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Journal ArticleDOI

Darunavir: pharmacokinetics and drug interactions.

01 Jan 2008-Antiviral Therapy (Antivir Ther)-Vol. 13, Iss: 1, pp 1-13
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
Citations
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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

Journal ArticleDOI
TL;DR: Recent technical advances that might be able to address limitations in nucleic acid amplification and detection in a cost-effective, robust, and user-friendly format are described.

752 citations

Journal ArticleDOI
TL;DR: A significant increase in prevalence of drug resistance over time since antiretroviral rollout in regions of sub-Saharan Africa is suggested; this rise is driven by NNRTI resistance in studies from east and southern Africa.

356 citations

Journal ArticleDOI
TL;DR: The present review will focus on the repurposing efficacy of the currently used drugs against COVID-19 and their mechanisms of action, pharmacokinetics, dosing, safety, and their future perspective.

304 citations

Journal ArticleDOI
TL;DR: Profiles of drug resistance suggest that a second-line treatment regimen based on protease inhibitors, with a backbone of nucleoside reverse transcriptase inhibitor, is a reasonable option for patients with HIV in sub-Saharan Africa who experience first- line treatment failure.
Abstract: Following large-scale roll-out of antiretroviral therapy in sub-Saharan Africa, the non-clinical efficacy of antiretroviral therapy has received little attention. We aimed to systematically review virological efficacy and drug-resistance outcomes of programmes of antiretroviral therapy in sub-Saharan Africa. 89 studies with heterogeneous design, definitions, and methods were identified. Overall, in on-treatment analysis, 10 351 (78%) of 13 288 patients showed virological suppression after 6 months of antiretroviral therapy, 7413 (76%) of 9794 after 12 months, and 3840 (67%) of 5690 after 24 months. Long-term virological data are scarce. Genotyping results were available for patients with virological failure (HIV-1 RNA greater than 1000 copies per mL). Most patients (839 of 849; 99%) were infected with a non-B HIV-1 subtype. However, drug-resistance patterns were largely similar to those in subtype B. Resistance profiles were associated with the antiretroviral drugs commonly used: the lamivudine-associated M184V mutation was most common, followed by K103N which is associated with non-nucleoside reverse transcriptase inhibitors. Thymidine-analogue mutations and the K65R mutation were less common. First-line antiretroviral therapy regimens used in sub-Saharan Africa are effective. Profiles of drug resistance suggest that a second-line treatment regimen based on protease inhibitors, with a backbone of nucleoside reverse transcriptase inhibitors, is a reasonable option for patients with HIV in sub-Saharan Africa who experience first-line treatment failure.

299 citations

References
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Journal ArticleDOI
TL;DR: These Guidelines were developed by the Panel* on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services and the Henry J. Kaiser Family Foundation.
Abstract: SUMMARY The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced extraordinary complexity into the treatment of HIV-infected persons. In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for the clinical management of HIV-infected adults and adolescents. This report recommends that care should be supervised by an expert, and makes recommendations for laboratory monitoring including plasma HIV RNA, CD4 cell counts and HIV drug resistance testing. The report also provides guidelines for antiretroviral therapy, including when to start treatment, what drugs to initiate, when to change therapy, and therapeutic options when changing therapy. Special considerations are provided for adolescents and pregnant women. As with treatment of other chronic conditions, therapeutic decisions require a mutual understanding between the patient and the health care provider regarding the benefits and risks of treatment. Antiretroviral regimens are complex, have major side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance due to non-adherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic

4,321 citations

Journal ArticleDOI
John M. Coffin1
27 Jan 1995-Science
TL;DR: Results lead to a simple steady-state model in which infection, cell death, and cell replacement are in balance, and imply that the unique feature of HIV is the extraordinarily large number of replication cycles that occur during infection of a single individual.
Abstract: Several recent reports indicate that the long, clinically latent phase that characterizes human immunodeficiency virus (HIV) infection of humans is not a period of viral inactivity, but an active process in which cells are being infected and dying at a high rate and in large numbers. These results lead to a simple steady-state model in which infection, cell death, and cell replacement are in balance, and imply that the unique feature of HIV is the extraordinarily large number of replication cycles that occur during infection of a single individual. This turnover drives both the pathogenic process and (even more than mutation rate) the development of genetic variation. This variation includes the inevitable and, in principle, predictable accumulation of mutations such as those conferring resistance to antiviral drugs whose presence before therapy must be considered in the design of therapeutic strategies.

2,020 citations

Journal ArticleDOI
TL;DR: Patients starting HAART in resource-poor settings have increased mortality rates in the first months on therapy, compared with those in developed countries, and timely diagnosis and assessment of treatment eligibility, coupled with free provision of HAART might reduce this excess mortality.

1,143 citations

Journal ArticleDOI
16 Aug 2006-JAMA
TL;DR: The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL, making delivery of state-of-the-art care challenging.
Abstract: Context Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society–USA panel has updated its recommendations as warranted by new developments in the field. Objective To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIVinfected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described. Data Sources and Study Selection A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel. Data Extraction and Synthesis Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel. Conclusions Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/µL and before it declines to 200/µL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced.

1,050 citations


"Darunavir: pharmacokinetics and dru..." refers methods in this paper

  • ...ART should ideally maintain plasma HIV-1 RNA levels below the limits of detection of the commercially available assays (that is, 17 ]....

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