Virological Failure on Long-Term Ritonavir-Boosted Darunavir for HIV Not Associated With Acquired DRV Resistance-Associated Mutations

Individuals living with HIV experiencing virological failure (VF) during long-term ritonavir-boosted darunavir (DRV/r) therapy were unlikely to have developed DRV resistance-associated mutations (RAMs), according to results from a study published in Open Forum Infectious Diseases.

Participants of the ANRS CO3 Aquitaine Cohort, initiated in 1987 as an open, prospective hospital-based cohort study of patients with HIV in France, were analyzed for this study. Patients who received DRV/r between 2007 and 2015 (N=1458) were assessed for DRV/r exposure, clinical outcomes, and RAMs.

Patients had a median follow-up of 24.7 months and 270 patients experienced VF. Patients who did or did not experience VF differed significantly in median CD4 count (327 vs 456 cells/mL; P <.001), CD4 nadir (154 vs 208 cells/mL; P <.001), <50 cp/mL HIV RNA (22.6% vs 50.2%; P <.001), and number previous therapeutic combinations (6 vs 5; P =.0118).

Among patients with VF, 22.0% were antiretroviral-experienced with VF, 7.1% were antiretroviral-experienced with virological success, and 6.8% were antiretroviral-naïve. At the time of VF, patients had a median CD4 cell count of 384 cells/mL (IQR, 204-585) and HIV-1 plasma viral load of 399 copies/mL (IQR, 95-7594).

DRV RAMs were detected among 29 patients. On average, these patients had received more previous therapeutic combinations (median, 10 vs 5; P <.001), were receiving more than 3 drugs (55.1% vs 22.3%), and had previous VF on protease inhibitors (96.6% vs 60.7%; P =.001).

Before initiating DRV/r therapy, 12 patients had 2 RAMs, 7 patients had 3 RAMs, 6 patients had at least 4 RAMs, and 4 patients had 1 RAM. Patients who acquired RAMs after initiating DRV/r were all antiretroviral-experienced with VF, received DRV/r twice daily, experienced VF onset between 12 and 55 months, and 66.7% acquired the V32I mutation.

After a long-term follow-up of the patients with DRV RAMs, results showed that 62.1% remained on DRV/r (dosage maintained n=9; dosage modified n=9) and plasma viral load was restored to less than 50 copies/mL. In total, 27.6% of patients (8/29) discontinued DRV/r therapy; 6 due to DRV resistance and 3 patients died.

This study may have been limited by not including data on cobicistat as it was not available in France.

The observed rate of acquiring DRV-associated RAMs following VF on long-term DRV/r therapy was low (0.4%), indicating a high genetic barrier for protease inhibitors resulting in a high efficacy against resistant viruses.

Reference

Chaussage H, Tumiotto C, Le Marec F, et al. A Low Level of Darunavir Resistance–Associated Mutation Emergence in Patients With Virological Failure During Long-term Use of Darunavir in People With HIV. The ANRS CO3 Aquitaine Cohort. Open Forum Infect Dis. 2020;7(12):ofaa567. doi:10.1093/ofid/ofaa567.