Xuan Li

Directly observed antiretroviral therapy improves adherence and viral load in drug users attending methadone maintenance clinics: A randomized controlled trial

OBJECTIVE To determine if directly observed antiretroviral therapy (DOT) is more efficacious than self-administered therapy for improving adherence and reducing HIV viral load (VL) among methadone-maintained opioid users. DESIGN Two-group randomized trial. SETTING Twelve methadone maintenance clinics with on-site HIV care in the Bronx, New York. PARTICIPANTS HIV-infected adults prescribed combination antiretroviral therapy. MAIN OUTCOMES MEASURES Between group differences at four assessment points from baseline to week 24 in: (1) antiretroviral adherence measured by pill count, (2) VL, and (3) proportion with undetectable VL (< 75 copies/ml). RESULTS Between June 2004 and August 2007, we enrolled 77 participants. Adherence in the DOT group was higher than in the control group at all post-baseline assessment points; by week 24 mean DOT adherence was 86% compared to 56% in the control group (p < 0.0001). Group differences in mean adherence remained significant after stratifying by baseline VL (detectable versus undetectable). In addition, during the 24-week intervention, the proportion of DOT participants with undetectable VL increased from 51% to 71%. CONCLUSIONS Among HIV-infected opioid users, antiretroviral DOT administered in methadone clinics was efficacious for improving adherence and decreasing VL, and these improvements were maintained over a 24-week period. DOT should be more widely available to methadone patients.

Factors associated with antiretroviral therapy adherence and medication errors among HIV-infected injection drug users

Background:Active drug use is often associated with poor adherence, but few studies have determined psychosocial correlates of adherence in injection drug users (IDUs). Methods:Of 1161 Intervention for Seropositive Injectors-Research and Evaluation study enrollees, 636 were taking antiretrovirals. We assessed self-reported adherence to self-reported antiretroviral regimens and medication errors, which we defined as daily doses that were inconsistent with standard or alternative antiretroviral prescriptions. Results:Most subjects (75%, n = 477) self-reported good (≥90%) adherence, which was strongly associated with an undetectable viral load. Good adherence was independently associated with being a high school graduate, not sharing injection equipment, fewer depressive symptoms, positive attitudes toward antiretrovirals, higher self-efficacy for taking antiretrovirals as prescribed, and greater sense of responsibility to protect others from HIV. Medication errors were made by 54% (n = 346) and were strongly associated with a detectable viral load and fewer CD4 cells. Errors were independently associated with nonwhite race and with depressive symptoms, poorer self-efficacy for safer drug use, and worse attitudes toward HIV medications. Conclusions:Modifiable factors associated with poor adherence, including depressive symptoms and poor self-efficacy, should be targeted for intervention. Because medication errors are prevalent and associated with a detectable viral load and fewer CD4 cells, interventions should include particular efforts to identify medication taking inconsistent with antiretroviral prescriptions.

Increasing Drug Resistance in Extensively Drug-Resistant Tuberculosis, South Africa

We expanded second-line tuberculosis (TB) drug susceptibility testing for extensively drug-resistant Mycobacterium tuberculosis isolates from South Africa. Of 19 patients with extensively drug-resistant TB identified during February 2008–April 2009, 13 (68%) had isolates resistant to all 8 drugs tested. This resistance leaves no effective treatment with available drugs in South Africa.

Racial Differences in Primary Care Opioid Risk Reduction Strategies

PURPOSE Racial disparities in treating pain with opioids are widely reported; however, differences in use of recommended strategies to reduce the risk of opioid misuse by race/ethnicity have not been evaluated. METHODS In a retrospective cohort of black and white patients with chronic noncancer pain prescribed opioid analgesics for at least 3 months, we assessed physicians’ use of 3 opioid risk reduction strategies: (1) urine drug testing, (2) regular office visits (at least 1 visit per 6 months on opioids and within 30 days of an opioid change), and (3) restricted early opioid refills (receipt of a refill >1 week early less than twice). Nonlinear mixed effect regression models accounted for clustering within physician and adjusted additively for demographics, substance abuse, mental health and medical comorbidities, health care factors, and practice site. RESULTS Of the 1,612 patients studied, 62.1% were black. Black patients were more likely than white patients to receive urine drug testing (10.4% vs 4.1%), regular office visits (56.4% vs 39.0%), and restricted early refills (79.4% vs 72.0%) (P <.001 for each). In fully adjusted models, black patients had significantly higher odds than their white counterparts of receiving regular office visits (odds ratio = 1.51; 95% confidence interval, 1.06–2.14) and restricted early refills (odds ratio = 1.55; 95% confidence interval, 1.03–2.32), but not urine drug testing (odds ratio = 1.41; 95% confidence interval, 0.78–2.54). CONCLUSIONS In this cohort of primary care patients receiving opioid analgesics on a long-term basis, use of risk reduction strategies was very limited overall; however, black patients were more likely than white patients to receive 2 of 3 guideline-recommended strategies. These data raise questions about lax monitoring, especially for white patients taking opioids long term.

