Author
Vanitha Sekar
Bio: Vanitha Sekar is an academic researcher from Tibotec. The author has contributed to research in topics: Darunavir & Ritonavir. The author has an hindex of 21, co-authored 31 publications receiving 1558 citations.
Topics: Darunavir, Ritonavir, Cmax, Tolerability, Etravirine
Papers
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TL;DR: Reports from resource-limited countries suggest that initial ART programmes are as effective as in resource-rich countries, which should limit HIV drug resistance if programme effectiveness continues during scale-up.
Abstract: Darunavir (TMC114) is a new HIV protease inhibitor that has demonstrated substantial antiretroviral activity against wild-type HIV-1 virus and multidrug-resistant strains Darunavir inhibits and is primarily metabolized by cytochrome P450 3A (CYP3A) isoenzymes and is coadministered with low-dose ritonavir (darunavir/r); ritonavir is an inhibitor of CYP3A isoenzymes and pharmacologically enhances darunavir, resulting in increased plasma concentrations and allowing for a lower daily dose The t1/2 (terminal elimination half-life) of darunavir is 15 h in the presence of ritonavir An extensive darunavir/r drug-drug interaction programme has been undertaken, covering a wide range of therapeutic areas Studies conducted in HIV-negative healthy volunteers and in HIV-infected patients show that the potential for interactions is well characterized and the interactions are manageable For most drugs investigated, no dose adjustments of darunavir/r or the co-administered drug are required This article reviews all the pharmacokinetic and drug-drug interaction studies conducted to date for darunavir/r, providing guidance on how to co-administer darunavir/r with many other antiretroviral or non-antiretroviral medications commonly used in HIV-infected individuals
305 citations
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TL;DR: Once-daily darunavir/ritonavir was both statistically noninferior and superior in virologic response to LPV/r, with a more favorable gastrointestinal and lipid profile, confirming DRV/ r as an effective, well tolerated, and durable option for antiretroviral-naive patients.
Abstract: OBJECTIVE Present 96-week data from ongoing ARTEMIS (AntiRetroviral Therapy with TMC114 ExaMined In Naive Subjects) trial. METHODS Randomized, open-label, phase III trial of antiretroviral-naive patients with HIV-1 RNA at least 5000 copies/ml (stratified by HIV-1 RNA and CD4 cell count) receiving darunavir/ritonavir (DRV/r) 800/100 mg once daily or lopinavir/ritonavir (LPV/r) 800/200 mg total daily dose (twice daily or once daily) and fixed-dose tenofovir/emtricitabine. Primary outcome measure was noninferiority of DRV/r vs. LPV/r in virologic response (<50 copies/ml, time-to-loss of virologic response) at 96 weeks (secondary outcome: superiority). RESULTS Six hundred eighty-nine patients were enrolled. At week 96, significantly more DRV/r (79%) than LPV/r patients (71%) had viral load less than 50 copies/ml, confirming statistical noninferiority (estimated difference: 8.4%; 95% confidence interval 1.9-14.8; P < 0.001; per-protocol) and superiority (P = 0.012; intent-to-treat) in virologic response. Median CD4 cell count increases from baseline were 171 and 188 cells/microl for DRV/r and LPV/r, respectively (P = 0.57; noncompleter=failure). Overall, 4% of DRV/r patients and 9% of LPV/r patients discontinued treatment due to adverse events. Lower rates of grade 2-4 treatment-related diarrhea were seen with DRV/r (4%) vs. LPV/r (11%; P < 0.001), whereas grade 2-4 treatment-related rash occurred infrequently in both arms (3 vs. 1%, respectively; P = 0.273). DRV/r patients had smaller median increases in triglycerides (0.1 and 0.6 mmol/l, respectively, P < 0.0001) and total cholesterol (0.6 and 0.9 mmol/l, respectively; P < 0.0001) than LPV/r patients; levels remained below National Cholesterol Education Program cut-offs for DRV/r. CONCLUSION At week 96, once-daily DRV/r was both statistically noninferior and superior in virologic response to LPV/r, with a more favorable gastrointestinal and lipid profile, confirming DRV/r as an effective, well tolerated, and durable option for antiretroviral-naive patients.
269 citations
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TL;DR: The results of this phase IIa proof-of-concept trial provide evidence that TMC435 has a spectrum of activity against multiple HCV genotypes, except for genotype 3.
110 citations
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TL;DR: No clinically relevant changes in DRV pharmacokinetics were observed when combined with TMC125; therefore DRV dose adjustment is not required; therefore TMC 125 efficacy is demonstrated and no dose adjustment of T MC125 is needed when Combined with DRV/r.
Abstract: ObjectiveTo evaluate the pharmacokinetics of TMC125 (etravirine) and darunavir (DRV) with low-dose ritonavir (DRV/r).DesignOpen-label, randomized, two-way crossover Phase I trial.MethodsThirty-two ...
102 citations
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TL;DR: Darunavir/rtv should be administered with food, but exposure to darunavIR is not affected by the type of meal, as no significant differences in dar unavir plasma concentrations were observed between different fed states.
