Julg and Bogner tenofovir DF/emtricitabine showed additionally greater gains in CD4 cell counts at week 96 (mean increase, 270 cells/mm3 versus 237 cells/mm3; p = 0.036, respectively). Nevertheless a limitation should be mentioned, as a higher percentage of patients in the zidovudine-3TC group discon- tinued the therapy prematurely (9%) than in the tenofovir- FTC group (4%). Adverse events of grade 2–4 occurred in ~72% of both groups, and most commonly included nausea (7%–9%), dizziness (7%–8%), fatique (8%), and diarrhea (5%–8%), but signiﬁcantly more patients in the zidovudine/ lamivudine group experienced a treatment-limiting toxicity (11% versus 5%; p = 0.008); anemia was the most common cause (14 versus 0 subjects in the emtricitabine/tenofovir DF group, p 0.001). Fourteen patients in the tenofovir DF/emtricitabine group versus 27 in the zidovudine/lamivudine group met the criteria for treatment failure in study 934 and had genotypic data for drug resistance available after 96 weeks of therapy (Pozniak et al 2006). Efavirenz resistance mutations were most com- mon (n = 10), followed by the M184V/I mutation, for those patients who were receiving tenofovir DF/emtricitabine. It should be mentioned that M184 occurred at a lower rate in patients on tenofovir DF/emtricitabine compared with the zidovudine/lamivudine group. However, the feared K65R mutation did not arise in any patient, but study 903, which evaluated a combination of efavirenz and tenofovir DF with lamivudine instead of emtricitabine, 8 out of 299 (2.7%) patients developed the K65R (Margot et al 2006). Atripla™ Atripla™ combines the individual strengths and weaknesses of these compounds. Of all combination therapies available at the moment, Atripla™ offers the most convenient dosing schedule and the fewest number of pills. The combination efavirenz/emtricitabine/tenofovir DF was in general much better tolerated and caused signiﬁcantly less body fat change compared with the well-known mainstay zidovudine/lami- vudine. In respect of these qualities, it seems to be more likely that patients will show a higher degree of adherence to this regimen compared with commonly available PI-based therapies. The concerns about the higher risk of missed doses in a once-daily regimen do not seem be proven, but clinical results should be awaited. Current international treatment guidelines recommend a ﬁxed-dose dual-NRTI backbone of emtricitabine/tenofovir DF or zidovudine/lamivudine combined with either efavirenz or a boosted PI for initial therapy of treatment-naive patients. Choosing efavirenz as combination for the nuke backbone 576 in Atripla™ is supported by the ACTG 5142 study, which demonstrated superior efﬁcacy and durability of an efavirenz- based regimen compared with a lopinavir-based combination. Choosing tenofovir DF/emtricitabine as the nuke backbone for efavirenz was supported by the 934 study, which showed that after 48 weeks, more patients treated with tenofovir DF/emtricitabine had viral suppression (84% versus 73%; p = 0.002) and fewer treatment-limiting toxicities (9% versus 4%) than the zidovudine/lamivudine arm (Galant 2006). Finally, some side effects could be a limiting factor in using Atripla™. Tenofovir DF has shown a potential risk of nephrotoxicity although no association has been observed in clinical trials with long-term follow-up. Nevertheless mul- tiple cases of acute renal failure and Fanconi’s syndrome have been reported and several studies have shown a decrease in the estimated GFR. These cases occurred mainly in patients with pre-existing renal diseases. Therefore, patients should receive a baseline renal function evaluation prior to receiving Atripla™, and regular monitoring of renal function during the therapy. Those patients with estimated GFR 50 mL/min should receive an alternative therapy. As mentioned, efavirenz is teratogenic and should be avoided in pregnancy and carefully used in women of repro- ductive age. Additionally the use of Atripla™ in patients with pre-existing psychiatric disorders should be evaluated in each case, as conditions may exacerbate during therapy with efavirenz. Common mild CNS complaints under efavirenz are self-limiting in most patients but should be monitored and eventually the therapy must be switched. In summary, Atripla™ represents the “one-pill-daily” version of a widely used antiretroviral drug combination, pooling potent efﬁcacy with a beneﬁcial tolerability and safety proﬁle. Due to its unique dosing schedule it will be a ﬁrst choice therapy in therapy naive patients. Drug interaction studies using the Atripla™ formulation remain to be conducted as well as directly comparative studies with other drug combinations. References Arendt G, de Nocker D, von Giessen HJ, et al. 2007. Neuropsychiatric side effects of efavirenz therapy. Expert Opin Drug Saf, 6:147–54. Barré-Sinoussi F, Chermann JC, et al. 1983. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deﬁciency syndrome (AIDS). Science, 220:868–71. Bartlett JA, Johnson J, Herrera G, et al. Abacavir/lamivudine in combination with efavirenz, amprenavir/ritonavir or stavudine: ESS40001 (CLASS) preliminary 48-week results. Abstract TuOrB1189, XIV International AIDS Conference 2002, Barcelona. Claas GJ, Julg B, Goebel FD, et al. 2007. Metabolic and anthropometric changes one year after switching from didanosine/stavudine to tenofovir in HIV-infected patients. Eur J Med Res, 12:54–60. Therapeutics and Clinical Risk Management 2008:4(4)