Publications (18)97.69 Total impact
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Article: Young age predicts poor antiretroviral adherence and viral load suppression among injection drug users.
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ABSTRACT: Previous studies of adherence to antiretroviral therapy (ART) for HIV among young injection drug users (IDU) have been limited because financial barriers to care disproportionately affect youth, thus confounding results. This study examines adherence among IDU in a unique setting where all medical care is provided free-of-charge. From May 1996 to April 2008, we followed a prospective cohort of 545 HIV-positive IDU of 18 years of age or older in Vancouver, Canada. Using generalized estimating equations (GEE), we studied the association between age and adherence (obtaining ART≥95% of the prescribed time), controlling for potential confounders. Using Cox proportional hazards regression, we also studied the effect of age on time to viral load suppression (<500 copies per milliliter), and examined adherence as a mediating variable. Five hundred forty-five participants were followed for a median of 23.8 months (interquartile range [IQR]=8.5-91.6 months). Odds of adherence were significantly lower among younger IDU (adjusted odds ratio [AOR]=0.76 per 10 years younger; 95% confidence interval [CI], 0.65-0.89). Younger IDU were also less likely to achieve viral load suppression (adjusted hazard ratio [AHR]=0.75 per 10 years younger; 95% CI, 0.64-0.88). Adding adherence to the model eliminated this association with age, supporting the role of adherence as a mediating variable. Despite absence of financial barriers, younger IDU remain less likely to adhere to ART, resulting in inferior viral load suppression. Interventions should carefully address the unique needs of young HIV-positive IDU.AIDS patient care and STDs 03/2012; 26(5):274-80. · 2.68 Impact Factor -
Article: Patterns of heroin and cocaine injection and plasma HIV-1 RNA suppression among a long-term cohort of injection drug users.
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ABSTRACT: Previous studies suggest that active drug use may compromise HIV treatment among HIV-positive injection drug users (IDU). However, little is known about the differential impacts of cocaine injection, heroin injection, and combined cocaine and heroin injection on plasma HIV-1 RNA suppression. Data were derived from a longstanding open prospective cohort of HIV-positive IDU in Vancouver, Canada. Kaplan-Meier methods and Cox proportional hazards regression were used to examine the impacts of different drug use patterns on rates of plasma HIV-1 RNA suppression. Between May 1996 and April 2008, 267 antiretroviral (ART) naïve participants were seen for a median follow-up duration of 50.6 months after initiating ART. The incidence density of HIV-1 RNA suppression was 65.2 (95%CI: 57.0-74.2) per 100 person-years. In Kaplan-Meier analyses, compared to those who abstained from injecting, individuals injecting heroin, cocaine, or combined heroin/cocaine at baseline were significantly less likely to achieve viral suppression (all p<0.01). However, none of the drug use categories remained associated with a reduced rate of viral suppression when considered as time-updated variables (all p>0.05). Active injecting at the time of ART initiation was associated with lower plasma HIV-1 RNA suppression rates; however, there was no difference in suppression rates when drug use patterns were examined over time. These findings imply that adherence interventions for active injectors should optimally be applied at the time of ART initiation.Drug and alcohol dependence 01/2012; 124(1-2):108-12. · 3.60 Impact Factor -
Article: Social and environmental predictors of plasma HIV RNA rebound among injection drug users treated with antiretroviral therapy.
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ABSTRACT: Evidence is needed to improve HIV treatment outcomes for individuals who use injection drugs (IDU). Although studies have suggested higher rates of plasma viral load (PVL) rebound among IDU on antiretroviral therapy (ART), risk factors for rebound have not been thoroughly investigated. We used data from a long-running community-recruited prospective cohort of IDU in Vancouver, Canada, linked to comprehensive ART and clinical monitoring records. Using proportional hazards methods, we modeled the time to confirmed PVL rebound above 1000 copies per milliliter among IDU on ART with sustained viral suppression, defined as 2 consecutive undetectable PVL measures. Between 1996 and 2009, 277 individuals had sustained viral suppression. Over a median follow-up of 32 months, 125 participants (45.1%) experienced at least 1 episode of virologic failure for an incidence of 12.6 [95% confidence interval (CI): 10.5 to 15.0] per 100 person-years. In a multivariate model, PVL rebound was independently associated with sex-trade involvement [adjusted hazard ratio (AHR) = 1.40, 95% CI: 1.08 to 1.82) and recent incarceration (AHR = 1.83, 95% CI: 1.33 to 2.52). Methadone maintenance therapy (AHR = 0.79, 95% CI: 0.66 to 0.94) was protective. No measure of illicit drug use was predictive. In this setting of free ART, several social and environmental factors predicted higher risks of viral rebound among IDU, including sex-trade involvement and incarceration. These findings should help inform efforts to identify individuals at risk of viral rebound and targeted interventions to treat and retain individuals in effective ART.JAIDS Journal of Acquired Immune Deficiency Syndromes 11/2011; 59(4):393-9. · 4.43 Impact Factor -
Article: Homelessness as a structural barrier to effective antiretroviral therapy among HIV-seropositive illicit drug users in a Canadian setting.
