Abstract
BACKGROUND: Darunavir (DRV) is a well-tolerated, potent protease inhibitor used once-daily in patients with no DRV resistance-associated mutations (RAMs) and twice-daily in those with DRV RAMs. Treatment guidelines encourage use of once-daily regimens to optimize patient adherence, convenience and tolerability. Several studies suggest that once-daily DRV retains efficacy in the setting of 1–2 DRV RAMs whereas 3 or more DRV RAMs (with multiple background PI RAMs) is needed for DRV resistance. Currently, there is little clinical data to support the long-term use of once-daily DRV in patients with DRV RAMs. METHODS: This is a retrospective study evaluating the 48-week clinical outcomes of 22 treatment-experienced patients with DRV RAMs switched to once-daily DRV between 2014 and 2017 at the Orlando Immunology Center. The primary endpoint was the proportion with virologic suppression (HIV-1 RNA< 50 copies/mL) at Week 48. Adherence, adverse events (AEs) and laboratory parameters were analyzed throughout the study. RESULTS: The median age (range) of the sample was 53 (21–77) years, median baseline CD4+ count was 609 cells/mm3, 18 (82%) had baseline HIV-1 RNA <50 copies/mL, 15 (69%) had previously used 1 or more PIs and median number (range) of baseline DRV RAMs was 2 (1–5) (Table 1). At Week 48, 20 (91%) had HIV-1 RNA <50 copies/mL; 2 (9%) virologic non-responders had HIV-1 RNA of 82 and 59,637 copies/mL and reported noncompliance (Figure 1). There was no significant change in median CD4+ count from baseline to Week 48 (+22, 95% confidence interval (CI): [−116.5; 56.0]). Once-daily DRV was associated with a significant median increase in HDL cholesterol (+82, 95% CI: [37.0; 101.0]) and a significant median decrease in LDL cholesterol (-60, 95% CI: [-89.5; -31.0]). There were no significant changes in the proportion of patients on lipid lowering therapy at baseline and week 48 (p = 0.33). There were no self-reported AEs or Grade 3–4 lab abnormalities through Week 48. CONCLUSION: Once-daily DRV maintained virologic control in this cohort of treatment-experienced patients with 1 or more baseline DRV RAMs and was safe and well-tolerated. This suggests that once-daily DRV may be effective in this population however further data are needed to validate this as a viable treatment option. DISCLOSURES: All authors: No reported disclosures.