Changes in renal, bone, lipid, and inflammation markers in HIV-1 patients after combination antiretroviral therapy simplification to dolutegravir monotherapy
Combination antiretroviral therapy (cART) can cause metabolic toxicities. How cART simplification to dual or monotherapies affects metabolic markers is unknown. We analyzed the metabolic effects of cART simplification to dolutegravir (DTG) monotherapy in the randomized clinical DOMONO (DOlutegravir MONOtherapy for HIV) trial including HIV-positive participants. Renal function, Framingham risk score (FRS), inflammation, and bone mineral density (BMD) with trabecular bone score (TBS) were measured during 48 weeks after simplification. The changes at 48 weeks by ontreatment analyses overall and for prior tenofovir disoproxil fumarate (TDF) exposure were analyzed separately, using Bonferroni corrected alpha (p ¼ 0.00096). Ninety-five patients initiated DTG monotherapy, including 80 discontinuing TDF. At week 48, the switch to DTG monotherapy resulted in an expected 7.8 ml/min estimated glomerular filtration decline. In patients on prior TDF, proteinuria improved (p < 0.00096), but proximal tubular dysfunction proportions did not change. Fasting lipids, FRS, and the inflammation markers C-reactive protein and CD4:CD8 T-cell ratio remained stable. Lumbar spine BMD improved (þ1.7%, p < 0.00096), while hip BMD and TBS remained comparable. Simplification of TDF-containing cART to DTG monotherapy ameliorated lumbar spine BMD and proteinuria with neutral effect on lipids and inflammation markers. Although DTG monotherapy should not be used in routine care and its role in strictly selected patients with primary HIV infection needs to be further elucidated, these observations remain relevant regarding DTG-based dual therapy without TDF.
|Keywords||Dolutegravir, tenofovir disoproxil fumarate, renal markers, bone markers, lipids, inflammation markers|
|Persistent URL||dx.doi.org/10.1177/0956462419848962, hdl.handle.net/1765/121187|
|Journal||International Journal of STD & AIDS|
Wijting, I.E.A, Rokx, C, Zillikens, M.C, Smits, S.A.A., de Vries-Sluijs, T, Schurink, C.A.M, … Rijnders, B.J.A. (2019). Changes in renal, bone, lipid, and inflammation markers in HIV-1 patients after combination antiretroviral therapy simplification to dolutegravir monotherapy. International Journal of STD & AIDS. doi:10.1177/0956462419848962