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ABSTRACT: Despite the advent of effective antiretroviral therapy (ART), HIV-seropositive injection drug users (IDU) continue to suffer from elevated levels of morbidity and mortality. Evidence is needed to identify social- and structural-level barriers to effective ART. We investigated the impact of homelessness on plasma HIV RNA response among illicit drug users initiating ART in a setting with free and universal access to HIV care. We accessed data from a long-running prospective cohort of community-recruited IDU linked to comprehensive HIV clinical monitoring and ART dispensation records. Using Cox proportional hazards with recurrent events modeling, we estimated the independent effect of homelessness on time to plasma HIV viral load suppression. Between May 1996 and September 2009, 247 antiretroviral naïve individuals initiated ART and contributed 1755 person-years of follow-up. Among these individuals, the incidence density of plasma HIV RNA suppression less than 500 copies/mm(3) was 56.7 (95% confidence interval [CI]: 46.9-66.0) per 100 person-years. In unadjusted analyses, homelessness was strongly associated with lower rates suppression (hazard ratio = 0.56, 95% CI: 0.40-0.78, p = 0.001), however, after adjustment for adherence this association was no longer significant (adjusted hazard ratio = 0.79, 95% CI: 0.56-1.11, p = 0.177). Homelessness poses a significant structural barrier to effective HIV treatment. However, since this relationship appears to be mediated by lower levels of ART adherence, interventions to improve adherence among members of this vulnerable population are needed.AIDS patient care and STDs 11/2011; 26(1):60-7. · 2.68 Impact Factor -
Article: Dose-response effect of incarceration events on nonadherence to HIV antiretroviral therapy among injection drug users.
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ABSTRACT: Although some studies have identified impressive clinical gains for incarcerated HIV-seropositive injection drug users (IDUs) undergoing antiretroviral therapy (ART), the effect of incarceration on adherence to ART remains undetermined. We used data from a long-term community-recruited cohort of HIV-seropositive IDUs, including comprehensive ART dispensation records, in a setting where HIV care is free. We estimated the relationship between the cumulative burden of incarceration, measured longitudinally, and the odds of < 95% adherence to ART, with use of multivariate modeling. From 1996 through 2008, 490 IDUs were recruited and contributed 2220 person-years of follow-up; 271 participants (55.3%) experienced an incarceration episode, with the number of incarcerations totaling 1156. In a multivariate model, incarceration had a strong dose-dependent effect on the likelihood of nonadherence to ART: 1-2 incarceration events (adjusted odds ratio [AOR], 1.49; 95% confidence interval [95% CI], 1.03-2.05), 3-5 events (AOR, 2.48; 95% CI, 1.62-3.65), and > 5 events (AOR, 3.11; 95% CI, 1.86-4.95). Among HIV-seropositive IDUs receiving ART, an increasing burden of incarceration was associated with poorer adherence in a dose-dependent fashion. Our findings support improved adherence support for HIV-seropositive IDUs experiencing incarceration.The Journal of Infectious Diseases 05/2011; 203(9):1215-21. · 6.41 Impact Factor -
Article: Female gender predicts lower access and adherence to antiretroviral therapy in a setting of free healthcare.
