The Experts below are selected from a list of 54 Experts worldwide ranked by ideXlab platform
Camlin Tierney - One of the best experts on this subject based on the ideXlab platform.
-
outcomes by sex following treatment initiation with Atazanavir Plus Ritonavir or efavirenz with abacavir lamivudine or tenofovir emtricitabine
Clinical Infectious Diseases, 2014Co-Authors: Kimberly Y Smith, Camlin Tierney, Katie R Mollan, Chakra B Budhathoki, Catherine Godfrey, David Katzenstein, Charles S Venuto, Gene D Morse, Margaret A FischlAbstract:Background. We aimed to evaluate treatment responses to Atazanavir Plus Ritonavir (ATV/r) or efavirenz (EFV) in initial antiretroviral regimens among women and men, and determine if treatment outcomes differ by sex. Methods. We performed a randomized trial of open-label ATV/r or EFV combined with abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) in 1857 human immunodeficiency virus type 1–infected, treatment-naive persons enrolled between September 2005 and November 2007 at 59 sites in the United States and Puerto Rico. Associations of sex with 3 primary study endpoints of time to virologic failure, safety, and tolerability events were analyzed using Cox proportional hazards models. Model-based population pharmacokinetic analysis was performed using nonlinear mixed effects modeling (NONMEM version VII). Results. Of 1857 participants, 322 were women. Women assigned to ATV/r had a higher risk of virologic failure with either nucleoside reverse transcriptase inhibitor backbone than women assigned to EFV, or men assigned to ATV/r. The effects of ATV/r and EFV upon safety and tolerability risk did not differ significantly by sex. With ABC/3TC, women had a significantly higher (32%) safety risk compared to men; with TDF/FTC, the safety risk was 20% larger for women compared to men, but not statistically significant. Women had slower ATV clearance and higher predose levels of ATV compared to men. Self-reported adherence did not differ significantly by sex. Conclusions. This is the first randomized clinical trial to identify a significantly earlier time to virologic failure in women randomized to ATV/r compared to women randomized to EFV. This finding has important clinical implications given that boosted protease inhibitors are often favored over EFV in women of childbearing potential. Clinical Trials Registration NCT00118898.
-
hiv 1 amino acid changes among participants with virologic failure associations with first line efavirenz or Atazanavir Plus Ritonavir and disease status
The Journal of Infectious Diseases, 2012Co-Authors: Katie R Mollan, Eric S Daar, Camlin Tierney, Margaret A Fischl, Paul E Sax, Maya Balamane, Ann C Collier, Christina M Lalama, Ronald J Bosch, David KatzensteinAbstract:More than 5 million individuals are receiving chronic antiretroviral therapy (ART) to suppress the replication of human immunodeficiency virus type 1 (HIV-1). Current US guidelines recommend monitoring of ART with measurement of HIV-1 RNA every 3–6 months to assess virologic response [1]. Virologic suppression with ART results in profound long-term clinical benefits including decrease in immunodeficiency and an increase in life span [2, 3]. Virologic failure reverses each of these benefits, and the recrudescence of viral replication, is associated with the selection of drug-resistant viruses and CD4 cell count decline [4–6]. Upon rebound of viremia on ART, recommendations include reinforcement of adherence and drug resistance testing of plasma HIV-1 to determine the optimal regimen to achieve virologic suppression. In AIDS Clinical Trials Group (ACTG) Study A5202, treatment-naive participants were randomized to Atazanavir Plus Ritonavir (ATV/r) or efavirenz (EFV) with either tenofovir DF/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). The major drug resistance mutations detected by sequencing and consensus alignment at the time of virologic failure were previously reported, where reverse transcriptase (RT) resistance-associated mutations were found to be more frequent among participants with virologic failure assigned to EFV-containing than ATV/r-containing treatment arms [7–9]. Here we present a thorough assessment of HIV-1 major and nonmajor mutations, and cumulative amino acid changes from pretreatment to virologic failure, to provide additional evidence for selection pressures and evolution of drug resistance in response to the different combinations of antiretrovirals.
