Differences in Calculated Glomerular Filtration Rates (GFR) in Efavirenz (EFV) or Tenofovir (TDF)-treated Adults in ESS40006
|
|
- Barnaby Burke
- 5 years ago
- Views:
Transcription
1 13th Conference on Retroviruses and Opportunistic Infections Denver, CO, USA. February 5-9, 2006 Poster Number 777 Differences in Calculated Glomerular Filtration Rates (GFR) in Efavirenz (EFV) or Tenofovir (TDF)-treated Adults in ESS40006 M Thompson 1, R Haubrich 2, D Margolis 3, S Schneider 4, R Schooley 5, K Pappa 6, J Sall 6, L Yau 6 and J Hernandez 6 1 AIDS Res. Con. of Atlanta, GA; 2 UCSD, San Diego, CA; 3 UNC, Chapel Hill, NC; 4 Saint Mary Med. Ctr. Care Clinic, Long Beach, CA; 5 UCSD, San Diego, CA; 6 GlaxoSmithKline, RTP, NC. Introduction Kidney disease is an important complication of HIV infection. Patients infected with HIV may develop HIV associated nephropathy (HIVAN) or, less commonly, an IgA-mediated anti-hiv immune complex glomerulonephritis. Likewise, patients with HIV and comorbidities such as Hepatitis B or C, diabetes, and hypertension may develop an array of associated nephropathies. In addition, antiretroviral therapies (ART) have been associated with renal dysfunction. ART drugs most commonly reported to cause nephrotoxic effects include: indinavir, adefovir and tenofovir disoproxil fumarate (TDF). 1-3 Several observational cohorts have reported a higher degree of nephrotoxicity in patients treated with TDF compared to nucleosides. 4-6 Recently the HIV Medicine Association of the Infectious Disease Society of America published guidelines for the management of chronic kidney disease in HIV infected patients. 7 The guidelines recommend that renal function be followed in patients infected with HIV by monitoring either creatinine clearance which can be calculated by the Cockcroft-Gault equation or by following glomerular filtration rate (GFR) as calculated by the simplified Modification of Diet in Renal Disease equation (MDRD). The MDRD formula includes race as a variable, while the Cockcroft-Gault method does not. Since this study includes a significant number of African-Americans, and because race has been strongly associated with HIVAN, we used the MDRD formula for these analyses. To explore the issue of tenofovir-associated nephrotoxicity, we analyzed the clinical trial database from ESS This study was designed as a randomized comparison of two regimens of amprenavir/ritonavir (APV/r) at doses of 600/100 mg vs 900/100 mg twice daily in subjects failing their current ART regimen. All patients also took abacavir. In addition, a non-randomized assignment was made to efavirenz (EFV) for NNRTI-naïve subjects or to TDF for NNRTI-experienced subjects. Patients took one additional nucleoside reverse transcriptase inhibitor as part of their regimen (Figure 1). To examine the effect of these regimens on renal function, we calculated GFR by MDRD using serum creatinine values obtained during the course of the trial. Because patients were not randomized to TDF or EFV in this study, this exploration should be regarded as an observational analysis, although within the closely monitored environment of a clinical trial.
2 Figure 1 Study Design PI failure >12 wks HIV RNA >1000 cpm CD4 >50/mm 3 FC Abacavir <5x FC Amprenavir <4x FC NRTIs <4x NNRTI naïve NNRTI failure 38 patients 76 patients r/apv 600/900 abacavir efavirenz 1 other NRTI r/apv 600/900 abacavir tenofovir 1 other NRTI Methods Descriptive statistics were summarized for subjects treated with EFV or TDF. Glomerular filtration rate was calculated for both groups on retrospective data by using the MDRD equation: GFR (ml/min/1.73m 2 ) = 186 X serum creatinine (mg/dl) X [age (yrs)] X [0.742 if female] X [1.212 if black] Potential predictors of GFR decline over 48 weeks of therapy were assessed using multiple regression analyses and include: baseline (BL) demographic data (age, weight, sex, and race) and other baseline characteristics (CDC HIV-1 classification, HIV risk factors, CD4+ cell count, plasma HIV-1 RNA, prior therapy, concurrent ART, and clinical laboratory results). No data were available for history of hypertension, Hepatitis C or diabetes but serum blood glucose at baseline and at Weeks 24 and 48 was used as a surrogate for diabetes. Data on the presence or absence of proteinuria were not available. Each potential predictor was studied using a univariate regression model with the Week 48 change from baseline in the calculated GFR as the dependent variable. Then predictors with a p-value of <0.1 in the univariate analyses were included a multiple regression model for the Week 48 change from baseline in calculated GFR (adjusted for the baseline calculated GFR). Significant covariates (p-value <0.05) were selected to remain in the final regression model based on the stepwise selection method. Results A total of 114 subjects were randomized in the ITT population for the comparison of APV/r dosing. Of these, 76 were assigned to TDF-containing regimens and 38 were assigned to EFV-containing regimens. Baseline (BL) demographics and disease characteristics, including BL serum creatinine and calculated GFR, are summarized for the ITT population in both groups (Table 1).
