9 results on '"Saag, M."'
Search Results
2. High-Level Viremia in Adults and Children Infected with Human Immunodeficiency Virus: Relation to Disease Stage and CD4+ Lymphocyte Levels
- Author
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Saag, M. S., primary, Crain, M. J., additional, Decker, W. D., additional, Campbell-Hill, S., additional, Robinson, S., additional, Brown, W. E., additional, Leuther, M., additional, Whitley, R. J., additional, Hahn, B. H., additional, and Shaw, G. M., additional
- Published
- 1991
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3. TURQUOISE-I Part 1b: Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with Ribavirin for Hepatitis C Virus Infection in HIV-1 Coinfected Patients on Darunavir.
- Author
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Wyles D, Saag M, Viani RM, Lalezari J, Adeyemi O, Bhatti L, Khatri A, King JR, Hu YB, Trinh R, Shulman NS, and Ruane P
- Subjects
- 2-Naphthylamine, Adolescent, Adult, Aged, Anilides therapeutic use, Body Mass Index, CD4 Lymphocyte Count, Carbamates therapeutic use, Coinfection drug therapy, Cyclopropanes, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, HIV-1 drug effects, HIV-1 isolation & purification, Hepacivirus drug effects, Hepacivirus isolation & purification, Humans, Lactams, Macrocyclic, Macrocyclic Compounds therapeutic use, Male, Middle Aged, Proline analogs & derivatives, Ribavirin therapeutic use, Ritonavir therapeutic use, Sulfonamides therapeutic use, Uracil analogs & derivatives, Uracil therapeutic use, Valine, Young Adult, Anti-Retroviral Agents therapeutic use, Darunavir therapeutic use, Hepatitis C drug therapy
- Abstract
Background: Ombitasvir/paritaprevir/ritonavir with dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) is approved for hepatitis C virus (HCV) genotype 1 (GT1) treatment in HIV-1 coinfected patients. In healthy controls, coadministration of OBV/PTV/r + DSV + darunavir (DRV) lowered DRV trough concentration (Ctrough) levels. To assess the clinical significance of this change, TURQUOISE-I, Part 1b, evaluated the efficacy and safety of OBV/PTV/r + DSV + RBV in coinfected patients on stable, DRV-containing antiretroviral therapy (ART)., Methods: Patients were HCV treatment-naive or interferon-experienced, had CD4+ lymphocyte count ≥200 cells/µL or ≥14%, and plasma HIV-1 RNA suppression on once-daily (QD) DRV-containing ART at screening. Patients were randomized to maintain DRV 800 mg QD or switch to twice-daily (BID) DRV 600 mg; all received OBV/PTV/r + DSV + RBV for 12 weeks., Results: Twenty-two patients were enrolled and achieved SVR12. No adverse events led to discontinuation. Coadministration had minimal impact on DRV maximum observed plasma concentration and area under the curve; DRV Ctrough levels were slightly lower with DRV QD and BID. No patient experienced plasma HIV-1 RNA >200 copies/mL during treatment., Conclusions: HCV GT1/HIV-1 coinfected patients on stable DRV-containing ART achieved 100% SVR12 while maintaining plasma HIV-1 RNA suppression. Despite DRV exposure changes, episodes of intermittent HIV-1 viremia were infrequent., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2017
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4. Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection.