-
Atazanavir Plus Ritonavir or efavirenz as part of a 3 drug regimen for initial treatment of hiv 1
Annals of Internal Medicine, 2011Co-Authors: Eric S Daar, Camlin Tierney, Margaret A Fischl, Katie R Mollan, Chakra B Budhathoki, Catherine Godfrey, Nasreen C Jahed, Laurie Myers, David Katzenstein, Awny FarajallahAbstract:Results: 463 eligible patients were randomly assigned to receive Atazanavir Plus Ritonavir and 465 were assigned to receive efavirenz, both with abacavir–lamivudine; 322 (70%) and 324 (70%), respectively, completed follow-up. The respective numbers of participants in each group who received tenofovir DF–emtricitabine were 465 and 464; 342 (74%) and 343 (74%) completed follow-up. Primary efficacy was similar in the group that received Atazanavir Plus Ritonavir and and the group that received efavirenz and did not differ according to whether abacavir–lamivudine or tenofovir DF–emtricitabine was also given. Hazard ratios for time to virologic failure were 1.13 (95% CI, 0.82 to 1.56) and 1.01 (CI, 0.70 to 1.46), respectively, although CIs did not meet prespecified criteria for equivalence. The time to safety (P 0.048) and tolerability (P 0.001) events was longer in persons given Atazanavir Plus Ritonavir than in those given efavirenz with abacavir–lamivudine but not with tenofovir DF– emtricitabine. Limitations: Neither HLA-B*5701 nor resistance testing was the standard of care when A5202 enrolled patients. The third drugs, Atazanavir Plus Ritonavir and efavirenz, were open-label; the nucleoside reverse transcriptase inhibitors were prematurely unblinded in the high viral load stratum; and 32% of patients modified or discontinued treatment with their third drug. Conclusion: Atazanavir Plus Ritonavir and efavirenz have similar antiviral activity when used with abacavir–lamivudine or tenofovir DF–emtricitabine. Primary Funding Source: National Institutes of Health.
-
Atazanavir Plus Ritonavir or efavirenz as part of a 3 drug regimen for initial treatment of hiv 1
Annals of Internal Medicine, 2011Co-Authors: Eric S Daar, Camlin Tierney, Margaret A Fischl, Katie R Mollan, Chakra B Budhathoki, Catherine Godfrey, Nasreen C Jahed, Laurie Myers, Paul E Sax, David KatzensteinAbstract:Few studies have compared once-daily treatment regimens for HIV-1. This randomized trial in antiretroviral-naive patients with HIV-1 showed that a once-daily Ritonavir-boosted protease inhibitor re...
-
bone mineral density and fractures in antiretroviral naive persons randomized to receive abacavir lamivudine or tenofovir disoproxil fumarate emtricitabine along with efavirenz or Atazanavir Ritonavir aids clinical trials group a5224s a substudy of actg a5202
The Journal of Infectious Diseases, 2011Co-Authors: Grace A Mccomsey, Eric S Daar, Camlin Tierney, Nasreen C Jahed, Laurie Myers, Paul E Sax, Douglas Kitch, Pablo Tebas, Kathleen MelbourneAbstract:(See the editorial commentary by Yin and Overton, on pages 1705–7.) Background. Long-term effects of abacavir (ABC)–lamivudine (3TC), compared with tenofovir (TDF)–emtricitabine (FTC) with efavirenz (EFV) or Atazanavir Plus Ritonavir (ATV/r), on bone mineral density (BMD) have not been analyzed. Methods. A5224s was a substudy of A5202, in which HIV-infected treatment-naive participants were randomized and blinded to receive ABC-3TC or TDF-FTC with open-label EFV or ATV/r. Primary bone end points included Dual-emission X-ray absorbtiometry (DXA)-measured percent changes in spine and hip BMD at week 96. Primary analyses were intentto-treat. Statistical tests used the factorial design and included linear regression, 2-samplet, log-rank, and Fisher’s exact tests. Results. Two hundred sixty-nine persons randomized to 4 arms of ABC-3TC or TDF-FTC with EFV or ATV/r. At baseline, 85% were male, and 47% were white non-Hispanic; the median HIV-1 RNA load was 4.6 log10 copies/ mL, the median age was 38 years, the median weight was 76 kg, and the median CD4 cell count was 233 cells/lL. At week 96, the mean percentage changes from baseline in spine and hip BMD for ABC-3TC versus TDF-FTC were -1.3% and -3.3% (P 5 .004) and -2.6% and -4.0% (P 5 .024), respectively; and for EFV versus ATV/r were -1.7% and -3.1% (P 5 .035) and -3.1% and -3.4% (P 5 .61), respectively. Bone fracture was observed in 5.6% of participants. The probability of bone fractures and time to first fracture were not different across components. Conclusions. Compared with ABC-3TC, TDF-FTC–treated participants had significantly greater decreases in spine and hip BMD, whereas ATV/r led to more significant losses in spine, but not hip, BMD than EFV. Clinical Trials Registration. NCT00118898.
