[Evidence-based therapeutic drug monitoring for saquinavir]. / Niveau de preuve du suivi therapeutique pharmacologique du saquinavir.

The human immunodeficiency virus (HIV) protease inhibitor saquinavir displays a large inter-individual variability in its pharmacokinetic parameters, related to a low absorption rate and an important hepatic metabolism. Based on literature, is the saquinavir therapeutic drug monitoring relevant? In naïve HIV-infected patients, the probability of achieving an undetectable HIV viral load at W48 was significantly associated with a saquinavir plasma trough concentration >100 ng/mL. Two studies in HIV-infected pre-treated patients reported that the genotypic inhibitory quotient was a predictive factor of virologic response with a threshold value around 40 ng/mL/mutation. Concerning the exposure-toxicity relationship, the risk of occurrence of grade 3-4 abdominal pains was more frequently associated with high concentrations of saquinavir, but without threshold value determination. Several studies, one of which was randomized, have reported the interest of saquinavir therapeutic drug monitoring to optimize the virologic response. Therefore, the level of evidence of the interest of saquinavir therapeutic drug monitoring is "recommended".

Costa Rican PWAs seek treatment access - no success in Roche negotiations.

AIDS: Costa Rican AIDS activists seeking compassionate access to protease inhibitors reported recently that negotiations with both their government and Hoffmann-La Roche, the maker of the protease inhibitor saquinavir, have failed in part because of the drug's high cost. Currently, AZT is the only regularly available anti-HIV drug in the country, and it is prescribed only for pregnant women. A month's supply of saquinavir costs about $800, compared to an average salary of $250. In an attempt to combat this disparity, a coalition of 200 activists negotiating with the government to get antiretrovirals approved in the national health system also sought compassionate access from Hoffmann-La Roche for 50 patients. The company's director in Costa Rica, however, refused to provide the drug for free or at a significant discount, saying he did not have the power to make such a decision. Protease inhibitors are made cost-effective in other countries because they lower the cost of keeping patients in the hospital. The Costa Rican government, however, claims that saquinavir would cost up to four times more than the expense of hospitalization. The drug industry should share the responsibility for providing AIDS drugs to countries and to individuals who cannot afford them. This can be accomplished by distributing the drugs via international agencies, licensing countries to produce the drugs at affordable prices, or pricing AIDS medications so that they are affordable.^ieng

Why the old saquinavir (Invirase) may be bad for your health.

AIDS: AIDS activists argue that the original formulation of saquinavir may be damaging to people's health and urge those who are considering using saquinavir to wait until the new version of the drug is available. Saquinavir's manufacturer, Roche Laboratories, is being criticized for aggressively marketing an inferior drug. The old formulation achieves a bioavailability of about four percent; therefore, very little of the drug is actually absorbed in the body. At the time of Food and Drug Administration (FDA) approval, doctors and researchers were aware of this low potency and noted that the dosage was potentially harmful; however, saquinavir can work well when taken with other protease inhibitors. Some physicians prescribe combinations with high (unapproved) doses of saquinavir, blaming bureaucracy for the FDA approval of the low-dosage (1,800 mg/day).^ieng

HIV-1 protease inhibitors. A review for clinicians.

OBJECTIVE: The clinical care of people infected with human immunodeficiency virus (HIV) has been substantially affected by the introduction of HIV-specific protease inhibitors (PIs). The 4 PIs available are saquinavir mesylate, ritonavir, indinavir sulfate, and nelfinavir mesylate. Comparison studies have not been reported; therefore, an assessment of the available data to aid clinicians and patients in choosing appropriate treatment will be presented. DATA SOURCES: A systematic review of peer-reviewed publications, abstracts from national and international conferences, and product registration information through September 1996. STUDY SELECTION AND DATA EXTRACTION: Criteria used to select studies include their relevance to PIs, having been published in the English language, and pertinence for clinicians. Data quality and validity included the venue of the publication and relevance to clinical care. DATA SYNTHESIS: Oral adminstration of ritonavir, indinavir, or nelfinavir generates sustainable drug serum levels to effectively inhibit the protease enzyme; however, saquinavir may not generate sustained levels necessary to inhibit the protease enzyme. Patients treated with ritonavir, indinavir, or nelfinavir experience similar reductions in viral load and increases in CD4+ lymphocytes; smaller effects occur among those treated with saquinavir. Two randomized placebo-controlled studies conducted among patients with severe immune system suppression and substantial zidovudine treatment experience demonstrated reduced HIV disease progression and reduced mortality with PI treatment. Genotypic resistance to PIs occurs; the clinical relevance of resistance is unclear. The costs of these agents including required monitoring impose new and substantial costs. CONCLUSIONS: The PIs have emerged as critical drugs for people with HIV infection. Optimal use involves combination with reverse transcriptase inhibitors. Resistance develops to each agent, and cross-resistance is likely. These agents must be used at full doses with attention to ensuring patient compliance. The expense of these agents may be offset by forestalling disease progression and death and returning people to productive life. Selecting the initial PI must be individualized, and factors to consider include proven activity, possible toxicities, dosing regimens, drug interactions, and costs.