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.
