[Show abstract][Hide abstract] ABSTRACT: Women who inject drugs (WWID) are at higher risk of HIV compared with their male counterparts as a result of multiple factors, including biological, behavioral, and sociostructural factors, yet comparatively little effort has been invested in testing and delivering prevention methods that directly target this group. In this article, we discuss the need for expanded prevention interventions for WWID, focusing on 2 safe, effective, and approved, yet underutilized biomedical prevention methods: opiate agonist therapy (OAT) and oral pre-exposure prophylaxis (PrEP). Although both interventions are well researched, they have not been well examined in the context of gender. We discuss the drivers of women injectors' higher HIV risk, review the effectiveness of OAT and PrEP interventions among women, and explain why these new HIV prevention tools should be prioritized for WWID. There is substantial potential for impact of OAT and PrEP programs for WWID in the context of broader gender-responsive HIV prevention initiatives. Although awaiting efficacy data on other biomedical approaches in the HIV prevention research "pipeline," we propose that the scale-up and implementation of these proven, safe, and effective interventions are needed now.
[Show abstract][Hide abstract] ABSTRACT: Importance
Injection drug use is the primary mode of transmission for hepatitis C virus (HCV) infection. Prior studies suggest opioid agonist therapy may reduce the incidence of HCV infection among injection drug users; however, little is known about the effects of this therapy in younger users.Objective
To evaluate whether opioid agonist therapy was associated with a lower incidence of HCV infection in a cohort of young adult injection drug users.Design, Setting, and Participants
Observational cohort study conducted from January 3, 2000, through August 21, 2013, with quarterly interviews and blood sampling. We recruited young adult (younger than 30 years) injection drug users who were negative for anti-HCV antibody and/or HCV RNA.Exposures
Substance use treatment within the past 3 months, including non–opioid agonist forms of treatment, opioid agonist (methadone hydrochloride or buprenorphine hydrochloride) detoxification or maintenance therapy, or no treatment.Main Outcomes and Measures
Incident HCV infection documented with a new positive result for HCV RNA and/or HCV antibodies. Cumulative incidence rates (95% CI) of HCV infection were calculated assuming a Poisson distribution. Cox proportional hazards regression models were fit adjusting for age, sex, race, years of injection drug use, homelessness, and incarceration.Results
Baseline characteristics of the sample (n = 552) included median age of 23 (interquartile range, 20-26) years; 31.9% female; 73.1% white; 39.7% who did not graduate from high school; and 69.2% who were homeless. During the observation period of 680 person-years, 171 incident cases of HCV infection occurred (incidence rate, 25.1 [95% CI, 21.6-29.2] per 100 person-years). The rate ratio was significantly lower for participants who reported recent maintenance opioid agonist therapy (0.31 [95% CI, 0.14-0.65]; P = .001) but not for those who reported recent non–opioid agonist forms of treatment (0.63 [95% CI, 0.37-1.08]; P = .09) or opioid agonist detoxification (1.45 [95% CI, 0.80-2.69]; P = .23). After adjustment for other covariates, maintenance opioid agonist therapy was associated with lower relative hazards for acquiring HCV infection over time (adjusted hazard ratio, 0.39 [95% CI, 0.18-0.87]; P = .02).Conclusions and Relevance
In this cohort of young adult injection drug users, recent maintenance opioid agonist therapy was associated with a lower incidence of HCV infection. Maintenance treatment with methadone or buprenorphine for opioid use disorders may be an important strategy to prevent the spread of HCV infection among young injection drug users.
JAMA Internal Medicine 10/2014; 174(12). DOI:10.1001/jamainternmed.2014.5416 · 13.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Pain is highly prevalent among persons with HIV. Alcohol may be used to "self-medicate" pain. This study examined the association between pain and risky alcohol use over time in a cohort of HIV-infected Russian drinkers.
This secondary analysis utilized longitudinal data from a randomized trial of a behavioral intervention. Subjects included HIV-infected adults who reported past 6-month risky drinking and unprotected sex and were recruited from HIV and addiction treatment sites in St. Petersburg, Russia. The main independent variable was pain that at least moderately interfered with daily living. The primary outcome was past month risky drinking amounts based on NIAAA guidelines. General estimating equations (GEE) logistic regression models were used to calculate odds ratios and 95% confidence intervals for the association between pain and risky drinking over time (i.e., baseline, 6 and 12 months), adjusting for potential confounders.
