HIV testing at a community health center before and after implementing universal screening.

This study analyzed the quality of HIV screening at one of the largest community health centers in Connecticut. The data indicated that implementing universal HIV screening increased the proportion of underrepresented minorities and women tested, reducing the HIV testing disparities that previously existed at this center.

Improvements in health-related quality of life among methadone maintenance clients in Dar es Salaam, Tanzania.

BACKGROUND: Injection of heroin has become widespread in Dar es Salaam, Tanzania and is spreading throughout the country. To prevent potential bridging of HIV epidemics, the Tanzanian government established a methadone maintenance treatment (MMT) clinic in February 2011. We assess the effect of MMT on health-related quality of life (HRQOL) and examine factors, particularly HIV infection and methadone dose, associated with changes in HRQOL. METHODS: This study utilized routine data on clients enrolling in methadone from February 2011 to April 2012 at Muhimbili National Hospital. Change in physical (PCS) and mental health (MCS) composite scores, as measured by the SF-12 tool, were the primary outcomes. Backward stepwise linear regression, with a criterion of p<0.2 was used to identify baseline exposure variables for inclusion in multivariable models, while adjusting for baseline scores. RESULTS: A total of 288 MMT clients received baseline and follow-up assessments. Mean methadone dose administered was 45mg (SD±25) and 76 (27%) were confirmed HIV-positive. Significant improvements were observed in PCS and MCS, with mean increases of 15.7 and 3.3, respectively. In multivariable models, clients who had previous poly-substance use with cocaine [p=0.040] had a significantly higher mean change in PCS. Clients who were living with HIV [p=0.002]; satisfied with current marital situation [p=0.045]; had a history of suicidal thoughts [p=0.021]; and previously experienced cognitive difficulties [p=0.012] had significantly lower mean change in PCS. Clients with shorter history of heroin use [p=0.012] and who received higher methadone doses [p=0.028] had significantly higher mean change in MCS, compared to their counterparts. CONCLUSION: Aspects of mental and physical health, risk behaviors and quality of life among drug users are intertwined and complex. Our research revealed positive short-term effects of MMT on HRQOL and highlights the importance of sustained retention for optimal benefits. Comprehensive supportive services in addition to provision of methadone are needed to address the complex health needs of people who inject drugs.

The Impact of Enhanced Screening and Treatment on Hepatitis C in the United States.

BACKGROUND: The effectiveness of interferon-free direct-acting antivirals (DAA) in treating chronic hepatitis C virus (HCV) is limited by low screening and treatment rates, particularly among people who inject drugs (PWIDs). METHODS: To evaluate the levels of screening and treatment with interferon-free DAAs that are required to control HCV incidence and HCV-associated morbidity and mortality, we developed a transmission model, stratified by age and by injection drug use, and calibrated it to epidemiological data in the United States from 1992 to 2014. We quantified the impact of administration of DAAs at current and at enhanced screening and treatment rates, focusing on outcomes of HCV incidence, prevalence, compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplants, and mortality from 2015 to 2040. RESULTS: Increasing annual treatment of patients 4-fold-from the approximately 100 000 treated historically to 400 000-is predicted to prevent 526 084 (95% confidence interval, 466 615-593 347) cases of cirrhosis and 256 315 (201 589-316 114) HCV-associated deaths. By simultaneously increasing treatment capacity and increasing the number of HCV infections diagnosed, total HCV prevalence could fall to as low as 305 599 (222 955-422 110) infections by 2040. Complete elimination of HCV transmission in the United States through treatment with DAAs would require nearly universal screening of PWIDs, with an annual treatment rate of at least 30%. CONCLUSIONS: Interferon-free DAAs are projected to achieve marked reductions in HCV-associated morbidity and mortality. Aggressive expansion in HCV screening and treatment, particularly among PWIDs, would be required to eliminate HCV in the United States.

Implementation and Operational Research: Linkage to Care Among Methadone Clients Living With HIV in Dar es Salaam, Tanzania.