Paul E Sax - One of the best experts on this subject based on the ideXlab platform.
-
hiv 1 amino acid changes among participants with virologic failure associations with first line efavirenz or Atazanavir Plus Ritonavir and disease status
The Journal of Infectious Diseases, 2012Co-Authors: Katie R Mollan, Eric S Daar, Camlin Tierney, Margaret A Fischl, Paul E Sax, Maya Balamane, Ann C Collier, Christina M Lalama, Ronald J Bosch, David KatzensteinAbstract:More than 5 million individuals are receiving chronic antiretroviral therapy (ART) to suppress the replication of human immunodeficiency virus type 1 (HIV-1). Current US guidelines recommend monitoring of ART with measurement of HIV-1 RNA every 3–6 months to assess virologic response [1]. Virologic suppression with ART results in profound long-term clinical benefits including decrease in immunodeficiency and an increase in life span [2, 3]. Virologic failure reverses each of these benefits, and the recrudescence of viral replication, is associated with the selection of drug-resistant viruses and CD4 cell count decline [4–6]. Upon rebound of viremia on ART, recommendations include reinforcement of adherence and drug resistance testing of plasma HIV-1 to determine the optimal regimen to achieve virologic suppression. In AIDS Clinical Trials Group (ACTG) Study A5202, treatment-naive participants were randomized to Atazanavir Plus Ritonavir (ATV/r) or efavirenz (EFV) with either tenofovir DF/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). The major drug resistance mutations detected by sequencing and consensus alignment at the time of virologic failure were previously reported, where reverse transcriptase (RT) resistance-associated mutations were found to be more frequent among participants with virologic failure assigned to EFV-containing than ATV/r-containing treatment arms [7–9]. Here we present a thorough assessment of HIV-1 major and nonmajor mutations, and cumulative amino acid changes from pretreatment to virologic failure, to provide additional evidence for selection pressures and evolution of drug resistance in response to the different combinations of antiretrovirals.
-
Atazanavir Plus Ritonavir or efavirenz as part of a 3 drug regimen for initial treatment of hiv 1
Annals of Internal Medicine, 2011Co-Authors: Eric S Daar, Camlin Tierney, Margaret A Fischl, Katie R Mollan, Chakra B Budhathoki, Catherine Godfrey, Nasreen C Jahed, Laurie Myers, Paul E Sax, David KatzensteinAbstract:Few studies have compared once-daily treatment regimens for HIV-1. This randomized trial in antiretroviral-naive patients with HIV-1 showed that a once-daily Ritonavir-boosted protease inhibitor re...
-
bone mineral density and fractures in antiretroviral naive persons randomized to receive abacavir lamivudine or tenofovir disoproxil fumarate emtricitabine along with efavirenz or Atazanavir Ritonavir aids clinical trials group a5224s a substudy of actg a5202
The Journal of Infectious Diseases, 2011Co-Authors: Grace A Mccomsey, Eric S Daar, Camlin Tierney, Nasreen C Jahed, Laurie Myers, Paul E Sax, Douglas Kitch, Pablo Tebas, Kathleen MelbourneAbstract:(See the editorial commentary by Yin and Overton, on pages 1705–7.) Background. Long-term effects of abacavir (ABC)–lamivudine (3TC), compared with tenofovir (TDF)–emtricitabine (FTC) with efavirenz (EFV) or Atazanavir Plus Ritonavir (ATV/r), on bone mineral density (BMD) have not been analyzed. Methods. A5224s was a substudy of A5202, in which HIV-infected treatment-naive participants were randomized and blinded to receive ABC-3TC or TDF-FTC with open-label EFV or ATV/r. Primary bone end points included Dual-emission X-ray absorbtiometry (DXA)-measured percent changes in spine and hip BMD at week 96. Primary analyses were intentto-treat. Statistical tests used the factorial design and included linear regression, 2-samplet, log-rank, and Fisher’s exact tests. Results. Two hundred sixty-nine persons randomized to 4 arms of ABC-3TC or TDF-FTC with EFV or ATV/r. At baseline, 85% were male, and 47% were white non-Hispanic; the median HIV-1 RNA load was 4.6 log10 copies/ mL, the median age was 38 years, the median weight was 76 kg, and the median CD4 cell count was 233 cells/lL. At week 96, the mean percentage changes from baseline in spine and hip BMD for ABC-3TC versus TDF-FTC were -1.3% and -3.3% (P 5 .004) and -2.6% and -4.0% (P 5 .024), respectively; and for EFV versus ATV/r were -1.7% and -3.1% (P 5 .035) and -3.1% and -3.4% (P 5 .61), respectively. Bone fracture was observed in 5.6% of participants. The probability of bone fractures and time to first fracture were not different across components. Conclusions. Compared with ABC-3TC, TDF-FTC–treated participants had significantly greater decreases in spine and hip BMD, whereas ATV/r led to more significant losses in spine, but not hip, BMD than EFV. Clinical Trials Registration. NCT00118898.