Baseline characteristics of participants (n=699) were mean age of 30 (SD ±5) years, 41% female, and 22% <9th grade education. Nearly one quarter (24%) had a CD4 cell count <200 cells/μl, and only 17% were on antiretroviral therapy. Nearly half (46%) reported at least moderate pain interference in the past month and 81% were drinking risky amounts. In adjusted longitudinal GEE models, pain was significantly associated with greater odds of reporting past month risky drinking (AOR = 1.34, 95% CI: 1.05-1.71, p value=0.02).
Among a cohort of HIV-infected Russian drinkers, pain that at least moderately interfered with daily living was associated with higher odds of reporting risky drinking amounts over time.
Drug and Alcohol Dependence 08/2014; 144. DOI:10.1016/j.drugalcdep.2014.08.013 · 3.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Importance
Buprenorphine opioid agonist treatment (OAT) has established efficacy for treating opioid dependency among persons seeking addiction treatment. However, effectiveness for out-of-treatment, hospitalized patients is not known.Objective
To determine whether buprenorphine administration during medical hospitalization and linkage to office-based buprenorphine OAT after discharge increase entry into office-based OAT, increase sustained engagement in OAT, and decrease illicit opioid use at 6 months after hospitalization.Design, Setting, and Participants
From August 1, 2009, through October 31, 2012, a total of 663 hospitalized, opioid-dependent patients in a general medical hospital were identified. Of these, 369 did not meet eligibility criteria. A total of 145 eligible patients consented to participation in the randomized clinical trial. Of these, 139 completed the baseline interview and were assigned to the detoxification (n = 67) or linkage (n = 72) group.Interventions
Five-day buprenorphine detoxification protocol or buprenorphine induction, intrahospital dose stabilization, and postdischarge transition to maintenance buprenorphine OAT affiliated with the hospital’s primary care clinic (linkage).Main Outcomes and Measures
Entry and sustained engagement with buprenorphine OAT at 1, 3, and 6 months (medical record verified) and prior 30-day use of illicit opioids (self-report).Results
During follow-up, linkage participants were more likely to enter buprenorphine OAT than those in the detoxification group (52 [72.2%] vs 8 [11.9%], P < .001). At 6 months, 12 linkage participants (16.7%) and 2 detoxification participants (3.0%) were receiving buprenorphine OAT (P = .007). Compared with those in the detoxification group, participants randomized to the linkage group reported less illicit opioid use in the 30 days before the 6-month interview (incidence rate ratio, 0.60; 95% CI, 0.46-0.73; P < .01) in an intent-to-treat analysis.Conclusions and Relevance
Compared with an inpatient detoxification protocol, initiation of and linkage to buprenorphine treatment is an effective means for engaging medically hospitalized patients who are not seeking addiction treatment and reduces illicit opioid use 6 months after hospitalization. However, maintaining engagement in treatment remains a challenge.Trial Registration
clinicaltrials.gov Identifier: NCT00987961
JAMA Internal Medicine 08/2014; 174(8):1369-1376. DOI:10.1001/jamainternmed.2014.2556 · 13.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Injection drug users (IDUs) are at increased risk of contracting HIV. From a clinical trial assessing an intervention to enhance the linkage of hospitalized patients to opioid treatment after discharge, we conducted multivariate analysis of baseline data from hospitalized IDUs with a history of opioid dependence (n = 104) to identify differences in factors predicting HIV drug and sex risk behaviors. Factors significantly associated with HIV drug risk were being non-Hispanic Caucasian and recent cocaine use. Being female, binge drinking, and poorer mental health were significantly associated with higher sex risk. Because factors predicting HIV sex risk behaviors differ from those predicting HIV drug risk, interventions aimed at specific HIV risks should have different behavioral and substance use targets.
AIDS and Behavior 07/2014; 19(3). DOI:10.1007/s10461-014-0754-7 · 3.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Few studies have assessed associations between craving and subsequent opioid use. We prospectively evaluated the relative utility of two craving questionnaires to predict opioid use among opioid-dependent patients in outpatient treatment.
Opioid-dependent patients (n = 147) initiating buprenorphine treatment were assessed every two weeks for 3 months. Craving was measured using the: (1) Desires for Drug Questionnaire (DDQ) and (2) Penn Alcohol-Craving Scale adapted for opioid craving (PCS). Multi-level logistic regression models estimated the effects of craving on the likelihood of opioid use. Craving assessed at time t was entered as a time-varying predictor of opioid use at time t + 1.
