Gregory M. Lucas

Detrimental effects of continued illicit drug use on the treatment of HIV-1 infection.

Objective: To identify the effects of substance abuse status (active, former, and never) on utilization of highly active antiretroviral therapy (HAART), medication adherence, and virologic and immunologic responses to therapy. Design: Prospective cohort study of 764 HIV‐1‐infected patients who attended an urban HIV clinic and participated in a standardized interview. Main Outcome Measures: Past utilization of HAART, self‐reported nonadherence with antiretroviral therapy, and changes in HIV‐1 RNA level and CD4+ lymphocyte count relative to prior peak and nadir, respectively. Results: Forty‐four percent of active drug users failed to utilize HAART compared with 22% of former drug users and 18% of non‐drug users (p < .001 for both comparisons). Among participants who were taking antiretroviral therapy when interviewed, active drug users were more likely to report medication nonadherence (34% vs. 24% of nonusers and 17% of former users), had a smaller median reduction in HIV‐1 RNA from baseline (0.8 log10 copies/ml vs. 1.7 in nonusers and 1.6 in former users), and had smaller median increases in CD4+ lymphocyte count from baseline (65 cells/mm3 vs. 116 in nonusers and 122 in former users) (p < .05 for all comparisons with active users). Conclusions: Active drug use was strongly associated with underutilization of HAART, nonadherence, and inferior virologic and immunologic responses to therapy, whereas former drug users and non‐drug users were similar in all outcomes. Effective strategies are needed that integrate HIV‐1 and substance abuse treatments.

Longitudinal assessment of the effects of drug and alcohol abuse on HIV-1 treatment outcomes in an urban clinic.

Objective To assess the temporal association of changes in substance abuse with antiretroviral therapy use and adherence, HIV-1 RNA suppression, and CD4 cell count changes in patients attending an urban clinic. Design Prospective cohort study. Methods Six-hundred and ninety-five HIV-1-infected individuals, who completed two or more semi-annual standardized surveys and in whom antiretroviral therapy was indicated, were included in the analysis. Surveys addressed antiretroviral therapy use and adherence, and use of illicit drugs and alcohol. Substance abuse was defined as active heroin, cocaine, or heavy alcohol use in the 6 months preceding survey. The units of analysis were consecutive pairs of surveys (couplets) in individual participants. Couplets in which participants denied substance abuse in both surveys were compared to couplets in which participants switched from non-use to substance abuse, and couplets in which participants reported substance abuse in both surveys were compared to couplets where participants switched from substance abuse to non-use. Results Switching from non-use to substance abuse was strongly associated with worsening antiretroviral therapy use and adherence, less frequent HIV-1 RNA suppression, and blunted CD4 cell increases, compared to remaining free of substance abuse. Alternatively, switching from substance abuse to non-use was strongly associated with improvements in antiretroviral therapy use and adherence, and HIV-1 treatment outcomes, compared to persisting with substance abuse. Conclusions This longitudinal study highlights the dynamic nature of substance abuse and its temporal association with the effectiveness of HIV-1 treatment in patients attending an inner-city clinic.

Highly active antiretroviral therapy and the incidence of HIV-1-associated nephropathy: a 12-year cohort study

Objective: to assess temporal changes in the incidence of human immunodeficiency virus-1-associated nephropathy (HIVAN), and the association with use of highly active antiretroviral therapy (HAART). Methods: HIVAN incidence and risk factors were assessed in 3976 HIV-1-infected individuals followed in clinical cohort in Baltimore, Maryland, USA from 1989 to 2001. The incidence of HIVAN, defined by biopsy or a conservative uniformly applied clinical coding protocol, was expressed in terms of person-years, and Poisson regression was used for multivariate analysis. Results: Ninety-four patients developed HIVAN over the course of the study for an incidence of 8.0 per 1000 person-years [95% confidence interval (CI), 6.5 to 9.8]. African American race and advanced immunosuppression were strongly associated with HIVAN risk. HIVAN incidence declined significantly in 1998–2001 compared with 1995–1997. Among patients with a prior diagnosis of AIDS, HIVAN incidence was 26.4, 14.4, and 6.8 per 1000 person-years in patients not receiving antiretroviral therapy, treated with nucleoside analogue therapy only, or treated with HAART, respectively (P < 0.001 for trend). In multivariate analysis, HIVAN risk was reduced 60% (95% CI, −30 to −80%) by use of HAART, and no patient developed HIVAN when HAART had been initiated prior to the development of AIDS. Conclusion: HAART was associated with a substantial reduction in HIVAN incidence. Additional follow-up will be needed to determine if renal damage in susceptible individuals is halted or merely slowed by HAART, particularly when control of viremia is incomplete or intermittent.

