aDivision of Infectious Diseases, Roger Williams Medical Center, Providence, Rhode Island, USA
bDepartment of Pharmacy Practice, University of Rhode Island, Kingston, Rhode Island, USA.
Nucleoside analogues remain an important backbone of antiretroviral therapy. The nucleoside backbone of emtricitabine (as Emtriva) and tenofovir (as Viread) demonstrated better tolerability than the combination of zidovudine and lamivudine (Combivir) in the Gilead 934 Study, when administered with efavirenz . Truvada is a fixed-dose combination pill containing emtricitabine (200 mg) and tenofovir (300 mg). We report three patients who had gastrointestinal intolerance to Truvada but who tolerated emtricitabine or lamivudine in combination with tenofovir.
A 58-year-old Puerto Rican woman was initially diagnosed with HIV in 1999. In 2002, she was initiated on a regimen of lamivudine, tenofovir and lopinavir/ritonavir (Kaletra), with good tolerability and CD4 cell response but persistent low-level viremia. In February 2005, she was changed to Truvada plus Kaletra to improve adherence. After initiating Truvada, she complained of nausea, heartburn, fatigue, diarrhea and epigastric pain. Truvada was stopped and lamivudine plus tenofovir restarted. Her symptoms resolved and she has continued to tolerate that regimen.
A 52-year-old Caucasian man was diagnosed with HIV in 1996. Before 2005, he was treated with multiple protease inhibitor-based antiretroviral regimens, with poor gastrointestinal tolerance. In April 2005, he was started on truvada, nevirapine and nelfinavir. On follow-up, he complained of nausea, bloating and epigastric gnawing pain, as well as diarrhea controlled with loperamide and dietary modifications. In September 2005, Truvada was changed to emtricitabine plus tenofovir; the nausea and epigastric pain resolved thereafter, an improvement described by the patient as a ‘like night and day’. He was subsequently diagnosed with and treated for Helicobacter pylori. He is currently tolerating a regimen of emtricitabine, tenofovir and nevirapine with a CD4 cell count of 400 cells/μl and a viral load under 50 copies/ml.
A 42-year-old Haitian man was diagnosed with AIDS in 1997. H. pylori infection was diagnosed and treated in 1997. Multiple previous antiretroviral regimens were unsuccessful because of non-adherence, although he tolerated emtricitabine and tenofovir as part of a triple therapy in 2004. In May 2005, he started Truvada and nevirapine. Nausea and bloating occurred with the initial doses, and he stopped both medications after 4 days. In September 2005, he restarted a regimen of lamivudine, tenofovir and nevirapine, with no gastrointestinal side effects.
The three patients described above primarily had upper gastrointestinal intolerance to Truvada but all three tolerated emtricitabine (as Emtriva) or lamivudine (as Epivir) in combination with tenofovir (as Viread). An association with previous gastrointestinal symptoms or H. pylori infection is suggested, but in each case, symptoms resolved promptly after the discontinuation of Truvada. To our knowledge, this is the first report of this observation.
In the Gilead 934 Study, 20 of the 257 patients receiving emtricitabine (as Emtriva) plus tenofovir (as Viread) complained of mild to moderate severity nausea, but only one patient discontinued therapy .
Truvada was approved by the US Food and Drug Administration in 2004. Pharmacokinetic data demonstrate that Truvada is bioequivalent to emtricitabine plus tenofovir in healthy volunteers . The inactive ingredients in Truvada are identical to those in Viread and Emtriva [2–4]. Each of the ingredients has been commonly used in medication formulations and is not known to induce gastrointestinal intolerance . Whereas differences in the active and inactive ingredients between the individual drug formulations (Emtriva, viread) and the fixed dose combination pill (Truvada) do not suggest an obvious cause of the difference in tolerability, this remains a question for further study.
The Gilead 934 Study includes long-term follow-up, in which study participants will discontinue Emtriva plus Viread and begin Truvada. More insight into the incidence and etiology of differences in the tolerability of truvada compared with the individual formulations awaits additional information from that study.
1. Gallant JE, Dejesus E, Arribas JR, Pozniak AL, Gazzard B, Campo RE, et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med 2006; 354:251–260.
2. Truvada package insert. Foster City, California: Gilead Sciences, Inc.; March 2006.
3. Viread package insert. Foster City, California: Gilead Sciences, Inc.; March 2006.
4. Emtriva package insert. Foster City, California: Gilead Sciences, Inc.; September 2005.
5. Food and Drugs Administration. Inactive ingredients database. Rockville, MD: FDA; April 2006.
© 2007 Lippincott Williams & Wilkins, Inc.