The role of nucleoside reverse transcriptase inhibitors usage in the incidence of hyperlactatemia and lactic acidosis in HIV/AIDS patients

Institute of Pharmacology, Clinical Pharmacology and Toxicology, Dr Subotica 1/III, School of Medicine, University of Belgrade, Belgrade, Serbia.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Impact Factor: 2.02). 05/2012; 66(4):308-11. DOI: 10.1016/j.biopha.2011.09.016
Source: PubMed


Hyperlactatemia and lactic acidosis (LA) are among the most dangerous and life-threatening side effect that occurs during therapy with some nucleoside reverse transcriptase inhibitors (NRTIs), mainly didanosine (ddI) and stavudine (d4T), also known as d-drugs. Therefore, we performed a prospective, follow-up study and aimed to examine the incidence rates (IR) and rate ratios (RR) of hyperlactatemia and LA for each NRTI. Three hundred and ninety-six HIV-patients were included in final analysis comprising 783.8 person-years of follow-up. Between 1st January 2000 and 1st January 2008, 19 cases of hyperlactatemia and 15 cases of LA were recorded. Between regimens with the significant impact for developing hyperlactatemia and LA the lowest IR was for didanosine (IR=2.87 per 100 person-years, 95%CI=0.45-9.25 and IR=4.31 per 100 person-years, 95%CI=1.07-13.91, respectively), and the highest for didanosine+stavudine (IR=10.17 per 100 person-years, 95%CI=1.02-19.76 and IR=7.39 per 100 person-years, 95%CI=1.02-13.05, respectively). Compared to didanosine alone the RR of hyperlactatemia was 2.67 (95%CI=1.11-12.52) for stavudine, and 4.06 (95%CI=1.31-15.48) for didanosine+stavudine. The RR of LA was 3.12 (95%CI=1.13-10.65) for stavudine, and 5.13 (95%CI=1.54-13.37) for didanosine+stavudine in comparison with didanosine alone. Other risk factors for AP were CD4 cell count less than 200 cells/mm³ and female sex. Our results suggest that the use of stavudine alone or in combination with didanosine should not be used as first-line therapy, especially in patients with CD4 cell count less than 200 cells/mm³ and females if other treatment options are available.

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    • "The extent to which antiretrovirals may complicate management of DKA is not known at present even though their use is currently associated with insulin resistance (Banerjee et al. 2011; Feeney & Mallon 2011). However, nucleoside reverse transcriptase inhibitors (NRTIs) such as didanosine, stavudine and zidovudine are notoriously associated with lactic acidosis due to mitochondrial toxicity (Dragovic & Jevtovic 2012) to the extent that stavudine is not currently used as first-line drug in the treatment for HIV/AIDS sub-Saharan countries (Leung et al. 2011). Should NRTIs be withheld from diabetic children at the risk of developing DKA who are also infected with HIV? "
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