Vancomycin-Resistant and Vancomycin-Susceptible Enterococcal Bacteremia: Comparison of Clinical Features and Outcomes

Vancomycin-resistant Enterococcus (VRE) is a major nosocomial pathogen. We collected clinical and laboratory data on 93 hospitalized adults with VRE bacteremia and 101 adults with vancomycin-susceptible enterococcal (VSE) bacteremia. Risk factors for VRE bacteremia included central venous catheterization, hyperalimentation, and prolonged hospitalization prior to the initial blood culture. VRE-infected patients were less likely to have undergone recent surgery or have polymicrobial bacteremia, suggesting a pathogenesis distinct from traditional VSE bacteremia. Prior exposure to metronidazole was the only significant pharmacologic risk factor for VRE bacteremia. Animal studies suggest metronidazole potentiates enterococcal overgrowth in the gastrointestinal tract and translocation into the bloodstream. An increasing APACHE II score was the major risk factor for death in a multivariate analysis, with VRE status being of only borderline significance.

Chronic Kidney Disease Incidence, and Progression to End-Stage Renal Disease, in HIV-Infected Individuals: A Tale of Two Races

BACKGROUND Little is known about the racial differences in the incidence and progression of HIV-related chronic kidney disease (CKD) that underlie African American-white disparities in HIV-related end-stage renal disease (ESRD). METHODS In a cohort in Baltimore, Maryland, we measured CKD incidence, glomerular filtration rate (GFR) slope, and progression to ESRD in 3332 African American and 927 white HIV-infected subjects. RESULTS A total of 284 subjects developed CKD, 100 (35%) of whom subsequently developed ESRD. African American subjects were at slightly increased risk for incident CKD, compared with white subjects (hazard ratio [HR], 1.9 [95% confidence interval {CI}, 1.2-2.8]). However, once CKD had commenced, the African American subjects developed ESRD markedly faster than did the white subjects (HR, 17.7 [95% CI, 2.5-127.0]), and, correspondingly, their GFR decline after diagnosis of CKD was 6-fold more rapid (P < .001). In the subset of African American subjects for whom kidney-biopsy data were available, progression to ESRD was significantly faster than that in white subjects with CKD, irrespective of the presence of HIV-associated nephropathy. CONCLUSIONS The results of this study suggest that African American-white disparities in HIV-related ESRD are explained predominantly by a more aggressive natural disease history in African Americans and less by racial differences in CKD incidence.

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 (β = 1.34 [1.18, 1.53]) and achieve viral suppression (β = 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 (β = 1.25 [1.06, 1.46]) and negatively associated with being homo- or bisexual (β = 0.55 [0.35, 0.97]), homeless (β = 0.58 [0.34, 0.98]), and increasing levels of alcohol addiction severity (β = 0.17 [0.03, 0.88]). The strongest correlate of achieving viral suppression was being on ART (β = 10.27 [5.79, 18.23]). Female gender (β = 1.91 [1.07, 3.41]), Hispanic ethnicity (β = 2.82 [1.44, 5.49]), and increased general health quality of life (β = 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.