Abstract: This open-label, randomized, crossover study investigated the bioavailability, short-term safety, and tolerability of darunavir (TMC114) coadministered with low-dose ritonavir under fasted conditions and after different meal types in HIV-negative healthy volunteers. All volunteers received ritonavir 100 mg twice daily on days 1 to 5, with a single darunavir 400-mg tablet given on day 3 (darunavir/rtv). Pharmacokinetic parameters for darunavir and ritonavir were determined under fasted conditions and following a standard breakfast, a high-fat breakfast, a nutritional protein-rich drink, or a croissant with coffee. Administration of darunavir/rtv in a fasting state resulted in a decrease in darunavir C(max) and AUC(last) of approximately 30% compared with administration after a standard meal. No significant differences in darunavir plasma concentrations were observed between different fed states. Darunavir/rtv should therefore be administered with food, but exposure to darunavir is not affected by the type of meal.
92 citations
Cited by
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University of Zurich1, Icahn School of Medicine at Mount Sinai2, University of North Carolina at Chapel Hill3, Monash University4, University Hospital of Lausanne5, University of California, San Diego6, Radboud University Nijmegen7, University of Buenos Aires8, Cornell University9, University of Amsterdam10, University of Alabama at Birmingham11, Johns Hopkins University School of Medicine12, University of California, San Francisco13
TL;DR: This report provides guidelines for when to initiate antiretroviral therapy, selection of appropriate initial regimens, patient monitoring, when to change therapy, and what regimens to use when changing.
Abstract: Context New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–infected adults in resource-rich settings. Objective To provide current recommendations for the treatment of adult HIV infection with ART and use of laboratory-monitoring tools. Guidelines include when to start therapy and with what drugs, monitoring for response and toxic effects, special considerations in therapy, and managing antiretroviral failure. Data Sources, Study Selection, and Data Extraction Data that had been published or presented in abstract form at scientific conferences in the past 2 years were systematically searched and reviewed by an International Antiviral Society–USA panel. The panel reviewed available evidence and formed recommendations by full panel consensus. Data Synthesis Treatment is recommended for all adults with HIV infection; the strength of the recommendation and the quality of the evidence increase with decreasing CD4 cell count and the presence of certain concurrent conditions. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions. CD4 cell count and HIV-1 RNA level should be monitored, as should engagement in care, ART adherence, HIV drug resistance, and quality-of-care indicators. Reasons for regimen switching include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Confirmed treatment failure should be addressed promptly and multiple factors considered. Conclusion New recommendations for HIV patient care include offering ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing and choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis.
2,357 citations
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2,135 citations
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TL;DR: The most recent version of the guidelines for the prevention and treatment of opportunistic infections (OI) in HIV-infected adults and adolescents was published in 2002 and 2004, respectively as mentioned in this paper.
Abstract: This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.
1,534 citations
01 Jan 2010
TL;DR: In this article, a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial is presented, which is based on a randomized trial.
Abstract: Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya (R T Lester MD, A Kariri BSc, S Karanja BSc, E Ngugi PhD, L J Gelmon MD, J Kimani, MBChB); Department of Medical Microbiology, University of Manitoba, Health Sciences Centre, Winnipeg, MB, Canada (R T Lester, T B Ball PhD, L J Gelmon, J Kimani, Prof F A Plummer MD); Division of Infectious Diseases, Department of Medicine, University of British Columbia, Vancouver, BC, Canada (R T Lester); School of Kinesiology and Health Sciences, Department of Psychology, York University, York, ON, Canada (P Ritvo PhD); Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada (E J Mills PhD); Department of Global Health, University of Washington, Seattle, WA, USA (M H Chung MD); Department of Economics (W Jack DPhil) and Georgetown Public Policy Institute (J Habyarimana PhD), Georgetown University, Washington, DC, USA; Collaboration for Outcome Research and Evaluation, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada (M Sadatsafavi MD, M Najafzadeh MSc, C A Marra PharmD); University of Nairobi Institute of Tropical and Infectious Diseases, Nairobi, Kenya (B Estambale MBChB); Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Eff ects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial
1,003 citations
01 Jan 2008
TL;DR: This report provides guidelines in key areas of antiretroviral management: when toinitiatetherapy, choice of initialimens, patient monitoring, and how best to approach treatment options, including optimal use of recently approved drugs in treatment-experienced patients.
Abstract: Context The availability of new antiretroviral drugs and formulations, including drugs in new classes, and recent data on treatment choices for antiretroviral-naive and -experienced patients warrant an update of the International AIDS Society–USA guidelines for the use of antiretroviral therapy in adult human immunodeficiency virus (HIV) infection. Objectives To summarize new data in the field and to provide current recommendations for the antiretroviral management and laboratory monitoring of HIV infection. This report provides guidelines in key areas of antiretroviral management: when toinitiatetherapy,choiceofinitialregimens,patientmonitoring,whentochangetherapy, and how best to approach treatment options, including optimal use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced patients.
1,001 citations