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ABSTRACT: Barriers to HIV treatment among injection drug users (IDU) are a major public health concern. However, there remain few long-term studies investigating key demographic and behavioral factors--and gender differences in particular--that may pose barriers to antiretroviral therapy (ART), especially in settings with universal healthcare. We evaluated access and adherence to ART in a long-term cohort of HIV-positive IDU in a setting where medical care and antiretroviral therapy are provided free of charge through a universal healthcare system. We evaluated baseline antiretroviral use and subsequent adherence to ART among a Canadian cohort of HIV-positive IDU. We used generalized estimating equation logistic regression to evaluate factors associated with 95% adherence to antiretroviral therapy estimated based on prescription refill compliance. Between May 1996 and April 2008, 545 IDU participants were followed for a median of 23.8 months (Inter-quartile range: 8.5-91.6), among whom 341 (63%) were male and 204 (37%) were female. Within the six-month period prior to the baseline interview, 133 (39%) men and 62 (30%) women were on ART (p=0.042). After adjusting for clinical characteristics as well as drug use patterns measured longitudinally throughout follow-up, female gender was independently associated with a lower likelihood of being 95% adherent to ART (Odds Ratio [OR]=0.70; 95% Confidence Interval: 0.53-0.93). Despite universal access to free HIV treatment and medical care, female IDU were less likely to access and adhere to antiretroviral therapy, a finding that was independent of drug use and clinical characteristics. These data suggest that interventions to improve access to HIV treatment among IDU must be tailored to address unique barriers to antiretroviral therapy faced by female IDU.BMC Infectious Diseases 04/2011; 11:86. · 3.12 Impact Factor -
Article: Methadone use among HIV-positive injection drug users in a Canadian setting.
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ABSTRACT: We examined methadone maintenance therapy (MMT) use among HIV-positive injection drug users (IDU) in Vancouver. Among 353 participants, 199 (56.3%) were on MMT at baseline, and 48 initiated MMT during follow-up. Female gender (adjusted odds ratio [AOR] = 1.73, 95% confidence interval [CI] = 1.14-2.62) and antiretroviral therapy use (AOR = 2.04, 95% CI = 1.46-2.86) were positively associated with MMT use, whereas frequent heroin injection (AOR = 0.34, 95% CI = 0.23-0.50), public injection (AOR = 0.76, 95% CI = 0.59-0.97), syringe borrowing (AOR = 0.54, 95% CI = 0.32-0.90), and nonfatal overdose (AOR = 0.58, 95% CI = 0.36-0.92) were negatively associated with MMT use. The rate of discontinuation of MMT was 12.46 (95% CI = 8.28-18.00) per 100 person years. Frequent heroin use (adjusted hazards ratio = 4.49, 95%CI = 1.81-11.13) was positively associated with subsequent discontinuation of MMT. These findings demonstrate the benefits of MMT among HIV-positive IDU and the need to improve access to and retention in MMT.Journal of substance abuse treatment 09/2010; 39(2):174-9. · 2.90 Impact Factor -
Article: Methadone maintenance therapy promotes initiation of antiretroviral therapy among injection drug users.
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ABSTRACT: Despite proven benefits of antiretroviral therapy (ART), many human immunodeficiency virus (HIV)-infected injection drug users (IDU) do not access treatment even in settings with free health care. We examined whether methadone maintenance therapy (MMT) increased initiation and adherence to ART among an IDU population with free health care. We examined prospectively a cohort of opioid-using antiretroviral-naive HIV-infected IDU and investigated factors associated with initiation of antiretroviral therapy as well as subsequent adherence. Factors associated independently with time to first initiation of antiretroviral therapy were modelled using Cox proportional hazards regression. Between May 1996 and April 2008, 231 antiretroviral-naive HIV-infected opioid-using IDU were enrolled, among whom 152 (65.8%) initiated ART, for an incidence density of 30.5 [95% confidence interval (CI): 25.9-35.6] per 100 person-years. After adjustment for time-updated clinical characteristics and other potential confounders, use of MMT was associated independently with more rapid uptake of antiretroviral therapy [relative hazard = 1.62 (95% CI: 1.15-2.28); P = 0.006]. Those prescribed methadone also had higher rates of ART adherence after first antiretroviral initiation [odds ratio = 1.49 (95% CI: 1.07-2.08); P = 0.019]. These results demonstrate that MMT contributes to more rapid initiation and subsequent adherence to ART among opioid-using HIV-infected IDU. Addressing international barriers to the use and availability of methadone may increase dramatically uptake of HIV treatment among this population.Addiction 03/2010; 105(5):907-13. · 4.31 Impact Factor -
Article: Ongoing drug use and outcomes from highly active antiretroviral therapy among injection drug users in a Canadian setting.