Comparison of antiretroviral adherence questions.

Our objective was to compare antiretroviral adherence questions to better understand concordance between measures. Among 53 methadone maintained HIV-infected drug users, we compared five measures, including two single item measures using qualitative Likert-type responses, one measure of percent adherence, one visual analog scale, and one multi-item measure that averaged responses across antiretrovirals. Responses were termed inconsistent if respondents endorsed the highest adherence level on at least one measure but middle levels on others. We examined ceiling effects, concordance, and correlations with VL. Response distributions differed markedly between measures. A ceiling effect was less pronounced for the single-item measures than for the measure that averaged responses for each antiretroviral: the proportion with 100% adherence varied from 22% (single item measure) to 58% (multi-item measure). Overall agreement between measures ranged from fair to good; 49% of participants had inconsistent responses. Though responses correlated with VL, single-item measures had higher correlations. Future studies should compare single-item questions to objective measures.

Culture conversion among HIV co-infected multidrug-resistant tuberculosis patients in Tugela Ferry, South Africa.

Background Little is known about the time to sputum culture conversion in MDR-TB patients co-infected with HIV, although such patients have, historically, had poor outcomes. We describe culture conversion rates among MDR-TB patients with and without HIV-co-infection in a TB-endemic, high-HIV prevalent, resource-limited setting. Methods Patients with culture-proven MDR-TB were treated with a standardized second-line regimen. Sputum cultures were taken monthly and conversion was defined as two negative cultures taken at least one month apart. Time-to-conversion was measured from the day of initiation of MDR-TB therapy. Subjects with HIV received antiretroviral therapy (ART) regardless of CD4 count. Results Among 45 MDR-TB patients, 36 (80%) were HIV-co-infected. Overall, 40 (89%) of the 45 patients culture-converted within the first six months and there was no difference in the proportion who converted based on HIV status. Median time-to-conversion was 62 days (IQR 48-111). Among the five patients who did not culture convert, three died, one was transferred to another facility, and one refused further treatment before completing 6 months of therapy. Thus, no patients remained persistently culture-positive at 6 months of therapy. Conclusions With concurrent second-line TB and ART medications, MDR-TB/HIV co-infected patients can achieve culture conversion rates and times similar to those reported from HIV-negative patients worldwide. Future studies are needed to examine whether similar cure rates are achieved at the end of MDR-TB treatment and to determine the optimal use and timing of ART in the setting of MDR-TB treatment.

Lack of sustained improvement in adherence or viral load following a directly observed antiretroviral therapy intervention.

BACKGROUND Methadone clinic-based directly observed antiretroviral therapy (DOT) has been shown to be more efficacious for improving adherence and suppressing human immunodeficiency virus (HIV) load than antiretroviral self-administration. We sought to determine whether the beneficial effects of DOT remain after DOT is discontinued. METHODS We conducted a post-trial cohort study of 65 HIV-infected opioid-dependent adults who had completed a 24-week randomized controlled trial of methadone clinic-based DOT versus treatment as usual (TAU). For 12 months after DOT discontinuation, we assessed antiretroviral adherence using monthly pill counts and electronic monitors. We also assessed viral load at 3, 6, and 12 months after DOT ended. We examined differences between DOT and TAU in (1) adherence, (2) viral load, and (3) proportion of participants with viral load of <75 copies/mL. RESULTS At trial end, adherence was higher among DOT participants than among TAU participants (86% and 54%, respectively; P < .001), and more DOT participants than TAU participants had viral loads of <75 copies/mL (71% and 44%, respectively; P = .03). However, after DOT ended, differences in adherence diminished by 1 month (55% for DOT vs 48% for TAU; P = .33) and extinguished completely by 3 months (49% for DOT vs 50% for TAU; P = .94). Differences in viral load between DOT and TAU disappeared by 3 months after the intervention, and the proportion of DOT participants with undetectable viral load decreased steadily after DOT was stopped until there was no difference (36% for DOT and 34% for TAU; P = .92). CONCLUSIONS Because the benefits of DOT for adherence and viral load among HIV-infected methadone patients cease after DOT is stopped, methadone-based DOT should be considered a long-term intervention.