Craving scores plateaued at approximately 2 weeks after initiation of buprenorphine. In adjusted regression models, a 1-point increase in PCS scores (on a 7-point scale) was associated with a significant increase in the odds of opioid use at the subsequent assessment (OR = 1.27, 95% CI 1.08; 1.49, p < 0.01). The odds of opioid use at the subsequent follow-up assessment increased significantly as DDQ desire and intention scores increased (OR = 1.25, 95%CI 1.03; 1.51, p < 0.05), but was not significantly associated with DDQ negative reinforcement (OR = 1.01, 95%CI 0.88; 1.17, p > 0.05) or DDQ control (OR = 0.97, 95%CI 0.85; 1.11, p > 0.05) scores.
Self-reported craving for opioids was modestly associated with subsequent relapse to opioid use among a cohort of patients treated with buprenorphine. Assessment of craving may provide clinical utility in predicting relapse among treated opioid-dependent patients.
The American Journal of Drug and Alcohol Abuse 02/2014; 40(2). DOI:10.3109/00952990.2013.848875 · 1.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: HIV infection leads to chronic inflammation and alterations in levels of inflammatory cytokines. The association between cytokine levels and mortality in HIV infection is not fully understood.
We analyzed data from a cohort of HIV-infected adults with alcohol problems who were recruited in 2001-2003, and were prospectively followed until 2010 for mortality using the National Death Index. The main independent variables were inflammatory biomarkers [interleukin-6 (IL-6), IL-10, tumor necrosis factor-α, C-reactive protein, serum amyloid A, monocyte chemotactic protein-1, and cystatin-C], measured at baseline in peripheral blood and categorized as high (defined as being in the highest quartile) vs. low. A secondary analysis was conducted using inflammatory burden score, defined as the number of biomarkers in the highest quartile (0, 1, 2 or ≥3). Cox models were used to assess the association between both biomarker levels and inflammatory burden with mortality adjusting for potential confounders.
Four hundred HIV-infected patients were included (74.8% men, mean age 42 years, 50% hepatitis C virus-infected). As of 31 December 2009, 85 patients had died. In individual multivariable analyses for each biomarker, high levels of IL-6 and C-reactive protein were significantly associated with mortality [hazard ratio = 2.49 (1.69-5.12), P <0.01] and [hazard ratio = 1.87 (1.11-3.15), P = 0.02], respectively. There was also a significant association between inflammatory burden score and mortality [hazard ratio = 2.18 (1.29-3.66) for ≥3 vs. 0, P = 0.04]. In the fully adjusted multivariable analysis, high levels of IL-6 remained independently associated with mortality [hazard ratio = 2.57 (1.58-4.82), P <0.01].
High IL-6 levels and inflammatory burden score were associated with mortality in a cohort of HIV-infected adults with alcohol problems.
AIDS (London, England) 01/2014; 28(7). DOI:10.1097/QAD.0000000000000184 · 5.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the association between hepatitis C virus (HCV) infection and overall and liver-related death in human immunodeficiency virus (HIV)-infected patients with alcohol problems.
We analyzed data from a cohort of HIV-infected adults with current or past alcohol problems enrolled between 2001 and 2003, searching for causes of death until 2010 using the National Death Index.
Participants were HIV-infected adults with current or past alcohol problems, recruited in Boston, MA from HIV clinics at two hospitals, homeless shelters, drug treatment programs, subject referrals, flyers, and another cohort study with comparable recruitment sites.
The primary and secondary outcomes were all-cause and liver-related mortality, respectively. The main independent variable was HCV RNA status (positive vs. negative). Mortality rates and Kaplan-Meier survival curves were calculated by HCV status for both overall and liver-related mortality. Cox proportional hazards models were used to assess the association between HCV infection and overall and liver-related death, adjusting for alcohol and drug use over time.
397 hundred adults (50% HCV-infected) were included. As of December 31, 2009, 83 cohort participants had died (60 HCV-infected, 23 HCV negatives; log rank test p<0.001), and 26 of those deaths were liver-related (21 HCV-infected, 5 HCV negatives; log rank test p<0.001). All-cause and liver-related mortality rates were 4.68 and 1.64 deaths per 100 person-years for HCV-infected patients and 1.65 and 0.36 per 100 person-years for those without HCV, respectively. In the fully adjusted Cox model, HCV infection was associated with both overall [HR 2.55 (95%CI:1.50-4.33), p<0.01], and liver-related mortality [HR 3.24 (95%CI:1.18-8.94), p=0.02].
