Skiest D.,Baystate Medical Center |
Skiest D.,Community Research Initiative |
Cohen C.,Community Research Initiative |
Mounzer K.,Philadelphia FIGHT |
And 15 more authors.
HIV Clinical Trials | Year: 2011
Background: Patients with multiclass-resistant HIV-1 have limited treatment options. Raltegravir, an inhibitor of integrase, has shown excellent efficacy when used with protease inhibitors (Pis) in patients with drug-resistant HIV-1. Limited data are available however about the outcomes when using raltegravir without Pis in this population. Methods: Medical records of subjects who received raltegravir as part of the Merck EAP study 0518 were reviewed and abstracted at participating sites. Eligibility criteria included HIV positivity, age ≥16 years, limited or no treatment options due to resistance or intolerance to multiple antiretroviral regimens, detectable viremia on current treatment regimen, and documented resistance to at least one drug in each antiretroviral class (PI, NNRTI, and nucleoside analogue). Demographic, clinical, and laboratory data were collected locally using a standardized collection form. Genotypic susceptibility scores (GSS) were determined from the most recent genotypic resistance test available prior to the initiation of raltegravir. The main objective was to compare virologic results in patients who received raltegravir with a PI versus those who received raltegravir without a PI. Results: Four hundred forty-two subjects were evaluated from the respective sites in the EAP trial, of whom 340 were evaluable. The baseline mean HIV RNA was 4.6 log copies/ mL, and the mean CD4 cell count was 159 cells/μL. The median number of total and new antiretroviral agents in the background regimen was 4 and 2, respectively. Among the 254 patients who received a PI, the most common PI used was darunavir (89%). Etra-virine was commonly used in both groups: 39% of the PI group and 67% of the non-PI group. At week 12, 67% of PI patients and 64% of non-PI patients achieved HIV RNA <75 copies/mL and 85% and 86%, respectively, achieved HIV RNA <400 copies/mL GSS, which was similar in both groups at baseline, predicted achieving an HIV RNA of <400 and 75 copies/mL at week 12 (P < .05). Conclusions: In treatment-experienced patients, the combination of raltegravir with a regimen not containing a PI (used with etravirine in two-thirds of patients) had similar virologic activity when compared to more standard regimens using raltegravir with a PI. The main determinant of efficacy was the number of active drugs as measured by GSS. These data expand the potential utility of raltegravir in patients with multidrug-resistant HIV. © 2011 Thomas Land Publishers, Inc.
Sulkowski M.S.,University of Baltimore |
Naggie S.,Duke University |
Lalezari J.,Clinical Research |
Fessel W.J.,Kaiser Permanente |
And 12 more authors.
JAMA - Journal of the American Medical Association | Year: 2014
IMPORTANCE: Treatment of hepatitis C virus (HCV) infection in patients also infected with human immunodeficiency virus (HIV) has been limited due to drug interactions with antiretroviral therapies (ARTs) and the need to use interferon. OBJECTIVE: To determine the rates of HCV eradication (sustained virologic response [SVR]) and adverse events in patients with HCV-HIV coinfection receiving sofosbuvir and ribavirin treatment. DESIGN, SETTING, AND PARTICIPANTS: Open-label, nonrandomized, uncontrolled phase 3 trial conducted at 34 treatment centers in the United States and Puerto Rico (August 2012-November 2013) evaluating treatment with sofosbuvir and ribavirin among patients with HCV genotypes 1, 2, or 3 and concurrent HIV. Patients were required to be receiving ART with HIV RNA values of 50 copies/mL or less and a CD4 T-cell count of more than 200 cells/μL or to have untreated HIV infection with a CD4 T-cell count of more than 500 cells/μL. Of the treatment-naive patients, 114 had HCV genotype 1 and 68 had HCV genotype 2 or 3, and 41 treatment experienced participants who had been treated with peginterferon-ribavirin had HCV genotype 2 or 3, for a total of 223 participants. INTERVENTIONS: Treatment-naive patients with HCV genotype 2 or 3 received 400 mg of sofosbuvir and weight-based ribavirin for 12 weeks and treatment-naive patients with HCV genotype 1 and treatment-experienced patients with HCV genotype 2 or 3 received the same treatment for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary study outcomewas the proportion of patients with SVR (serum HCV <25 copies/mL) 12 weeks (SVR12) after cessation of HCV therapy. RESULTS: Among treatment-naive participants, 87 patients (76%) of 114 (95%CI, 67%-84%) with genotype 1, 23 patients (88%) of 26 with genotype 2 (95%CI, 70%-985), and 28 patients (67%) of 42 with genotype 3 (95%CI, 51%-80%) achieved SVR12. Among treatment-experienced participants, 22 patients (92%) of 24 with genotype 2 (95%CI, 73%-99%) and 16 patients (94%) of 17 (95%CI, 71%-100%) achieved SVR12. The most common adverse events were fatigue, insomnia, headache, and nausea. Seven patients (3%) discontinued HCV treatment due to adverse events. No adverse effect on HIV disease or its treatment was observed. CONCLUSIONS AND RELEVANCE: In this open-label, nonrandomized, uncontrolled study, patients with HIV who were coinfected with HCV genotype 1, 2, or 3 who received the oral, interferon-free combination of sofosbuvir and ribavirin for 12 or 24 weeks had high rates of SVR12. Further studies of this oral regimen in diverse populations of coinfected patients are warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01667731. Copyright 2014 American Medical Association. All rights reserved.
Azzoni L.,Wistar Institute |
Foulkes A.S.,University of Massachusetts Amherst |
Liu Y.,University of Massachusetts Amherst |
Li X.,BG Medicine |
And 11 more authors.