3 Table 1 Baseline Demographics and Disease Characteristics Median (range) or % APV + TDF (n=76) APV + EFV (n=38) Age (years) 42 (26-65) 43 (24-64) Sex (% male) 80% 92% Race (% white, black) 59%, 25% 34%, 50% Weight (kg) 78.9 (46-126) 81.5 (52-123) CDC Classification, % (A, B, C) 37%, 30%, 33% 37%, 29%, 34% HIV Risk Factors Heterosexual contact 33% 37% Homosexual contact 66% 74% Injectable drug use 8% 5% HIV-1 RNA, log 10 copies/ml 4.09 ( ) 4.08 ( ) CD4, cells/mm ( ) 229 (53-896) Serum Creatinine (mg/dl) 0.8 ( ) 0.9 ( ) Calculated GFR (ml/min/1.73m 2 ) 108 (58-196) 107 (51-237) Serum Glucose (mg/dl) 92 (67-224) 93 (67-236) Duration of Prior ART (months) ( ) ( ) Duration of Prior PI Therapy (months) ( ) ( ) Duration of Prior NRTI Therapy (months) ( ) ( ) The baseline characteristics for both groups of patients were comparable with respect to age, weight and HIV-disease; a higher proportion of patients in the EFV group were male and black. Due to the study design, the duration of prior ART therapy was generally longer in the TDF group compared to the EFV group (57 vs 37 months); however, there were no differences in the baseline median glucose levels, creatinine levels or the calculated GFR. At baseline, the median calculated GFR in the EFV-treated subjects was 107 ml/min/1.73m 2 and in the TDF-treated subjects was 108 ml/min/1.73m 2. In an intent-to-treat observed analysis, the group receiving TDF had a statistically significant median reduction from baseline in calculated GFR were seen at both Weeks 24 (p <0.001) and 48 (p <0.001) (Figure 2). At 24 weeks, the magnitude of the change from baseline in the TDF treated group was -10 ml/min/1.73m 2, and the change from baseline in the EFV group was +12 ml/min/1.73m 2. At 48 weeks, the magnitude of change in the TDF treated group was -11 ml/min/1.73m 2, and the change from baseline in the EFV group was +0.4 ml/min/1.73m 2. The group receiving EFV had a statistically significant median increase from baseline in calculated GFR at Week 24 (+12 ml/min/1.73m 2 ) but there was no difference at Week 48.
4 Figure 2 Change in Calculated GFR from Baseline for Individual Subjects at Weeks 24 and APV+TDF APV+EFV 60 Median Change from Baseline Week 24 Week 48 Week 24 Week 48 n = Signed Rank p-value = <0.001 < Statistically significant differences in the median change in calculated GFR from BL between the EFV-treated and TDF-treated subjects were observed at both weeks 24 (p<0.001) and 48 (p=0.004) (Figure 3). Figure 3 Fold Change in IC50 (+APL / APL) Determined by Two Different Assays Wk 2 Wk 4 Wk 8 Wk 12 Wk 16 WK 24 Wk 32 Wk 40 Wk Median change from baseline with IQR p<0.001* p=0.004* -30 n = n = TDF EFV IQR = interquartile range, Q1 = 25 th percentile, Q3 = 75 th percentile * p-values were based on the Wilcoxon rank-sum test The results of the univariate regression analysis exploring for predictors of the change in calculated GFR are shown in Table 2. Univariate predictors of change in GFR were baseline calculated GFR and serum creatinine (p <0.001), baseline viral load >50,000 or >100,000 copies/ml, TDF in the regimen (p <0.1), and baseline glucose (p <0.05). The parameter estimates of the final multiple regression model adjusted for BL calculated GFR are shown in Figure 4. The only predictor for the decline in calculated GFR over 48 weeks in the final multiple regression model after adjusting for BL calculated GFR was TDF use in the current regimen (p <0.001).
5 Table 2 Results of Univariate Regression Models Predicting Week 48 Change in Calculated GFR from Baseline Age (years) Weight (kg) Race White Black Hispanic Sex BL CDC Classification HIV Risk Factors BL calculated GFR*** BL serum creatinine (mg/dl)*** BL serum glucose (mg/dl)** BL CD4+ cell count (cells/mm 3 ) BL CD4+ cell count <50 cells/mm3 BL CD4+ cell count <200 cells/mm3 TDF in current regimen* 3TC in current regimen d4t in current regimen ddi in current regimen ZDV in current regimen BL viral load (log 10 copies/ml) BL viral load >5000 copies/ml BL viral load >10,000 copies/ml BL viral load >20,000 copies/ml BL viral load >50,000 copies/ml* BL viral load >100,000 copies/ml* Prior NNRTI experience (yes/no) Prior PI experience (yes/no) Prior NRTI exposure (months) Prior NNRTI exposure (months) Prior PI exposure (months) *p-value <0.1, **p-value<0.05, ***p-value<0.001 Figure 4 Multiple Regression Model Predicting Week 48 Change in Calculated GFR from Baseline TDF in current regimen (p<0.001) BL calculated GFR (p<0.001) Parameter Estimates and 95% Confidence Intervals
6 Discussion Randomized, controlled clinical trials of tenofovir given over at least 48 weeks (GS 934, 903, 907) have not shown evidence of renal dysfunction associated with TDF use. Reports of renal disorders associated with TDF use have been sporadic over the past few years The majority of these cases of renal impairment occurred in subjects with other identified risk factors such as lower CD4 cell count, prior adefovir use, low body weight, decreased renal function at baseline, and diabetes. However, in this study population none of these risk factors were significantly different between the subjects treated with TDF or EFV-containing regimens at baseline. Since this trial was not a randomized comparison of TDF compared with EFV, it is possible that factors other than TDF use alone were responsible for the reduction in calculated GFR from baseline. Patients on TDF had significantly longer duration of prior therapy compared to the EFV group. However, none of the parameters explored to evaluate these differences, including months of prior NRTIs were identified to be predictors of the change in calculated GFR. The time on prior therapy for individual drugs was not ascertained. In addition, nucleoside agents have shown not to exhibit clinically significant changes in calculated GFR. 11 Other factors that were not accounted for in this analysis include non-antiretroviral concomitant therapies, hypertension, diabetes, and Hepatitis C that may have influenced renal function. Baseline proteinuria was not assessed. Because all patients in this trial were on a boosted PI regimen, we were unable to address the issue of whether ritonavir plays a role in TDF nephrotoxicity. Conclusion A small but statistically significant decline in the median calculated GFR was observed at 24 and 48 weeks of therapy for NNRTI-experienced subjects treated with TDF in this study. The clinical significance of this change in calculated GFR is not known. This decline was not seen in the NNRTI-naïve subjects treated with EFV, and an increase in median calculated GFR was observed in this group at 24 weeks. TDF use was the only predictor of calculated GFR decline using multiple regression analysis (after adjusting for BL calculated GFR). Glomerular filtration rates should be followed in patients at risk for chronic kidney disease and in those on antiretroviral therapy with higher risk of causing nephrotoxicity. Calculated GFR should be routinely monitored in clinical trials of antiretroviral therapy and results which include GFR grouped by National Kidney Foundation (NKF) category should be reported for regimens in clinical trials. 