R E V I E W Atripla™ – HIV therapy in one pill Boris Julg Johannes R Bogner Medizinische Poliklinik, Department of Infectious Diseases, University of Munich Medical School, Downtown Campus, Germany Correspondence: Johannes Bogner Medizinische Poliklinik der LMU München, Department of infectious diseases Pettenkoferstrasse 8a, 80336 Munich, Germany Tel +49 89 51603598 Email johannes.bogner@med. uni-muenchen.de Abstract: In July 2006 Atripla™ was approved by the US Food and Drug Administration (FDA), combining the active ingredients of one NNRTI and two NRTIs. Atripla™ is the ﬁrst “one-pill- daily” regimen licensed for the treatment of HIV-1 infection in patients older than 18 years. H was licensed in Europe in December 2007 Atripla™ contains efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg. It therefore combines 3 compounds which have been widely used before and which were recommended for initial therapy due to their potency, tolerability, and safety proﬁle. Efﬁcacy and safety data of efavirenz, tenofovir DF, and emtricitabine are reviewed and compared with other antiretroviral drugs, which are used as initial therapy for treatment-naive patient. Keywords: Atripla™ antiretroviral therapy, new “one-pill-daily” regimen, review efﬁcacy and safety data Background It is almost 25 years since in 1983 the human immunodeﬁciency virus type I (HIV-1) was deﬁned as the primary cause of the acquired immunodeﬁciency syndrome (Barré-Sinoussi et al 1983; Gallo et al 1984). Worldwide, the number of HIV-1 infected persons exceeds 33 million, the majority of whom live in the developing countries of Sub-Saharan Africa, Asia, and South America. With the introduction of protease inhibitors and non-nucleotide reverse transcriptase inhibitors to antiretroviral treatment regimens between 1995 and 1996, the so-called highly active antiretroviral therapy (HAART) was established result- ing in a dramatic decrease in the mortality and morbidity of HIV infection. Nevertheless eradication of the virus still remains impossible. This implies that besides efﬁcacy of antiretroviral therapy, health care providers have to focus on long-term toxicity, develop- ment of drug resistances, and tolerance by the patient, leading to an improved long-term adherence behavior. It has therefore been a goal of the pharmaceutical industry to reduce the daily pill-burden and to simplify antiretroviral therapy by developing a “one-pill- daily” regimen. To achieve this goal Bristol-Myers Squibb Co. and Gilead Sciences Inc. formed a joint venture, and in July 2006 Atripla™ was approved by the US Food and Drug Administration (FDA), combining the active ingredients of one non-nucleoside reverse transcriptase inhibitor, efavirenz, and two nucleoside reverse transcriptase inhibitors, tenofovir disoproxil fumarate (DF) and emtricitabine, all well-known substances. H was licensed in Europe in December 2007. As of October 2007 there were 31 compounds and combinations formally approved by the FDA for the treatment of HIV infections. These compounds can be classiﬁed in 6 categories according to their point of intervention with the HIV replicative cycle: nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), CCR5-chemokine receptor antagonists, and recently approved the integrase inhibitors. While HAART originally consisted of a pill burden of 20–30 pills per day, this has been gradually diminished over the past few years. Fixed drug formulations combin- ing 2 or 3 NRTIs, eg, Combivir®, Trizivir®, Kivexa®, or 2 PIs, eg, Kaletra®, became Therapeutics and Clinical Risk Management 2008:4(4) 573–577 © 2008 Dove Medical Press Limited. All rights reserved 573