Effectiveness, Safety, and Tolerability of a Switch to Dual Therapy with Dolutegravir Plus Cobicistat-Boosted Darunavir in Treatment-Experienced Patients with Human Immunodeficiency Virus

Abstract

BackgroundDual regimen with dolutegravir plus cobicistat-boosted darunavir (DTG/DRV/c) is reasonable alternative option for patients with existing resistance and/or intolerance to nucleoside reverse transcriptase inhibitors (NRTIs).Material and MethodsAll patients who switched to DTG/DRV/c among treatment-experienced patients with human immunodeficiency virus (HIV) in a tertiary university hospital were selected. We analyzed the effectiveness, safety, and tolerability based on serial laboratory data and clinical findings. The primary endpoint was defined as the proportion of patients with plasma HIV RNA below 50 copies/mL at week 48 after switch. Secondary endpoints included evaluation of safety and tolerability.ResultsThirty-one patients were retrospectively analyzed. The main reasons for the change to DTG/DRV/c were treatment failure in 13 patients (41.9%), simplification in 12 patients (38.7%), and adverse drug reaction in 6 patients (19.4%). Among the 13 patients who switched owing to treatment failure, the proportion of patients in whom the viral loads were suppressed to less than 50 copies/mL increased from 0% at baseline to 45% at 4 weeks, 50% at 12 weeks, 50% at 24 weeks, and 66.7% at 48 weeks. HIV virus levels decreased and CD4+ T cell counts increased during the follow-up period. In non-treatment failure patients (18 patients), the levels of viral suppression and CD4+ T cells were maintained. There were no significant differences in renal function, liver function, glucose levels, and lipid profile before and after regimen changes. The tolerability was very good: 30 patients (96.8%) tolerated the drugs well and only 1 patient discontinued owing to no improvement in renal insufficiency. Two patients (6.4%) in treatment failure group failed to reach viral suppression.ConclusionThe use of DTG/DRV/c in HIV treatment-experienced patients appears to be a very good regimen for switch therapy that is effective and well tolerated, without significant adverse drug reaction.

High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO

“…Finally, PI drugs could also constitute an efficient option for these children and adolescents, as most of these ARV drugs, especially darunavir, remained fully efficient (15/15; 100%). Indeed, the use of dolutegravir in combination with darunavir in cART-experienced HIV-infected patients has been demonstrated to be convenient in switch therapy 55 , 56 . However, the cobicistat-boosted darunavir (darunavir/c) formulation should be preferred to ritonavir-boosted darunavir (darunavir/r), as darunavir/r reduces the plasma concentrations of dolutegravir when prescribed in combination, 57 unlike darunavir/c, which has very minimal impact on dolutegravir plasma concentrations 58 …”

Two’s a Company, Three’s a Crowd: A Review of Initiating or Switching to a Two-Drug Antiretroviral Regimen in Treatment-Naïve and Treatment-Experienced Patients Living with HIV-1

“…No participant developed new drug resistance mutations throughout the study [49]. Additional observational studies have demonstrated similar results although DRV/r and/or DTG was allowed twice daily [48] while another retrospective study demonstrated the feasibility of cobicistat-boosted DRV with DTG once daily in treatment-experienced patients [50].…”

Boosted Darunavir and Dolutegravir Dual Therapy among a Cohort of Highly Treatment-Experienced Individuals

“…Similarly, a study of 31 treatment-experienced individuals in Korea demonstrated high success rates with a switch to cobicistat-boosted darunavir with dolutegravir. Of 18 individuals who were baseline suppressed, 100% maintained viral suppression and of 13 individuals who were baseline non-suppressed, 11 reached viral suppression [18]. A smaller study evaluated a switch from complex salvage regimens to ritonavir-boosted darunavir with dolutegravir among 13 individuals with transmitted NRTI resistance and found that all 13 individuals tolerated the regimen with continued viral suppression after 12 months [19].…”

“…Median duration since HIV diagnosis was 22 years (IQR 16-28). Median duration of prior ART use was 19 years (IQR [13][14][15][16][17][18][19][20][21][22]. Of the 65 individuals, 100% had prior exposure to nucleoside(tide) reverse transcriptase inhibitors (NRTI), 85% to non-nucleoside reverse transcriptase inhibitors (NNRTI), 89% to protease inhibitors (PI) and 57% to integrase strand transfer inhibitors (INSTI).…”