12 Further analysis of other trials involving TDF may be helpful in further identifying high risk patients for the development of nephrotoxicity. References 1. Perazella MA. Drug induced renal failure: Update on new medications and new mechanisms of nephrotoxicity. Am J Med Sci 2003; 325: Benhamou Y et al. Safety and efficacy of adefovir dipivoxil in patients coinfected with HIV and lamivudine resistant hepatitis B viruses: an open label pilot study. Lancet 2001; 3587: Rifkin BS et al. Tenofovir-associated nephrotoxicity: Fanconi syndrome and renal failure. Am J Med 2004; 117: Gallant JE et al. Changes in renal function associated with tenofovir disoproxil fumarate treatment, compared with nucleoside reverse-transcriptase inhibitor treatment. CID 2005; 40: Mauss S et al. Antiretroviral therapy with tenofovir is associated with mild renal dysfunction. AIDS 2005; 19(1): Stebbing J et al. Case-control data regarding renal dysfunction and tenofovir DF. Contagion 2005; 2(7): Gupta SK et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. CID 2005; 40: Gaspar G et al. Fanconi syndrome and acute renal failure in a patient treated with tenofovir: a call to action. AIDS 2004; 18: Peyriere H et al. Renal tubular dysfunction associated with tenofovir therapy: report of 7 cases. JAIDS 2004; 35: Karras A et al. Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus. CID 2003; 36: Sutherland-Phillips D et al. Regimens containing abacavir (ABC), lamivudine (3TC), zidovudine (ZDV), and efavirenz (EFV) do not affect GFR during long-term treatment of HIV naive subjects. Poster H-349 at 45th ICAAC, Dec 2005, Washington, DC. 12. Levey AS et al. National kidney foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003; 139: Acknowledgements We gratefully acknowledge the many study participants, clinical investigators and staff, and the Clinical Trials Management Services (CTMS) and GlaxoSmithKline (GSK) study teams PEARL Study Investigators: A Barile, J Baxter, S Becker, P Benson, D Blazes, A Burnside Jr, D Butcher, P Cimoch, D Cohen, G Coodley, T File, J Glaser, M Goetz, B Gripshover, S Hammer, S Jacobson, A Kelly, T Larson, D Parks, G Perez, P Piliero, D Richman, M Sands, M Sension, A Taege, J Timpone, P Wolfe, W Woodward, and D Wright CTMS: M Carrier, W Crumpton, N Haige, T Hardin, P Kilgore, S McKinney, R Perkins, and G Sproles GSK: T Becom, L Chandler, A Pierce, S Ross, and S Hessenthaler
43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) A Cutrell, J Hernandez, M Edwards, J Fleming, W Powell, T Scott
43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Poster H-2013 Clinical Risk Factors for Hypersensitivity Reactions to Abacavir: Retrospective Analysis of Over 8,000 Subjects
More informationRenal safety of tenofovir containing antiretroviral regimen in a Singapore cohort
Chua et al. AIDS Research and Therapy 2012, 9:19 SHORT REPORT Open Access Renal safety of tenofovir containing antiretroviral regimen in a Singapore cohort Arlene C Chua 1*, Ryan M Llorin 1, Kelvin Lai
More informationChanges in Renal Function Associated with Tenofovir Disoproxil Fumarate Treatment, Compared with Nucleoside Reverse-Transcriptase Inhibitor Treatment
HIV/AIDS BRIEF REPORT Changes in Renal Function Associated with Tenofovir Disoproxil Fumarate Treatment, Compared with Nucleoside Reverse-Transcriptase Inhibitor Treatment Joel E. Gallant, Michelle A.
More informationAnumber of clinical trials have demonstrated
IMPROVING THE UTILITY OF PHENOTYPE RESISTANCE ASSAYS: NEW CUT-POINTS AND INTERPRETATION * Richard Haubrich, MD ABSTRACT The interpretation of a phenotype assay is determined by the cut-point, which defines
More informationIntegrase Strand Transfer Inhibitors on the Horizon
NORTHWEST AIDS EDUCATION AND TRAINING CENTER Integrase Strand Transfer Inhibitors on the Horizon David Spach, MD Clinical Director, Northwest AETC Professor of Medicine, University of Washington Presentation
More informationStudy No.: Title: Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment: Objectives: Primary Outcome/Efficacy Variable:
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
More information3rd IAS Conference on HIV Pathogenesis and Treatment. Poster Number Abstract #
3rd IAS Conference on HIV Pathogenesis and Treatment 24 27 July 2005, Rio de Janeiro, Brazil Poster Number Abstract # TuFo0106 TuFo0106 Characterization of Anemia in HIV-infected (HIV+) Subjects Treated
More informationSpecial Challenges and Co-Morbidities
Special Challenges and Co-Morbidities Renal Disease/ Hypertension/ Diabetes in African-Americans M. Keith Rawlings, MD Medical Director Peabody Health Center AIDS Arms, Inc Dallas, TX Chair, Internal Medicine
More informationRenal safety of tenofovir in HIV-infected patients who switch from stavudine or zidovudine to tenofovir
Original Article Vol. 29 No. 3 Renal safety of tenofovir:- Wiwattanathum P & Sungkanuparph S. 113 Renal safety of tenofovir in HIV-infected patients who switch from stavudine or zidovudine to tenofovir
More informationReal Life Experience of Dolutegravir and Lamivudine Dual Therapy As a Switching Regimen in HIVTR Cohort
Real Life Experience of Dolutegravir and Lamivudine Dual Therapy As a Switching Regimen in HIVTR Cohort Yagci-Caglayik D 1, Gokengin D 2, Inan A 3, Ozkan-Ozdemir H 4, Inan D 5, Akbulut A 6, Korten V 1,
More informationSINGLE. Efficacy and safety of dolutegravir (DTG) in treatment-naïve subjects
