Lactic acidosis in HIV-infected patients: Causes, treatment and prevention

Abstract

Lactic acidosis is the most serious, sometimes life-threatening, adverse effect of nucleoside reverse transcriptase inhibitor (NRTI) usage in HIV infected patients. The reported incidence rate of lactic acidosis due to an NRTI based regimen is low, but the fatality rate is estimated at around 60 - 80% in those HIV-infected patients who develop lactic acidosis during NRTI usage. The mechanism of NRTI induced lactic acidosis is based on inhibition of mitochondrial DNA polymerase - γ and consequent mitochondrial depletion and deficit in the respiratory chain function. All NRTIs may interact with polymerase - γ, but dideoxynucleosides, such as stavudine (d4T), zalcitabine (ddC) and didanosine (ddI), also known as d-drugs, are the most potent. In resource limited settings, where d-drugs still remain the first line treatment option, the highest incidence of NRTI-induced lactic acidosis is due to stavudine (d4T), followed by didanosine (ddI) usage. Lactic acidosis developed even more frequently when stavudine and didanosine were prescribed together. Zidovudine (AZT) could potentially induce lactic acidosis, while significant events are not reported with other NRTI drugs, such as lamivudine, abacavir and tenofovir. Risk factors associated with lactic acidosis are female sex, advanced HIV-1 induced immunodeficiency, obesity and prolonged duration of NRTI-based antiretroviral treatment. Renal and liver abnormalities, especially hepatitis B and hepatitis C virus coinfection, are associated with a higher incidence of lactic acidosis. Lactic acidosis induced with NRTI usage is treated by NRTI withdrawal, especially in life-threatening clinical conditions with serum lactate level of 5 mmol/L and higher. Within several days the outcome is favourable in most cases. Recovery is complete, especially when no other d-drug is re-administered. Even though current HIV/AIDS treatment guidelines discourage the usage of ddrugs, national HIV treatment guidelines from low-middle income countries are still unable to abandon these drugs. Thus, NRTI-associated lactic acidosis is still issue of concern in the resource limited settings. © 2014 by Nova Science Publishers, Inc. All rights reserved.