BACKGROUND: The first methadone maintenance treatment clinic in Tanzania was launched in February 2011 to address an emerging HIV epidemic among people who inject drugs. We conducted a retrospective cohort study to understand factors associated with linkage to HIV care and explore how a methadone maintenance treatment clinic can serve as a platform for integrated HIV care and treatment. METHODS: This study used routine programmatic and clinical data on clients enrolled in methadone at Muhimbili National Hospital from February 2011 to January 2013. Multivariable proportional hazards regression model was used to examine time to initial CD4 count. RESULTS: Final analyses included 148 HIV-positive clients, contributing 31.7 person-years. At 30, 60, and 90 days, the probability of CD4 screening was 40% [95% confidence interval (CI): 32% to 48%], 55% (95% CI: 47% to 63%), and 63% (95% CI: 55% to 71%), respectively. Clients receiving high methadone doses (≥ 85 mg/d) [adjusted hazard ratio (aHR): 1.68, 95% CI: 1.03 to 2.74] had higher likelihood of CD4 screening than those receiving low doses (<85 mg/d). Clients with primary education or lower (aHR: 1.62, 95% CI: 1.05 to 2.51) and self-reported poor health (aHR: 1.96, 95% CI: 1.09 to 3.51) were also more likely to obtain CD4 counts. Clients with criminal arrest history (aHR: 0.56, 95% CI: 0.37 to 0.85]) were less likely to be linked to care. Among 17 antiretroviral therapy eligible clients (CD4 ≤ 200), 12 (71%) initiated treatment, of which 7 (41%) initiated within 90 days. CONCLUSIONS: Levels of CD4 screening and antiretroviral therapy initiation were similar to Sub-Saharan programs caring primarily for people who do not inject drugs. Adequate methadone dosing is important in retaining clients to maximize HIV treatment benefits and allow for successful linkage to services.

The pharmacokinetic and pharmacodynamic interactions between buprenorphine/naloxone and elvitegravir/cobicistat in subjects receiving chronic buprenorphine/naloxone treatment.

BACKGROUND: Interactions between HIV and opioid-dependence therapies are known to occur. We sought to determine if such interactions occurred between buprenorphine/naloxone and elvitegravir boosted with cobicistat. METHODS: We performed a within-subject open-labeled pharmacokinetic and pharmacodynamic study in 17 HIV-seronegative subjects stabilized on at least 2 weeks of buprenorphine/naloxone therapy. Subjects underwent baseline and steady state evaluation of the effect of elvitegravir 150 mg once daily boosted with 150 mg once daily of cobicistat (EVG/COBI) on buprenorphine/naloxone parameters. Safety was monitored throughout the study. RESULTS: Compared with baseline values, buprenorphine mean AUCtau (69.0 versus 95.6 hr*ng/mL) and mean Cmax (8.4 versus 9.3 ng/mL) increased significantly in the presence of EVG/COBI. Compared with baseline values, norbuprenorphine mean AUCtau (103.4 versus 163.4 hr*ng/mL) and mean Cmax (6.9 versus 9 ng/mL) also increased significantly after achieving steady state EVG/COBI. Naloxone mean AUCtau (0.57 versus 0.45 hr*ng/mL) and mean Cmax (0.25 versus 0.16 ng/mL) decreased after the addition of EVG/COBI. The AUCtau, Cmax and Ctau of EVG and cobicistat did not significantly differ from historical controls. Opioid withdrawal or overdose was not observed among subjects in this study. CONCLUSION: The addition of EVG/COBI to stabilized patients receiving buprenorphine/naloxone modestly increased buprenorphine and norbuprenorphine levels without affecting the opioid pharmacodynamics.

Pharmacokinetic drug interactions and adverse consequences between psychotropic medications and pharmacotherapy for the treatment of opioid dependence.

BACKGROUND: Psychiatric comorbidities among opioid-dependent patients are common. Many medications used to treat both conditions are metabolized through complimentary cytochrome P450 isoenzymes. When medication-assisted treatment for opioid dependence is concurrently used with psychotropic medications, problematic pharmacokinetic drug interactions may occur. METHODS: We reviewed relevant English language articles identified through the MedLine, Scopus, and Embase databases from 1950 to December 2009 using the specific generic names of medications and keywords such as pharmacokinetics and drug interactions with buprenorphine, methadone, and naltrexone. Selected references from these articles were reviewed. Additionally, a review was conducted of abstracts and conference proceedings from national and international meetings from 1990 to 2009. A total of 60 studies were identified and reviewed. RESULTS: Clinical case series and carefully controlled pharmacokinetic interaction studies have been conducted between methadone, buprenorphine, or naltrexone and some psychoactive medications. Important pharmacokinetic drug interactions have been demonstrated within each class of medications affecting either methadone and buprenorphine or psychoactive drugs. Few studies, however, have been conducted with naltrexone. CONCLUSIONS: Several interactions between methadone, buprenorphine, or naltrexone and psychoactive medications are described and may have important clinical consequences. To optimize care, clinicians must be alerted to these interactions.

Pharmacokinetic interactions between buprenorphine/naloxone and once-daily lopinavir/ritonavir.