Hepatitis C virus infection is independently associated with all-cause and liver-related mortality in human immunodeficiency virus-infected patients with alcohol problems, even when accounting for alcohol and other drug use.
[Show abstract][Hide abstract] ABSTRACT: This study examined associations between substance use behaviors and self-reported health among hospitalized heroin users. Of the 112 participants, 53 (47%) reported good or better health. In multivariable logistic regression models, each day of heroin use in the last month was associated with an 8% lower odds of reporting health as good or better (OR=.92; 95% CI 0.87, 0.97, p<.05). Cocaine, cannabis, cigarettes, alcohol use, unintentional overdose, nor injection drug use was associated with health status.
[Show abstract][Hide abstract] ABSTRACT: AIMS: To evaluate whether pain was associated with increased risk of using heroin, stimulants or cannabis among HIV-infected drinkers in Russia. DESIGN: Secondary analysis of longitudinal data from the HERMITAGE study, a behavioral randomized controlled trial, with data collected at baseline, 6 month and 12 month visits. SETTING: Recruitment occurred at HIV and addiction treatment sites in St. Petersburg, Russian Federation. PARTICIPANTS: Six-hundred and ninety-nine HIV-infected adult drinkers. MEASUREMENTS: The primary outcome was past month illicit drug use; secondary outcomes examined each drug (heroin, stimulants and cannabis) separately. The main predictor was pain that at least moderately interfered with daily living. General estimating equations (GEE) logistic regression models were used to evaluate the association between pain and subsequent illicit drug use adjusting for potential confounders. FINDINGS: Participants reporting pain appeared to have higher odds of using illicit drugs, although the results did not reach statistical significance (adjusted Odds Ratio [OR]=1.32; 95% CI: 0.99, 1.76, p=0.06). There was a significant association between pain and heroin use (OR=1.54; 95% CI: 1.11 to 2.15, p=0.01) but not use of other drugs (OR=0.75; 95% CI: 0.40 to 1.40, p=0.35 for stimulants and OR=0.70; 95% CI: 0.45 to 1.07, p=0.09 for cannabis). CONCLUSIONS: HIV-infected Russian drinkers who report pain are more likely to use heroin over time than HIV-infected Russian drinkers who do not report pain. Pain may be an unrecognized risk factor for persistent heroin use with implications for HIV transmission in Russia.
[Show abstract][Hide abstract] ABSTRACT: Background:
The effect of alcohol on liver disease in HIV infection has not been well characterized.
We performed a cross-sectional multivariable analysis of the association between lifetime alcohol use and liver fibrosis in a longitudinal cohort of HIV-infected patients with alcohol problems. Liver fibrosis was estimated with 2 noninvasive indices, "FIB-4," which includes platelets, liver enzymes, and age; and aspartate aminotransferase/platelet ratio index ("APRI"), which includes platelets and liver enzymes. FIB-4 <1.45 and APRI <0.5 defined the absence of liver fibrosis. FIB-4 >3.25 and APRI >1.5 defined advanced liver fibrosis. The main independent variable was lifetime alcohol consumption (<150 kg, 150 to 600 kg, >600 kg).
Subjects (n = 308) were 73% men, mean age 43 years, 49% with hepatitis C virus (HCV) infection, 60% on antiretroviral therapy, 49% with an HIV RNA load <1,000 copies/ml, and 18.7% with a CD4 count <200 cells/mm(3) . Forty-five percent had lifetime alcohol consumption >600 kg, 32.7% 150 to 600 kg, and 22.3% <150 kg; 33% had current heavy alcohol use, and 69% had >9 years of heavy episodic drinking. Sixty-one percent had absence of liver fibrosis and 10% had advanced liver fibrosis based on FIB-4. In logistic regression analyses, controlling for age, gender, HCV infection, and CD4 count, no association was detected between lifetime alcohol consumption and the absence of liver fibrosis (FIB-4 <1.45) (adjusted odds ratio [AOR] = 1.12 [95% CI: 0.25 to 2.52] for 150 to 600 kg vs. <150 kg; AOR = 1.11 [95% CI: 0.52 to 2.36] for >600 kg vs. <150 kg; global p = 0.95). Additionally, no association was detected between lifetime alcohol use and advanced liver fibrosis (FIB-4 >3.25). Results were similar using APRI, and among those with and without HCV infection.
