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1دورية أكاديمية
المؤلفون: Rhee, Soo-Yon, Jordan, Michael R, Raizes, Elliot, Chua, Arlene, Parkin, Neil, Kantor, Rami, Van Zyl, Gert U, Mukui, Irene, Hosseinipour, Mina C, Frenkel, Lisa M, Ndembi, Nicaise, Hamers, Raph L, Rinke de Wit, Tobias F, Wallis, Carole L, Gupta, Ravindra K, Fokam, Joseph, Zeh, Clement, Schapiro, Jonathan M, Carmona, Sergio, Katzenstein, David, Tang, Michele, Aghokeng, Avelin F, De Oliveira, Tulio, Wensing, Annemarie MJ, Gallant, Joel E, Wainberg, Mark A, Richman, Douglas D, Fitzgibbon, Joseph E, Schito, Marco, Bertagnolio, Silvia, Yang, Chunfu, Shafer, Robert W
المصدر: PloS one. 10(12)
مصطلحات موضوعية: Humans, HIV-1, HIV Infections, Ritonavir, Reverse Transcriptase Inhibitors, Protease Inhibitors, Treatment Failure, Drug Therapy, Combination, Drug Resistance, Viral, Mutation, Point-of-Care Systems, Lopinavir, Genotyping Techniques, Darunavir, Atazanavir Sulfate, Drug Therapy, Combination, Drug Resistance, Viral, General Science & Technology, MD Multidisciplinary
الوصف: The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naïve individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naïve individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy.
الوصول الحر: https://escholarship.org/uc/item/65p0b1qgTest
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2دورية أكاديمية
المؤلفون: La Rosa, Alberto M, Harrison, Linda J, Taiwo, Babafemi, Wallis, Carole L, Zheng, Lu, Kim, Peter, Kumarasamy, Nagalingeswaran, Hosseinipour, Mina C, Jarocki, Bernadette, Mellors, John W, Collier, Ann C
المصدر: The Lancet HIV, 3(6)
مصطلحات موضوعية: Health Services Accessibility, Africa South of the Sahara, Adult, CD4 Lymphocyte Count, India, Brazil, Drug Resistance, Viral, HIV Infections, Anti-HIV Agents, Humans, Health Resources, Antiretroviral Therapy, Highly Active, HIV-1
الوصف: For second-line antiretroviral therapy, WHO recommends a boosted protease inhibitor plus nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs). However, concerns about toxicity and cross-resistance motivated a search for regimens that do not contain NRTIs. We aimed to assess whether boosted lopinavir plus raltegravir would be non-inferior to boosted lopinavir plus NRTIs for virological suppression in resource-limited settings.
العلاقة: https://doi.org/10.17615/r2ze-yy37Test; https://cdr.lib.unc.edu/downloads/rn301647p?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/rn301647pTest
الإتاحة: https://doi.org/10.17615/r2ze-yy37Test
https://cdr.lib.unc.edu/downloads/rn301647p?file=thumbnailTest
https://cdr.lib.unc.edu/downloads/rn301647pTest -
3دورية أكاديمية
المؤلفون: Kumarasamy, Nagalingeswaran, Aga, Evgenia, Ribaudo, Heather J, Wallis, Carole L, Katzenstein, David A, Stevens, Wendy S, Norton, Michael R, Klingman, Karin L, Hosseinipour, Mina C, Crump, John A, Supparatpinyo, Khuanchai, Badal-Faesen, Sharlaa, Bartlett, John A
مصطلحات موضوعية: ACTG 5230, intensification, protease inhibitor monotherapy, second-line antiretroviral therapy, Acquired Immunodeficiency Syndrome, Adult, Africa, Antiviral Agents, Asia, Developing Countries, Drug Therapy, Female, HIV-1, Humans, Lopinavir, Male, Middle Aged, Pilot Projects, Plasma, RNA, Viral, Ritonavir, Treatment Outcome, Viral Load, Young Adult
جغرافية الموضوع: United States
الوصف: BACKGROUND: The AIDS Clinical Trials Group (ACTG) A5230 study evaluated lopinavir/ritonavir (LPV/r) monotherapy following virologic failure (VF) on first-line human immunodeficiency virus (HIV) regimens in Africa and Asia. METHODS: Eligible subjects had received first-line regimens for at least 6 months and had plasma HIV-1 RNA levels 1000-200 000 copies/mL. All subjects received LPV/r 400/100 mg twice daily. VF was defined as failure to suppress to <400 copies/mL by week 24, or confirmed rebound to >400 copies/mL at or after week 16 following confirmed suppression. Subjects with VF added emtricitabine 200 mg/tenofovir 300 mg (FTC/TDF) once daily. The probability of continued HIV-1 RNA <400 copies/mL on LPV/r monotherapy through week 104 was estimated with a 95% confidence interval (CI); predictors of treatment success were evaluated with Cox proportional hazards models. RESULTS: One hundred twenty-three subjects were enrolled. Four subjects died and 2 discontinued prematurely; 117 of 123 (95%) completed 104 weeks. Through week 104, 49 subjects met the primary endpoint; 47 had VF, and 2 intensified treatment without VF. Of the 47 subjects with VF, 41 (33%) intensified treatment, and 39 of 41 subsequently achieved levels <400 copies/mL. The probability of continued suppression <400 copies/mL over 104 weeks on LPV/r monotherapy was 60% (95% CI, 50%-68%); 80%-85% maintained levels <400 copies/mL with FTC/TDF intensification as needed. Ultrasensitive assays on specimens with HIV-1 RNA level <400 copies/mL at weeks 24, 48, and 104 revealed that 61%, 62%, and 65% were suppressed to <40 copies/mL, respectively. CONCLUSIONS: LPV/r monotherapy after first-line VF with FTC/TDF intensification when needed provides durable suppression of HIV-1 RNA over 104 weeks. CLINICAL TRIALS REGISTRATION: NCT00357552.
وصف الملف: application/pdf
العلاقة: Clin Infect Dis; https://www.ncbi.nlm.nih.gov/pubmed/25694653Test; civ109; https://hdl.handle.net/10161/13768Test
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4دورية أكاديمية
المؤلفون: Bartlett, John A, Ribaudo, Heather J, Wallis, Carole L, Aga, Evgenia, Katzenstein, David A, Stevens, Wendy S, Norton, Michael R, Klingman, Karin L, Hosseinipour, Mina C, Crump, John A, Supparatpinyo, Khuanchai, Badal-Faesen, Sharlaa, Kallungal, Beatrice A, Kumarasamy, Nagalingeswaran
مصطلحات موضوعية: Acquired Immunodeficiency Syndrome, Adenine, Adult, Africa, Anti-HIV Agents, Deoxycytidine, Drug Administration Schedule, Drug Therapy, Combination, Emtricitabine, Female, Health Resources, Humans, India, Lopinavir, Male, Medication Adherence, Middle Aged, Mutation, Organophosphonates, Patient Selection, Pilot Projects, RNA, Viral, Reverse Transcriptase Inhibitors, Ritonavir, Surveys and Questionnaires, Tenofovir, Thailand, Treatment Failure
جغرافية الموضوع: England
الوصف: OBJECTIVE: To evaluate virologic response rates of lopinavir/ritonavir (LPV/r) monotherapy as second-line antiretroviral treatment (ART) among adults in resource-limited settings (RLSs). DESIGN: An open-label pilot study of LPV/r monotherapy in participants on first-line nonnucleoside reverse transcriptase inhibitor three-drug combination ART with plasma HIV-1 RNA 1000-200 000 copies/ml. METHODS: Participants were recruited from five sites in Africa and Asia within the AIDS Clinical Trials Group (ACTG) network. All participants received LPV/r 400/100 mg twice daily. The primary endpoint was remaining on LPV/r monotherapy without virologic failure at week 24. Participants with virologic failure were offered addition of emtricitabine and tenofovir (FTC/TDF) to LPV/r. RESULTS: Mutations associated with drug resistance were encountered in nearly all individuals screened for the study. One hundred and twenty-three participants were enrolled, and 122 completed 24 weeks on study. A high proportion remained on LPV/r monotherapy without virologic failure at 24 weeks (87%). Archived samples with HIV-1 RNA levels less than 400 copies/ml at week 24 (n=102) underwent ultrasensitive assay. Of these individuals, 62 had levels less than 40 copies/ml and 30 had levels 40-200 copies/ml. Fifteen individuals experienced virologic failure, among whom 11 had resistance assessed and two had emergent protease inhibitor mutations. Thirteen individuals with virologic failure added FTC/TDF and one individual added FTC/TDF without virologic failure. At study week 48, 11 of 14 adding FTC/TDF had HIV-1 RNA levels less than 400 copies/ml. CONCLUSION: In this pilot study conducted in diverse RLS, LPV/r monotherapy as second-line ART demonstrated promising activity.
