physicians who conducted HIV testing were more likely to report addiction specialty training (33% vs 19%, P = 0.001), practicing in addiction settings (28% vs 16%, P = 0.006), and having treated more than 50 patients with buprenorphine (50% vs 31%, P < 0.0001) than those who did not. Compared with physicians who did not conduct HIV testing, physicians who conducted HIV testing had a lower proportion of buprenorphine patients who were white (75% vs 82%, P = 0.01) or dependent upon prescription opioids (57% vs 70%, P < 0.0001). In multivariate analysis, physicians who conducted HIV testing were more likely to have treated more than 50 patients with buprenorphine (odds ratio = 1.777, 95% CI 1.011-3.124) and had fewer patients dependent upon prescription opioids (odds ratio = 0.986 95% CI 0.975-0.998) than physicians who did not. CONCLUSIONS: Interventions to increase HIV testing among physicians prescribing buprenorphine are needed.

Factors affecting clinician educator encouragement of routine HIV testing among trainees.

BACKGROUND: Adoption of CDC recommendations for routine, voluntary HIV screening of all Americans age 13­64 years has been slow. One method to increase adherence to clinical practice guidelines is through medical school and residency training. OBJECTIVE: To explore the attitudes, barriers, and behaviors of clinician educators (CEs) regarding advocating routine HIV testing to their trainees. DESIGN/PARTICIPANTS: We analyzed CE responses to a 2009 survey of Society of General Internal Medicine members from community, VA, and university-affiliated clinics regarding HIV testing practices. MAIN MEASURES: Clinician educators were asked about their outpatient practices, knowledge and attitudes regarding the revised CDC recommendations and whether they encouraged trainees to perform routine HIV testing. Associations between HIV testing knowledge and attitudes and encouraging trainees to perform routine HIV testing were estimated using bivariate and multivariable logistic regression. RESULTS: Of 515 respondents, 367 (71.3%) indicated they supervised trainees in an outpatient general internal medicine clinic. These CEs demonstrated suboptimal knowledge of CDC guidelines and over a third reported continued risk-based testing. Among CEs, 196 (53.4%) reported that they encourage trainees to perform routine HIV testing. Higher knowledge scores (aOR 5.10 (2.16, 12.0)) and more positive attitudes toward testing (aOR 8.83 (4.21, 18.5)) were independently associated with encouraging trainees to screen for HIV. Reasons for not encouraging trainees to screen included perceived low local prevalence (37.2%), competing teaching priorities (34.6%), and a busy clinic environment (34.0%). CONCLUSIONS: Clinician educators have a special role in the dissemination of the CDC recommendations as they impact the knowledge and attitudes of newly practicing physicians. Despite awareness of CDC recommendations, many CEs do not recommend universal HIV testing to trainees. Interventions that improve faculty knowledge of HIV testing recommendations and address barriers in resident clinics may enhance adoption of routine HIV testing.

Hepatic safety and antiretroviral effectiveness in HIV-infected patients receiving naltrexone.

BACKGROUND: We sought to determine the impact of naltrexone on hepatic enzymes and HIV biomarkers in HIV-infected patients. METHODS: We used data from the Veterans Aging Cohort Study-Virtual Cohort, an electronic database of administrative, pharmacy, and laboratory data. We restricted our sample to HIV-infected patients who received an initial oral naltrexone prescription of at least 7 days duration. We examined aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and HIV biomarker (CD4 and HIV RNA) values for the 365 days prior to, during, and for the 365 days post-naltrexone prescription. We also examined cases of liver enzyme elevation (LEE; defined as >5 times baseline ALT or AST or >3.5 times baseline if baseline ALT or AST was >40 IU/l). RESULTS: Of 114 HIV-infected individuals, 97% were men, 45% white, 57% Hepatitis C co-infected; median age was 49 years; 89% of the sample had a history of alcohol dependence and 32% had opioid dependence. Median duration of naltrexone prescription was 49 (interquartile range 30 to 83) days, representing 9,525 person-days of naltrexone use. Mean ALT and AST levels remained below the upper limit of normal. Two cases of LEE occurred. Mean CD4 count remained stable and mean HIV RNA decreased after naltrexone prescription. CONCLUSIONS: In HIV-infected patients, oral naltrexone is rarely associated with clinically significant ALT or AST changes and does not have a negative impact on biologic parameters. Therefore, HIV-infected patients with alcohol or opioid dependence can be treated with naltrexone.

Oral substitution treatment of injecting opioid users for prevention of HIV infection.