In this cohort of HIV-infected patients with alcohol problems, we found no significant association between lifetime alcohol consumption and the absence of liver fibrosis or the presence of advanced liver fibrosis, suggesting that alcohol may be less important than other known factors that promote liver fibrosis in this population.
Alcoholism Clinical and Experimental Research 05/2013; 37(9). DOI:10.1111/acer.12129 · 3.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Both HIV and HCV cause chronic inflammation and alterations in serum inflammatory cytokines. The impact of inflammatory cytokines on liver fibrosis is not well understood. Methods: We studied the association between IL-6, IL-10 and TNF-alpha and liver fibrosis in HIV-infected patients with current or past alcohol problems (CAGE ≥2 or physician investigator diagnosis). Liver fibrosis was estimated with FIB-4 (FIB-4 <1.45 defined absence of liver fibrosis and FIB-4 >3.25 defined advanced fibrosis). Logistic regression was used to assess the association between cytokines and fibrosis, adjusting for age, sex, CD4, HIV RNA, current antiretroviral therapy, Body Mass Index and HCV. Secondary analyses explored whether the association between HCV and liver fibrosis was mediated by these cytokines. Results: Participants (n=308) were all HIV-infected, 73% male, mean age 42 years, half with detectable HCV-RNA, 60.7% had absence of liver fibrosis and 10.1% had advanced fibrosis. In models that adjusted for each cytokine separately, higher levels of IL-6 were significantly associated with absence of fibrosis [adjusted OR (95% CI): 0.43 (0.19, 0.98), p=0.05] and were borderline significant for advanced fibrosis [adjusted OR (95% CI): 8.16 (0.96, 69.54), p= 0.055]. In the final model, only higher levels of IL-6 remained significantly associated with advanced liver fibrosis [adjusted OR (95% CI): 11.78 (1.17, 118.19), p=0.036]. Adjustment for inflammatory cytokines attenuated the adjusted OR for the association between HCV and fibrosis in the case of IL-6 [for absence of fibrosis from 0.32 (0.17, 0.57) p<0.01 to 0.47 (0.23, 0.96) p=0.04; and for advanced fibrosis from 7.22 (2.01, 25.96) p<0.01 to 6.62 (1.20, 36.62) p=0.03], suggesting IL-6 may be a partial mediator of the association between HCV and liver fibrosis. Conclusion: IL-6 was strongly and significantly associated with liver fibrosis in a cohort of HIV-infected patients with alcohol problems. IL-6 may be a useful predictive marker for liver fibrosis for HIV-infected patients.
AIDS research and human retroviruses 04/2013; 29(8). DOI:10.1089/AID.2012.0348 · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
The purpose of this study was to examine the association between risky drinking amounts and serum aminotransferase levels in HIV-infected adults with and without hepatitis C virus (HCV) infection.
In a prospective cohort of HIV-infected adults with current or past alcohol problems, we assessed whether drinking risky amounts (as defined by the National Institute on Alcohol Abuse and Alcoholism) was associated with higher levels of serum aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) over time, stratifying analyses by HCV status. Generalized linear mixed effects regression models were used to examine the association between risky drinking and natural log-transformed AST and ALT over time.
Among HIV/HCV-coinfected persons (n = 200), risky drinking was associated with a higher adjusted mean AST (62.2 vs. 51.4 U/L; adjusted ratio of means 1.2, 95% CI [1.07, 1.37], p = .003) and ALT (51.3 vs. 41.6 U/L; adjusted ratio of means 1.2, 95% CI [1.07, 1.42], p = .004) compared with non-risky drinking. In contrast, among HIV-infected adults without HCV infection (n = 197), there were no significant differences between those who did and did not drink risky amounts in AST (34.7 vs. 33.3 U/L; adjusted ratio of means = 1.0, 95% CI [0.95, 1.14], p = .36) or ALT (29.1 vs. 28.7 U/L; adjusted ratio of means = 1.0, 95% CI [0.91, 1.13], p = .78).
Among HIV-infected adults with HCV, those who drink risky amounts have higher serum aminotransferase levels than those who do not drink risky amounts. These results suggest that drinking risky amounts may be particularly harmful in HIV/HCV-coinfected adults and supports recommendations that providers pay special attention to drinking in this population.
Journal of studies on alcohol and drugs 03/2013; 74(2):266-70. DOI:10.15288/jsad.2013.74.266 · 2.76 Impact Factor