Directly Administered Antiretroviral Therapy in Methadone Clinics Is Associated with Improved HIV Treatment Outcomes, Compared with Outcomes among Concurrent Comparison Groups

BACKGROUND Directly administered antiretroviral therapy (DAART) in methadone clinics has the potential to improve treatment outcomes for human immunodeficiency virus (HIV)-infected injection drug users (IDUs). METHODS DAART was provided at 3 urban methadone clinics. Eighty-two participants who were initiating or reinitiating highly active antiretroviral therapy (HAART) received supervised doses of therapy at the clinic on the mornings on which they received methadone. Treatment outcomes in the DAART group were compared with outcomes in 3 groups of concurrent comparison patients, who were drawn from the Johns Hopkins HIV Cohort. The concurrent comparison patients were taking HAART on a self-administered basis. The 3 groups of concurrent comparison patients were as follows: patients with a history of IDU who were receiving methadone at the time HAART was used (the IDU-methadone group; 75 patients), patients with a history of IDU who were not receiving methadone at the time that HAART was used (the IDU-nonmethadone group; 244 patients), and patients with no history of IDU (the non-IDU group; 490 patients). RESULTS At 12 months, 56% of DAART participants achieved an HIV type 1 RNA level <400 copies/mL, compared with 32% of participants in the IDU-methadone group (P=.009), 33% of those in the IDU-nonmethadone group (P=.001), and 44% of those in the non-IDU group (P=.077). The DAART group experienced a median increase in the CD4 cell count of 74 cells/mm3, compared with 21 cells/mm3 in the IDU-methadone group (P=.04), 33 cells/mm3 in the IDU-nonmethadone group (P=.09), and 84 cells/mm3 in the non-IDU group (P=.98). After adjustment for other covariates in a logistic regression model, DAART participants were significantly more likely to achieve viral suppression than were patients in each of the 3 comparison groups. CONCLUSIONS These results suggest that methadone clinic-based DAART has the potential to provide substantial clinical benefit for HIV-infected IDUs.

Limited effectiveness of antiviral treatment for hepatitis C in an urban HIV clinic

Objective:To evaluate predictors and trends of referral for hepatitis C virus (HCV) care, clinic attendance and treatment in an urban HIV clinic. Design and methods:A retrospective cohort analysis in which 845 of 1318 co-infected adults who attended the Johns Hopkins HIV clinic between 1998 and 2003 after an on-site viral hepatitis clinic was opened, attended regularly (≥ 1 visit/year for ≥ 2 years). Logistic regression was used to examine predictors of referral. Results:A total of 277 (33%) of 845 were referred for HCV care. Independent predictors of referral included percentage elevated alanine aminotransferase levels [adjusted odds ratio (AOR) for 10% increase,1.16; 95% confidence interval (CI), 1.10–1.22] and CD4 cell count > 350 cells/μl (AOR, 3.20; 95% CI, 2.10–4.90), while injection drug use was a barrier to referral (AOR, 0.26; 95% CI, 0.11–0.64). Overall referral rate increased from < 1% in 1998 to 28% in 2003; however, even in 2003, 65% of those with CD4 cell count > 200 cells/μl were not referred. One hundred and eighty-five (67%) of 277 referred kept their appointment, of whom 32% failed to complete a pre-treatment evaluation. Of the remaining 125, only 69 (55%) were medically eligible for treatment, and 29 (42%) underwent HCV treatment. Ninety percent of 29 were infected with genotype 1 and 70% were African American; six (21%) achieved sustained virologic response (SVR). Only 0.7% of the full cohort achieved SVR. Conclusions:Although the potential for SVR and the recent marked increase in access to HCV care are encouraging, overall effectiveness of anti-HCV treatment in this urban, chiefly African American, HCV genotype 1 HIV clinic is extremely low. New therapies and treatment strategies are an urgent medical need.

Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patients individual circumstances.

Buprenorphine use : The international experience

The confluence of the heroin injection epidemic and the human immunodeficiency virus (HIV) infection epidemic has increased the call for expanded access to effective treatments for both conditions. Buprenorphine and methadone are now listed on the World Health Organizations Model Essential Drugs List. In France, which has the most extensive experience, buprenorphine has been associated with a dramatic decrease in deaths due to overdose, and buprenorphine diversion appears to be associated with inadequate dosage, social vulnerability, and prescriptions from multiple providers. Other treatment models (in the United States, Australia, Germany, and Italy) and buprenorphine use in specific populations are also reviewed in the present article. In countries experiencing a dual epidemic of heroin use and HIV infection, such as former states of the Soviet Union and other eastern European and Asian countries, access to buprenorphine and methadone may be one potential tool for reducing the spread of HIV infection among injection drug users and for better engaging them in medical care.