Resistance profile analysis of treatment-experienced HIV-1- infected patients switching to elvitegravir/cobicistat/ emtricitabine/tenofovir alafenamide (E/C/F/TAF) plus darunavir (DRV)

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.

Study methods:

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. 

Results:

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.
 

Conclusions:

• 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