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Biotech / Medical : Agouron Pharmaceuticals (AGPH) -- Ignore unavailable to you. Want to Upgrade?

To: Izzy who wrote (5594)	10/26/1998 10:24:00 AM
From: jake burns	Respond to of 6136

IMNR/Remune news out this morning, and it's very positive. biz.yahoo.com

To: Izzy who wrote (5594)	10/29/1998 9:55:00 AM
From: Oliver & Co	Read Replies (1) \| Respond to of 6136

"Maintenance Antiretroviral Therapies in HIV-Infected Subjects With Undetectable Plasma HIV RNA After Triple-Drug Therapy" New England Journal of Medicine (10/29/98) Vol. 339, No. 18, P. 1261; Havlir, Diane V.; Marschner, Ian C.; Hirsch, Martin S.; et al. Researchers for the AIDS Clinical Trials Group Study 343 Team report that triple-drug therapy with indinavir, lamivudine, and zidovudine better sustains the suppression of plasma HIV RNA in HIV-positive patients than maintenance therapy with indinavir alone or a combination of zidovudine and lamivudine. The researchers, led by Dr. Diane V. Havlir of the University of California at San Diego, investigated less intensive maintenance programs among patients who had CD4 cell counts of less than 200 per cubic millimeter following triple-drug therapy. The patients were divided into three groups: 106 continued triple-drug therapy, 103 received monotherapy with indinavir, and 107 subjects received zidovudine and lamivudine. Only 4 percent of patients maintaining triple-drug therapy lost viral suppression (defined as a plasma level of at least 200 copies of HIV RNA per millimeter on two consecutive measurements during therapy), with 23 percent of monotherapy subjects and 23 percent of dual-therapy patients showing loss of viral suppression. Those at higher risk for loss of viral suppression had greater increases in CD4 cell counts during induction therapy, higher viral loads at baseline, and slower rates of viral clearance. The authors also note that zidovudine-resistance mutations in HIV RNA at baseline were strongly predictive of viral suppression loss in patients receiving the dual therapy of zidovudine and lamivudine.

To: Izzy who wrote (5594)	10/29/1998 9:56:00 AM
From: Oliver & Co	Respond to of 6136

"A Randomized Trial of Three Maintenance Regimens Given After Three Months of Induction Therapy With Zidovudine, Lamivudine, and Indinavir in Previously Untreated HIV-1-Infected Patients" New England Journal of Medicine (10/29/98) Vol. 339, No. 18, P. 1269; Pialoux, Gilles; Raffi, Francois; Brun-Vezinet, Francoise; et al. Two-drug maintenance therapy following a three-month regimen of triple-drug therapy for HIV-positive individuals is less effective than continuation of the triple-drug therapy, according to French researchers. To determine whether problems related to compliance and tolerability could be reduced through the administration of a two-drug regimen rather than a three-drug regimen, researchers from the Trilege Study Team investigated maintenance programs on viral suppression in 378 patients. The patients, who were antiretroviral naive, received three months of induction treatment with lamivudine, zidovudine, and indinavir. Of the initial patients, 279 had plasma HIV-1 RNA levels fall below 500 copies per cubic millimeter after two months. These patients were then assigned to either continued triple-drug therapy or two-drug maintenance therapy with zidovudine and lamivudine or zidovudine and indinavir. The researchers observed that 31 percent of the patients receiving zidovudine plus lamivudine and 21 percent of those on zidovudine plus indinavir had virologic failure. Comparatively, 9 percent of patients who continued triple-drug therapy experienced virologic failure. The authors note that among patients who switched to dual-therapy, even those subjects with maximally suppressed HIV-1 RNA (defined as less than 50 copies per millimeter) had a higher failure rate. The scientists concluded that two-drug therapy is less effective in sustaining a reduced viral load than triple-drug therapy.

To: Izzy who wrote (5594)	10/29/1998 10:05:00 AM
From: Oliver & Co	Respond to of 6136

"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. ====================================================================== 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