NRTI-associated lactic acidosis: a rare HIV medicine side effect

Lactic acid is a substance the body produces as part of normal metabolism. When it builds up in the blood faster than it is cleared, the blood becomes more acidic, which is called lactic acidosis, and it needs urgent hospital assessment whatever the cause.

Prescribing information for UK-licensed lamivudine and zidovudine tablets describes lactic acidosis, usually associated with hepatomegaly and hepatic steatosis, as having been reported with the use of nucleoside analogues. It describes it as a very rare side effect with a high mortality. This page concerns only that medicine-related form; many other conditions, including infection, kidney failure and diabetes, also raise lactate.

NRTIs, also called nucleoside analogues, were the backbone of HIV treatment for many years. The UK prescribing document explains that nucleoside and nucleotide analogues may affect mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine. Mitochondria are the cell structures that produce energy, and impaired function is the proposed route to lactic acidosis, fatty liver and fat loss under the skin (lipoatrophy). The document links zidovudine to loss of subcutaneous fat that has been linked to mitochondrial toxicity.

It also reports mitochondrial dysfunction in HIV-negative infants exposed in the womb or after birth to nucleoside analogues, predominantly with zidovudine-containing regimens, which is why babies exposed in this way are followed up. Your HIV team can tell you which of your medicines belong to this group.

The prescribing information advises caution when using zidovudine in anyone, particularly obese women, who has hepatomegaly, hepatitis or other known risk factors for liver disease and hepatic steatosis, including certain medicines and alcohol. It says lactic acidosis generally occurred after a few or several months of treatment. An HIV i-Base report from 2000, which is historical and should not be read as current practice, recorded that lactic acidosis had been linked to all nucleoside analogues and could be fatal in over half of the cases reported at that time.

The i-Base report describes the clinical syndrome in a small group of patients as including nausea, vomiting, abdominal complaints, liver failure and pancreatitis, with raised blood lactate. These symptoms are non-specific and have many other causes, such as infections, other medicines, hepatitis or pancreatitis. For that reason, the prescribing information emphasises monitoring for symptomatic hyperlactataemia, progressive hepatomegaly and rapidly rising liver enzymes.

If you are taking HIV medicines and develop persistent nausea, vomiting, abdominal pain, or unusual tiredness or weakness, contact your HIV clinic or NHS 111 promptly. If you are severely unwell, call 999 or go to A&E and tell staff which HIV medicines you take.

Diagnosis relies on a blood test showing a raised lactate and acidic blood, together with tests of liver and kidney function and a search for other causes. This is done in hospital. The prescribing information says that treatment with the nucleoside analogue should be discontinued if there is symptomatic hyperlactataemia with metabolic or lactic acidosis, progressive hepatomegaly or rapidly rising aminotransferase levels.

Supportive care in hospital follows. The i-Base 2000 report describes a small experimental protocol using intravenous B vitamins and L-carnitine alongside stopping the NRTI, with lactate normalising in all six patients over 4 to 20 days, but this was an early case series and is not a current standard. Your HIV team will choose an alternative HIV regimen once you are stable.

Most people taking modern HIV treatment will never experience this. The important message is not to stop or change antiretroviral treatment on your own, because regimens are chosen to keep the virus controlled and any change should be planned with your clinic. Raise any new symptom with your clinic, keep appointments for blood tests, and tell your doctors about alcohol use and other medicines that affect the liver.

HIV treatment in the UK is provided free through NHS HIV clinics, and the monitoring of side effects is part of routine follow-up. Private clinics exist but should coordinate with your NHS HIV service, since regimens and monitoring need to be consistent.