BACKGROUND: Injecting drug users are vulnerable to infection with Human Immunodeficiency Virus (HIV) and other blood borne viruses as a result of collective use of injecting equipment as well as sexual behaviour OBJECTIVES: To assess the effect of oral substitution treatment for opioid dependent injecting drug users on risk behaviours and rates of HIV infections SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and PsycINFO to May 2011. We also searched reference lists of articles, reviews and conference abstracts SELECTION CRITERIA: Studies were required to consider the incidence of risk behaviours, or the incidence of HIV infection related to substitution treatment of opioid dependence. All types of original studies were considered. Two authors independently assessed each study for inclusion DATA COLLECTION AND ANALYSIS: Two authors independently extracted key information from each of the included studies. Any differences were resolved by discussion or by referral to a third author. MAIN RESULTS: Thirty-eight studies, involving some 12,400 participants, were included. The majority were descriptive studies, or randomisation processes did not relate to the data extracted, and most studies were judged to be at high risk of bias. Studies consistently show that oral substitution treatment for opioid-dependent injecting drug users with methadone or buprenorphine is associated with statistically significant reductions in illicit opioid use, injecting use and sharing of injecting equipment. It is also associated with reductions in the proportion of injecting drug users reporting multiple sex partners or exchanges of sex for drugs or money, but has little effect on condom use. It appears that the reductions in risk behaviours related to drug use do translate into reductions in cases of HIV infection. However, because of the high risk of bias and variability in several aspects of the studies, combined totals were not calculated. AUTHORS' CONCLUSIONS: Oral substitution treatment for injecting opioid users reduces drug-related behaviours with a high risk of HIV transmission, but has less effect on sex-related risk behaviours. The lack of data from randomised controlled studies limits the strength of the evidence presented in this review.

A meta-analysis of the efficacy of nonphysician brief interventions for unhealthy alcohol use: implications for the patient-centered medical home.

Brief physician interventions can reduce alcohol consumption. Physicians may not have the time to provide brief interventions, and it is unclear whether nonphysicians can do so effectively. We conducted a systematic review and meta-analysis to examine the efficacy of brief interventions by nonphysician clinicians for unhealthy alcohol use. We searched the English-language literature in MEDLINE and other databases covering the domains of alcohol problems, primary care, nonphysician, and brief interventions. Studies of brief interventions delivered at least in part by nonphysicians in primary care and examining drinking outcomes were included. Sensitivity analyses examined the effect of excluding studies that contributed disproportionately to the heterogeneity of results. Thirteen studies, conducted 1996-2008, met our criteria. Seven studies with a total of 2,633 patients were included in the meta-analysis. Nonphysician interventions were associated with 1.7 (95% confidence interval [CI]=-.03 to -3.5) fewer standard drinks per week than control conditions (p = .054). Excluding the one study that increased heterogeneity, the effect was smaller but reached statistical significance; nonphysician counseling was associated with 1.4 (95% CI = .3- 2.4) fewer standard drinks per week compared to control (p = .012). Nonphysician brief interventions are modestly effective at reducing drinking in primary care patients with unhealthy alcohol use.

General internists' beliefs, behaviors, and perceived barriers to routine HIV screening in primary care.

The Centers for Disease Control and Prevention (CDC) recommends routine HIV screening in primary care but little is known about general internists' views of this practice. We conducted a national, cross-sectional, Internet-based survey of 446 general internists in 2009 regarding their HIV screening behaviors, beliefs, and perceived barriers to routine HIV screening in outpatient internal medicine practices. Internists' awareness of revised CDC guidelines was high (88%), but only 52% had increased HIV testing, 61% offered HIV screening regardless of risk, and a median 2% (range 0-67%) of their patients were tested in the past month. Internists practicing in perceived higher risk communities reported greater HIV screening. Consent requirements were a barrier to screening, particularly for VA providers and those practicing in states with HIV consent statutes inconsistent with CDC guidelines. Interventions that promote HIV screening regardless of risk and streamlined consent requirements will likely increase adoption of routine HIV screening in general medicine practices.

Provider and practice characteristics associated with use of rapid HIV Testing by general internists.

