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Erschienen in: Drugs 5/2008

01.04.2008 | Current Opinion

Efficacy and Safety of Once-Daily Regimens in the Treatment of HIV Infection

verfasst von: Dr Jean-Michel Molina

Erschienen in: Drugs | Ausgabe 5/2008

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Abstract

Early versions of highly-active antiretroviral therapy (HAART) characteristically involved complicated combinations of different drugs, which were taken as varying numbers of pills and as multiple doses each day. With the recent availability of once-daily treatment drugs, simpler regimens are becoming increasingly popular because of increased convenience. To help physicians make informed decisions about updating their patients’ treatment regimens, this article compares newer once-daily administration regimens with older twice-daily administration regimens in terms of efficacy, durability, potential for adverse effects and patient adherence.
More than ten antiretroviral drugs or drug combinations are now approved for once-daily administration in some countries: abacavir, didanosine, emtricitabine, lamivudine, tenofovir disoproxil fumarate (DF), efavirenz, atazanavir, atazanavir plus ritonavir, fosamprenavir plus ritonavir and coformulated lopinavir/ritonavir. In addition, some drugs have been coformulated for once-daily administration (abacavir/lamivudine; emtricitabine/tenofovir DF; and efavirenz/emtricitabine/ tenofovir DF).
Clinical studies have validated the efficacy of HAART drug combinations for once-daily or twice-daily administration in patients who were treatment-naive or who required salvage therapy. On the basis of efficacy measures reflecting lowered viral load (percentage of patients with HIV RNA levels <400 copies/mL or <50 copies/mL), once-daily administration regimens were consistently found to be at least as effective as twice-daily regimens, and sometimes more effective.
Most of the regimens studied for efficacy relied on a combination of two nucleoside reverse transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor (NNRTI). Efavirenz was the most commonly-used NNRTI, and it was used in combination with lamuvidine or emtricitabine, plus didanosine, abacavir or tenofovir DF. In regimens that replaced efavirenz with once-daily protease inhibitors, those with atazanavir or lopinavir/ritonavir were similarly efficacious as either once-daily or twice-daily regimens.
In terms of adherence to specific regimens, reviewed studies showed that once-daily HAART regimens were often superior and were at least non-inferior to twice-daily regimens, with no significant decrease in efficacy.
In conclusion, once-daily HAART regimens have been validated in clinical trials as safely used, well tolerated and effective. Such regimens are likely to improve patient adherence because they are simpler and more convenient than earlier therapeutic regimens.
Literatur
1.
Zurück zum Zitat Bangsberg DR, Perry S, Charlebois ED, et al. Non-adherence to highly active antiretroviral therapy predicts progression to AIDS. AIDS 2001; 15: 1181–3PubMedCrossRef Bangsberg DR, Perry S, Charlebois ED, et al. Non-adherence to highly active antiretroviral therapy predicts progression to AIDS. AIDS 2001; 15: 1181–3PubMedCrossRef
2.
Zurück zum Zitat Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000; 133: 21–30PubMed Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000; 133: 21–30PubMed
3.
Zurück zum Zitat Golin C, Perry S, Charlebois E, et al. A prospective study of predictors of adherence to combination antiretroviral medication. J Gen Intern Med 2002; 17: 1181–3 Golin C, Perry S, Charlebois E, et al. A prospective study of predictors of adherence to combination antiretroviral medication. J Gen Intern Med 2002; 17: 1181–3
4.
Zurück zum Zitat Liu H, Miller L, Hays R, et al. Repeated measures longitudinal analyses of HIV virologic response as a function of percent adherence, dose timing, genotypic sensitivity, and other factors. J Acquir Immune Defic Syndr 2006; 41: 315–22PubMedCrossRef Liu H, Miller L, Hays R, et al. Repeated measures longitudinal analyses of HIV virologic response as a function of percent adherence, dose timing, genotypic sensitivity, and other factors. J Acquir Immune Defic Syndr 2006; 41: 315–22PubMedCrossRef
