Low creatinine clearance reported greater risk for lactic acidosis than any HIV drug

Keith Alcorn
Estimated reading time 3 minutes
This article is more than 22 years old.

A French case control study of patients diagnosed with lactic acidosis whilst receiving nucleoside analogue therapy has revealed that low creatinine clearance and a CD4 cell count below 250 cells/mm3 prior to commencing therapy were the only significant risk factors for the condition. The findings are published in the May 15 edition of Clinical Infectious Diseases.

Doctors at the Hopital Saint-Andre in Bourdeaux identified nine cases of lactic acidosis (plasma lactic acid >5 mM and plasma pH

Lactic acidosis cases were excluded if they had been exposed to other drugs or toxins associated with lactic acidosis, or if they had cirrhosis, cancer or sepsis.

Glossary

lactic acidosis

High blood levels of lactic acid, a substance involved in metabolism. Lactic acidosis is a rare side-effect of nucleoside analogues.

renal

Relating to the kidneys.

creatinine

Breakdown product of creatine phosphate in muscle, usually produced at a fairly constant rate by the body (depending on muscle mass). As a blood test, it is an important indicator of the health of the kidneys because it is an easily measured by-product of muscle metabolism that is excreted unchanged by the kidneys.

plasma

The fluid portion of the blood.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

The median age of cases was 36 years, and the median time since diagnosis of HIV infection was nine years. The median duration of antiretroviral therapy was four years, and at the time of lactic acidosis diagnosis, cases had been taking their current nucleoside analogue(s) for a median of 12 weeks. Five patients had developed an infectious disease less than 14 days prior to lactic acidosis diagnosis, and five patients had a history of renal failure.

The only factors identified as significant risks factors for lactic acidosis were creatinine clearance 3 prior to commencing therapy. No specific drug was found to be associated with lactic acidosis, and there was no significant difference in total drug exposure between cases and controls.

A trend towards greater incidence was seen in women, as in other cohorts, and the majority of lactic acidosis cases were coinfected with hepatitis B or C.

The authors note that more attention needs to be paid to the management of NRTI therapy in patients with renal failure, and that previous case reports and cohort studies on lactic acidosis have not published data on creatinine clearance or renal function.

They highlight a number of issues that need to be considered in management of patients with renal insufficiency or symptoms of lactic acidosis:

  • NRTI dose reduction in the presence of renal insuffiency is not adequately defined; poor creatinine clearance may not allow the kidneys to compensate for elevated lactate levels, and may reduce drug clearance

  • There is no consensus on how to measure drug clearance in the presence of renal insufficiency: should intracellular levels be monitored, rather than plasma levels?

  • The evaluation of renal function is especially important if any acute infection is present, or if nephrotoxic drugs have been administered

HIV-associated nephropathy, the major cause of renal insufficiency in people with HIV, is much more common in people of African and Caribbean descent in the United States. Its frequency amongst people of African origin in other parts of the world has not been well characterised.

Further information on this website

Lactic acidosis

Creatinine clearance (definition of test)

Reference

Bonnet F et al. Risk factors for lactic acidosis in HIV-infected patients treated with nucleoside reverse-transcriptase inhibitors: a case control study. Clinical Infectious Diseases 36 (electronic edition), 2003.

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