Human immunodeficiency virus genotype and hypertriglyceridemia

Many HIV patients develop a progressive syndrome of abnormal body fat distribution accompanied by hypertriglyceridemia. Antiretroviral agents are thought to be etiologic in the syndrome, often termed "highly active antiretroviral therapy (HAART)-associated lipodystrophy." In the course of clinical HIV genotype testing, we observed that our HIV patients with hypertriglyceridemia had viral genotypes that were more highly mutated than those of our therapy-matched control patients. Hypertriglyceridemia was statistically associated with predicted resistance for three nucleoside reverse transcriptase inhibitors: zidovudine, abacavir, and stavudine. Statistical analysis of 51 patients in retrospect revealed a strong association of mutations at reverse transcriptase codons M41 and T215 with hypertriglyceridemia (chi-square (chi(2)) = 8.375, P=.0038; and chi(2)=7.445, P=.0064, respectively). This was in contrast to silent mutations, which occurred at equivalent rates in retroviral genotypes of patients with and without hypertriglyceridemia. The findings imply that the HIV genotype itself may be a significant etiologic factor in antiretroviral-associated lipodystrophy.