Diagnosis

Current laboratory tests cannot reliably detect or predict who is at risk for mitochondrial toxicity. Many studies have used blood lactate level as a surrogate marker for mitochondrial damage, but not everyone with associated conditions such as peripheral neuropathy or lipoatrophy has elevated lactate, and some people with elevated lactate have no such side-effects. Moreover, it is difficult to get consistently accurate readings because variables such as physical activity, use of a tourniquet, and delays in blood processing can alter test results.1 A large Swiss study found that routine lactate screening of HIV-positive patients is not cost-effective.2

Other measures of lactic acidosis include blood pH, serum bicarbonate, anion gap, and lactate/ pyruvate ratio. Neither the British HIV Association (BHIVA) nor the Infectious Diseases Society of America (IDSA) recommends routine lactate monitoring of HIV-positive people, but patients with symptoms of hyperlactataemia should be assessed.1

Some researchers have proposed measuring the ratio of mitochondrial DNA (mtDNA) to nuclear DNA. A Canadian team that developed a polymerase chain reaction assay to measure mtDNA in white blood cells found that the ratio in patients with hyperlactataemia was about 43% lower than the ratio seen in untreated HIV-positive patients and 68% lower compared with HIV-negative people.3 However, other studies have shown that blood mtDNA level is not reduced in patients taking nucleoside reverse transcriptase inhibitors (NRTIs), nor does it predict lipoatrophy or other conditions linked to mitochondrial toxicity.4 5 6

Two research teams have recently reported on the use of the 13-methionine breath test to assess mitochondrial impairment in the liver. One study found that the breath test agreed with mtDNA blood test results.7 The second found that patients treated with NRTIs had decreased exhalation of 13CO2 (a form of carbon dioxide) compared with HIV-negative controls and that HIV-positive patients with hyperlactataemia had lower levels than those with normal serum lactate.8 

In patients with suspected mitochondrial toxicity, a muscle, liver, or fat sample can be examined for mitochondrial damage.

References

  1. Schambelan M et al. Management of metabolic complications associated with antiretroviral therapy for HIV-1 infection: recommendations of an International AIDS Society-USA panel. J Acquir Immune Defic Syndr 31: 257-275, 2002
  2. Imhof A et al. Risk factors for and outcome of hyperlactatemia in HIV-infected persons: is there a need for routine lactate monitoring? Clin Infect Dis 41: 721-728, 2005
  3. Cote HC et al. Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV-infected patients. N Engl J Med 346: 811-820, 2002
  4. McComsey G et al. Extensive investigations of mitochondrial DNA genome in treated HIV-infected subjects: beyond mitochondrial DNA depletion. J Acquir Immune Defic Syndr 39: 181-188, 2005
  5. Hoy JF et al. Changes in mitochondrial DNA in peripheral blood mononuclear cells from HIV-infected patients with lipoatrophy randomized to receive abacavir. J Infect Dis 190(4): 688-692, 2004
  6. Cherry CL et al. Tissue-specific associations between mitochondrial DNA levels and current treatment status in HIV-infected individuals. J Acquir Immune Defic Syndr 42: 435-440, 2006
  7. Banasch M et al. 13C-methionine breath test detects distinct hepatic mitochondrial dysfunction in HIV-infected patients with normal serum lactate. J Acquir Immune Defic Syndr 40: 149-154, 2005
  8. Milazzo L et al. 13C-methionine breath test detects drug-related hepatic mitochondrial dysfunction in HIV-infected patients. J Acquir Immune Defic Syndr 41: 252-253, 2006
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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