6.
Zurück zum Zitat Molina JM, Journot V, Morand-Joubert L, et al. Simplification therapy with once-daily emtricitabine, didanosine, and efavirenz in HIV-1-infected adults with viral suppression receiving a protease inhibitor-based regimen: a randomized trial. J Infect Dis 2005; 191: 830–9PubMedCrossRef Molina JM, Journot V, Morand-Joubert L, et al. Simplification therapy with once-daily emtricitabine, didanosine, and efavirenz in HIV-1-infected adults with viral suppression receiving a protease inhibitor-based regimen: a randomized trial. J Infect Dis 2005; 191: 830–9PubMedCrossRef
7.
Zurück zum Zitat Stone VE, Jordan J, Toison J, et al. Perspectives on adherence and simplicity for HIV-infected patients on antiretroviral therapy: self-report of the relative importance of multiple attributes of highly active antiretroviral therapy (HAART) regimens in predicting adherence. J Acquir Immune Defic Syndr 2004; 36: 808–16PubMedCrossRef Stone VE, Jordan J, Toison J, et al. Perspectives on adherence and simplicity for HIV-infected patients on antiretroviral therapy: self-report of the relative importance of multiple attributes of highly active antiretroviral therapy (HAART) regimens in predicting adherence. J Acquir Immune Defic Syndr 2004; 36: 808–16PubMedCrossRef
8.
Zurück zum Zitat Johnson M, Gathe J, Podzamczer D, et al. A once-daily lopinariv/ritonavir-based regimen provides noninferior antiretroviral activity compared with a twice-daily regimen. J Acquir Immune Defic Syndr 2006; 43: 153–60PubMedCrossRef Johnson M, Gathe J, Podzamczer D, et al. A once-daily lopinariv/ritonavir-based regimen provides noninferior antiretroviral activity compared with a twice-daily regimen. J Acquir Immune Defic Syndr 2006; 43: 153–60PubMedCrossRef
9.
Zurück zum Zitat Molina J-M, Podsadecki T, Johnson M, et al. A lopinavir/ ritonavir-based once-daily regimen results in better compliance and is non-inferior to a twice-daily regimen through 96 weeks. AIDS Res Human Retrovir 2007; 23: 1505–14CrossRef Molina J-M, Podsadecki T, Johnson M, et al. A lopinavir/ ritonavir-based once-daily regimen results in better compliance and is non-inferior to a twice-daily regimen through 96 weeks. AIDS Res Human Retrovir 2007; 23: 1505–14CrossRef
10.
Zurück zum Zitat Moyle GJ, DeJesus E, Cahn P, et al. Abacavir once or twice daily combined with once-daily lamivudine and efavirenz for the treatment of antiretroviral-naive HIV-infecetd adults: results of the Ziagen Once Daily in Antiretroviral Combination Study. J Acquir Immune Defic Syndr 2005; 38: 417–25PubMedCrossRef Moyle GJ, DeJesus E, Cahn P, et al. Abacavir once or twice daily combined with once-daily lamivudine and efavirenz for the treatment of antiretroviral-naive HIV-infecetd adults: results of the Ziagen Once Daily in Antiretroviral Combination Study. J Acquir Immune Defic Syndr 2005; 38: 417–25PubMedCrossRef
11.
Zurück zum Zitat Sosa N, Hill-Zabala C, DeJesus E, et al. Abacavir and lamivudine fixed-dose combination tablet once daily compared with abacavir and lamivudine twice daily in HIV-infected patients over 48 weeks (ESS30008, SEAL). J Acquir Immune Defic Syndr 2005; 40: 422–7PubMedCrossRef Sosa N, Hill-Zabala C, DeJesus E, et al. Abacavir and lamivudine fixed-dose combination tablet once daily compared with abacavir and lamivudine twice daily in HIV-infected patients over 48 weeks (ESS30008, SEAL). J Acquir Immune Defic Syndr 2005; 40: 422–7PubMedCrossRef
12.
Zurück zum Zitat Gallant JE, Staszewski S, Pozniak AL, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA 2004; 292: 191–201PubMedCrossRef Gallant JE, Staszewski S, Pozniak AL, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA 2004; 292: 191–201PubMedCrossRef
13.