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Cooper DA, Heera J, Goodrich J, Tawadrous M, Saag M, Dejesus E, Clumeck N, Walmsley S, Ting N, Coakley E, Reeves JD, Reyes-Teran G, Westby M, Van Der Ryst E, Ive P, Mohapi L, Mingrone H, Horban A, Hackman F, Sullivan J, and Mayer H
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- Adolescent, Adult, Aged, Alkynes, Anti-HIV Agents standards, Anti-Retroviral Agents, Antiviral Agents pharmacology, Benzoxazines pharmacology, Benzoxazines standards, Cyclohexanes pharmacology, Cyclohexanes standards, Cyclopropanes, Double-Blind Method, Drug Combinations, Drug Resistance, Viral, Drug Therapy, Combination, Female, HIV-1 physiology, Humans, Lamivudine administration & dosage, Male, Maraviroc, Middle Aged, Receptors, CCR5 metabolism, Treatment Outcome, Triazoles pharmacology, Triazoles standards, Viral Load, Viral Tropism, Young Adult, Zidovudine administration & dosage, Anti-HIV Agents pharmacology, Benzoxazines therapeutic use, CCR5 Receptor Antagonists, Cyclohexanes therapeutic use, HIV Infections drug therapy, HIV-1 drug effects, Triazoles therapeutic use
- Abstract
Background: The MERIT (Maraviroc versus Efavirenz in Treatment-Naive Patients) study compared maraviroc and efavirenz, both with zidovudine-lamivudine, in antiretroviral-naive patients with R5 human immunodeficiency virus type 1 (HIV-1) infection., Methods: Patients screened for R5 HIV-1 were randomized to receive efavirenz (600 mg once daily) or maraviroc (300 mg once or twice daily) with zidovudine-lamivudine. Coprimary end points were proportions of patients with a viral load <400 and <50 copies/mL at week 48; the noninferiority of maraviroc was assessed., Results: The once-daily maraviroc arm was discontinued for not meeting prespecified noninferiority criteria. In the primary 48-week analysis (n = 721), maraviroc was noninferior for <400 copies/mL (70.6% for maraviroc vs 73.1% for efavirenz) but not for <50 copies/mL (65.3% vs 69.3%) at a threshold of -10%. More maraviroc patients discontinued for lack of efficacy (11.9% vs 4.2%), but fewer discontinued for adverse events (4.2% vs 13.6%). In a post hoc reanalysis excluding 107 patients (15%) with non-R5 screening virus by the current, more sensitive tropism assay, the lower bound of the 1-sided 97.5% confidence interval for the difference between treatment groups was above -10% for each end point., Conclusions: Twice-daily maraviroc was not noninferior to efavirenz at <50 copies/mL in the primary analysis. However, 15% of patients would have been ineligible for inclusion by a more sensitive screening assay. Their retrospective exclusion resulted in similar response rates in both arms Trial registration. ClinicalTrials.gov identifier: (NCT00098293) .
- Published
- 2010
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5. A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1.
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Saag M, Goodrich J, Fätkenheuer G, Clotet B, Clumeck N, Sullivan J, Westby M, van der Ryst E, and Mayer H
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- Adult, Aged, Cyclohexanes adverse effects, Double-Blind Method, Female, Genotype, HIV genetics, HIV Fusion Inhibitors adverse effects, Humans, Least-Squares Analysis, Male, Maraviroc, Middle Aged, Patient Selection, Phenotype, Placebos, Triazoles adverse effects, Viral Load, Young Adult, Cyclohexanes therapeutic use, HIV Fusion Inhibitors therapeutic use, HIV Infections drug therapy, Triazoles therapeutic use
- Abstract
Background: Maraviroc, a CCR5 antagonist, is active against R5 but not X4 or dual- or mixed-tropic strains of human immunodeficiency virus type 1 (HIV-1). A phase 2b study was conducted to determine the safety and efficacy of maraviroc in combination with optimized background therapy in treatment-experienced patients infected with dual- or mixed-tropic HIV-1., Methods: Treatment-experienced patients with an HIV-1 RNA level 5000 copies/mL who had received 3 classes of drugs and/or were infected with virus resistant to 2 drug classes and were infected with non-R5 HIV-1 were randomized to receive optimized background therapy plus maraviroc (once or twice daily) or placebo. The primary end point was change in HIV-1 RNA level from baseline to 24 weeks., Results: Among 167 patients infected with dual- or mixed-tropic HIV-1, baseline mean HIV-1 RNA levels were >5 log(10) copies/mL and median CD4(+) cell counts were <50 cells/microL. From baseline to 24 weeks, patients who received placebo demonstrated a mean decrease in HIV-1 RNA levels of 0.97 log(10) copies/mL, compared with mean decreases of 0.91 and 1.20 log(10) copies/mL for those who received maraviroc once (P =.83) or twice (P +.38) daily, respectively. Mean increases in CD4(+) cell counts from baseline were 36 cells/microL for patients who received placebo, 60 cells/microL among patients who received maraviroc once daily, and 62 cells/microL among patients who received maraviroc twice daily. The incidences of serious adverse events were similar among groups., Conclusions: In this exploratory study involving extensively treatment-experienced patients with advanced, non-R5 HIV-1 infection, neither superiority nor noninferiority was statistically demonstrated for either maraviroc dosage compared with placebo at 24 weeks of treatment., Trial Registration: Clinicaltrials.gov identifier NCT00098748 .
