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First-line therapy and mitochondrial damage: different nucleosides, different findings
Francisco Blanco1, Teresa García-Benayas, Juan José de la Cruz
1Service of Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain.
HIV Clinical Trials
|February 11, 2003
Summary
Didanosine plus stavudine (ddI+d4T) antiretroviral therapy significantly increases serum lactate and lipoatrophy in HIV patients compared to zidovudine plus lamivudine (AZT+3TC). Elevated liver enzymes may indicate harmful lactate increases.
Area of Science:
- HIV/AIDS Research
- Pharmacology
- Metabolic Disorders
Background:
- Antiretroviral therapy (ART) can cause body shape changes and metabolic issues like hyperlactatemia.
- Nucleoside analogue reverse transcriptase inhibitors (NRTIs) are implicated in mitochondrial damage and ART complications.
- The specific roles of different NRTIs in these adverse effects are not fully understood.
Purpose of the Study:
- To compare the incidence of hyperlactatemia and lipodystrophy in treatment-naïve HIV patients starting highly active antiretroviral therapy (HAART).
- To evaluate two different NRTI backbone combinations: zidovudine plus lamivudine (AZT+3TC) versus didanosine plus stavudine (ddI+d4T).
Main Methods:
- A prospective, longitudinal, observational study was conducted over 12 months.
- Drug-naïve HIV-infected patients were enrolled and initiated on HAART with either AZT+3TC or ddI+d4T.
- Serum lactate levels and lipodystrophy were monitored periodically.
Main Results:
- Patients on ddI+d4T showed significantly increased mean lactate levels (2.6 mmol/L) compared to AZT+3TC (<2 mmol/L).
- Hyperlactatemia (>or=2 mmol/L) affected 71% of ddI+d4T patients by 12 months, versus <10% on AZT+3TC.
- Subcutaneous lipoatrophy was significantly more frequent (35% vs. 8%) in the ddI+d4T group.
Conclusions:
- ddI+d4T regimens lead to greater serum lactate increases and lipoatrophy within the first year of HAART compared to AZT+3TC.
- Elevated lactate dehydrogenase (LDH), amylase, gamma-glutamyltransferase (GGT), and alkaline phosphatase (AP) may signal potentially harmful lactate level increases.