Zurück zum Zitat Saag MS, Cahn P, Raffi F, et al. Efficacy and safety of emtricitabine vs stavudine in combination therapy in antiretroviralnaive patients: a randomized trial. JAMA 2004; 292: 180–9PubMedCrossRef Saag MS, Cahn P, Raffi F, et al. Efficacy and safety of emtricitabine vs stavudine in combination therapy in antiretroviralnaive patients: a randomized trial. JAMA 2004; 292: 180–9PubMedCrossRef
14.
Zurück zum Zitat Gallant J, DeJesus E, Arribas J, et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med 2006; 354: 251–60 Gallant J, DeJesus E, Arribas J, et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med 2006; 354: 251–60
15.
Zurück zum Zitat Pozniak A, Gallant J, DeJesus E, et al. Tenofovir disproxil fumarate, emtricitabine, and efavirenz versus fixed-dose zidovudine/lamivudine and efavirenz in antiretroviral-naive patients. J Acquir Immune Defic Syndr 2006; 43: 535–40PubMed Pozniak A, Gallant J, DeJesus E, et al. Tenofovir disproxil fumarate, emtricitabine, and efavirenz versus fixed-dose zidovudine/lamivudine and efavirenz in antiretroviral-naive patients. J Acquir Immune Defic Syndr 2006; 43: 535–40PubMed
16.
Zurück zum Zitat Niel-Malan D, Krantz E, David N, et al. Efficacy and safety of atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy requirements in antiretroviral-naive patients. J Acquir Immune Defic Syndr 2008 Feb 5–8; 47: 161–7CrossRef Niel-Malan D, Krantz E, David N, et al. Efficacy and safety of atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy requirements in antiretroviral-naive patients. J Acquir Immune Defic Syndr 2008 Feb 5–8; 47: 161–7CrossRef
17.
Zurück zum Zitat Squires K, Lazzarin A, Gatell JM, et al. Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV. J Acquir Immune Defic Syndr 2004; 36: 1011–9PubMedCrossRef Squires K, Lazzarin A, Gatell JM, et al. Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV. J Acquir Immune Defic Syndr 2004; 36: 1011–9PubMedCrossRef
18.
Zurück zum Zitat Molina JM, Ferchal F, Rancinan C, et al. Once-daily combination therapy with emtricitabine, didanosine, and efavirenz in human immunodeficiency virus-infected patients. J Infect Dis 2000; 182: 599–602PubMedCrossRef Molina JM, Ferchal F, Rancinan C, et al. Once-daily combination therapy with emtricitabine, didanosine, and efavirenz in human immunodeficiency virus-infected patients. J Infect Dis 2000; 182: 599–602PubMedCrossRef
19.
Zurück zum Zitat Molina J-M, Journot V, Furco A, et al. Five-year follow up of once-daily therapy with entricitabine, didanosine and efavirenz (Montana ANRS 091 trial). Antivir Ther 2007; 12: 417–22PubMed Molina J-M, Journot V, Furco A, et al. Five-year follow up of once-daily therapy with entricitabine, didanosine and efavirenz (Montana ANRS 091 trial). Antivir Ther 2007; 12: 417–22PubMed
20.
Zurück zum Zitat Johnson M, Grinsztejn B, Rodriguez C, et al. Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures. AIDS 2005; 19: 153–62PubMedCrossRef Johnson M, Grinsztejn B, Rodriguez C, et al. Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures. AIDS 2005; 19: 153–62PubMedCrossRef
21.
Zurück zum Zitat Molina J, Wilkin A, Domingo P, et al. Once-daily vs twice-daily lopinavir/ritonavir in antiretroviral-naive patients: 96-week results. International AIDS Society; Third IAS Conference on HIV Pathogenesis and Treatment; 2005 Jul 24–27; Rio de Janeiro, p. WePe123C12 Molina J, Wilkin A, Domingo P, et al. Once-daily vs twice-daily lopinavir/ritonavir in antiretroviral-naive patients: 96-week results. International AIDS Society; Third IAS Conference on HIV Pathogenesis and Treatment; 2005 Jul 24–27; Rio de Janeiro, p. WePe123C12
22.
Zurück zum Zitat Moyle G. The Assessing Patients’ Preferred Treatments (APPT-1) Study. Int J STD AIDS. 2003; 14 Suppl. 1: 34–6PubMedCrossRef Moyle G. The Assessing Patients’ Preferred Treatments (APPT-1) Study. Int J STD AIDS. 2003; 14 Suppl. 1: 34–6PubMedCrossRef
23.
Zurück zum Zitat van Leth F, Phanuphak P, Ruxrungtham K, et al. Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. Lancet 2004; 363: 1253–63PubMedCrossRef van Leth F, Phanuphak P, Ruxrungtham K, et al. Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. Lancet 2004; 363: 1253–63PubMedCrossRef