SINGLE Efficacy and safety of dolutegravir (DTG) in treatment-naïve subjects SE/HIV/0023/14 January 2014 PHASE III DTG TRIALS IN TREATMENT-NAÏVE ADULT SUBJECTS WITH HIV SINGLE 1 N=833 Phase III non-inferiority,
More informationTDF containing ART: Efficacy and Safety. Dr Lloyd B. Mulenga Adult Infectious Diseases Centre University Teaching Hospital Lusaka, Zambia
TDF containing ART: Efficacy and Safety Dr Lloyd B. Mulenga Adult Infectious Diseases Centre University Teaching Hospital Lusaka, Zambia 1 Indications Treatment of HIV-1 in combination with other antiretroviral
More informationCOMPETING INTEREST OF FINANCIAL VALUE
BHIVA AUTUMN CONFERENCE 2012 Including CHIVA Parallel Sessions Dr Ian Williams University College London Medical School COMPETING INTEREST OF FINANCIAL VALUE > 1,000: Speaker Name Statement Ian Williams
More informationManagement of NRTI Resistance
NORTHWEST AIDS EDUCATION AND TRAINING CENTER Management of NRTI Resistance David Spach, MD Principal Investigator, NW AETC Professor of Medicine, Division of Infectious Diseases University of Washington
More informationSupplementary Data. Supplementary Table S2. Antiretroviral Therapies Taken with Ledipasvir/Sofosbuvir
Supplementary Data Statistical Analysis Due to the limited number of patients with acute kidney injury and concern for model overfitting, covariates included in multivariable logistic regression analyses
More informationSupplemental Digital Content 1. Combination antiretroviral therapy regimens utilized in each study
Supplemental Digital Content 1. Combination antiretroviral therapy regimens utilized in each study Study Almeida 2011 Auld 2011 Bassett 2012 Bastard 2012 Boulle 2008 (a) Boulle 2008 (b) Boulle 2010 Breen
More informationGlomerular filtration rates in HIV-infected patients treated with and without tenofovir: a prospective, observational study
Journal of Antimicrobial Chemotherapy Advance Access published December 17, 2008 Journal of Antimicrobial Chemotherapy doi:10.1093/jac/dkn499 Glomerular filtration rates in HIV-infected patients treated
More informationTDF Renal Dysfunction
TDF Renal Dysfunction Sarala Naicker MBChB, FRCP, PhD Division of Nephrology Dept of Internal Medicine University of the Witwatersrand Johannesburg South Africa SA HIV Clinician Society Conference Cape
More informationPAEDIATRIC HIV INFECTION. Dr Ashendri Pillay Paediatric Infectious Diseases Specialist
PAEDIATRIC HIV INFECTION Dr Ashendri Pillay Paediatric Infectious Diseases Specialist Paediatric HIV Infection Epidemiology Immuno-pathogenesis Antiretroviral therapy Transmission Diagnostics Clinical
More informationTenofovir plasma exposures and Creatinine Clearance changes in 1st line Regimen of African patients in Cameroon and Senegal: ANRS12115 DAYANA study
Abstract O_03 Tenofovir plasma exposures and Creatinine Clearance changes in 1st line Regimen of African patients in Cameroon and Senegal: ANRS12115 DAYANA study M.P. Lê Pharmacy Resident Clinical Pharmacology
More informationSTRIBILD (aka. The Quad Pill)
NORTHWEST AIDS EDUCATION AND TRAINING CENTER STRIBILD (aka. The Quad Pill) Brian R. Wood, MD Medical Director, NW AETC ECHO Assistant Professor of Medicine, University of Washington Presentation prepared
More informationThe impact of antiretroviral drugs on renal function
The impact of antiretroviral drugs on renal function Professor Bruce Hendry Renal Medicine King s College London King s College Hospital NHS Foundation Trust 1 DISCLOSURES: BRUCE HENDRY I have received
More informationPerspective Resistance and Replication Capacity Assays: Clinical Utility and Interpretation
Perspective Resistance and Replication Capacity Assays: Clinical Utility and Interpretation Resistance testing has emerged as an important tool for antiretroviral management. Research continues to refine
More informationEffects of cobicistat on tenofovir exposure and its long-term tolerability: is it time to rethink at TAF trials?
Effects of cobicistat on tenofovir exposure and its long-term tolerability: is it time to rethink at TAF trials? Sara Baldelli 1, Andrea Giacomelli 2, Davide Minisci 2, Cristina Mazzali 3, Laura Milazzo
More informationAntiretroviral Dosing in Renal Impairment
Protease Inhibitors (PIs) Atazanavir Reyataz hard capsules 300 mg once daily taken with ritonavir 100 mg once daily No dosage adjustment is needed for atazanavir in renal impairment Atazanavir use in haemodialysis
More informationHIV Treatment Update. Awewura Kwara, MD, MPH&TM Associate Professor of Medicine and Infectious Diseases Brown University
HIV Treatment Update Awewura Kwara, MD, MPH&TM Associate Professor of Medicine and Infectious Diseases Brown University Outline Rationale for highly active antiretroviral therapy (HAART) When to start
More informationThe impact of antiretroviral drugs on Cardiovascular Health
The impact of antiretroviral drugs on Cardiovascular Health José López-Sendón Hospital Universitario La Paz. IdiPaz Madrid. Spain Research grants and honoraria from (research committees, clinical trials,
More informationUpdate on HIV-Related Kidney Diseases. Agenda
Update on HIV-Related Kidney Diseases ANDY CHOI THE MEDICAL MANAGEMENT OF HIV/AIDS DECEMBER 15, 2006 Agenda 1. EPIDEMIOLOGY: A) END STAGE RENAL DISEASE (ESRD) B) CHRONIC KIDNEY DISEASE (CKD) 2. HIV-ASSOCIATED
More informationKimberly Adkison, 1 Lesley Kahl, 1 Elizabeth Blair, 1 Kostas Angelis, 2 Herta Crauwels, 3 Maria Nascimento, 1 Michael Aboud 1
Pharmacokinetics of Dolutegravir and Rilpivirine After Switching to the Two-Drug Regimen From an Efavirenz- or Nevirapine- Based Antiretroviral Regimen: SWORD-1 & -2 Pooled PK Analysis Kimberly Adkison,
More informationLiver Toxicity in Epidemiological Cohorts
SUPPLEMENT ARTICLE Liver Toxicity in Epidemiological Cohorts Stephen Becker Pacific Horizon Medical Group, San Francisco, California Hepatotoxicity has been demonstrated to be associated with antiretroviral
More informationTenofovir-induced nephrotoxicity: A retrospective cohort study
ORIGINAL ARTICLE Tenofovir-induced nephrotoxicity: A retrospective cohort study Hui Moon Koh, MClinPharm (UKM) 1, Suresh Kumar, MRCP (UK) 2 1 Department of Pharmacy, Sungai Buloh Hospital, Selangor, Malaysia,
More informationVitamin D Deficiency in HIV: A Shadow on Long-Term Management?
