Twice-daily amprenavir I 200 mg versus amprenavir 600 mg/ritonavir 100 mg, in combination with at least 2 other antiretroviral drugs, in HIV-I-infected patients

Jeffrey P. Nadler, Joseph C. Gathe, Richard B Pollard, Gary J. Richmond, Qiming Liao, Sandy Griffith, Charles Tracey Lancaster, Jaime E. Hernandez, Keith A. Pappa, Marianna McDonald, Terri Becom, Ashwin Hirani, Brian Wine, Claressa Jolly, Carol Humpries

Research output: Contribution to journalArticle

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Abstract

Background: Low-dose ritonavir (RTV) boosts plasma amprenavir (APV) exposure. Little has been published on the efficacy, tolerability, and safety of APV 600 mg/RTV 100 mg (APV600/RTV) twice daily (BID) compared to APV 1200 mg BID (APV1200). Methods: ESS40011 was a 24-week, multicenter, open-label, clinical trial in which antiretroviral therapy-naïve and -experienced HIV-1-infected adults were randomized 3:1 to receive either APV600/RTV BID or APV1200 BID, in combination with ≥ 2 non-protease inhibitor antiretroviral drugs. Non-inferiority of the APV600/RTV regimen to the APV1200 regimen was established if the 95% lower confidence limit for the difference in proportion of patients achieving HIV-1 RNA <200 copies/mL at week 24 with APV 600/RTV minus APV1200 was ≥-0.12. Late in the conduct of the trial, patients not yet completing 24 weeks of therapy were given the option of continuing treatment for an additional 24-week period. Results: 211 patients were randomized, 158 to APV600/RTV and 53 to APV1200. At week 24, APV600/RTV was similar to or better than APV1200 (HIV-1 RNA <200 copies/mL in 62% [73/118] vs 53% [20/38] of patients; intent-to-treat: observed analysis). In the APV600/RTV arm, significantly more patients achieved HIV-1 RNA <50 copies/mL (48% [57/118] vs 29% [11/38] with APV1200, P = 0.04), and greater mean reduction from baseline in HIV-1 RNA was observed (-2.21 vs -1.59 log10 copies/mL, P = 0.028). The two treatment arms were similar with respect to mean overall change from baseline in CD4+ count, frequency of drug-related grade 1-4 adverse events, and frequency of discontinuing treatment due to adverse events (most commonly nausea, diarrhea, vomiting or fatigue; 7% vs 8%), although a lower proportion of patients in the APV600/RTV arm experienced drug-related oral/perioral paresthesia (2% vs 8%). Eleven (73%) of 15 patients who had HIV-1 RNA <200 copies/mL at week 24 and chose to continue study treatment maintained this level of virologic suppression at follow-up 24 weeks later. Conclusions: APV600 RTV BID was similar to or better than APV1200 BID in virologic response. Virologic results in a small number of patients who continued treatment for 24 weeks post-study suggest that virologic suppression with APV600 RTV BID is durable.

Original languageEnglish (US)
Article number10
JournalBMC Infectious Diseases
Volume3
DOIs
StatePublished - Jun 10 2003
Externally publishedYes

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Ritonavir
HIV-1
Pharmaceutical Preparations
RNA
Therapeutics
amprenavir
Paresthesia
CD4 Lymphocyte Count
Nausea
Vomiting
Fatigue
Diarrhea
Clinical Trials
Safety

ASJC Scopus subject areas

  • Infectious Diseases

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Twice-daily amprenavir I 200 mg versus amprenavir 600 mg/ritonavir 100 mg, in combination with at least 2 other antiretroviral drugs, in HIV-I-infected patients. / Nadler, Jeffrey P.; Gathe, Joseph C.; Pollard, Richard B; Richmond, Gary J.; Liao, Qiming; Griffith, Sandy; Lancaster, Charles Tracey; Hernandez, Jaime E.; Pappa, Keith A.; McDonald, Marianna; Becom, Terri; Hirani, Ashwin; Wine, Brian; Jolly, Claressa; Humpries, Carol.

In: BMC Infectious Diseases, Vol. 3, 10, 10.06.2003.