- Published
- 2009
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6. Phenotypic drug susceptibility testing predicts long-term virologic suppression better than treatment history in patients with human immunodeficiency virus infection.
- Author
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Call SA, Saag MS, Westfall AO, Raper JL, Pham SV, Tolson JM, Hellmann NS, Cloud GA, and Johnson VA
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- Adult, Anti-HIV Agents therapeutic use, CD4 Lymphocyte Count, Cohort Studies, Drug Resistance, Microbial, Drug Resistance, Multiple, Drug Therapy, Combination, Female, HIV-1 isolation & purification, HIV-1 physiology, Humans, Male, Phenotype, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, RNA, Viral blood, Reverse Transcriptase Inhibitors therapeutic use, Risk Factors, Treatment Failure, Viral Load, Anti-HIV Agents pharmacology, HIV Infections drug therapy, HIV Infections virology, HIV-1 drug effects, Reverse Transcriptase Inhibitors pharmacology
- Abstract
To assess the value of phenotypic drug susceptibility testing as a predictor of antiretroviral treatment response in human immunodeficiency virus (HIV)-infected people, drug susceptibility testing was performed retrospectively on plasma samples collected at baseline in a cohort of 86 antiretroviral-experienced, HIV-infected people experiencing treatment failure and initiating a new antiretroviral treatment regimen. Two separate criteria for reduced drug susceptibility were evaluated. In multivariate analyses, phenotypic susceptibility was an independent predictor of time to treatment failure (adjusted hazards ratio [HR], 0.70; 95% confidence interval [CI], 0.55-0.90; and adjusted HR, 0.76; 95% CI, 0.61-0.95, with reduced drug susceptibility cutoffs defined as 4.0-fold and 2.5-fold higher than reference virus IC(50) values, respectively). Previous protease inhibitor experience was also a significant independent predictor. Notably, drug susceptibility predicted on the basis of treatment history alone was not predictive of time to treatment failure. In this cohort, phenotypic testing results enhanced the ability to predict sustained long-term suppression of virus load.
- Published
- 2001
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7. Evaluation of distinct blood lymphocyte populations in human immunodeficiency virus type 1-infected subjects in the absence or presence of effective therapy.
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Derdeyn CA, Kilby JM, Miralles GD, Li LF, Sfakianos G, Saag MS, Hockett RD, and Bucy RP
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- Cells, Cultured, DNA, Viral blood, Drug Therapy, Combination, Freezing, HIV-1 genetics, Humans, In Situ Hybridization, Lymphocyte Activation, Proviruses, RNA, Viral blood, RNA, Viral genetics, T-Lymphocytes immunology, Viral Load, Virus Activation, Virus Latency, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections virology, HIV-1 physiology, Leukocytes, Mononuclear virology
- Abstract
Virus reservoirs can persist in human immunodeficiency virus type 1 (HIV-1)-infected subjects despite effective plasma virus suppression. To compare viral dynamics in the absence and presence of antiretroviral therapy, blood mononuclear cells from 19 subjects with high plasma RNA levels and 18 subjects following prolonged virus suppression were examined, by use of in situ hybridization, to detect virus RNA expression before and after in vitro T cell activation. This approach reveals circulating lymphocytes expressing HIV-1 RNA before activation and an increase in cells with detectable HIV-1 RNA transcription after in vitro activation. The frequencies of these 2 cell populations are strongly correlated with plasma virus load and appear to be stable once a new steady state is established during therapy. The frequency of viral RNA-positive cells is equivalent to the frequency of cells that produce infectious virus. Thus, in HIV-1-infected subjects there are distinct virus reservoirs comprising both latent and replication-active cells.