PLoS Medicine | Year: 2012
Background: Global programs of anti-HIV treatment depend on sustained laboratory capacity to assess treatment initiation thresholds and treatment response over time. Currently, there is no valid alternative to CD4 count testing for monitoring immunologic responses to treatment, but laboratory cost and capacity limit access to CD4 testing in resource-constrained settings. Thus, methods to prioritize patients for CD4 count testing could improve treatment monitoring by optimizing resource allocation. Methods and Findings: Using a prospective cohort of HIV-infected patients (n = 1,956) monitored upon antiretroviral therapy initiation in seven clinical sites with distinct geographical and socio-economic settings, we retrospectively apply a novel prediction-based classification (PBC) modeling method. The model uses repeatedly measured biomarkers (white blood cell count and lymphocyte percent) to predict CD4 + T cell outcome through first-stage modeling and subsequent classification based on clinically relevant thresholds (CD4 + T cell count of 200 or 350 cells/μl). The algorithm correctly classified 90% (cross-validation estimate = 91.5%, standard deviation [SD] = 4.5%) of CD4 count measurements <200 cells/μl in the first year of follow-up; if laboratory testing is applied only to patients predicted to be below the 200-cells/μl threshold, we estimate a potential savings of 54.3% (SD = 4.2%) in CD4 testing capacity. A capacity savings of 34% (SD = 3.9%) is predicted using a CD4 threshold of 350 cells/μl. Similar results were obtained over the 3 y of follow-up available (n = 619). Limitations include a need for future economic healthcare outcome analysis, a need for assessment of extensibility beyond the 3-y observation time, and the need to assign a false positive threshold. Conclusions: Our results support the use of PBC modeling as a triage point at the laboratory, lessening the need for laboratory-based CD4 + T cell count testing; implementation of this tool could help optimize the use of laboratory resources, directing CD4 testing towards higher-risk patients. However, further prospective studies and economic analyses are needed to demonstrate that the PBC model can be effectively applied in clinical settings. © 2012 Azzoni et al.
Brooks A.C.,Treatment Research Institute |
DiGuiseppi G.,Treatment Research Institute |
Laudet A.,National Development and Research Institute |
Rosenwasser B.,Philadelphia FIGHT |
And 5 more authors.
Journal of Substance Abuse Treatment | Year: 2012
Training community-based addiction counselors in empirically supported treatments (ESTs) far exceeds the ever-decreasing resources of publicly funded treatment agencies. This feasibility study describes the development and pilot testing of a group counseling toolkit (an approach adapted from the education field) focused on relapse prevention (RP). When counselors (N = 17) used the RP toolkit after 3 hours of training, their content adherence scores on "coping with craving" and "drug refusal skills" showed significant improvement, as indicated by very large effect sizes (Cohen's d = 1.49 and 1.34, respectively). Counselor skillfulness, in the "adequate-to-average" range at baseline, did not change. Although this feasibility study indicates some benefit to counselor EST acquisition, it is important to note that the impact of the curriculum on client outcomes is unknown. Because a majority of addiction treatment is delivered in group format, a multimedia curriculum approach may assist counselors in applying ESTs in the context of actual service delivery. © 2012 Elsevier Inc.
Lee S.R.,Orasure Technologies, Inc. |
Kardos K.W.,Orasure Technologies, Inc. |
Schiff E.,University of Miami |
Berne C.A.,West Corporation |
And 16 more authors.
Journal of Virological Methods | Year: 2011
The availability of a highly accurate, rapid, point-of-care test for hepatitis C virus (HCV) may be useful in addressing the problem of under-diagnosis of HCV, by increasing opportunities for testing outside of traditional clinical settings. A new HCV rapid test device (OraQuick® HCV Rapid Antibody Test), approved recently in Europe for use with venous blood, fingerstick blood, serum, plasma, or oral fluid was evaluated in a multi-center study and performance compared to established laboratory-based tests for detection of HCV.The HCV rapid test was evaluated in prospective testing of subjects with signs and/or symptoms of hepatitis, or who were at risk for hepatitis C using all 5 specimen types. Performance was assessed relative to HCV serostatus established by laboratory methods (EIA, RIBA and PCR) approved in Europe for diagnosis of hepatitis C infection. Sensitivity to antibody in early infection was also compared to EIA in 27 seroconversion panels. In addition, the reliability of the oral fluid sample for accurate detection of anti-HCV was assessed by studying the impact of various potentially interfering conditions of oral health, use of oral care products and consumption of food and drink.In this large study of at-risk and symptomatic persons, the overall specificities of the OraQuick® HCV Rapid Antibody Test were equivalent (99.6-99.9%) for all 5 specimen types and the 95% CIs substantially overlapped. Overall sensitivities were virtually identical for venous blood, fingerstick blood, serum and plasma (99.7-99.9%). Observed sensitivity was slightly lower for oral fluid at 98.1% though the upper CI (99.0%) was equal to the lower CI for venous blood and fingerstick blood. Most of the HCV positive subjects which gave nonreactive results in oral fluid had serological and virological results consistent with resolved infection. Sensitivity for anti-HCV in early seroconversion was virtually identical between the HCV rapid test and EIA. Detection of anti-HCV in oral fluid appeared generally robust to conditions of oral health, consumption of food and drink and use of oral care products.The OraQuick® HCV Rapid Antibody Test demonstrated clinical performance that was equivalent to current laboratory-based EIA. This new, HCV rapid test appears suitable as an aid in the diagnosis of HCV infection and may increase testing opportunities due to its simplicity and flexibility to use multiple specimen types, including fingerstick blood and oral fluid. © 2010 Elsevier B.V.