BACKGROUND: Rapid HIV testing could increase routine HIV testing. Most previous studies of rapid testing were conducted in acute care settings, and few described the primary care providers' perspective. OBJECTIVE: To identify characteristics of general internal medicine physicians with access to rapid HIV testing, and to determine whether such access is associated with differences in HIV-testing practices or perceived HIV-testing barriers. DESIGN: Web-based cross-sectional survey conducted in 2009. PARTICIPANTS: A total of 406 physician members of the Society of General Internal Medicine who supervise residents or provide care in outpatient settings. MAIN MEASURES: Surveys assessed provider and practice characteristics, HIV-testing types, HIV-testing behavior, and potential barriers to HIV testing. RESULTS: Among respondents, 15% had access to rapid HIV testing. In multivariable analysis, physicians were more likely to report access to rapid testing if they were non-white (OR 0.45, 95% CI 0.22, 0.91), had more years since completing training (OR 1.06, 95% CI 1.02, 1.10), practiced in the northeastern US (OR 2.35; 95% CI 1.28, 4.32), or their practice included a higher percentage of uninsured patients (OR 1.03; 95% CI 1.01, 1.04). Internists with access to rapid testing reported fewer barriers to HIV testing. More respondents with rapid than standard testing reported at least 25% of their patients received HIV testing (51% versus 35%, p = 0.02). However, access to rapid HIV testing was not significantly associated with the estimated proportion of patients receiving HIV testing within the previous 30 days (7.24% vs. 4.58%, p = 0.06). CONCLUSION: Relatively few internists have access to rapid HIV testing in outpatient settings, with greater availability of rapid testing in community-based clinics and in the northeastern US. Future research may determine whether access to rapid testing in primary care settings will impact routinizing HIV testing.

Food insecurity is associated with poor virologic response among HIV-infected patients receiving antiretroviral medications.

BACKGROUND AND OBJECTIVE: Food insecurity negatively impacts HIV disease outcomes in international settings. No large scale U.S. studies have investigated the association between food insecurity and severity of HIV disease or the mechanism of this possible association. The objective of this study was to examine the impact of food insecurity on HIV disease outcomes in a large cohort of HIV-infected patients receiving antiretroviral medications. DESIGN: This is a cross-sectional study. PARTICIPANTS AND SETTING: Participants were HIV-infected patients enrolled in the Veterans Aging Cohort Study between 2002-2008 who were receiving antiretroviral medications. MAIN MEASUREMENTS: Participants reporting "concern about having enough food for you or your family in the past 30 days" were defined as food insecure. Using multivariable logistic regression, we explored the association between food insecurity and both low CD4 counts (<200 cells/µL) and unsuppressed HIV-1 RNA (>500 copies/mL). We then performed mediation analysis to examine whether antiretroviral adherence or body mass index mediates the observed associations. KEY RESULTS: Among 2353 HIV-infected participants receiving antiretroviral medications, 24% reported food insecurity. In adjusted analyses, food insecure participants were more likely to have an unsuppressed HIV-1 RNA (AOR 1.37, 95% CI 1.09, 1.73) compared to food secure participants. Mediation analysis revealed that neither antiretroviral medication adherence nor body mass index contributes to the association between food insecurity and unsuppressed HIV-1 RNA. Food insecurity was not independently associated with low CD4 counts. CONCLUSIONS: Among HIV-infected participants receiving antiretroviral medications, food insecurity is associated with unsuppressed viral load and may render treatment less effective. Longitudinal studies are needed to test the potential causal association between food insecurity, lack of virologic suppression, and additional HIV outcomes.

Alcohol consumption and depressive symptoms over time: a longitudinal study of patients with and without HIV infection.

BACKGROUND: The impact of alcohol consumption on depressive symptoms over time among patients who do not meet criteria for alcohol abuse or dependence is not known. OBJECTIVE: To evaluate the impact of varying levels of alcohol consumption on depressive symptoms over time in patients with and without HIV infection. DESIGN: We used data from the Veterans Aging Cohort Study (VACS). We used generalized estimating equation models to assess the association of alcohol-related categories, as a fixed effect, on the time-varying outcome of depressive symptoms. PARTICIPANTS: VACS is a prospectively enrolled cohort study of HIV-infected patients and age-, race- and site-matched HIV uninfected patients. MAIN MEASURES: Hazardous, binge drinking, alcohol abuse and alcohol dependence were defined using standard criteria. Depressive symptoms were measured by the Patient Health Questionnaire (PHQ-9). KEY RESULTS: Among the 2446 patients, 19% reported past but not current alcohol use, 50% non-hazardous drinking, 8% hazardous drinking, 14% binge drinking, and 10% met criteria for alcohol or dependence. At baseline, depressive symptoms were higher in hazardous and binge drinkers than in past and non-hazardous drinkers (OR=2.65; CI=1.50/4.69; p<.001) and similar to those with abuse or dependence. There was no difference in the association between alcohol-related category and depressive symptoms by HIV status (OR=0.99; CI=.83/1.18; p=.88). Hazardous drinkers were 2.53 (95% CI=1.34/4.81) times and binge drinkers were 2.14 (95% CI=1.49/3.07) times more likely to meet criteria for depression when compared to non-hazardous drinkers. The associations between alcohol consumption and depressive symptoms persisted over three years and were responsive to changes in alcohol-related categories. CONCLUSIONS: HIV-infected and HIV-uninfected hazardous and binge drinkers have depressive symptoms that are more severe than non-hazardous and non-drinkers and similar to those with alcohol abuse or dependence. Patients who switch to a higher or lower level of drinking experience a similar alteration in their depressive symptoms. Interventions to decrease unhealthy alcohol consumption may improve depressive symptoms.