- Published
- 1999
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8. Decrease of cytomegalovirus replication in human immunodeficiency virus infected-patients after treatment with highly active antiretroviral therapy.
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O'Sullivan CE, Drew WL, McMullen DJ, Miner R, Lee JY, Kaslow RA, Lazar JG, and Saag MS
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- AIDS-Related Opportunistic Infections immunology, AIDS-Related Opportunistic Infections virology, Adult, CD4 Lymphocyte Count, Cytomegalovirus drug effects, Cytomegalovirus Infections etiology, Cytomegalovirus Infections immunology, DNA, Viral blood, Drug Therapy, Combination, Female, Humans, Leukocytes virology, Male, RNA, Viral blood, Viral Load, AIDS-Related Opportunistic Infections drug therapy, Antiviral Agents therapeutic use, Cytomegalovirus physiology, Cytomegalovirus Infections drug therapy, Virus Replication drug effects
- Abstract
Cytomegalovirus (CMV) viremia, as measured by a hybrid capture assay, was used to measure the effectiveness of "immune reconstitution" in human immunodeficiency virus (HIV)-infected subjects treated with highly active antiretroviral therapy (HAART). Of the 28 enrolled patients (mean age, 38 years), 86% were male and 68% were antiretrovirally naive. Of the 23 patients who returned for follow-up, baseline median characteristics were 4.1 log10 CMV DNA copies/106 white blood cells (WBCs), 5.1 log10 HIV RNA copies/mL, and 35 CD4 cells/mm3. After initiation of HAART, median log10 CMV DNA copies/106 WBCs at means of 33, 87, and 385 days were 4.0, 3.3, and 2.5, respectively. Median log10 HIV RNA levels declined from 5.1 to 1.7 at 385 days with a commensurate rise in median CD4 T cells to 166/mm3. Immune reconstitution secondary to HAART results in a significant and progressive decline in CMV viremia in the absence of specific anti-CMV therapy.
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- 1999
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9. Use of changes in plasma levels of human immunodeficiency virus type 1 RNA to assess the clinical benefit of antiretroviral therapy.
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Marschner IC, Collier AC, Coombs RW, D'Aquila RT, DeGruttola V, Fischl MA, Hammer SM, Hughes MD, Johnson VA, Katzenstein DA, Richman DD, Smeaton LM, Spector SA, and Saag MS
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- Acquired Immunodeficiency Syndrome diagnosis, Acquired Immunodeficiency Syndrome mortality, Acquired Immunodeficiency Syndrome prevention & control, Adult, CD4 Lymphocyte Count, Disease Progression, Double-Blind Method, Drug Monitoring, Female, HIV Infections blood, HIV Infections virology, HIV-1 isolation & purification, Humans, Male, Plasma virology, Prognosis, RNA, Viral blood, RNA, Viral isolation & purification, Retrospective Studies, Risk, Anti-HIV Agents therapeutic use, Antiviral Agents therapeutic use, HIV Infections drug therapy, HIV-1 drug effects, RNA, Viral analysis
- Abstract
Data from 1330 human immunodeficiency virus type 1 (HIV-1)-infected patients enrolled in seven antiretroviral treatment trials were analyzed to characterize the clinical benefit of treatment-mediated reductions in plasma HIV-1 RNA levels. The risk of a new AIDS-defining event or death was reduced proportionally to the magnitude of the reduction of the HIV-1 RNA level during the first 6 months of therapy. Pretherapy HIV-1 RNA levels were prognostic independently of on-therapy levels. In addition, the reduction in risk associated with any given reduction of the level of HIV-1 RNA did not vary by pretherapy level. Having either a reduction in HIV-1 RNA level or an increase in CD4+ lymphocyte count, or both, was associated with a delay in clinical disease progression. This indicates that patient prognosis should be assessed using both HIV-1 RNA and CD4+ lymphocyte responses to therapy.
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- 1998
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