-
Atazanavir Plus Ritonavir or efavirenz as part of a 3 drug regimen for initial treatment of hiv 1
Annals of Internal Medicine, 2011Co-Authors: Eric S Daar, Camlin Tierney, Margaret A Fischl, Katie R Mollan, Chakra B Budhathoki, Catherine Godfrey, Nasreen C Jahed, Laurie Myers, Paul E Sax, David KatzensteinAbstract:Treatment guidelines for initial HIV-1 therapy recommend 2 nucleoside reverse transcriptase inhibitors (NRTIs) with a non-NRTI (NNRTI), Ritonavir-boosted protease inhibitor, or integrase inhibitor (1, 2). Abacavir–lamivudine and tenofovir disoproxil fumarate (DF)–emtricitabine are efficacious, once-daily NRTIs (3–5). The preferred NNRTI is efavirenz, and Atazanavir Plus Ritonavir is 1 of the preferred protease inhibitors (1, 6, 7). AIDS Clinical Trials Group (ACTG) Study A5202 compared efficacy, safety, and tolerability of abacavir–lamivudine or tenofovir DF–emtricitabine with Atazanavir Plus Ritonavir or efavirenz. After scheduled interim data review, the data and safety monitoring board noted inferior virologic efficacy of abacavir–lamivudine compared with tenofovir DF–emtricitabine among patients with HIV-1 RNA levels of 100 000 copies/mL or more at screening (8). We now report the final results of the primary study objectives comparing Atazanavir Plus Ritonavir against efavirenz.
Eric S Daar - One of the best experts on this subject based on the ideXlab platform.
-
hiv 1 amino acid changes among participants with virologic failure associations with first line efavirenz or Atazanavir Plus Ritonavir and disease status
The Journal of Infectious Diseases, 2012Co-Authors: Katie R Mollan, Eric S Daar, Camlin Tierney, Margaret A Fischl, Paul E Sax, Maya Balamane, Ann C Collier, Christina M Lalama, Ronald J Bosch, David KatzensteinAbstract:More than 5 million individuals are receiving chronic antiretroviral therapy (ART) to suppress the replication of human immunodeficiency virus type 1 (HIV-1). Current US guidelines recommend monitoring of ART with measurement of HIV-1 RNA every 3–6 months to assess virologic response [1]. Virologic suppression with ART results in profound long-term clinical benefits including decrease in immunodeficiency and an increase in life span [2, 3]. Virologic failure reverses each of these benefits, and the recrudescence of viral replication, is associated with the selection of drug-resistant viruses and CD4 cell count decline [4–6]. Upon rebound of viremia on ART, recommendations include reinforcement of adherence and drug resistance testing of plasma HIV-1 to determine the optimal regimen to achieve virologic suppression. In AIDS Clinical Trials Group (ACTG) Study A5202, treatment-naive participants were randomized to Atazanavir Plus Ritonavir (ATV/r) or efavirenz (EFV) with either tenofovir DF/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). The major drug resistance mutations detected by sequencing and consensus alignment at the time of virologic failure were previously reported, where reverse transcriptase (RT) resistance-associated mutations were found to be more frequent among participants with virologic failure assigned to EFV-containing than ATV/r-containing treatment arms [7–9]. Here we present a thorough assessment of HIV-1 major and nonmajor mutations, and cumulative amino acid changes from pretreatment to virologic failure, to provide additional evidence for selection pressures and evolution of drug resistance in response to the different combinations of antiretrovirals.