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ABSTRACT: The effect of ongoing illicit drug use on HIV treatment remains controversial, especially in countries where access to HIV treatment for active injection drug users (IDUs) is limited because of presumed non-adherence. We sought to investigate the influence of drug use patterns on adherence to antiretroviral therapy and virological suppression among IDUs. Using generalized estimating equation logistic regression, we explored the effect of abstinence versus ongoing drug use on adherence and virological suppression using data from a community-recruited cohort of IDUs in Vancouver (BC, Canada). A total of 381 HIV-positive IDUs were included in this analysis, among whom the median follow-up time was 30 months. In a multivariate model, no relationship was found between abstinence (reference) and active injection (adjusted odds ratio [AOR] 0.88, 95% confidence interval [CI] 0.65-1.17) and non-injection (AOR 0.97, 95% CI 0.67-1.41) drug use with adherence. In subanalyses, ongoing injection drug use was associated with a lower odds of virological suppression in comparison to abstinence (AOR 0.74, 95% CI 0.57-0.97; P=0.026) and both active IDUs and active non-IDUs had lower odds of virological suppression compared with abstinent participants when longer periods of virological suppression were considered. Given the absence of a strong relationship between abstinence and ongoing drug use and adherence among HIV-positive IDUs, programmes that restrict antiretrovirals to abstinent individuals should be re-examined. The lower rates of virological suppression associated with ongoing drug use nevertheless highlight the importance of comprehensive systems of care and addiction treatment for active drug users.Antiviral therapy 01/2010; 15(5):789-96. · 3.16 Impact Factor -
Article: Lopinavir/ritonavir pharmacokinetics in a substitution of high-dose soft-gelatin capsule to tablet formulation.
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ABSTRACT: Guidelines recommend that when soft-gelatin capsules of lopinavir/ritonavir are co-administered with CYP3A4-inducing agents, doses should be increased to 4 capsules (533 mg/133 mg) twice daily. No evidence is available to guide dosing of lopinavir/ritonavir in tablet formulation in this setting. A single-center study is conducted to compare the pharmacokinetics of high-dose lopinavir/ritonavir in 34 patients on stable HAART regimens including 4 soft-gelatin capsules twice daily who then switch to 3 tablets (600 mg/150 mg) twice daily. Median C(min) on soft-gelatin capsule and tablets is 4700 ng/mL (interquartile range [IQR] 2310, 6000 ng/mL) and 5640 ng/mL (IQR 4290, 8080 ng/mL), respectively, for those on inducing agents (n = 17). For patients not on inducing agents (n = 17), median C(min) on soft-gelatin capsule and tablets is 5170 ng/mL (IQR 3640, 6210 ng/mL) and 5640 ng/mL (IQR 4290, 8080 ng/mL), respectively. Among treatment-experienced patients on lopinavir/ritonavir capsules 533/133 mg twice daily, a switch to tablets 600/150 mg twice daily produces comparable pharmacokinetics, regardless of whether they receive concomitant CYP3A4-inducing antiretroviral agents.The Journal of Clinical Pharmacology 03/2009; 49(2):155-61. · 2.91 Impact Factor -
Article: Predicting hospitalization among HIV-infected antiretroviral naïve patients starting HAART: determining clinical markers and exploring social pathways.
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ABSTRACT: In the era of highly active antiretroviral therapy (HAART), hospitalization as a measure of morbidity has become of increasing interest. The objectives of this study were to determine clinical predictors of hospitalization among HIV-infected persons initiating HAART and to explore the impact of gender and drug use on hospitalization. The analysis was based on a cohort of HIV-positive individuals initiating HAART between 1996 and 2001. Information on hospitalizations was obtained through data linkage with the BC Ministry of Health. Cox-proportional hazard models were used to assess variables associated with time to hospitalization. A total of 1,605 people were eligible and 672 (42%) were hospitalized for one or more days. The final multivariate model indicated that there was an increased risk of hospitalization among those with high baseline HIV RNA (HR for > 100,000 copies/mL: 1.26; 95%CI: 1.16-1.59) or low CD4 cell counts (HR [95% CI] compared to > or = 200 cells/mm3: 1.62 [1.28-2.06] and 1.29 [1.07-1.56] for < 50 and 50-199 cells/mm(3), respectively). Other factors, including adherence, previous hospitalization, gender and injection drug use remained predictive of hospitalization. These findings highlight the importance of closely monitoring patients starting therapy with low CD4 cell counts in order to mediate or prevent outcomes requiring hospitalization.AIDS Care 03/2008; 20(3):297-303. · 1.60 Impact Factor -
Article: Tenofovir-based rescue therapy for advanced liver disease in 6 patients coinfected with HIV and hepatitis B virus and receiving lamivudine.
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ABSTRACT: We summarize the clinical history and laboratory results following the introduction of tenofovir among 6 patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) who presented with severe liver disease while receiving lamivudine-based highly active antiretroviral therapy. In all cases, the introduction of tenofovir led to a sustained undetectable HBV and HIV loads, with marked clinical and laboratory improvement in liver function. We provide supporting evidence for the role of tenofovir in the management of advanced HBV infection in HIV-positive patients after the development of lamivudine resistance.Clinical Infectious Diseases 03/2008; 46(3):e28-30. · 9.15 Impact Factor -
Article: HIV therapy, hepatitis C virus infection, antibiotics and obesity, a mitochondria killer mix?