HIV treatment outcomes among HIV-infected, opioid-dependent patients receiving buprenorphine/naloxone treatment within HIV clinical care settings: results from a multisite study.

BACKGROUND: Having opioid dependence and HIV infection are associated with poor HIV-related treatment outcomes. METHODS: HIV-infected, opioid-dependent subjects (N = 295) recruited from 10 clinical sites initiated buprenorphine/naloxone (BUP/NX) and were assessed at baseline and quarterly for 12 months. Primary outcomes included receiving antiretroviral therapy (ART), HIV-1 RNA suppression, and mean changes in CD4 lymphocyte count. Analyses were stratified for the 119 subjects not on ART at baseline. Generalized estimating equations were deployed to examine time-dependent correlates for each outcome. RESULTS: At baseline, subjects on ART (N = 176) were more likely than those not on ART (N = 119) to be older, heterosexual, have lower alcohol addiction severity scores, and lower HIV-1 RNA levels; they were less likely to be homeless and report sexual risk behaviors. Subjects initiating BUP/NX (N = 295) were significantly more likely to initiate or remain on ART and improve CD4 counts over time compared with baseline; however, these improvements were not significantly improved by longer retention on BUP/NX. Retention on BUP/NX for three or more quarters was, however, significantly associated with increased likelihood of initiating ART (ß = 1.34 [1.18, 1.53]) and achieve viral suppression (ß = 1.25 [1.10, 1.42]) for the 64 of 119 (54%) subjects not on ART at baseline compared with the 55 subjects not retained on BUP/NX. In longitudinal analyses, being on ART was positively associated with increasing time of observation from baseline and higher mental health quality of life scores (ß = 1.25 [1.06, 1.46]) and negatively associated with being homo- or bisexual (ß = 0.55 [0.35, 0.97]), homeless (ß = 0.58 [0.34, 0.98]), and increasing levels of alcohol addiction severity (ß = 0.17 [0.03, 0.88]). The strongest correlate of achieving viral suppression was being on ART (ß = 10.27 [5.79, 18.23]). Female gender (ß = 1.91 [1.07, 3.41]), Hispanic ethnicity (ß = 2.82 [1.44, 5.49]), and increased general health quality of life (ß = 1.02 [1.00,1.04]) were also independently correlated with viral suppression. Improvements in CD4 lymphocyte count were significantly associated with being on ART and increased over time. CONCLUSIONS: Initiating BUP/NX in HIV clinical care settings is feasible and correlated with initiation of ART and improved CD4 lymphocyte counts. Longer retention on BPN/NX was not associated with improved prescription of ART, viral suppression, or CD4 lymphocyte counts for the overall sample in which the majority was already prescribed ART at baseline. Among those retained on BUP/NX, HIV treatment outcomes did not worsen and were sustained. Increasing time on BUP/NX, however, was especially important for improving HIV treatment outcomes for those not on ART at baseline, the group at highest risk for clinical deterioration. Retaining subjects on BUP/NX is an important goal for sustaining HIV treatment outcomes for those on ART and improving them for those who are not. Comorbid substance use disorders (especially alcohol), mental health problems, and quality-of-life indicators independently contributed to HIV treatment outcomes among HIV-infected persons with opioid dependence, suggesting the need for multidisciplinary treatment strategies for this population.

Drug treatment outcomes among HIV-infected opioid-dependent patients receiving buprenorphine/naloxone.