-
Atazanavir Plus Ritonavir or efavirenz as part of a 3 drug regimen for initial treatment of hiv 1
Annals of Internal Medicine, 2011Co-Authors: Eric S Daar, Camlin Tierney, Margaret A Fischl, Katie R Mollan, Chakra B Budhathoki, Catherine Godfrey, Nasreen C Jahed, Laurie Myers, David Katzenstein, Awny FarajallahAbstract:Results: 463 eligible patients were randomly assigned to receive Atazanavir Plus Ritonavir and 465 were assigned to receive efavirenz, both with abacavir–lamivudine; 322 (70%) and 324 (70%), respectively, completed follow-up. The respective numbers of participants in each group who received tenofovir DF–emtricitabine were 465 and 464; 342 (74%) and 343 (74%) completed follow-up. Primary efficacy was similar in the group that received Atazanavir Plus Ritonavir and and the group that received efavirenz and did not differ according to whether abacavir–lamivudine or tenofovir DF–emtricitabine was also given. Hazard ratios for time to virologic failure were 1.13 (95% CI, 0.82 to 1.56) and 1.01 (CI, 0.70 to 1.46), respectively, although CIs did not meet prespecified criteria for equivalence. The time to safety (P 0.048) and tolerability (P 0.001) events was longer in persons given Atazanavir Plus Ritonavir than in those given efavirenz with abacavir–lamivudine but not with tenofovir DF– emtricitabine. Limitations: Neither HLA-B*5701 nor resistance testing was the standard of care when A5202 enrolled patients. The third drugs, Atazanavir Plus Ritonavir and efavirenz, were open-label; the nucleoside reverse transcriptase inhibitors were prematurely unblinded in the high viral load stratum; and 32% of patients modified or discontinued treatment with their third drug. Conclusion: Atazanavir Plus Ritonavir and efavirenz have similar antiviral activity when used with abacavir–lamivudine or tenofovir DF–emtricitabine. Primary Funding Source: National Institutes of Health.
-
Atazanavir Plus Ritonavir or efavirenz as part of a 3 drug regimen for initial treatment of hiv 1
Annals of Internal Medicine, 2011Co-Authors: Eric S Daar, Camlin Tierney, Margaret A Fischl, Katie R Mollan, Chakra B Budhathoki, Catherine Godfrey, Nasreen C Jahed, Laurie Myers, Paul E Sax, David KatzensteinAbstract:Few studies have compared once-daily treatment regimens for HIV-1. This randomized trial in antiretroviral-naive patients with HIV-1 showed that a once-daily Ritonavir-boosted protease inhibitor re...
-
bone mineral density and fractures in antiretroviral naive persons randomized to receive abacavir lamivudine or tenofovir disoproxil fumarate emtricitabine along with efavirenz or Atazanavir Ritonavir aids clinical trials group a5224s a substudy of actg a5202
The Journal of Infectious Diseases, 2011Co-Authors: Grace A Mccomsey, Eric S Daar, Camlin Tierney, Nasreen C Jahed, Laurie Myers, Paul E Sax, Douglas Kitch, Pablo Tebas, Kathleen MelbourneAbstract:(See the editorial commentary by Yin and Overton, on pages 1705–7.) Background. Long-term effects of abacavir (ABC)–lamivudine (3TC), compared with tenofovir (TDF)–emtricitabine (FTC) with efavirenz (EFV) or Atazanavir Plus Ritonavir (ATV/r), on bone mineral density (BMD) have not been analyzed. Methods. A5224s was a substudy of A5202, in which HIV-infected treatment-naive participants were randomized and blinded to receive ABC-3TC or TDF-FTC with open-label EFV or ATV/r. Primary bone end points included Dual-emission X-ray absorbtiometry (DXA)-measured percent changes in spine and hip BMD at week 96. Primary analyses were intentto-treat. Statistical tests used the factorial design and included linear regression, 2-samplet, log-rank, and Fisher’s exact tests. Results. Two hundred sixty-nine persons randomized to 4 arms of ABC-3TC or TDF-FTC with EFV or ATV/r. At baseline, 85% were male, and 47% were white non-Hispanic; the median HIV-1 RNA load was 4.6 log10 copies/ mL, the median age was 38 years, the median weight was 76 kg, and the median CD4 cell count was 233 cells/lL. At week 96, the mean percentage changes from baseline in spine and hip BMD for ABC-3TC versus TDF-FTC were -1.3% and -3.3% (P 5 .004) and -2.6% and -4.0% (P 5 .024), respectively; and for EFV versus ATV/r were -1.7% and -3.1% (P 5 .035) and -3.1% and -3.4% (P 5 .61), respectively. Bone fracture was observed in 5.6% of participants. The probability of bone fractures and time to first fracture were not different across components. Conclusions. Compared with ABC-3TC, TDF-FTC–treated participants had significantly greater decreases in spine and hip BMD, whereas ATV/r led to more significant losses in spine, but not hip, BMD than EFV. Clinical Trials Registration. NCT00118898.
