Abstract
Introduction
This was a descriptive non-interventional study in HIV-1-infected patients treated with DRV/r conducted in the clinical setting, with a single-arm prospective design. The primary objective was to collect data on utilization of darunavir/ritonavir (DRV/r) under the conditions described in the marketing authorization. Efficacy (measured as viral load [VL] <50 copies/mL and CD4+ cell count) was evaluated for DRV/r in combination with other antiretroviral (ARV) agents in routine clinical practice in Italy.
Materials and Methods
Here we describe an analysis of effectiveness and durability data from two cohorts of DRV/r-experienced patients with HIV-1 infection, already receiving DRV/r according to usual clinical practice, collected prospectively from June 2009 to December 2012: Cohort 1, data from patients from the DRV/r Early Access Program (TMC114-C226 study; N=235 patients) and Cohort 2, a separate cohort of ARV-DRV/r-experienced patients (N=407 patients), treated with DRV/r in the market. Patient characteristics are shown in Table 1.
Results
The median length of DRV/r exposure during the study was 925 days (interquartile range [IQR] 692–1006) in Cohort 1, and 581 (IQR 508–734) days in Cohort 2. Of those patients that completed the study, 94% and 87% of patients were virologically suppressed in Cohort 1 and 2, respectively, at last study visit (LSV). As expected, the virological suppression rate was higher in patients with baseline VL <50 copies/mL (Table 2). Mean CD4+ cell counts improved from baseline to LSV in both cohorts (Cohort 1: +54 cells/µL [95% CI 31, 77] and Cohort 2: +59 cells/µL [95% CI 44, 73]). High persistence rates were seen in both cohorts, with 75.3% of patients in Cohort 1 and 82.6% in Cohort 2 remaining on treatment at LSV; very few patients discontinued due to virologic failure (Table 1). Other reasons for study discontinuation are shown in Table 1. Very few patients changed DRV/r dosing during the study, 15 from 1200 to 800 mg o.d.
Conclusions
In patients already treated with DRV/r, DRV/r-based ARV treatment provided effective viral suppression with long-lasting durability, low virological response failure, low discontinuation rates and good tolerability. These data confirm DRV/r to be an effective treatment choice in previously treated patients.
Table 1.
Patient characteristics
| Baseline characteristics Parameters | Cohort 1 (N=235) N, (%) | Cohort 2 (N=407) N, (%) |
|---|---|---|
| Age, yrs, mean±SD | 49.3±7.1 | 46.6±9.4 |
| Female, n (%) | 45 (19.1) | 107 (26.3) |
| VL (HIV-RNA) <50 copies/mL, n (%)a at study enrolment | 192 (85) | 298 (74.9) |
| CD4+<100 cells/µL, n (%)b at study enrolment | 7 (3.1) | 25 (6.2) |
| Duration of HIV infection, n (%) | ||
| 0–1 year | 0 | 53 (13.0) |
| >1–10 years | 6 (2.6) | 82 (20.1) |
| >10–15 years | 62 (26.4) | 66 (16.2) |
| >15–20 years | 89 (37.9) | 85 (20.9) |
| >20 years | 76 (32.3) | 110 (27.0) |
| NA | 2 (0.9) | 11 (2.7) |
| CDC clinical stage, n (%) | ||
| A | 30 (12.8) | 139 (34.2) |
| B | 80 (34.0) | 121 (29.7) |
| C | 125 (53.2) | 147 (36.1) |
| Time since first DRV dose (days), at study enrolment – mean±SD | 1242±208 | 501±402 |
| Study Duration, days – mean±SD | 812±286 | 583±188 |
| DRV dose at study entry, mg/day, n (%) | ||
| 1200 | 232 | 262 |
| 800 | 3 | 145 |
VL data only available in 226 Cohort 1 and 398 Cohort 2 patients.
CD4+ data only available in 226 Cohort 1 and 403 Cohort 2 patients.
Table 2.
Patient characteristics
| Virological EfficacyParameters | Cohort 1 (N=235) N, (%) | Cohort 2 (N=407) N, (%) |
|---|---|---|
| LSV VL [HIV-RNA <50 copies/mL], n (%)a | ||
| All | 203 (88.6) | 331 (83.6) |
| BL VL <50 copies/mL | 177 (94.1) | 263 (89.2) |
| BL VL ≥50 copies/mL | 19 (59.4) | 60 (65.2) |
| No values for BL VL | 7 (77.8) | 8 (88.9) |
| Total discontinuations at LSV, n (%) | 56 (24.7) | 71 (17.4) |
| Reasons for discontinuation, n (%) | ||
| Insufficient virological response | 8 (3.4) | 4 (1.0) |
| Death | 10 (4.3) | 9 (2.2) |
| Study emergent adverse event | 3 (1.3) | 9 (2.2) |
| Other study emergent medical reason | 0 | 1 (0.2) |
| Lack of compliance | 4 (1.7) | 8 (2.0) |
| Lost to follow-up | 23 (9.8) | 18 (4.4) |
| Other | 9 (3.8) | 20 (4.9) |
VL data only available in 226 Cohort 1 and 398 Cohort 2 patients.