Christian Callebaut, Clinical Virology, Gilead USA, presented the findings of their clinical trial GS-US-292-0119.
Virologically suppressed, treatment-experienced patients on complex multi-tablet regimens were randomised to either switch to a simpler, more convenient antiretroviral regimen or remain on their current optimised ART.
After 48 weeks:
- The regimen consisting of E/C/F/TAF DRV demonstrated maintained viral suppression in 94.4% of patients.
- In the DRV-containing “Stay on Baseline Regimen” arm, maintained viral suppression was 76.1%
All patients had documented resistance to 2 classes of antiretroviral (ARV) agents at baseline. Detailed ARV regimens and the resistance profile of the study population are described.
The Stanford HIVdb algorithm version 8.01 was used to calculate genotypic susceptibility scores (GSS).
For each drug, a 5-point scale was used:
- Susceptible = 1
- Potential low-level resistance = 0.75
- Low-level resistance = 0.5
- Intermediate-level resistance = 0.25
- High-level resistance = 0
The total GSS for a given regimen was calculated as the sum of the scores for each individual drug.
A total of 94.8% had documented resistance to 2 classes of ARVs, including:
- protease inhibitors: 34.8%
- non-nucleoside RT inhibitors: 88.1% and
- NRTIs 94.8%.
The most common resistance associated mutations (RAMs) were:
- Protease Inhibitor RAMs: L90M (15.6%) and V82A/F/L/S/T (14.8%).
- NNRTI-RAMs: K103N/S (63%) and Y181C/I/V (19.3%) and
- NRTI-RAMs: M184V/I (83%) and K65R (23.7%).
Thymidine analog mutations (TAMs) were present in 42.2% of patients (59.6% with one or two TAMs and 40.4% with three TAMs).
The distribution of GSS at study entry was similar across treatment groups.
Patients in the E/C/F/TAF DRV arm maintained virologic suppression similarly, regardless of the DRV dosage received before switching (33/33 and 51/56 with treatment success in the 600 mg BID and 800 mg QD groups, respectively).
In the E/C/F/TAF DRV arm,
- 11/89 patients (12.4%) had GSS <2,
- 51/89 patients (57.3%) had GSS ≥2 and <3, and
- 27/89 patients (30.3%) had GSS ≥3.
Within each treatment group, patients maintained virologic suppression similarly regardless of their GSS at study entry.
- Despite the high incidence of pre-existing resistance in this population, including resistance to ≥2 classes of ARV agents and presence of K65R or ≤3 TAMs, strategic simplification to E/C/F/TAF DRV was statistically superior to staying on the baseline regimen.
- Patients benefited from switching regimen regardless of their prior DRV dose and their GSS.
- Treatment with E/C/F/TAF DRV offers a simpler and more convenient option for treatment-experienced patients on complex multi-tablet regimens.
Details of the study can be found here: https://clinicaltrials.gov/ct2/show/study/NCT01968551