25.
Zurück zum Zitat Podzamczer D, Ferrer E, Gatell J, et al. Early viroloic failure with a combination of tenofovir, didanosine, and efavirenz. Antiviral Ther 2005; 10: 171–7 Podzamczer D, Ferrer E, Gatell J, et al. Early viroloic failure with a combination of tenofovir, didanosine, and efavirenz. Antiviral Ther 2005; 10: 171–7
26.
Zurück zum Zitat Leon A, Martinez E, Malloloas J, et al. Early virological failure in treatment-naive HIV-infected adults receiving didanosine and tenofovir plus efavirenz or nevirapine. AIDS Res Human Retrovir 2005; 19: 213–5 Leon A, Martinez E, Malloloas J, et al. Early virological failure in treatment-naive HIV-infected adults receiving didanosine and tenofovir plus efavirenz or nevirapine. AIDS Res Human Retrovir 2005; 19: 213–5
27.
Zurück zum Zitat Gallant J, Rodriguez A, Weinberg W, et al. Early virologic nonresponse to tenofovir, abacavir, and lamuvidine in HIV-infected antiretroviral-naive HIV-infected patients. J Infect Dis 2005; 193: 1921–30CrossRef Gallant J, Rodriguez A, Weinberg W, et al. Early virologic nonresponse to tenofovir, abacavir, and lamuvidine in HIV-infected antiretroviral-naive HIV-infected patients. J Infect Dis 2005; 193: 1921–30CrossRef
28.
Zurück zum Zitat Khanlou HYV, Guyer B, Farthing C. Early virologic failure in a pilot study evaluating the efficacy of therapy containing once-daily abacavir, lamivudine, and tenofovir DF in treatmentnaive HIV-infected patients. AIDS Patient Care STDS 2005; 19: 135–40PubMedCrossRef Khanlou HYV, Guyer B, Farthing C. Early virologic failure in a pilot study evaluating the efficacy of therapy containing once-daily abacavir, lamivudine, and tenofovir DF in treatmentnaive HIV-infected patients. AIDS Patient Care STDS 2005; 19: 135–40PubMedCrossRef
29.
Zurück zum Zitat Landman R, Descamps D, Peytavi G, et al. Early virologic failure and rescue therapy of tenofovir, abacavir, and maluvidine for initial treatment of HIV-1 infection. HIV Clin Trials 2005; 6: 291–301PubMedCrossRef Landman R, Descamps D, Peytavi G, et al. Early virologic failure and rescue therapy of tenofovir, abacavir, and maluvidine for initial treatment of HIV-1 infection. HIV Clin Trials 2005; 6: 291–301PubMedCrossRef
30.
Zurück zum Zitat Bertz R, Chiu Y-L, Foit C, et al. Estimation of selective pressure by lopinavir/ritonavir (LPV/r) vs nelfinavir (NFV) by examination of terminal-phase pharmacokinetics (PK) at steady-state [abstract no. 44]. 5th International Workshop on Clinical Pharmacology of HIV Therapy; 2004 Apr 1–3; Rome Bertz R, Chiu Y-L, Foit C, et al. Estimation of selective pressure by lopinavir/ritonavir (LPV/r) vs nelfinavir (NFV) by examination of terminal-phase pharmacokinetics (PK) at steady-state [abstract no. 44]. 5th International Workshop on Clinical Pharmacology of HIV Therapy; 2004 Apr 1–3; Rome
31.
Zurück zum Zitat Taylor S, Allen S, Fidler S, et al. Stop study: after discontinuation of efavirenz, plasma concentrations may persist for 2 weeks or longer [abstract no. 131]. 11th Conference on Retroviral Opportunistic Infection; 2004 Feb 8–11; San Francisco (CA) Taylor S, Allen S, Fidler S, et al. Stop study: after discontinuation of efavirenz, plasma concentrations may persist for 2 weeks or longer [abstract no. 131]. 11th Conference on Retroviral Opportunistic Infection; 2004 Feb 8–11; San Francisco (CA)
32.
Zurück zum Zitat Killingley B, Pozniak A. The first once-daily single-tablet regimen for the treatment of HIV-infected patients. Drugs Today 2007; 43: 427–42PubMedCrossRef Killingley B, Pozniak A. The first once-daily single-tablet regimen for the treatment of HIV-infected patients. Drugs Today 2007; 43: 427–42PubMedCrossRef
Metadaten
Titel
Efficacy and Safety of Once-Daily Regimens in the Treatment of HIV Infection
verfasst von
Dr Jean-Michel Molina
Publikationsdatum
01.04.2008
Verlag
Springer International Publishing
Erschienen in
Drugs / Ausgabe 5/2008
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI
https://doi.org/10.2165/00003495-200868050-00001

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