BACKGROUND: This study was conducted to examine the pharmacokinetic interactions between buprenorphine/naloxone (BUP/NLX) and lopinavir/ritonavir (LPV/r) in HIV-seronegative subjects chronically maintained on BUP/NLX. METHODS: This study was an open labeled pharmacokinetic study in twelve HIV-seronegative subjects stabilized on at least 3 weeks of BUP/NLX therapy. Subjects sequentially underwent baseline and steady-state pharmacokinetic evaluation of once-daily LPV/r (800/200 mg). RESULTS: Compared to baseline values, BUP AUC0-24h (46.8 vs. 46.2 ng*hr/mL) and Cmax (6.54 vs. 5.88 ng/mL) did not differ significantly after achieving steady-state LPV/r. Similar analyses of norBUP, the primary metabolite of BUP, demonstrated no significant difference in norBUP AUC0-24 hours (73.7 vs. 52.7 ng x h/mL); however, Cmax (5.29 vs. 3.11 ng/mL) levels were statistically different (P < 0.05) after LPV/r administration. Naloxone concentrations were similarly unchanged for AUC0-24 hours (0.421 vs. 0.374 ng x hr/mL) and Cmax (0.186 vs. 0.186 ng/mL). Using standardized measures, no objective opioid withdrawal was observed. The AUC0-24 hours and Cmin of LPV in this study did not significantly differ from historical controls (159.6 vs. 171.3 microg x hr/mL) and (2.3 vs. 1.3 microg/mL). CONCLUSIONS: The addition of LPV/r to stabilized patients receiving BUP/NLX did not affect buprenorphine pharmacokinetics but did increase the clearance of norbuprenorphine. Pharmacodynamic responses indicate that the altered norbuprenorphine clearance did not lead to opioid withdrawal. Buprenorphine/naloxone and LPV/r can be safely coadministered without need for dosage modification.

Persistence of virological benefits following directly administered antiretroviral therapy among drug users: results from a randomized controlled trial.

BACKGROUND: Although directly administered antiretroviral therapy (DAART) has demonstrated impressive biological benefits compared with self-administered therapy (SAT) among drug users, the persistence of DAART after transition to SAT has not been examined. METHODS: We conducted a community-based, prospective, randomized controlled trial of 6 months of DAART compared with SAT. The primary outcome was the proportion of subjects who achieved virological success at 6 months postintervention, defined as either a 1.0 log10 reduction from baseline or HIV-1 RNA <400 copies per milliliter. Secondary outcomes included the change from baseline in HIV-1 RNA and CD4 lymphocyte count. RESULTS: Of the 53 subjects in the SAT arm and 88 subjects in the DAART arm, 52 and 82, respectively, provided blood samples at 6 months postintervention. The DAART (n = 88) and SAT (n = 53) arms did not differ on virological success (DAART 58.0% vs. SAT 56.6%, P = 0.64), mean reduction in log10 HIV-1 RNA (-0.79 vs. -0.31 log10 copies/mL, P = 0.53), or mean change in CD4 lymphocyte count (+60.2 vs. -15.4 cells/mL, P = 0.12). In the multivariate analysis, only high levels of social support significantly predicted virological success. CONCLUSIONS: This analysis, from the first randomized controlled trial of DAART among active drug users, failed to show the persistence of the DAART intervention at improving virological outcomes. Additional strategies are needed to ensure the on-treatment benefits persist following the cessation of DAART.

Clinical outcomes of hepatitis C treatment in a prison setting: feasibility and effectiveness for challenging treatment populations.

BACKGROUND: More than one-third of people in the United States with hepatic C virus (HCV) infection pass through the correctional system annually. Data are lacking on outcomes of treatment with pegylated interferon plus ribavirin (PEG-RBV) in correctional settings. METHODS: During 2002-2006, we analyzed patients in the Connecticut Department of Correction who received PEG-RBV. We assessed the rates of sustained virological response, hospitalization, and use of medications to treat psychiatric disorders and anemia. RESULTS: Of 138 treatment-naive patients referred for treatment, 68 (49%) were approved. Overall, sustained virological response occurred in 47.1% of patients (for HCV genotype 1, 43.1%; for HCV genotypes 2 and 3, 58.8%). Only 9 patients (13%) discontinued treatment because of adverse effects. Multiple regression analysis revealed that not achieving a sustained virological response was correlated with HCV genotype 1 infection plus cirrhosis (adjusted odds ratio, 12.9; 95% confidence interval, 1.1-148) and baseline major depression (adjusted odds ratio, 3.4; 95% confidence interval, 1.01-11.6), but not with HIV infection, a baseline HCV RNA level >or=400,000 IU/mL, or black race. Compared with baseline, the rate of prescription of a new mood stabilizer (2.2 vs. 0.8 prescriptions per person-year) or an opioid (1.8 vs. 0.5 prescriptions per person-year) was higher during treatment, whereas there was no change in the rate of prescription of benzodiazepines and antipsychotic medications. CONCLUSIONS: These results support the feasibility and clinical effectiveness of PEG-RBV for the treatment of chronic HCV infection in correctional facilities.