Research output: Contribution to journalArticle

Nadler, JP, Gathe, JC, Pollard, RB, Richmond, GJ, Liao, Q, Griffith, S, Lancaster, CT, Hernandez, JE, Pappa, KA, McDonald, M, Becom, T, Hirani, A, Wine, B, Jolly, C & Humpries, C 2003, 'Twice-daily amprenavir I 200 mg versus amprenavir 600 mg/ritonavir 100 mg, in combination with at least 2 other antiretroviral drugs, in HIV-I-infected patients', BMC Infectious Diseases, vol. 3, 10. https://doi.org/10.1186/1471-2334-3-10
Nadler, Jeffrey P. ; Gathe, Joseph C. ; Pollard, Richard B ; Richmond, Gary J. ; Liao, Qiming ; Griffith, Sandy ; Lancaster, Charles Tracey ; Hernandez, Jaime E. ; Pappa, Keith A. ; McDonald, Marianna ; Becom, Terri ; Hirani, Ashwin ; Wine, Brian ; Jolly, Claressa ; Humpries, Carol. / Twice-daily amprenavir I 200 mg versus amprenavir 600 mg/ritonavir 100 mg, in combination with at least 2 other antiretroviral drugs, in HIV-I-infected patients. In: BMC Infectious Diseases. 2003 ; Vol. 3.
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title = "Twice-daily amprenavir I 200 mg versus amprenavir 600 mg/ritonavir 100 mg, in combination with at least 2 other antiretroviral drugs, in HIV-I-infected patients",
abstract = "Background: Low-dose ritonavir (RTV) boosts plasma amprenavir (APV) exposure. Little has been published on the efficacy, tolerability, and safety of APV 600 mg/RTV 100 mg (APV600/RTV) twice daily (BID) compared to APV 1200 mg BID (APV1200). Methods: ESS40011 was a 24-week, multicenter, open-label, clinical trial in which antiretroviral therapy-na{\"i}ve and -experienced HIV-1-infected adults were randomized 3:1 to receive either APV600/RTV BID or APV1200 BID, in combination with ≥ 2 non-protease inhibitor antiretroviral drugs. Non-inferiority of the APV600/RTV regimen to the APV1200 regimen was established if the 95{\%} lower confidence limit for the difference in proportion of patients achieving HIV-1 RNA <200 copies/mL at week 24 with APV 600/RTV minus APV1200 was ≥-0.12. Late in the conduct of the trial, patients not yet completing 24 weeks of therapy were given the option of continuing treatment for an additional 24-week period. Results: 211 patients were randomized, 158 to APV600/RTV and 53 to APV1200. At week 24, APV600/RTV was similar to or better than APV1200 (HIV-1 RNA <200 copies/mL in 62{\%} [73/118] vs 53{\%} [20/38] of patients; intent-to-treat: observed analysis). In the APV600/RTV arm, significantly more patients achieved HIV-1 RNA <50 copies/mL (48{\%} [57/118] vs 29{\%} [11/38] with APV1200, P = 0.04), and greater mean reduction from baseline in HIV-1 RNA was observed (-2.21 vs -1.59 log10 copies/mL, P = 0.028). The two treatment arms were similar with respect to mean overall change from baseline in CD4+ count, frequency of drug-related grade 1-4 adverse events, and frequency of discontinuing treatment due to adverse events (most commonly nausea, diarrhea, vomiting or fatigue; 7{\%} vs 8{\%}), although a lower proportion of patients in the APV600/RTV arm experienced drug-related oral/perioral paresthesia (2{\%} vs 8{\%}). Eleven (73{\%}) of 15 patients who had HIV-1 RNA <200 copies/mL at week 24 and chose to continue study treatment maintained this level of virologic suppression at follow-up 24 weeks later. Conclusions: APV600 RTV BID was similar to or better than APV1200 BID in virologic response. Virologic results in a small number of patients who continued treatment for 24 weeks post-study suggest that virologic suppression with APV600 RTV BID is durable.",
author = "Nadler, {Jeffrey P.} and Gathe, {Joseph C.} and Pollard, {Richard B} and Richmond, {Gary J.} and Qiming Liao and Sandy Griffith and Lancaster, {Charles Tracey} and Hernandez, {Jaime E.} and Pappa, {Keith A.} and Marianna McDonald and Terri Becom and Ashwin Hirani and Brian Wine and Claressa Jolly and Carol Humpries",
year = "2003",
month = "6",
day = "10",
doi = "10.1186/1471-2334-3-10",
language = "English (US)",
volume = "3",
journal = "BMC Infectious Diseases",
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TY - JOUR

T1 - Twice-daily amprenavir I 200 mg versus amprenavir 600 mg/ritonavir 100 mg, in combination with at least 2 other antiretroviral drugs, in HIV-I-infected patients

AU - Nadler, Jeffrey P.

AU - Gathe, Joseph C.

AU - Pollard, Richard B

AU - Richmond, Gary J.

AU - Liao, Qiming

AU - Griffith, Sandy

AU - Lancaster, Charles Tracey

AU - Hernandez, Jaime E.

AU - Pappa, Keith A.

