Darunavir, an HIV-1 protease inhibitor, is rarely associated with drug resistance development, according to study results published in HIV Research & Clinical Practice.

Reduced antiretroviral treatment effectiveness and possible virologic failure in HIV-1 is caused by drug resistance. Additionally, resistance-associated mutations can be transmitted to others, which can reduce the treatment options available and their effectiveness in the larger populations. As a result, antiretroviral treatment regimens with a higher barrier to resistance are recommended as initial therapy in cases where resistance test results are pending or unavailable, and when there is the potential for suboptimal treatment adherence.

Darunavir demonstrates potent antiviral activity against both wild-type and multidrug-resistant HIV-1, with a high barrier to the development of resistance. Darunavir once daily has been diversely studied in clinical trials and demonstrates excellent efficacy and safety. Furthermore, guidelines in both Europe and the United States recommend darunavir as an initial antiretroviral regimen. Previous evaluation of post-baseline HIV-1 resistance data from 7 phase 2 and phase 3 clinical studies using once-daily darunavir 800 mg-based antiretroviral regimens has previously been published; this study is an extension of that data with post-baseline findings from 3 recent studies evaluating resistance across a total of 10 clinical studies of once-daily darunavir 800 mg-based regimens.

Patients who were treatment-naïve and virologically failing or suppressed from 10 phase 2 and phase 3 studies of boosted once-daily darunavir 800 mg-based regimens were included in the current study. Three of the phase 3 studies focused on the once-daily darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg single-tablet regimen. Post-baseline resistance was evaluated upon protocol-defined virologic failure, and resistance-associated mutations were identified using International Antiviral Society-USA mutation lists.

Results demonstrated that the development of resistance to darunavir-based regimens is rare. Of the 3635 included patients, 250 patients met the protocol-defined virologic failure criteria; 205 of those patients had post-baseline genotypes/phenotypes. One or more darunavir and/or primary protease inhibitor resistance-associated mutations had developed or were identified in a total of 4 (0.1%) patients. Only 1 (<0.1%) of these patients lost darunavir phenotype susceptibility; this patient had prior lopinavir virologic failure. In total, 3317 patients were using nucelos(t)ide reverse transcriptase inhibitors (primarily tenofovir and emtricitabine), and 1 or more resistance-associate mutation was identified in 13 (0.4%) of these patients. None of the 1949 patients who received D/C/F/TAF had post-baseline darunavir, primary protease inhibitor, or tenofovir resistance-associated mutations; 2 (0.1%) of these patients developed an emtricitabine resistance-associated mutation.

One noted limitation is that the studies did not include integrase inhibitor-based regimens, as they were unavailable at the time when some studies in this analysis occurred. Another limitation is the inclusion only of data from controlled clinical trials, rather than real-world data.

“Across a large, diverse population using [once-daily] darunavir 800 mg-based regimens and formulations, resistance development remains rare,” the researchers concluded.

Disclosure: This clinical trial was supported by Janssen Scientific Affairs, LLC. Please see the original reference for a full list of authors’ disclosures.

Reference

Lathouwers E, Seyedkazemi S, Luo D, Brown K, De Meyer S, Wong EY. Pooled resistance analyses of darunavir once-daily regimens and formulations across 10 clinical studies of treatment-naïve and treatment-experienced patients with human immunodeficiency virus-1 infection. HIV Res Clin Pract. 2020;21(2-3):83-39.