Dolutegravir-based Antiretroviral Therapy in People With HIV With Solid Organ Transplantation: A Single-arm Pilot Clinical Trial (DTG-SOT)

Abstract

Background: This study assessed the pharmacokinetic interactions between dolutegravir (DTG)-based antiretroviral therapy (ART) and immunosuppressants in solid organ transplantation (SOT) recipients with HIV and ART safety.

Methods: A phase IV, single-center, open-label, single-arm clinical trial (DTG-SOT, NCT03360682) including adult SOT recipients with HIV conducted between 2017 and 2019. People with HIV with plasma viral load <50 copies/mL during ≥12 months and receiving stable raltegravir-based ART during ≥6 months were switched to tenofovir disoproxil fumarate/emtricitabine or lamivudine/abacavir + DTG and followed up for 48 weeks. Immunosuppressant pharmacokinetic parameters were compared before and 2 weeks after ART switch (primary outcome). Efficacy and safety were analyzed at 48 weeks by intention-to-treat analysis.

Results: Nineteen consecutive participants (median, 57 years; interquartile range, 51-60), mostly liver recipients (63.2%), received DTG/lamivudine/abacavir (63.2%) and DTG + emtricitabine/tenofovir disoproxil fumarate (36.8%). Pharmacokinetic parameters changed, albeit not significantly, before and after ART, for mycophenolic acid (maximum [Cmax] +63%, trough [Cmin] +53%, area under the curve [AUC] +16%; n = 7) and cyclosporine A (Cmax -64%, Cmin +14%, AUC -47%; n = 2), with smaller changes for tacrolimus (Cmax +14%, Cmin -29%, AUC -9%; n = 7). No participants experienced acute rejection or virological failure and CD4+ cell counts and percentages remained unchanged during follow-up. Three (15.8%) discontinued treatment because of adverse events. Estimated glomerular filtration rate decreased (P = 0.0015) and creatinine increased (P = 0.0001) slightly.

Conclusions: DTG-based ART lacked clinically significant drug-drug interactions with tacrolimus and mycophenolic acid. Switching to DTG-based ART was effective in people with HIV SOT recipients. More studies are needed to evaluate DTG safety in this setting.

Keywords: HIV infection; dolutegravir; drug-drug interactions; immunosuppressants; solid organ transplantation.