AIDS Rev. 2014;16:59-74 (Supplementary Data) Vitamin D Deficiency in HIV: A Shadow on Long-Term Management? Chloe Orkin, et al.: Vitamin D deficiency in HIV (Supplementary Data) Chloe Orkin 1, David A.
More informationSomnuek Sungkanuparph, M.D.
HIV Drug Resistance Somnuek Sungkanuparph, M.D. Associate Professor Division of Infectious Diseases Department of Medicine Faculty of Medicine Ramathibodi Hospital Mahidol University Adjunct Professor
More informationABC/3TC/ZDV ABC PBO/3TC/ZDV
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
More informationAbacavir is associated with increased risk of cardiovascular disease in HIV-infected patients: A UK clinic case-control study
Abacavir is associated with increased risk of cardiovascular disease in HIV-infected patients: A UK clinic case-control study Collins Iwuji, Duncan Churchill, Yvonne Gilleece, Martin Fisher Brighton and
More informationHigher Risk of Hyperglycemia in HIV-Infected Patients Treated with Didanosine Plus Tenofovir
6131_06_p333-337 4/5/06 10:28 AM Page 333 AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 22, Number 4, 2006, pp. 333 337 Mary Ann Liebert, Inc. Higher Risk of Hyperglycemia in HIV-Infected Patients Treated
More informationVIKING STUDIES Efficacy and safety of dolutegravir in treatment-experienced subjects
VIKING STUDIES Efficacy and safety of dolutegravir in treatment-experienced subjects IL/DLG/0040/14 June 2014 GSK (Israel) Ltd. Basel 25, Petach Tikva. Tel-03-9297100 Medical information service: il.medinfo@gsk.com
More informationA Genetic Test to Screen for Abacavir Hypersensitivity Reactions
The Future of Pharmacogenetics in HIV Clinical Care A Genetic Test to Screen for Abacavir Hypersensitivity Reactions Evan Collins & Misty Bath CANAC/ACIIS 15 th Annual Conference Vancouver, BC April 2007
More informationInvestigating the effect of antiretroviral switch to tenofovir alafenamide on lipid profiles in people living with HIV within the UCD ID Cohort
Investigating the effect of antiretroviral switch to tenofovir alafenamide on lipid profiles in people living with HIV within the UCD ID Cohort A. Lacey 1, W. Tinago 1, E. Alvarez Barco 1, A.J. Macken
More informationPediatric Antiretroviral Resistance Challenges
Pediatric Antiretroviral Resistance Challenges Thanyawee Puthanakit, MD The HIVNAT, Thai Red Cross AIDS research Center The Research Institute for Health Science, Chiang Mai University Outline The burden
More information2 nd Line Treatment and Resistance. Dr Rohit Talwani & Dr Dave Riedel 12 th June 2012
2 nd Line Treatment and Resistance Dr Rohit Talwani & Dr Dave Riedel 12 th June 2012 Overview Basics of Resistance Treatment failure Strategies to manage treatment failure Mutation Definition: A change
More informationACCEPTED. Title Page: Full Title: Elvitegravir/cobicistat/emtricitabine/tenofovir DF in HIV-Infected Patients with Mild. to Moderate Renal Impairment
JAIDS Journal of Acquired Immune Deficiency Syndromes Publish Ahead of Print DOI: 10.1097/QAI.0000000000000476 Title Page: Full Title: Elvitegravir/cobicistat/emtricitabine/tenofovir DF in HIV-Infected
More informationAntiretroviral treatment outcomes after the introduction of tenofovir in the public-sector in South Africa
Antiretroviral treatment outcomes after the introduction of tenofovir in the public-sector in South Africa Alana T Brennan, Kate Shearer, Mhairi Maskew, Prudence Ive, Ian Sanne, Matthew P Fox Health Economics
More informationThis is the author s version of a work that was submitted/accepted for publication in the following source:
This is the author s version of a work that was submitted/accepted for publication in the following source: Kelly, Mark D., Gibson, Abby, Bartlett, Harry, Rowling, Diane, & Patten, John (2013) Tenofovir-associated
More informationProteinuria, Creatinine Clearance, and Immune Activation in Antiretroviral- Naive HIV-Infected Subjects
BRIEF REPORT Proteinuria, Creatinine Clearance, and Immune Activation in Antiretroviral- Naive HIV-Infected Subjects Samir K. Gupta, 1 Lauren Komarow, 2 Roy M. Gulick, 4 Richard B. Pollard, 5 Gregory K.
