title: Recent availability of two novel, fixed formulations of antiretroviral nucleoside analogues: a 12-month prospective, open-label survey of their practical use and therapeutic perspectives in antiretroviral-naive and -experienced patients.
abstract: The recent introduction of novel, fixed nucleoside-nucleotide reverse transcriptase inhibitor (NRTI) combinations (tenofovir-emtricitabine, and abacavir-lamivudine) expanded the spectrum of available formulations and concurrently increased patients' adherence levels. A prospective survey of the open-label use of these two fixed combinations was performed in 158 patients belonging to our single-center cohort of more than 1,000 HIV-infected subjects enrolled in the last 18 months, and followed for at least 12 months. During the last 18 months, 95 consecutive, evaluable patients (60.1%) received for the first time tenofovir-emtricitabine, or abacavir-lamivudine (63 patients, 39.9%), and were followed for at least 12 months with periodic clinical and laboratory examinations. Among the 53 evaluable patients who were naïve to all antiretrovirals, tenofovir-emtricitabine has been given to 42 subjects (79.2%), mostly associated with efavirenz (26 cases), or different boosted protease inhibitors (16 subjects), whereas abacavir-lamivudine was administered to 11 patients (in 10 cases of 11, together with boosted protease inhibitors). In the remaining 105 patients, tenofovir-emtricitabine or abacavir-lamivudine therapy represented a switch from a prior combination antiretroviral regimen, and was predominantly associated with boosted protease inhibitors (61 patients), versus efavirenz or nevirapine (26 cases), or other drug combinations containing protease inhibitors (the remaining 18 patients). Among the 105 pretreated patients, the prescription of tenofovir-emtricitabine (53 patients) was as frequent as that of abacavir-lamivudine (52 cases), and the therapeutic change was primarily prompted by toxicity or poor tolerability (59 patients), followed by therapeutic failure and viral resistance (46 cases as a whole), and always encompassed a regimen simplification also. Both fixed combinations were well tolerated, and an adherence rate more than 90% was estimated among evaluable patients. From a tolerability point of view, the emtricitabine-tenofovir association was never withdrawn due to untoward events, while only two cases of early abacavir-lamivudine suspension occurred, due to a probable abacavir hypersensitivity reaction. From our preliminary experience, a major role seems to be played by tenofovir-emtricitabine in first-line treatments (preferably among "compact" regimens based on efavirenz), while the proportionally increased abacavir-lamivudine prescription to pretreated patients is mostly attributable to the different genetic barrier of abacavir (which was often associated with boosted protease inhibitors, in this last patient group). The present availability of two more fixed NRTI combinations favored by their single pill, once-daily administration strongly encourages randomized, controlled "head to head" studies in both first-line and experienced patents, in order to better exploit and target their therapeutic potential, and their most effective associations.
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Infectious Diseases, "Alma Mater Studiorum" University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy. Roberto.manfredi@unibo.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Manfredi
authors.forename: Leonardo
authors.initials: L
authors.lastname: Calza
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D000099227:Abacavir
chemical_list: D000225:Adenine; D019380:Anti-HIV Agents; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D000068679:Emtricitabine; D019259:Lamivudine; D063065:Organophosphonates; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000099227:Abacavir