BACKGROUND: Buprenorphine/naloxone allows the integration of opioid dependence and HIV treatment. METHODS: We conducted a prospective study in HIV-infected opioid-dependent patients to investigate the impact of buprenorphine/naloxone treatment on drug use. Self-report and chart review assessments were conducted every 3 months (quarters 1-4) for 1 year. Outcomes were buprenorphine/naloxone treatment retention, drug use, and addiction treatment processes. RESULTS: Among 303 patients enrolled between July 2005 and December 2007, retention in buprenorphine/naloxone treatment was 74%, 67%, 59%, and 49% during Quarters 1, 2, 3, and 4, respectively. Past 30-day illicit opioid use decreased from 84% of patients at baseline to 42% in retained patients over the year. Patients were 52% less likely to use illicit opioids for each quarter in treatment (Odds ratio = 0.66; 95% CI: 0.61 to 0.72). Buprenorphine/naloxone doses and office visits approximated guidelines published by the United States Department of Health and Human Services. Urine toxicology monitoring was less frequent than recommended. CONCLUSIONS: Buprenorphine/naloxone provided in HIV treatment settings can decrease opioid use. Strategies are needed to improve retention and address ongoing drug use in this treatment population.

Hepatic safety and lack of antiretroviral interactions with buprenorphine/naloxone in HIV-infected opioid-dependent patients.

BACKGROUND: The safety of buprenorphine/naloxone (bup/nx) in HIV-infected patients has not been established. Prior reports raise concern about hepatotoxicity and interactions with atazanavir. METHODS: We conducted a prospective cohort study of 303 opioid-dependent HIV-infected patients initiating bup/nx treatment. We assessed changes in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) over time. We compared bup/nx doses in patients receiving the antiretroviral atazanavir to those not receiving atazanavir. We conducted surveillance for pharmacodynamic interactions. RESULTS: Median AST [37.0 vs. 37.0 units/liter (U/L) respective interquartile ranges (IQRs) 26-53 and 26-59] and ALT (33.0 vs. 33.0 U/L, respective IQRs 19-50 and 18-50) values did not change over time among 141 patients comparing pre-bup/nx exposure with post-bup/nx exposure measures. During bup/nx exposure, 207 subjects demonstrated no significant change in median AST (36.0 vs. 35.0 U/L, respective IQRs 25-57 and 25-61) and ALT (29.0 vs. 31.0 U/L, respective IQRs 19-50 and 18-50) values collected a median of 6 months apart. Analyses restricted to patients with hepatitis C and HIV co-infection yielded similar results, except a small but significant decrease in first to last AST, during treatment with bup/nx (P = 0.048). Mean bup/nx dose, ranging 16.0-17.8 mg, did not differ over time or with co-administration of atazanavir. No pharmacodynamic interactions were noted. CONCLUSIONS: Buprenorphine/naloxone did not produce measurable hepatic toxicity or pharmacodynamic interaction with atazanavir in HIV-infected opioid-dependent patients.

The impact of cocaine use on outcomes in HIV-infected patients receiving buprenorphine/naloxone.

BACKGROUND: Cocaine use is common in opioid-dependent HIV-infected patients, but its impact on treatment outcomes in these patients receiving buprenorphine/naloxone is not known. METHODS: We conducted a prospective study in 299 patients receiving buprenorphine/naloxone who provided baseline cocaine data and a subset of 266 patients who remained in treatment for greater than or equal to one quarter. Assessments were conducted at baseline and quarterly for 1 year. We evaluated the association between baseline and in-treatment cocaine use on buprenorphine/naloxone retention, illicit opioid use, antiretroviral adherence, CD4 counts, HIV RNA, and risk behaviors. RESULTS: Sixty-six percent (197 of 299) of patients reported baseline cocaine use and 65% (173 of 266) of patients with follow-up data reported in-treatment cocaine use. Baseline and in-treatment cocaine use did not impact buprenorphine/naloxone retention, antiretroviral adherence, CD4 lymphocytes, or HIV risk behaviors. However, baseline cocaine use was associated with a 14.8 (95% confidence interval [CI], 9.0-24.2) times greater likelihood of subsequent cocaine use (95% CI, 9.0-24.2), a 1.4 (95% CI, 1.02-2.00) times greater likelihood of subsequent opioid use, and higher log10 HIV RNA (P < 0.016) over time. In-treatment cocaine use was associated with a 1.4 (95% CI, 1.01-2.00) times greater likelihood of concurrent opioid use. CONCLUSIONS: Given cocaine use negatively impacts opioid and HIV treatment outcomes, interventions to address cocaine use in HIV-infected patients receiving buprenorphine/naloxone treatment are warranted.