More informationAbstract PS8/2. Double-blind treatment phase D/C/F/TAF. + matching D/C + F/TDF placebo D/C/F/TAF. D/C + F/TDF + matching D/C/F/TAF placebo
WEEK 8 RESULTS OF AMBER: A PHASE 3, RANDOMISED, DOUBLE-BLIND TRIAL IN ANTIRETROVIRAL TREATMENT (ART)-NAÏVE HIV--INFECTED ADULTS TO EVALUATE THE EFFICACY AND SAFETY OF THE ONCE-DAILY, SINGLE-TABLET REGIMEN
More informationSafety Profile of Viread and Truvada. Ian McGowan, MD PhD FRCP Cape Town MTN Regional Meeting September, 2008
Safety Profile of Viread and Truvada Ian McGowan, MD PhD FRCP Cape Town MTN Regional Meeting September, 2008 Overview Safety assessment in drug development Physiology 101 Renal Bone Liver Safety profile
More informationFanconi-like syndrome and rhabdomyolysis in a person with HIV infection. on highly active antiretroviral treatment including tenofovir
1 Letter to the Editor Fanconi-like syndrome and rhabdomyolysis in a person with HIV infection on highly active antiretroviral treatment including tenofovir The nucleotide analogue, tenofovir disoproxil
More informationNOTICE TO PHYSICIANS. Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases, National Institutes of Health
NOTICE TO PHYSICIANS DATE: March 10, 2003 TO: FROM: SUBJECT: HIV/AIDS Health Care Providers Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases, National Institutes of Health
More informationImpact of Tenofovir on Renal Function in HIV-Infected, Antiretroviral-Naive Patients
CLINICAL SCIENCE Impact of Tenofovir on Renal Function in HIV-Infected, Antiretroviral-Naive Patients Michael Horberg, MD,* Beth Tang, MA, William Towner, MD, Michael Silverberg, PhD,* Susan Bersoff-Matcha,
More informationMDR HIV and Total Therapeutic Failure. Douglas G. Fish, MD Albany Medical College Albany, New York Cali, Colombia March 30, 2007
MDR HIV and Total Therapeutic Failure Douglas G. Fish, MD Albany Medical College Albany, New York Cali, Colombia March 30, 2007 Objectives Case study Definitions Fitness Pathogenesis of resistant virus
More informationPlasma tenofovir trough concentrations are associated with renal dysfunction in Japanese patients with HIV infection: a retrospective cohort study
Kunimoto et al. Journal of Pharmaceutical Health Care and Sciences (2016) 2:22 DOI 10.1186/s40780-016-0056-5 RESEARCH ARTICLE Open Access Plasma tenofovir trough concentrations are associated with renal
More informationWhat's new in the WHO ART guidelines How did markets react?
WHO 2013 ARV Guidelines What's new in the WHO ART guidelines How did markets react? Dr. J. Perriëns Coordinator, HIV Technology and Commodities HIV department, WHO, Geneva When to start in adults Starting
More informationProtease Inhibitors and Renal Function in Patients with HIV Infection: a Systematic Review
Infect Dis Ther (2015) 4:15 50 DOI 10.1007/s40121-014-0056-4 REVIEW Protease Inhibitors and Renal Function in Patients with HIV Infection: a Systematic Review Corinne Isnard Bagnis Hans-Jürgen Stellbrink
More informationCurrent aspects of renal diseases in HIV infection. Eric DAUGAS Service de Néphrologie Hôpital Bichat Paris France
Current aspects of renal diseases in HIV infection Eric DAUGAS Service de Néphrologie Hôpital Bichat Paris France 1996 = HAART highly active antiretroviral therapy combination of three antiretroviral agents
More informationRenal Impairment in Patients Receiving a Tenofovir-cART Regimen: Impact of Tenofovir Trough Concentration
BASIC AND TRANSLATIONAL SCIENCE Renal Impairment in Patients Receiving a Tenofovir-cART Regimen: Impact of Tenofovir Trough Concentration Isabelle Poizot-Martin, MD,* Caroline Solas, PhD, Julie Allemand,
More informationClinical Commissioning Policy: Use of cobicistat (Tybost ) as a booster in treatment of HIV positive adults and adolescents
Clinical Commissioning Policy: Use of cobicistat (Tybost ) as a booster in treatment of HIV positive adults and adolescents 1 Clinical Commissioning Policy: Use of cobicistat (Tybost ) as a booster in
More informationPediatric HIV Update NORTHWEST AIDS EDUCATION AND TRAINING CENTER
NORTHWEST AIDS EDUCATION AND TRAINING CENTER Pediatric HIV Update Christian B. Ramers, MD, MPH Assistant Medical Director, Family Health Centers of San Diego HIV/HCV Distance Education Specialist - NWAETC,
More informationHIV Treatment: New and Veteran Drugs Classes
HIV Treatment: New and Veteran Drugs Classes Jonathan M Schapiro, MD National Hemophilia Center Stanford University School of Medicine Rome, March 2013 Overview Many excellent antiretroviral agents are
More informationA Study on Estimated Glomerular Filtration Rate As A Predictor of Renal Dysfunction Among Adult Hiv Patients on Highly Active Antiretroviral Therapy
IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-issn: 2279-0853, p-issn: 2279-0861.Volume 16, Issue 10 Ver. IX (Oct. 2017), PP 28-34 www.iosrjournals.org A Study on Estimated Glomerular Filtration
More informationAntiretroviral Therapy: What to Start
FLOWED: 05-14-2015 Chicago, IL: May 18, 2015 Antiretroviral Therapy: What to Start Eric S. Daar, MD Professor of Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles,
More informationSupplementary information
Supplementary information Dose-response Curve Slope Sets Class-Specific Limits on Inhibitory Potential of Anti-HIV Drugs Lin Shen 1,2, Susan Peterson 1, Ahmad R. Sedaghat 1, Moira A. McMahon 1,2, Marc
More information0.14 ( 0.053%) UNAIDS 10% (94) ( ) (73-94/6 ) 8,920
