PIs and Non-Nukes Cause Similar Metabolic Problems
May 10, 2007
By Will Boggs, MD
(Reuters Health) - The long-term metabolic consequences of antiretroviral therapy (ART) are similar with protease inhibitors (PI), nonnucleoside reverse transcriptase inhibitors (NNRTI), or the combination thereof, according to a report in the April 15th issue of the Journal of Acquired Immune Deficiency Syndromes.
"When providers choose an antiretroviral treatment, they need to consider the toxicities associated with these treatments in addition to their potency and tolerability," Dr. Judith C. Shlay told Reuters Health.
Dr. Shlay from Denver Public Health, Colorado and associates assessed long-term changes in metabolic parameters and body composition among ART-naive patients randomized to one of three highly active ART strategies: a PI strategy, an NNRTI strategy, or a PI + NNRTI strategy. All three groups received nucleoside reverse transcriptase inhibitor (NRTI) treatment(s).
After a median follow-up of 62 months, LDL cholesterol and HDL cholesterol increased with all three strategies. The authors report that LDL cholesterol increased most in the PI + NNRTI group, and the HDL cholesterol increased most in the NNRTI group.
Also, triglyceride levels increased most in the PI + NNRTI group.
Insulin levels and insulin resistance increased within the first month after initiation of the PI strategy, the researchers note, but all three strategies resulted in increases over the long term, with no differences seen by strategy. Glucose levels also increased with all three strategies.
Regardless of strategy, ART was associated with mean increases in weight, body-mass index, and fat-free mass within the first 4 months. Subcutaneous tissue areas (predominantly adipose tissue) also increased by the 4-month follow-up.
Visceral adipose tissue showed early significant increases for the PI and NNRTI strategies, the report indicates, but over the course of the study, these increases showed no difference among the strategies.
"PI + NNRTI strategy is associated with the least favorable lipid effects," Dr. Shlay said. "Patients placed on these medications should be monitored closely, particularly if they initiate therapy at higher triglyceride levels."
"Regardless of strategy, gradual increases were noted in insulin, glucose, and insulin resistance during follow-up," Dr. Shlay said. "This, coupled with the changes in regional body composition seen regardless of strategy (i.e., increases in visceral fat and loss of lower extremity peripheral fat), suggests that the NRTIs may be responsible for the development of lipoatrophy and insulin resistance."
"Finally, due to the gradual increases in insulin, insulin resistance, and glucose noted, this supports the need for ongoing monitoring of glucose levels as well as the development of diabetes," Dr. Shlay concluded.
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