Efficacy and Safety of Once-Daily Regimens in the Treatment of HIV Infection
- 118 Downloads
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.
KeywordsRitonavir Efavirenz Abacavir Atazanavir Tenofovir Disoproxil Fumarate
Cecilia Hofmann, PhD, of C. Hofmann & Associates, assisted in the development of this article. Abbott Laboratories provided financial support for this project. Dr Molina has acted as a consultant for Abbott Laboratories, Bristol-Myers Squibb, Gilead Sciences and Pfizer, and received honoraria from Abbott Laboratories, Bristol-Myers Squibb, GlaxoSmithKline, Tibotec and Pfizer.
- 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: 1181–3Google Scholar
- 7.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: 808–16PubMedCrossRefGoogle Scholar
- 10.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: 417–25PubMedCrossRefGoogle Scholar
- 14.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: 251–60Google Scholar
- 21.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. WePe123C12Google Scholar
- 24.US National Institutes of Health. Study of lopinavir/ritonavir tablets versus soft gel capsules and once daily versus twice-daily administration, when co-administered with NRTIs in antiretroviral naive HIV-1 infected subjects [online]. Available from URL: http://www.clinicaltrials.gov/ct2/show/NCT00262522?.term=NCT00262522&rank=l [Accessed 2008 Feb 22]
- 25.Podzamczer D, Ferrer E, Gatell J, et al. Early viroloic failure with a combination of tenofovir, didanosine, and efavirenz. Antiviral Ther 2005; 10: 171–7Google Scholar
- 26.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: 213–5Google Scholar
- 30.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; RomeGoogle Scholar
- 31.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)Google Scholar