AIDS 07/2006; 20(9):1343-5. · 6.24 Impact Factor -
Article: HIV therapy, hepatitis C virus infection, antibiotics and obesity, a mitochondria killer mix?
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ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.AIDS 06/2006; 20(9):1343-1345. · 6.24 Impact Factor -
Article: Comparable pharmacokinetics of generic indinavir (Inhibisam) versus brand indinavir (Crixivan) when boosted with ritonavir.
JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2005; 38(3):363-4. · 4.43 Impact Factor -
Article: Simplification of therapeutic drug monitoring for twice-daily regimens of lopinavir/ritonavir for HIV infection.
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ABSTRACT: Cost and inconvenience limit the application of full 12-hour pharmacokinetic (PK) analysis for routine therapeutic drug monitoring of antiretroviral medications. We explore whether lopinavir (LPV) and ritonavir (RTV) exposures can be estimated with limited sampling for patients taking twice-daily LPV/RTV. One hundred and one PK profiles from 81 patients, most receiving salvage therapies including twice-daily LPV/RTV, were obtained for the analysis. After a minimum of 2 weeks on a stable regimen, blood was drawn immediately before and at 1, 2, 4, 6, 8, 10, and 12 hours after a timed medication dose. Plasma drug concentrations were determined by a validated HPLC-MS-MS assay. Peak concentrations, evening troughs, and AUC0-12 h were entered into linear and log10-log10 linear regression models to determine the best correlation with LPV and RTV plasma concentrations using a maximum of 2 time points. The accuracy and precision of PK parameter estimates of the resultant models were tested on data collected for an additional 25 patients. Twelve models using various combinations of 2 timed LPV concentrations afforded accurate (maximum % bias = -6.45) and precise (relative standard deviation < 15%) estimates for the LPV peak concentration or AUC0-12h. Four sets of 2 concentrations provided simultaneous estimates of both PK parameters, with the best estimates derived from data collected at 2 and 6 hours postdose. Evening trough concentrations were the best estimators of the daily nadir; however, no adequate substitute for collecting blood 12 hours postdose emerged from this analysis.Therapeutic Drug Monitoring 11/2004; 26(5):516-23. · 2.49 Impact Factor -
Article: Staging for antiretroviral therapy among HIV-infected drug users.
JAMA The Journal of the American Medical Association 10/2004; 292(10):1175-7. · 30.03 Impact Factor -
Article: Prevalence of bone mineral density abnormalities and related risk factors in an ambulatory HIV clinic population.
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ABSTRACT: Bone mineral density (BMD) abnormalities are observed frequently among human immunodeficiency virus (HIV)-infected patients. Risk factors for reduced BMD in the setting of HIV have been previously studied, but detailed antiretroviral treatment history is often not available. A cross-sectional observational study was conducted between 2005 and 2007 among unselected HIV-infected adults attending an ambulatory urban HIV clinic. Dual-energy X-ray absorptiometry (DXA) scans of lumbar spine and femoral neck, full laboratory profile, detailed questionnaire, and antiretroviral history were obtained. Univariate and multivariate logistic regression analyses were performed to investigate factors associated with BMD below the expected range for age. Two hundred ninety patients completed the study: 80% Caucasians, 89% males, with median age of 49 yr. Low BMD as assessed by Z-score was present in 19.7% of the patients. By multivariate analysis, only lower body mass index (BMI) was an independent risk factor for low BMD. Cumulative exposure to protease inhibitors, non-nucleosides, and individual nucleoside and nucleotide analogs were not independently associated with low BMD. In conclusion, a 19.7% prevalence of abnormal BMD by DXA scan was identified in an unselected group of HIV-infected adults. Lower BMI was independently associated with low BMD. No correlation was found between abnormal BMD and cumulative exposure to any antiretroviral agents.Journal of Clinical Densitometry 13(4):456-61. · 1.29 Impact Factor
Top co-authors
Top Journals
Institutions
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2012
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Boston Medical Center
Boston, MA, USA
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2008–2012
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University of British Columbia - Vancouver
- British Colombia Centre for Excellence in HIV/AIDS
Vancouver, British Columbia, Canada
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2010
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BC Centre for Excellence in HIV/AID
Vancouver, British Columbia, Canada
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2004
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British Columbia Centre of Excellence for Women's Health
Vancouver, British Columbia, Canada
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