AU - McDonald, Marianna

AU - Becom, Terri

AU - Hirani, Ashwin

AU - Wine, Brian

AU - Jolly, Claressa

AU - Humpries, Carol

PY - 2003/6/10

Y1 - 2003/6/10

N2 - Background: Low-dose ritonavir (RTV) boosts plasma amprenavir (APV) exposure. Little has been published on the efficacy, tolerability, and safety of APV 600 mg/RTV 100 mg (APV600/RTV) twice daily (BID) compared to APV 1200 mg BID (APV1200). Methods: ESS40011 was a 24-week, multicenter, open-label, clinical trial in which antiretroviral therapy-naïve and -experienced HIV-1-infected adults were randomized 3:1 to receive either APV600/RTV BID or APV1200 BID, in combination with ≥ 2 non-protease inhibitor antiretroviral drugs. Non-inferiority of the APV600/RTV regimen to the APV1200 regimen was established if the 95% lower confidence limit for the difference in proportion of patients achieving HIV-1 RNA <200 copies/mL at week 24 with APV 600/RTV minus APV1200 was ≥-0.12. Late in the conduct of the trial, patients not yet completing 24 weeks of therapy were given the option of continuing treatment for an additional 24-week period. Results: 211 patients were randomized, 158 to APV600/RTV and 53 to APV1200. At week 24, APV600/RTV was similar to or better than APV1200 (HIV-1 RNA <200 copies/mL in 62% [73/118] vs 53% [20/38] of patients; intent-to-treat: observed analysis). In the APV600/RTV arm, significantly more patients achieved HIV-1 RNA <50 copies/mL (48% [57/118] vs 29% [11/38] with APV1200, P = 0.04), and greater mean reduction from baseline in HIV-1 RNA was observed (-2.21 vs -1.59 log10 copies/mL, P = 0.028). The two treatment arms were similar with respect to mean overall change from baseline in CD4+ count, frequency of drug-related grade 1-4 adverse events, and frequency of discontinuing treatment due to adverse events (most commonly nausea, diarrhea, vomiting or fatigue; 7% vs 8%), although a lower proportion of patients in the APV600/RTV arm experienced drug-related oral/perioral paresthesia (2% vs 8%). Eleven (73%) of 15 patients who had HIV-1 RNA <200 copies/mL at week 24 and chose to continue study treatment maintained this level of virologic suppression at follow-up 24 weeks later. Conclusions: APV600 RTV BID was similar to or better than APV1200 BID in virologic response. Virologic results in a small number of patients who continued treatment for 24 weeks post-study suggest that virologic suppression with APV600 RTV BID is durable.

AB - Background: Low-dose ritonavir (RTV) boosts plasma amprenavir (APV) exposure. Little has been published on the efficacy, tolerability, and safety of APV 600 mg/RTV 100 mg (APV600/RTV) twice daily (BID) compared to APV 1200 mg BID (APV1200). Methods: ESS40011 was a 24-week, multicenter, open-label, clinical trial in which antiretroviral therapy-naïve and -experienced HIV-1-infected adults were randomized 3:1 to receive either APV600/RTV BID or APV1200 BID, in combination with ≥ 2 non-protease inhibitor antiretroviral drugs. Non-inferiority of the APV600/RTV regimen to the APV1200 regimen was established if the 95% lower confidence limit for the difference in proportion of patients achieving HIV-1 RNA <200 copies/mL at week 24 with APV 600/RTV minus APV1200 was ≥-0.12. Late in the conduct of the trial, patients not yet completing 24 weeks of therapy were given the option of continuing treatment for an additional 24-week period. Results: 211 patients were randomized, 158 to APV600/RTV and 53 to APV1200. At week 24, APV600/RTV was similar to or better than APV1200 (HIV-1 RNA <200 copies/mL in 62% [73/118] vs 53% [20/38] of patients; intent-to-treat: observed analysis). In the APV600/RTV arm, significantly more patients achieved HIV-1 RNA <50 copies/mL (48% [57/118] vs 29% [11/38] with APV1200, P = 0.04), and greater mean reduction from baseline in HIV-1 RNA was observed (-2.21 vs -1.59 log10 copies/mL, P = 0.028). The two treatment arms were similar with respect to mean overall change from baseline in CD4+ count, frequency of drug-related grade 1-4 adverse events, and frequency of discontinuing treatment due to adverse events (most commonly nausea, diarrhea, vomiting or fatigue; 7% vs 8%), although a lower proportion of patients in the APV600/RTV arm experienced drug-related oral/perioral paresthesia (2% vs 8%). Eleven (73%) of 15 patients who had HIV-1 RNA <200 copies/mL at week 24 and chose to continue study treatment maintained this level of virologic suppression at follow-up 24 weeks later. Conclusions: APV600 RTV BID was similar to or better than APV1200 BID in virologic response. Virologic results in a small number of patients who continued treatment for 24 weeks post-study suggest that virologic suppression with APV600 RTV BID is durable.

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