0.14 UNAIDS 0.053% 2 250 60 10% 94 73 20 73-94/6 8,920 12 43 Public Health Service Task Force Recommendations 5-10% for Use of Antiretroviral Drugs in 10-20% Pregnant HIV-1-Infected Women for Maternal
More informationCLINICAL PEARLS OF NEW HIV MEDICATIONS PHARMACIST OBJECTIVES TECHNICIAN OBJECTIVES. At the end of this presentation pharmacists will be able to:
CLINICAL PEARLS OF NEW HIV MEDICATIONS Cindy Lou Zoellner, PharmD, BCPS Added Qualifications in Infectious Diseases Senior Clinical Pharmacy Specialist in HIV Parkland Health & Hospital System Volunteer
More informationNNRTI Resistance NORTHWEST AIDS EDUCATION AND TRAINING CENTER
NORTHWEST AIDS EDUCATION AND TRAINING CENTER NNRTI Resistance David H. Spach, MD Principal Investigator, NW AETC Professor of Medicine, Division of Infectious Diseases University of Washington Last Updated:
More informationC Orkin, 1 G Moyle, 2 M Fisher, 3 H Wang, 4 J Ewan 4 and ROCKET I Study Group. Chelsea and Westminster Hospital, London, UK;
Switching from Kivexa [KVX] (ABC/3TC) + Efavirenz [EFV] to [ATR] (EFV/FTC/TDF) Reduces Cholesterol in Hypercholesterolaemic Subjects: Primary Endpoint Results of a 24- Week Randomised Study C Orkin, 1
More informationREVIEW No Assessment of safety a. Have all relevant studies on safety been included Yes X No (if no, please provide reference and information)
Expert peer review on application for addition of fixed dose combination formulations of antiretroviral medications in the EML (Adults) REVIEW No. 2 Abacavir + lamivudine (ABC+ 3TC) Tablet (dispersible):
More informationThe advent of protease inhibitors (PIs) as PROCEEDINGS CLINICAL EXPECTATIONS OF EFFICACY: PROTEASE INHIBITOR POTENCY * Benjamin Young, MD, PhD
CLINICAL EXPECTATIONS OF EFFICACY: PROTEASE INHIBITOR POTENCY * Benjamin Young, MD, PhD ABSTRACT Tremendous strides were made in reducing the morbidity and mortality associated with HIV infection with
More informationSimilar Risk of Renal Events Among Patients Treated With Tenofovir or Entecavir for Chronic Hepatitis B
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2012;10:941 946 Similar Risk of Renal Events Among Patients Treated With Tenofovir or Entecavir for Chronic Hepatitis B ROBERT G. GISH,* MARGARET D. CLARK, STEVE
More informationFrailty and age are independently associated with patterns of HIV antiretroviral use in a clinical setting. Giovanni Guaraldi
Frailty and age are independently associated with patterns of HIV antiretroviral use in a clinical setting Giovanni Guaraldi Potential conflicts of interest Research funding: Jansen, Gilead, MSD, BMS Consultancies:
More informationGuidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Visit the AIDSinfo website to access the most up-to-date guideline. Register for e-mail notification of guideline
More informationResistance Workshop. 3rd European HIV Drug
3rd European HIV Drug Resistance Workshop March 30-April 1 st, 2005 Christine Hughes, PharmD Clinical Associate Professor Faculty of Pharmacy & Pharmaceutical Sciences University of Alberta Tenofovir resistance
More informationNORTHWEST AIDS EDUCATION AND TRAINING CENTER. HIV and the Kidney. Leah Haseley, MD. Presentation prepared by: LH NW AETC ECHO June 2012
NORTHWEST AIDS EDUCATION AND TRAINING CENTER HIV and the Kidney Leah Haseley, MD Presentation prepared by: LH NW AETC ECHO June 2012 Etiology of renal disease in HIV 1985- The virus 1995- The antivirals
More informationShort communication Impact of tenofovir dose adjustment on both estimated glomerular filtration rate and tenofovir trough concentration
Antiviral Therapy 2017; 22:529 533 (doi: 10.3851/IMP3137) Short communication Impact of tenofovir dose adjustment on both estimated glomerular filtration rate and tenofovir trough concentration Sylvie
More informationBHIVA Best of CROI Feedback Meetings. London Birmingham North West England Cardiff Gateshead Edinburgh
BHIVA Best of CROI Feedback Meetings London Birmingham North West England Cardiff Gateshead Edinburgh BHIVA Best of CROI Feedback Meetings 2010 COMPLICATIONS OF HIV DISEASE AND TREATMENT Overview Cardiovascular
More informationContinuing Education for Pharmacy Technicians
Continuing Education for Pharmacy Technicians HIV/AIDS TREATMENT Michael Denaburg, Pharm.D. Birmingham, AL Objectives: 1. Identify drugs and drug classes currently used in the management of HIV infected
More informationClinical skills building - HIV drug resistance
Clinical skills building - HIV drug resistance Richard Lessells Clinical case 44-year old HIV-positive male HIV diagnosis 2010 Pre-treatment CD4+ count not known Initiated first-line ART (TDF/FTC/EFV)
More informationAntiretroviral Treatment Strategies: Clinical Case Presentation
Antiretroviral Treatment Strategies: Clinical Case Presentation Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan Chia-Jui, Yang M.D Disclosure No conflicts of interests.
More informationCURRICULUM VITAE. Miguel Goicoechea, M.D.
CURRICULUM VITAE Miguel Goicoechea, M.D. Office: Telephone: University of California at San Diego Antiviral Research Center 150 West Washington Street, Suite 100 San Diego, CA 92103-2005 (619) 543-8080
More informationIndividual Study Table Referring to the Dossier SYNOPSIS. Final Clinical Study Report for Study AI424138
Name of Sponsor/Company: Bristol-Myers Squibb Name of Finished Product: Reyataz Name of Active Ingredient: Atazanavir () Individual Study Table Referring to the Dossier (For National Authority Use Only)
More informationART=antiretroviral therapy; C=cobicistat; D=darunavir; F=emtricitabine; STR=single-tablet regimen; TAF=tenofovir alafenamide.
