Evaluation of kidney function in HIV-infected patients receiving an antiretroviral regimen containing one or two inhibitors of the tubular secretion of creatinine

HIV Med. 2019 Nov;20(10):648-656. doi: 10.1111/hiv.12784. Epub 2019 Jul 19.

Abstract

Objectives: The aim of this study was to determine the evolution of renal function in patients receiving one or two inhibitors, according to different baseline factors. Some antiretroviral drugs such as rilpivirine (RPV), dolutegravir (DTG), or cobicistat (COBI), interact with the tubular secretion of creatinine, but there are no data about their impact in renal function evaluation in patients with renal disease or when these drugs are used concomitantly.

Methods: A prospective cohort study was carried out in HIV-infected patients who switched to a dual regimen including DTG, RPV or darunavir/COBI, separately or in combination. The primary endpoint was the evolution of the serum creatinine-based estimated glomerular filtration rate (eGFR-scr). A control group not receiving any transporter inhibitor was included.

Results: A total of 288 patients on different dual regimens were included (DTG + RPV, 92; DTG + darunavir/COBI, 23; DTG, 26; COBI, 19; control group, 128). In patients receiving two transporter inhibitors, eGFR-scr decreased by a mean of -8.4 mL/min/1.73 m2 , similar to that observed with the separate use of DTG or COBI (mean of both groups, -8.6 mL/min/1.73 m2 ), while eGFR-scr improved in the control group. Similar evolution of proteinuria and tubular dysfunction was observed in all the groups, and there were no significant changes in the cystatin C-based eGFR. Mean eGFR-scr change inversely correlated with baseline eGFR-scr value (r = -0.39; P < 0.01), with a lower eGFR-scr decrease in patients with chronic kidney disease.

Conclusions: Similar eGFR-scr decreases were observed in patients using different antiretroviral drugs inhibiting the tubular transport of creatinine, separately or in combination, with no alterations in proteinuria or cystatin C-based eGFR. The lack of additional changes when the drugs were used in combination, and the lower impact in cases of previous chronic kidney disease, suggest that there are compensatory mechanisms for creatinine secretion.

Keywords: estimated glomerular filtration rate; creatinine; dual regimen; kidney; renal transporters.

MeSH terms

  • Adult
  • Anti-Retroviral Agents / adverse effects*
  • Anti-Retroviral Agents / therapeutic use
  • Case-Control Studies
  • Creatinine / blood*
  • Darunavir / adverse effects*
  • Female
  • Glomerular Filtration Rate
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / adverse effects*
  • Heterocyclic Compounds, 3-Ring / adverse effects*
  • Humans
  • Kidney Diseases / blood
  • Kidney Diseases / chemically induced*
  • Male
  • Middle Aged
  • Oxazines
  • Piperazines
  • Prospective Studies
  • Pyridones
  • Rilpivirine / adverse effects*

Substances

  • Anti-Retroviral Agents
  • HIV Protease Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Creatinine
  • dolutegravir
  • Rilpivirine
  • Darunavir

Associated data

  • GENBANK/NCT02491242
  • GENBANK/NCT02209740