-
bone mineral density and fractures in antiretroviral naive persons randomized to receive abacavir lamivudine or tenofovir disoproxil fumarate emtricitabine along with efavirenz or Atazanavir Ritonavir aids clinical trials group a5224s a substudy of actg a5202
The Journal of Infectious Diseases, 2011Co-Authors: Grace A Mccomsey, Eric S Daar, Camlin Tierney, Nasreen C Jahed, Laurie Myers, Douglas Kitch, Pablo Tebas, Kathleen Melbourne, Belinda HaAbstract:(See the editorial commentary by Yin and Overton, on pages 1705–7.) Background. Long-term effects of abacavir (ABC)–lamivudine (3TC), compared with tenofovir (TDF)–emtricitabine (FTC) with efavirenz (EFV) or Atazanavir Plus Ritonavir (ATV/r), on bone mineral density (BMD) have not been analyzed. Methods. A5224s was a substudy of A5202, in which HIV-infected treatment-naive participants were randomized and blinded to receive ABC-3TC or TDF-FTC with open-label EFV or ATV/r. Primary bone end points included Dual-emission X-ray absorbtiometry (DXA)-measured percent changes in spine and hip BMD at week 96. Primary analyses were intentto-treat. Statistical tests used the factorial design and included linear regression, 2-samplet, log-rank, and Fisher’s exact tests. Results. Two hundred sixty-nine persons randomized to 4 arms of ABC-3TC or TDF-FTC with EFV or ATV/r. At baseline, 85% were male, and 47% were white non-Hispanic; the median HIV-1 RNA load was 4.6 log10 copies/ mL, the median age was 38 years, the median weight was 76 kg, and the median CD4 cell count was 233 cells/lL. At week 96, the mean percentage changes from baseline in spine and hip BMD for ABC-3TC versus TDF-FTC were -1.3% and -3.3% (P 5 .004) and -2.6% and -4.0% (P 5 .024), respectively; and for EFV versus ATV/r were -1.7% and -3.1% (P 5 .035) and -3.1% and -3.4% (P 5 .61), respectively. Bone fracture was observed in 5.6% of participants. The probability of bone fractures and time to first fracture were not different across components. Conclusions. Compared with ABC-3TC, TDF-FTC–treated participants had significantly greater decreases in spine and hip BMD, whereas ATV/r led to more significant losses in spine, but not hip, BMD than EFV. Clinical Trials Registration. NCT00118898.
David Katzenstein - One of the best experts on this subject based on the ideXlab platform.
-
outcomes by sex following treatment initiation with Atazanavir Plus Ritonavir or efavirenz with abacavir lamivudine or tenofovir emtricitabine
Clinical Infectious Diseases, 2014Co-Authors: Kimberly Y Smith, Camlin Tierney, Katie R Mollan, Chakra B Budhathoki, Catherine Godfrey, David Katzenstein, Charles S Venuto, Gene D Morse, Margaret A FischlAbstract:Background. We aimed to evaluate treatment responses to Atazanavir Plus Ritonavir (ATV/r) or efavirenz (EFV) in initial antiretroviral regimens among women and men, and determine if treatment outcomes differ by sex. Methods. We performed a randomized trial of open-label ATV/r or EFV combined with abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) in 1857 human immunodeficiency virus type 1–infected, treatment-naive persons enrolled between September 2005 and November 2007 at 59 sites in the United States and Puerto Rico. Associations of sex with 3 primary study endpoints of time to virologic failure, safety, and tolerability events were analyzed using Cox proportional hazards models. Model-based population pharmacokinetic analysis was performed using nonlinear mixed effects modeling (NONMEM version VII). Results. Of 1857 participants, 322 were women. Women assigned to ATV/r had a higher risk of virologic failure with either nucleoside reverse transcriptase inhibitor backbone than women assigned to EFV, or men assigned to ATV/r. The effects of ATV/r and EFV upon safety and tolerability risk did not differ significantly by sex. With ABC/3TC, women had a significantly higher (32%) safety risk compared to men; with TDF/FTC, the safety risk was 20% larger for women compared to men, but not statistically significant. Women had slower ATV clearance and higher predose levels of ATV compared to men. Self-reported adherence did not differ significantly by sex. Conclusions. This is the first randomized clinical trial to identify a significantly earlier time to virologic failure in women randomized to ATV/r compared to women randomized to EFV. This finding has important clinical implications given that boosted protease inhibitors are often favored over EFV in women of childbearing potential. Clinical Trials Registration NCT00118898.
