Hyperglycemia and the development of diabetes mellitus is an emerging side effect of all of the protease inhibitors currently in use. As of November 1997, the FDA has received reports of 234 PI-related hyperglycemia from among the tens of thousands of people receiving PI therapy.

This small observational study looked at 8 men (mean age 47) receiving indinavir (IDV) therapy who developed new-onset hyperglycemia, and then switched to nelfinavir (NFV). None of these patients were receiving any other drugs known to affect glucose tolerance (such as growth hormone, pentamidine, and others), but four of the eight (50%) had a family history of adult-onset diabetes.

Two patients stopped indinavir immediately after developing hyperglycemia, with one being treated with hyperglycemia drugs for four days, after which the hyperglycemia resolved. The other was not treated, and his hyperglycemia resolved over a period of a few weeks. Six patients switched directly from indinavir to nelfinavir; three of them have had no significant improvement in their hyperglycemia.

In terms of the impact of the switch to nelfinavir on viral load, results were decidedly mixed. Four of the eight patients were undetectable at the time treatment was changed; two of them experienced viral rebound after switching to nelfinavir, but they had not switched their underlying RTI treatment at the time of the change. Both patients did manage to get to undetectable again after switching their nucleoside analogs treatment.

While it is difficult to draw firm conclusions from this small study, the researchers suggest that although NFV may have a lesser tendency to effect glucose metabolism than IDV, the occurrence of viral load rebound following the switch from IDV to NFV is cause for concern. When new treatment options are limited, they conclude, it may be preferable to continue IDV and treat the diabetes rather than switch to a new PI (or to a non-nucleoside reverse transcriptase regimen) and risk an increase in viral load.