7th Conference - Abstract 55

Differences in Anion Gap with Different Nucleoside RTI Combinations

R. MOORE*, J. KERULY, and R. CHAISSON. Johns Hopkins Univ., Baltimore, MD

Mitochondrial toxicity is a known adverse effect of nucleoside RTI use. One possible manifestation of this toxicity is lactic acidosis. We analyzed longitudinal data from 509 patients in the Johns Hopkins HIV Cohort who received dual RTIs and a protease inhibitor after January 1, 1996. The anion gap (AG) (Na - [Cl + CO2]) was computed using all electrolyte measurements obtained during therapy. The mean AG was computed and the highest AG was determined for individual dual RTI regimens. Median number of electrolyte measurements per dual RTI regimen was 7 over a median duration of 320 days. The percentage of patients who developed AG > 16 and the overall mean AG for all measurements was: d4T/3TC = 8.1% (mean AG = 10.2), d4T/ddI = 5.0% (mean AG = 9.0), ZVD/3TC = 3.1% (mean AG = 9.2), and ZVD/ddI = 2.5% (mean AG = 8.9). By multivariate logistic regression analysis adjusting for patient age, CD4 level, and duration of therapy, d4T/3TC use was associated with a relative odds of 2.8 (95% CI: 1.2, 6.4; p=0.01) compared to ZVD/3TC. d4T/ddI and ZVD/ddI were not significantly different from ZVD/3TC. By multivariate regression, the overall mean of the AG distribution for d4T/3TC use was 1.0 meq/L (95% CI: 0.8, 1.2; p<0.001) higher than for the other dual RTIs. Concurrent use of an NNRTI was also associated with a higher overall mean AG (p < 0.03) but was not associated with an AG > 16.
d4T/3TC use is associated with a significantly higher AG distribution than other dual RTI use. Whether this difference has clinical significance is not known but may indicate a higher incidence of lactic acidosis.

Key Words: Lactic acidosis, Mitochondrial toxici, Nucleosides