-
hiv 1 amino acid changes among participants with virologic failure associations with first line efavirenz or Atazanavir Plus Ritonavir and disease status
The Journal of Infectious Diseases, 2012Co-Authors: Katie R Mollan, Eric S Daar, Camlin Tierney, Margaret A Fischl, Paul E Sax, Maya Balamane, Ann C Collier, Christina M Lalama, Ronald J Bosch, David KatzensteinAbstract:More than 5 million individuals are receiving chronic antiretroviral therapy (ART) to suppress the replication of human immunodeficiency virus type 1 (HIV-1). Current US guidelines recommend monitoring of ART with measurement of HIV-1 RNA every 3–6 months to assess virologic response [1]. Virologic suppression with ART results in profound long-term clinical benefits including decrease in immunodeficiency and an increase in life span [2, 3]. Virologic failure reverses each of these benefits, and the recrudescence of viral replication, is associated with the selection of drug-resistant viruses and CD4 cell count decline [4–6]. Upon rebound of viremia on ART, recommendations include reinforcement of adherence and drug resistance testing of plasma HIV-1 to determine the optimal regimen to achieve virologic suppression. In AIDS Clinical Trials Group (ACTG) Study A5202, treatment-naive participants were randomized to Atazanavir Plus Ritonavir (ATV/r) or efavirenz (EFV) with either tenofovir DF/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). The major drug resistance mutations detected by sequencing and consensus alignment at the time of virologic failure were previously reported, where reverse transcriptase (RT) resistance-associated mutations were found to be more frequent among participants with virologic failure assigned to EFV-containing than ATV/r-containing treatment arms [7–9]. Here we present a thorough assessment of HIV-1 major and nonmajor mutations, and cumulative amino acid changes from pretreatment to virologic failure, to provide additional evidence for selection pressures and evolution of drug resistance in response to the different combinations of antiretrovirals.
-
Atazanavir Plus Ritonavir or efavirenz as part of a 3 drug regimen for initial treatment of hiv 1
Annals of Internal Medicine, 2011Co-Authors: Eric S Daar, Camlin Tierney, Margaret A Fischl, Katie R Mollan, Chakra B Budhathoki, Catherine Godfrey, Nasreen C Jahed, Laurie Myers, David Katzenstein, Awny FarajallahAbstract:Results: 463 eligible patients were randomly assigned to receive Atazanavir Plus Ritonavir and 465 were assigned to receive efavirenz, both with abacavir–lamivudine; 322 (70%) and 324 (70%), respectively, completed follow-up. The respective numbers of participants in each group who received tenofovir DF–emtricitabine were 465 and 464; 342 (74%) and 343 (74%) completed follow-up. Primary efficacy was similar in the group that received Atazanavir Plus Ritonavir and and the group that received efavirenz and did not differ according to whether abacavir–lamivudine or tenofovir DF–emtricitabine was also given. Hazard ratios for time to virologic failure were 1.13 (95% CI, 0.82 to 1.56) and 1.01 (CI, 0.70 to 1.46), respectively, although CIs did not meet prespecified criteria for equivalence. The time to safety (P 0.048) and tolerability (P 0.001) events was longer in persons given Atazanavir Plus Ritonavir than in those given efavirenz with abacavir–lamivudine but not with tenofovir DF– emtricitabine. Limitations: Neither HLA-B*5701 nor resistance testing was the standard of care when A5202 enrolled patients. The third drugs, Atazanavir Plus Ritonavir and efavirenz, were open-label; the nucleoside reverse transcriptase inhibitors were prematurely unblinded in the high viral load stratum; and 32% of patients modified or discontinued treatment with their third drug. Conclusion: Atazanavir Plus Ritonavir and efavirenz have similar antiviral activity when used with abacavir–lamivudine or tenofovir DF–emtricitabine. Primary Funding Source: National Institutes of Health.
-
Atazanavir Plus Ritonavir or efavirenz as part of a 3 drug regimen for initial treatment of hiv 1
Annals of Internal Medicine, 2011Co-Authors: Eric S Daar, Camlin Tierney, Margaret A Fischl, Katie R Mollan, Chakra B Budhathoki, Catherine Godfrey, Nasreen C Jahed, Laurie Myers, Paul E Sax, David KatzensteinAbstract:Few studies have compared once-daily treatment regimens for HIV-1. This randomized trial in antiretroviral-naive patients with HIV-1 showed that a once-daily Ritonavir-boosted protease inhibitor re...
