icon-    folder.gif   Conference Reports for NATAP  
  16th CROI
Conference on Retroviruses and Opportunistic Infections Montreal, Canada
February 8-11, 2009
Back grey_arrow_rt.gif
HIV and Diabetes/Hyperlipidemia Cause Kidney Decline
  CROI Feb 8-12 2009, Montreal, Canada
From Jules: In this study of a cohort of patients Andy Choi reported that HIV+ individuals showed decline in kidney function as measured by GFR more quickly than expected, more quickly than in the general population, and of note HAART may reverse or slow decline but GFR still declined in HIV+ individuals in this study while on HAART. So, this means HIV can cause kidney decline and HAART can slow it but decline may continue despite fully suppressive HAART. Choi also reported importantly that patients that intermittent viral blips were strongly associated with "kidney harm" (GFR decline) suggesting that ART interruptions can cause GFR decline.; each log increase in viral load was assoiated with an accekerated GFR loss of -6.9 mL/min/1.73m2 per year. He also reported that traditional risk factors, which are common in HIV+ are important risk factors for kidney disease in this study population: diabetes and hyperlipidemia cause GFR to decline. HIV gets into the kidney upon infection with HIV. As well, HIV gets into the CNS immediately after HIV infection, within 24-48 hours. In addition, HIV causes inflammation, which is associated in HIV+ and HIV- individuals with the development of comorbidities. HAART suppresses but does not eliminate inflammation, it may still persists despite complete viral suppression. HIV is the main culprit in the development of comorbidities due to HIV accelerating the aging of important naive and memory CD4 cells. In brief, these are the reasons why aging with HIV has become the major issue today, because this underlies all the discussion about the development of non-AIDS events and death. These issues also underlie the question about when to begin HAART, because the results of numerous cohort studies find earlier HAART reduces rates for non-AIDS events and death.
Kidney Function May Keep Fading in People With Viral Load Blips (see slides below)
16th Conference on Retroviruses and Opportunistic Infections, February 8-11, 2009, Montreal
Mark Mascolini
People in whom antiretrovirals control viral replication lose kidney function more slowly than people with uncontrolled viremia, according to results of a 615-person study at the University of California, San Francisco (UCSF) [1]. But even people with relatively well-controlled viral replication see their kidneys falter at a rate faster than aging alone can explain. In this group, the kidney risk ran higher in people with intermittent viremia--usually called "blips." UCSF investigators studied 615 SCOPE cohort members who had an outpatient serum creatinine measurement. They estimated kidney function by the Modification of Diet in Renal Disease (MDRD) equation, which factors in age, gender, race, and standardized serum creatinine. The study group included people with and without antiretroviral experience, but the analysis did not consider individual antiretrovirals or antiretroviral classes. Nor did the researchers compare black patients (28.5% of the cohort) with whites (50.7%) or others, although blacks run a higher risk of kidney ailments than whites regardless of HIV infection. Cohort members averaged 45.3 years in age, and 87% were men. CD4 count averaged 434 and viral load just a bit over 1000 copies. While 15% had hepatitis C virus infection, 14.5% had hypertension, and 11.1% had abnormal lipids. Median observation time stood at 2.7 years, and each person had a median of 10 glomerular filtration rate (GFR) measurements.
Among people starting their first antiretroviral regimen, the rate of GFR decline averaged 4.7 mL/min/1.73m(2) per year before starting treatment and 1.9 mL/min/1.73(2) per year after starting antiretrovirals. In other words, starting therapy correlated with a 2.8 mL/min/1.73(2) yearly improvement in GFR slope. The overall unadjusted rate of GFR decline measured 2.6 mL/min/1.73(2) per year. That compares with an expected age-related drop of 0.4 mL/min/1.73(2) per year in people without HIV. A yearly fall of 3 mL/min/1.73(2) is generally considered rapid. In analyses adjusted for kidney function risk factors, GFR slope in this cohort fell 0.7 mL/min/1.73(2) per year of age, 1.8 mL/min/1.73(2) per year in women, 2.7 mL/min/1.73(2) per year in people with hyperlipidemia, and 4.4 mL/min/1.73(2) per year in those with diabetes. CD4 count, viral load, and antiretroviral therapy did not significantly affect GFR drop-offs in this analysis.
Andy Choi and colleagues then divided cohort members into four groups according to antiretroviral treatment status and viral load above or below 1000 copies--untreated controllers, untreated noncontrollers, antiretroviral-treated controllers, and antiretroviral-treated noncontrollers. Multivariate longitudinal models adjusted for age, gender, race, and time-updated CD4 count, viral load, antiretroviral therapy, and comorbid conditions figured that MDRD-determined GFR decline was lowest in untreated controllers, highest in untreated noncontrollers, and intermediate in the two antiretroviral-treated groups. Compared with untreated controllers, yearly GFR declines in the other groups were:
• Untreated noncontrollers: -5.8 mL/min/1.73m(2) (95% confidence interval [CI] -8.1 to -3.4)
• Treated controllers: -5.2 mL/min/1.73m(2) (95% CI -7.5 to -3.0)
• Treated noncontrollers: -5.3 mL/min/1.73m(2) (95% CI -7.6 to -3.3)
Further analysis linked waning GFR in antiretroviral-treated controllers to transient blips below 1000 copies, not to CD4 count. CD4 count did not appear to be a major predictor of kidney function in people with either treated or untreated HIV infection. Choi and coworkers proposed that unremitting viral control--with no blips--may be essential to maintaining kidney function. This study could not weigh the impact of HIV itself--and the associated inflammation--on GFR. The results do suggest, though, that antiretroviral therapy slows a steep decline in GFR seen in people with uncontrolled HIV infection. Choi noted that the analysis did not have the statistical power to calculate the potential impact of regimens containing drugs known to affect kidney function, such as tenofovir and indinavir. But when the researchers did sort out people taking those antiretrovirals, they found no evidence of a drug-specific impact on GFR.
1. Choi A, Shlipak M, Hunt P, Martin J, Deeks S. HIV-infected Persons continue to lose kidney function despite successful ART. 16th Conference on Retroviruses and Opportunistic Infections, February 8-11, 2009, Montreal. Abstract 38.