Back HIV-Related Conditions Liver & Kidney Kidney Function Remains Stable among French HIV Patients on Long-term Antiretroviral Therapy

Kidney Function Remains Stable among French HIV Patients on Long-term Antiretroviral Therapy

alt

Kidney function has remained stable among patients on long-term antiretroviral therapy (ART), according to findings from a large French study described in the December 15, 2009 issue of Clinical Infectious Diseases. Glomerular filtration rate (GFR, a common measure of kidney function) improved slightly during the first year and a half of treatment, then decreased back to the baseline level and remained steady thereafter. Indinavir (Crixivan) was linked to poorer kidney function, but not tenofovir (Viread).

Research looking at kidney function in people with HIV has produced inconsistent results. People with more advanced HIV disease may develop HIV-associated nephropathy, or kidney damage; black patients are at particularly high risk. Some studies have shown that certain antiretroviral drugs -- notably indinavir and tenofovir (also in the Truvada and Atripla coformulations) -- can cause kidney impairment in susceptible individuals, but effective ART is also associated with improved kidney function. Kidney function typically declines with age, and it is unclear how these factors interact in people with HIV.

In the present study, Catherine Leport and colleagues with the ANRS CO8 APROCO-COPILOTE study looked at changes in kidney function, according to GFR, among 1121 HIV positive cohort participants who started triple combination ART between 1997 and 1999. About three-quarters were men and most (90%) were white. The median age was 37 years, with 12% age 50 or older.

Results

  • At the start of the study, the median GFR was 93 mL/min/1.73m2.
  • On average, over a median follow-up period of 7 years, GFR increased from treatment initiation to month 16 on ART (+0.72 mL/min/1.73m2 per month).
  • The GFR increase during the first 16 months was smaller and slower among men, patients with a low body mass index, those diagnosed with AIDS (CD4 count < 200 cells/mm3), and those who used indinavir.
  • After the initial 16 months, GFR returned to the baseline level and remained stable for the remainder of the follow-up period up to 7 years.
  • About 40% of participants had GFR < 60 mL/min/1.73m2(indicating significant decline) at baseline or at some point during follow-up, but only 5% had impaired kidney function indicated by 2 or more consecutive low values.
  • Patients with GFR < 60 mL/min/1.73m2had about twice the mortality rate (4.1 per 100 person-years) as those with higher values (1.6-1.8 per 100 person-years).

Based on these results, the study authors concluded, "Clinicians should closely monitor renal function in combination ART-treated patients, especially in those who have been exposed to indinavir."

In their discussion, they suggested that these long-term data suggest that the evolution of kidney function is "favorable" during prolonged ART, likely due to long-term control of HIV replication, and that the degree of deterioration was consistent with normal aging.

Although used by 40% of participants in this study, indinavir -- one of the first approved protease inhibitors -- is no longer included as a preferred drug in current U.S. antiretroviral treatment guidelines. The investigators did not express particular caution concerning the now widely used tenofovir, but this was used by only about 200 patients for a median of 20 months. Among tenofovir recipients, those with a GFR < 90 mL/min/1.73m2 when they started fared no worse than those with higher levels.

Université Paris-Diderot, UFR Medecine, AP-HP, site Bichat, Paris, France; Université Paris-Descartes University AP-HP, Paris, France; Hôpital Européen Georges Pompidou, Paris, France; Hôpital Pitié-Salpêtrière, Paris, France; INSERM U897, Université Victor Segalen, ISPED, Bordeaux, France; Hôpital La Cavale Blanche, Brest, France; Hôpital L’Archet, Nice, France; Hôtel-Dieu, Nantes, France.

12/18/09

Reference

C Leport, V Bouteloup, J Rossert, and others. Long-term evolution and determinants of renal function in HIV-infected patients who began receiving combination antiretroviral therapy in 1997-99, ANRS CO8 APROCO-COPILOTE. Clinical Infectious Diseases49(12): 1950-1954 (Abstract)