Rationale, design, and sample characteristics of a randomized controlled trial of directly observed antiretroviral therapy delivered in methadone clinics.

BACKGROUND Directly observed therapy (DOT) programs for HIV treatment have demonstrated feasibility, acceptability, and improved viral suppression, but few have been rigorously tested. We describe a randomized controlled trial testing the efficacy of an antiretroviral DOT program in methadone maintenance clinics. Our objective was to determine if DOT is more efficacious than self-administered antiretroviral therapy for reducing HIV viral load, improving adherence, and reducing drug resistance among opioid dependent drug users receiving methadone treatment. METHODS Participants were randomized to treatment as usual (TAU) or antiretroviral DOT for the 24-week intervention. TAU participants received standard adherence counseling, and DOT participants received standard adherence counseling plus directly observed antiretroviral therapy, which was delivered at the same time as they received daily methadone. Assessments occurred at baseline, weekly for 8 weeks, and then monthly for 4 months. Our primary outcomes were between-group changes from baseline to the end of the intervention in: HIV viral load, antiretroviral adherence, and number of viral mutations. RESULTS Between June 2004 and August 2007, we screened 3231 methadone-maintained patients and enrolled 77; 39 participants were randomized to DOT and 38 to TAU. 65 completed the 24-week intervention. CONCLUSIONS Our trial will allow rigorous evaluation of the efficacy of directly observed antiretroviral therapy delivered in methadone clinics for improving adherence and clinical outcomes. This detailed description of trial methodology can serve as a template for the development of future DOT programs and can guide protocols for studies among HIV-infected drug users receiving methadone for opioid dependence.

Directly observed antiretroviral therapy eliminates adverse effects of active drug use on adherence.

BACKGROUND The impact of adherence enhancing interventions on the relationship between active drug use and adherence is largely unknown. METHODS We conducted a 24-week randomized controlled trial of antiretroviral directly observed therapy (DOT) vs. treatment as usual (TAU) among HIV-infected methadone patients. Our outcome measure was pill count antiretroviral adherence, and our major independent variables were treatment arm (DOT vs. TAU) and active drug use (opiates, cocaine, or both opiates and cocaine). We defined any drug use as ≥ 1 positive urine toxicology result, and frequent drug use as ≥ 50% tested urines positive. We used mixed-effects linear models to evaluate associations between adherence and drug use, and included a treatment arm-by-drug use interaction term to evaluate whether DOT moderates associations between drug use and adherence. RESULTS 39 participants were randomized to DOT and 38 to TAU. We observed significant associations between adherence and active drug use, but these were limited to TAU participants. Adherence was worse in TAU participants with any opiate use than in TAU participants without (63% vs. 75%, p<0.01); and worse among those with any polysubstance (both opiate and cocaine) use than without (60% vs. 73%, p=0.01). We also observed significant decreases in adherence among TAU participants with frequent opiate or frequent polysubstance use, compared to no drug use. Among DOT participants, active drug use was not associated with worse adherence. CONCLUSIONS Active opiate or polysubstance use decreases antiretroviral adherence, but the negative impact of drug use on adherence is eliminated by antiretroviral DOT.

Impact of adherence counseling dose on antiretroviral adherence and HIV viral load among HIV-infected methadone maintained drug users

Abstract Adherence counseling can improve antiretroviral adherence and related health outcomes in HIV-infected individuals. However, little is known about how much counseling is necessary to achieve clinically significant effects. We investigated antiretroviral adherence and HIV viral load relative to the number of hours of adherence counseling received by 60 HIV-infected drug users participating in a trial of directly observed antiretroviral therapy delivered in methadone clinics. Our adherence counseling intervention combined motivational interviewing and cognitive-behavioral counseling, was designed to include six 30 minute individual counseling sessions with unlimited “booster” sessions, and was offered to all participants in the parent trial. We found that, among those who participated in adherence counseling, dose of counseling had a significant positive relationship with antiretroviral adherence measured after the conclusion of counseling. Specifically, a liner mixed-effects model revealed that each additional hour of counseling was significantly associated with a 20% increase in post-counseling adherence. However, the number of cumulative adherence counseling hours was not significantly associated with HIV viral load, also measured after the conclusion of counseling. Our findings suggest that more intensive adherence counseling interventions may have a greater impact on antiretroviral adherence than less intensive interventions; however, it remains unknown how much counseling is required to impact HIV viral load.