title: A 48-week pilot study switching suppressed patients to darunavir/ritonavir and etravirine from enfuvirtide, protease inhibitor(s), and non-nucleoside reverse transcriptase inhibitor(s).
abstract: Treatment options for HIV-infected patients can be limited due to viral drug resistance to antiretroviral agents. Enfuvirtide (ENF) is an injectable entry/fusion inhibitor that is effective in achieving viral suppression when used in combination with protease inhibitors (PIs) in patients with pre-existing resistance. However, ENF treatment is associated with injection site reactions and dosing fatigue. This multicenter, open-label, Phase IIIb, 48-week pilot study assessed safety, tolerability, and effectiveness of the PI darunavir (DRV), boosted with ritonavir (DRV/r), and the non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (ETR), when substituted for ENF/PI (±NNRTI)-based therapy. Ten virologically suppressed (HIV RNA less than 50 copies/ml) men who were intolerant to ENF were enrolled. Median (range) CD4+ count was 301 (187-663) cells/mm(3). Two patients discontinued the study; all remaining patients maintained a viral load of less than 50 copies/ml at Week 48. Viral load increased to greater than 50 copies/ml in two patients, but was eventually re-suppressed without the need for changes in treatment. Median (range) increase (last observation carried forward) in CD4+ count from baseline to Week 48 was 64 (-53-100) cells/mm(3). Two grade 3 adverse events (AEs), nausea and weight loss, and one serious AE, acute cholecystitis, were reported; each AE resolved without treatment interruption. Most common AEs related to study drug were fatigue, rash, headache, and diarrhea. Decreases in triglycerides, low-density lipoprotein, and high-density lipoprotein, were observed. This study suggests that a DRV/r- and ETR-based regimen can be substituted for an ENF-based regimen while maintaining virologic suppression.
authors.affiliation: Light Source Medical, Los Angeles, California 90036, USA. pjruane@lightsourcemedical.com
authors.forename: Peter
authors.initials: P
authors.lastname: Ruane
authors.forename: Brian
authors.initials: B
authors.lastname: Alas
authors.forename: Robert
authors.initials: R
authors.lastname: Ryan
authors.forename: Amy
authors.initials: A
authors.lastname: Perniciaro
authors.forename: James
authors.initials: J
authors.lastname: Witek
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D018791:CD4 Lymphocyte Count; D000069454:Darunavir; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage* / Q000009:adverse effects; D015658:HIV Infections / Q000188:drug therapy*; D016333:HIV Protease / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D010865:Pilot Projects; D011724:Pyridazines / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D009570:Nitriles; D010446:Peptide Fragments; D011724:Pyridazines; D011743:Pyrimidines; D012367:RNA, Viral; D013449:Sulfonamides; C451734:etravirine; D000077560:Enfuvirtide; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; D019438:Ritonavir; D000069454:Darunavir