"Fat Accumulation and HIV-1 Protease Inhibitors"
Lancet (10/24/98) Vol. 352, No. 9137, P. 1392; Stricker, Raphael
B.; Goldberg, Billi; Martinez, Esteban
In a letter to the editor of the Lancet, two San Francisco
researchers respond to a Sept. 5 letter in which Esteban Martinez
and Jose Gatell of Spain postulated that HIV-1 protease
inhibitors might cause fat accumulation by interfering with two
insulin degrading enzymes. However, Raphael B. Stricker and
Billi Goldberg note that the two enzymes named are likely not
affected by HIV-1 protease inhibitors, which deter aspartic
proteases. The authors suggest that the interaction of protease
inhibitor with cathepsins are responsible for the effect.
Cathepsins are involved in the degradation of insulin, glucagon,
and insulin-like growth factors and binding proteins. The
authors also hypothesize that aspartic protease inhibitors might
be useful as a treatment for people without HIV who experience
wasting. In reply, Martinez asserts that insulin may be a
substrate of HIV-1 protease and that the substrate could be
shared by several enzymes. He contends that it is possible that
the inhibitor of one of the enzymes could also inhibit the other
enzymes. Martinez also advises against the use of the drugs for
wasting, since they are also associated with abnormal fat
deposits, hyperlipidemia, and insulin resistance.
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As I told you, I just came back from the "HIV Speakers Forum" Conference. About this subject there was not much, the speaker (Kathleen Mulligan, PhD, from UCSF) basically had no answers. Something very interesting was, that all this metabolic abnormalities were seen in some patients before the era of PI's, actually, 3tc(Epivir) maybe implicated in all of this.
The worst PI, as far as metabolic abnormalities is concerned, is Norvir.
Hope you are doing well.
JLL |