AMBER A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naïve HIV-1 patients Eron JJ, Orkin C, Gallant J, Molina J-M, Negredo E, Antinori A, Mills
More informationSecond-Line Therapy NORTHWEST AIDS EDUCATION AND TRAINING CENTER
NORTHWEST AIDS EDUCATION AND TRAINING CENTER Second-Line Therapy David Spach, MD Clinical Director, Northwest AETC Professor of Medicine, Division of Infectious Diseases University of Washington Presentation
More informationModule Summary of Product Characteristics
Module 1.3.1 Summary of Product Characteristics 1. NAME OF THE MEDICINAL PRODUCT Tenofovir Disoproxil Teva 245 mg Film-coated Tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each film-coated tablet
More informationPrinciples of Antiretroviral Therapy
Principles of Antiretroviral Therapy Ten Principles of Antiretroviral Therapy Skills Building Workshop: Clinical Management of HIV Infection and Antiretroviral Therapy, 11 th ICAAP, November 21st, 2011,
More informationNovedades en el tratamiento de la hepatitis B: noticias desde la EASL. Maria Buti Hospital Universitario Valle Hebrón Barcelona
Novedades en el tratamiento de la hepatitis B: noticias desde la EASL Maria Buti Hospital Universitario Valle Hebrón Barcelona Milestones in CHB treatment Conventional IFN 1991 Lamivudine (LAM) 1998 Adefovir
More informationTenofovir Alafenamide (TAF)
Frontier AIDS Education and Training Center Tenofovir Alafenamide (TAF) Brian R. Wood, MD Assistant Professor of Medicine, University of Washington Medical Director, Frontier AETC ECHO January 28, 2016
More informationICAAC/IDSA DC, Oct. 26, 2008
Tenofovir (TDF)- or Abacavir (ABC)-selected Minority Subpopulations in Viremic Subjects Detected by Ultra-deep Sequencing R. T. D Aquila 1, E. Rouse 2, J. Horton 2, A. Kheshti 1,3, S. Raffanti 1,3, K.
More informationIntroduction to HIV Drug Resistance. Kevin L. Ard, MD, MPH Massachusetts General Hospital Harvard Medical School
Introduction to HIV Drug Resistance Kevin L. Ard, MD, MPH Massachusetts General Hospital Harvard Medical School Objectives 1. Describe the epidemiology of HIV drug resistance in sub-saharan Africa. 2.
More informationChan HLY, Chan CK, Hui AJ, et al. Tenofovir Disoproxil Fumarate in Chronic HBV Infected Patients with Normal ALT and High HBV DNA Levels
Online supplement to: Chan HLY, Chan CK, Hui AJ, et al. Tenofovir Disoproxil Fumarate in Chronic HBV Infected Patients with Normal ALT and High HBV DNA Levels Supplementary Figure 1. CONSORT disposition
More informationMEDICAL COVERAGE GUIDELINES ORIGINAL EFFECTIVE DATE: 03/07/18 SECTION: DRUGS LAST REVIEW DATE: 02/19/19 LAST CRITERIA REVISION DATE: ARCHIVE DATE:
FUZEON (enfuvirtide) Non-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document. Coverage for services, procedures, medical devices and drugs
More informationContraceptive Research and Development Organization
COMMONLY USED ABBREVIATIONS AND ACRONYMS IN MTN PROTOCOLS 3TC ACASI AE AIDS ALT ART ARV AST AUC BMD BV CDC cgmp CFR CI CONRAD Cmax Cmin CORE C-PMPA lamivudine audio computer-assisted self interview adverse
More informationDRUGS IN PIPELINE. Pr JC YOMBI UCL-AIDS REFERENCE CENTRE BREACH Sept 27, 2015
DRUGS IN PIPELINE Pr JC YOMBI UCL-AIDS REFERENCE CENTRE BREACH Sept 27, 2015 N(t)RTI The Development of TAF TAF Delivers the High Potency of TDF While Minimizing Off- Target Kidney and Bone Side Effects
More informationDepartment of General Medicine, Juntendo University School of Medicine, Tokyo; and 2
Jpn. J. Infect. Dis., 69, 33 38, 2016 Original Article Raltegravir and Abacavir/Lamivudine in Japanese Treatment-Naäƒve and Treatment-Experienced Patients with HIV Infection: a 48-Week Retrospective Pilot
More informationWhole genome deep sequencing of HIV reveals extensive multi-class drug resistance in Nigerian patients failing first-line antiretroviral therapy
Whole genome deep sequencing of HIV reveals extensive multi-class drug resistance in Nigerian patients failing first-line antiretroviral therapy K El Bouzidi 1,, RP Datir 1, V Kwaghe 3, S Roy 1, D Frampton
More informationPrevalence of Comorbidities among HIV-positive patients in Taiwan
Prevalence of Comorbidities among HIV-positive patients in Taiwan Chien-Ching Hung, MD, PhD Department of Internal Medicine National Taiwan University Hospital, Taipei, Taiwan % of participants Comorbidity
More information1950 CID 2009:49 (15 December) HIV/AIDS. Received 17 April 2009; accepted 31 July 2009; electronically published 13 November 2009.
HIV/AIDS BRIEF REPORT Long-Term Evolution and Determinants of Renal Function in HIV-Infected Patients Who Began Receiving Combination Antiretroviral Therapy in 1997 1999, ANRS CO8 APROCO-COPILOTE Catherine
More informationCabotegravir + Rilpivirine as Long-Acting Maintenance Therapy: LATTE-2 Week 32 Results
Slide 1 Cabotegravir + Rilpivirine as Long-Acting Maintenance Therapy: LATTE-2 Week 32 Results David A. Margolis, 1 Juan Gonzalez-Garcia, 2 Hans-Jürgen Stellbrink, 3 Joe Eron, 4 Yazdan Yazdanpanah, 5 Sandy
More informationWhat are the most promising opportunities for dose optimisation?
What are the most promising opportunities for dose optimisation? Andrew Hill Liverpool University, UK Global Financial Crisis How can we afford to treat 15-30 million people with HIV in the future? Lowering
More informationGSK Medicine: Study Number: Title: Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment: Objectives:
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
More informationDTG Versus LPV/r in Second Line (DAWNING): Outcomes by WHO- Recommended NRTI Backbone
DTG Versus LPV/r in Second Line (DAWNING): Outcomes by WHO- Recommended NRTI Backbone Aboud M, 1 Brites C, 2 Lu H, 3 Supparatpinyo K, 4 Hercilla L, 5 Sievers J, 1 Nascimento MC, 1 Hopking J, 6 Underwood
More information