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Effectiveness of Once/Day Dolutegravir Plus Boosted Darunavir as a Switch Strategy in Heavily Treated Patients with Human Immunodeficiency Virus
Author(s) -
Navarro Jordi,
Santos José Ramón,
Silva Ana,
Burgos Joaquin,
Falcó Vicenç,
Ribera Esteban,
Imaz Arkaitz,
Curran Adrian
Publication year - 2019
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.2227
Subject(s) - darunavir , dolutegravir , interquartile range , medicine , discontinuation , viral load , regimen , ritonavir , retrospective cohort study , human immunodeficiency virus (hiv) , immunology , antiretroviral therapy
Study Objective Dual therapy with once/day dolutegravir ( DTG ) plus boosted darunavir ( DRV /b) may be a suitable and effective strategy with a high genetic barrier to resistance in patients infected with human immunodeficiency virus ( HIV ). Our aim was to evaluate the effectiveness of DTG plus DRV /b ( DTG + DRV /b) as a switch strategy in HIV ‐infected patients, irrespective of their history of virologic failure ( VF ). Design Multicenter retrospective cohort study. Setting Human immunodeficiency outpatient treatment clinics at three university hospitals in Spain. Patients Fifty HIV ‐infected adults who had a stable antiretroviral treatment ( ART ) regimen and an undetectable viral load for at least 6 months, and whose ART was switched to once/day DTG + DRV /b between January 2015 and January 2018 were included in the analysis. Historical genotype at the time of VF was available in 44 patients. Measurements and Main Results Patients were followed until VF or treatment discontinuation for any reason. The primary outcome was the percentage of patients with a viral load of 50 copies/mL or lower at the last follow‐up visit. Secondary outcomes included changes in CD 4 + cell count, lipid profile, and renal function. Of the 50 patients included, median time of viral suppression was 52 months (interquartile range [IQR] 18–103 mo) and nadir CD 4 + 89 cells/mm 3 (IQR 37–241 cells/mm 3 ). Patients had a history of a median of 8 ART combinations (IQR 4–11 combinations) and 3 VFs (IQR 2–8 VFs). The historical genotypes from 44 patients showed 41 patients (93.2%) with nucleoside/nucleotide reverse transcriptase inhibitor ( NRTI ) resistance‐associated mutations ( RAM s), 32 (72.7%) with nonnucleoside reverse transcriptase inhibitor ( NNRTI ) RAM s, and 12 (27.3%) with primary protease inhibitor ( PI ) RAM s; 7 (15.9%) had darunavir RAM s, and no patients had baseline integrase strand transfer inhibitor RAM s. Thirty‐seven patients (84.1%) had resistance to at least two antiretroviral classes. After a median of 25 months (IQR 17–28 mo) of follow‐up, 49 patients (98%) maintained a viral load of 50 copies/ mL or lower , and 1 patient (2%) had VF . No new RAM s emerged at VF . At week 4, serum creatinine concentration increased a median of 0.12 mg/dl (0.03–0.23 mg/ dl) . At last visit, total cholesterol and low‐density lipoprotein cholesterol levels increased by a median of 9 mg/ dl (IQR −18 to 40 mg/ dl ) and 16 mg/ dl (IQR −9 to 40 mg/ dl ), respectively, whereas CD 4 + cell count remained stable (median +13 cell/mm 3 ). Conclusion In this cohort of heavily treated HIV ‐infected patients with virologic suppression, switching to the combination of DTG + DRV /b was a convenient regimen that was highly effective and had good tolerability.