وصف الملف: application/pdf
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5دورية أكاديمية
المؤلفون: Bartlett, John A., Ribaudo, Heather J., Wallis, Carole L., Aga, Evgenia, Katzenstein, David A., Stevens, Wendy S., Norton, Michael R., Klingman, Karin L., Hosseinipour, Mina C., Crump, John A., Supparatpinyo, Khuanchai, Badal-Faesen, Sharlaa, Kallungal, Beatrice A., Kumarasamy, Nagalingeswaran
المصدر: AIDS (London, England), 26(11)
مصطلحات موضوعية: Adenine, Combination, India, Health Resources, Surveys and Questionnaires, Treatment Failure, Mutation, Patient Selection, Lopinavir, Journal Article, RNA, Acquired Immunodeficiency Syndrome, Humans, Tenofovir, Female, Organophosphonates, Anti-HIV Agents, Viral, Emtricitabine, Ritonavir, Viral Load, Deoxycytidine, Adult, Thailand, Medication Adherence, Drug Therapy, Africa, Reverse Transcriptase Inhibitors, Male, Pilot Projects
الوصف: To evaluate virologic response rates of lopinavir/ritonavir (LPV/r) monotherapy as second-line antiretroviral treatment (ART) among adults in resource-limited settings (RLS).
العلاقة: https://doi.org/10.17615/pqnm-2a10Test; https://cdr.lib.unc.edu/downloads/pr76f8956?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/pr76f8956Test
الإتاحة: https://doi.org/10.17615/pqnm-2a10Test
https://cdr.lib.unc.edu/downloads/pr76f8956?file=thumbnailTest
https://cdr.lib.unc.edu/downloads/pr76f8956Test -
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المساهمون: Rhee, Soo-Yon, Jordan, Michael R., Raizes, Elliot, Chua, Arlene, Parkin, Neil, Kantor, Rami, Van Zyl, Gert U., Mukui, Irene, Hosseinipour, Mina C., Frenkel, Lisa M., Ndembi, Nicaise, Hamers, Raph L., Rinke de Wit, Tobias F., Wallis, Carole L., Gupta, Ravindra K., Fokam, Joseph, Zeh, Clement, Schapiro, Jonathan M., Carmona, Sergio, Katzenstein, David, Tang, Michele, Aghokeng, Avelin F., De Oliveira, Tulio, Wensing, Annemarie M. J., Gallant, Joel E., Wainberg, Mark A., Richman, Douglas D., Fitzgibbon, Joseph E., Schito, Marco, Bertagnolio, Silvia, Yang, Chunfu, Shafer, Robert W.
المصدر: PLoS One. 10(12).
مصطلحات موضوعية: Research Article, Atazanavir Sulfate, Darunavir, Drug Resistance, Viral, Drug Therapy, Combination, Genotyping Techniques, HIV Infections, HIV-1, Humans, Lopinavir, Mutation, Point-of-Care Systems, Protease Inhibitors, Reverse Transcriptase Inhibitors, Ritonavir, Treatment Failure
الوصف: The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naïve individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naïve individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy. ; R01 AI068581/AI/NIAID NIH HHS/United States ; R56 AI068581/AI/NIAID NIH HHS/United States ; WHO_001/World Health Organization/International ; WT097410/WT/WETP NIH ...
العلاقة: cdc:37751; http://stacks.cdc.gov/view/cdc/37751Test/
الإتاحة: http://stacks.cdc.gov/view/cdc/37751Test/
النص الكامل