Julg and Bogner available and simpliﬁed therapy regimens. Nevertheless because most HIV-infected patients are likely to require prolonged and continuous antiretroviral therapy, there was a need for simpler, once-daily, well-tolerated regimens with minimal long-term toxicity and durable efﬁcacy. Current US and European guidelines favor backbone combination therapy consisting of 2 NRTIs plus either an NNRTI or a boosted PI (NIH 2007, EACS 2007). Tenofovir DF or zidovudine plus emtricitabine or lamivudine form the dual NRTI backbone in recommended NNRTI- or PI-based regimens. Except in women who currently are, or wish to become, pregnant efavirenz is the NNRTI of choice while ritonavir-boosted lopinavir (or low-dose ritonavir with ata- zanavir, saquinavir) are the PIs of choice. The new “one-pill-daily” combination Atripla™ contains: efavirenz 600 mg, emtricitabine 200 mg, and tenofovir DF 300 mg. It therefore combines 3 compounds which have been widely used before and which were recommended for initial therapy because of its excellent potency, tolerability and favorable safety proﬁle. We review relevant efﬁcacy and safety data of efavirenz, tenofovir DF, and emtricitabine compared with other common alterna- tive drugs, which are used as initial therapy in treatment- naive patient. Efavirenz Of all three compounds included in Atripla™, efavirenz has been available the longest and was the third NNRTI approved. The 006 Study in 1999 showed a superiority of efavirenz over indinavir (each given in combination with AZT + 3TC) (Staszewski et al 1999). Since then, efavirenz has been compared with other drugs in many large random- ized studies. In general efavirenz showed better efﬁcacy, as observed in the CLASS study, where efavirenz, used in combination with ABC + 3TC, was more effective than d4T or boosted amprenavir (Bartlett et al 2002). The ACTG 5095 study showed superiority of efavirenz over abacavir when used in combination with AZT + 3TC (Gulick et al 2004). The ACTG 384 trial showed a better efﬁcacy of efavirenz compared with nelﬁnavir (Robbins et al 2003; Shafer et al 2003), whereas in AI424-034 efavirenz was not superior but at least comparable to atazanavir (Squires et al 2004). More recently the ACTG 5142 trial evaluated 3 different 2-class antiretroviral regimens in 753 treatment-naive patients: efavirenz + 2 NRTIs; lopinavir/ritonavir + 2 NRTIs; lopina- vir/ritonavir plus efavirenz. ACTG 5142 could demonstrate the superiority of efavirenz to lopinavir/ritonavir in terms of time to virological failure and suppression of HIV RNA 574 to below 50 copies/mL. However, the efavirenz arm did not achieve quite as robust a CD4 count increase as the other two arms (Zuger 2006; Riddler et al 2006). Efavirenz is well tolerated, but mild to moderate CNS side effects including dizziness and numbness are typical and appear relatively often in the ﬁrst days to weeks of treatment. Although these symptoms seem to resolve during the course of treatment, mild effects may persist (Lochet et al 2003; Arendt et al 2007). It therefore has to be decided in each case if efavirenz should be replaced or if the patient is able to tolerate those symptoms. Another disadvantage should be mentioned: the rapid development of drug resistance when efavirenz is used as monotherapy or quasi-monotherapy due to failure of viral suppression by the backbone drugs. Once mutations like the point mutation at position 103 (K103N) occur, it indicates resistance towards all approved NNRTIs. Only the new NNRTI TMC 125, which is still in the approval process, seems to be unaffected by those muta- tions. One possible explanation for the rapid development of resistance mutations is the long half-life of NNRTIs (Muro et al 2005). Tenofovir DF Similar to nucleoside analogs which target the enzyme reverse transcriptase, tenofovir DF acts as a false building block. Unlike the nucleoside analogs, it is monophosphorylated and therefore referred to as a nucleotide analog. In the 902 and 907 studies, in which tenofovir was added to an existing HAART, the viral load fell by approximately 0.6 logs after 48 weeks (Schooley et al 2002; Squires et al 2003). Equivalent potency comparing tenofovir to d4T (with a backbone regimen of 3TC + efavirenz) in treatment-naive patients was shown in the 903 Study. Especially side effects such as polyneuropathy and lipid changes were signiﬁcantly reduced when tenofovir was used. Investigator-reported lipodystrophy was less com- mon in the tenofovir DF group compared with the stavudine group (9 [3%] of 299 vs 58 [19%] of 301, p 0.001) (Gallant et al 2004). In 2001, the drug was approved and is now widely used in antiretroviral therapies. Several studies have recently shown an improvement of lipid proﬁles, serum lactate, and lipodystrophy in HIV-positive patients after switch to teno- fovir (Llibre et al 2006; Claas et al 2007). The RAVE study, a randomized, open-label, comparative study of switching from a thymidine nucleoside analog to either tenofovir DF or abacavir in 105 individuals with clinically evident lipoatrophy, showed signiﬁcant improvement in limb fat mass over 48 weeks in both groups. It should be mentioned that mean total cholesterol, low density lipoprotein cholesterol, and Therapeutics and Clinical Risk Management 2008:4(4)