-
Atazanavir Plus Ritonavir or efavirenz as part of a 3 drug regimen for initial treatment of hiv 1
Annals of Internal Medicine, 2011Co-Authors: Eric S Daar, Camlin Tierney, Margaret A Fischl, Katie R Mollan, Chakra B Budhathoki, Catherine Godfrey, Nasreen C Jahed, Laurie Myers, Paul E Sax, David KatzensteinAbstract:Treatment guidelines for initial HIV-1 therapy recommend 2 nucleoside reverse transcriptase inhibitors (NRTIs) with a non-NRTI (NNRTI), Ritonavir-boosted protease inhibitor, or integrase inhibitor (1, 2). Abacavir–lamivudine and tenofovir disoproxil fumarate (DF)–emtricitabine are efficacious, once-daily NRTIs (3–5). The preferred NNRTI is efavirenz, and Atazanavir Plus Ritonavir is 1 of the preferred protease inhibitors (1, 6, 7). AIDS Clinical Trials Group (ACTG) Study A5202 compared efficacy, safety, and tolerability of abacavir–lamivudine or tenofovir DF–emtricitabine with Atazanavir Plus Ritonavir or efavirenz. After scheduled interim data review, the data and safety monitoring board noted inferior virologic efficacy of abacavir–lamivudine compared with tenofovir DF–emtricitabine among patients with HIV-1 RNA levels of 100 000 copies/mL or more at screening (8). We now report the final results of the primary study objectives comparing Atazanavir Plus Ritonavir against efavirenz.
R B Wilber - One of the best experts on this subject based on the ideXlab platform.
-
Atazanavir Plus Ritonavir or saquinavir and lopinavir Ritonavir in patients experiencing multiple virological failures
AIDS, 2005Co-Authors: Margaret Johnson, Adriano Lazzarin, Edwin Dejesus, Beatriz Grinsztejn, Claudia Rodriguez, Jeffrey Coco, Kenneth A Lichtenstein, Anna Rightmire, Serap Sankoh, R B WilberAbstract:Comment in: Atazanavir/Ritonavir versus lopinavir/Ritonavir: equivalent or different efficacy profiles? [AIDS. 2005] Corrected and republished from: Atazanavir Plus Ritonavir or saquinavir, and lopinavir/Ritonavir in patients experiencing multiple virological failures. [AIDS. 2005]
-
Atazanavir Plus Ritonavir or saquinavir and lopinavir Ritonavir in patients experiencing multiple virological failures
AIDS, 2005Co-Authors: Margaret Johnson, Adriano Lazzarin, Edwin Dejesus, Beatriz Grinsztejn, Claudia Rodriguez, Jeffrey Coco, Kenneth A Lichtenstein, Anna Rightmire, Serap Sankoh, R B WilberAbstract:OBJECTIVE: To evaluate Atazanavir/Ritonavir (ATV/RTV) (300/100 mg) once daily, Atazanavir/saquinavir (ATV/SQV) (400/1200 mg) once daily, and lopinavir/Ritonavir (LPV/RTV) (400/100 mg) twice daily, each with tenofovir (300 mg) once daily and a nucleoside reverse transcriptase inhibitor in treatment-experienced HIV-infected patients. METHODS: Randomized, open-label, 48-week multicenter trial of 358 randomized adult patients who had failed two or more prior HAART regimens with baseline HIV RNA > or = 1000 copies/ml and CD4 cell count > or = 50 x 10(6) cells/l. RESULTS: The primary efficacy endpoint [plasma HIV RNA reduction assessed by time-averaged difference (TAD)] was similar for ATV/RTV and LPV/RTV [TAD 0.13; 97.5% confidence interval, -0.12 to 0.39] at 48 weeks. Mean reductions from baseline for ATV/RTV and LPV/RTV were comparable at 1.93 and 1.87 log10 copies/ml, respectively. Mean CD4 cell count increases were 110 and 121 x 10(6) cells/l for ATV/RTV, and LPV/RTV, respectively. The efficacy of ATV/SQV was lower than LPV/RTV by both these parameters. Declines in total cholesterol and fasting triglycerides were greater with ATV/RTV and ATV/SQV than with LPV/RTV (P < or = 0.005). Lipids in the LPV/RTV arm at week 48 generally increased from baseline. Lipid-lowering agents were used more frequently in the LPV/RTV arm than in the ATV arms (P < 0.05 versus ATV/RTV), as were antidiarrheal agents (P < or = 0.04 versus both ATV treatments). No new or unique safety findings emerged. CONCLUSIONS: ATV boosted with RTV is as effective and well tolerated as LPV/RTV in treatment-experienced patients, with a more favorable impact on serum lipids. Pharmacokinetically enhanced ATV provides a suitable choice for therapy of treatment-experienced HIV-infected patients.