indinavir-sulfate and Retroviridae-Infections

The use of anti-retroviral protease inhibitors in combination with nucleoside analog or non nucleoside reverse transcriptase inhibitors (HAART) has led to dramatic decreases in the mortality seen with HIV infected patients. In concert with these treatment regimens, especially with the inclusion of the anti-retroviral protease inhibitors (PI), a complex series of metabolic complications occurred. These included alterations of fat and carbohydrate metabolism. In some patients, one could observe either lipoatrophy (fat wasting) as well as lipohypertrophy (fat deposition) or both. The problem is that the lack of a case definition of the altered fat metabolism confuses diagnoses. In vitro, interference with fat cell differentiation has been demonstrated by PI. Further, in vitro studies demonstrate that indinavir, a PI currently used in HIV treatment, can interact with the insulin responsive glucose transporter (GLUT4). The activity of the GLUT4 is inhibited by indinavir and eventual insulin resistance has been shown (i.e. in vivo and in vitro). Also, controversy exists regarding insulin signaling in fat cells. Finally, the relationships between hyperlipidemia and/or lipolysis and altered carbohydrate metabolism (i.e. mild glucose intolerance, insulin resistance) suggest an association with cardiovascular risk in protease treated patients (Metabolic Syndrome X). In short, while multiple problems exist, no one mechanism can account for the changes observed.

Topics: Adipose Tissue; Antiretroviral Therapy, Highly Active; Endopeptidases; Glucose Transporter Type 4; Humans; Indinavir; Monosaccharide Transport Proteins; Muscle Proteins; Protease Inhibitors; Retroviridae; Retroviridae Infections

Clinical cohort studies suggest that as many as 60% of patients experience virologic failure of a first-line antiretroviral regimen. Second-line and rescue (or salvage) regimens have a poorer success record: Most studies presented to date show a short-term virologic response rate of only approximately 30% in treatment-experienced individuals. That rate will improve with better understanding of what causes initial virologic failure, continued development of new antiretroviral agents (including drugs with new mechanisms of action) and new treatment strategies (including dual-protease inhibitor regimens), and more widespread use of resistance testing. Further clinical research is needed to improve salvage options, and physicians should consider enrolling treatment-experienced patients in clinical trials.

Topics: Anti-HIV Agents; Carbamates; CD4 Lymphocyte Count; Dideoxynucleosides; Drug Therapy, Combination; Furans; HIV Protease Inhibitors; Humans; Indinavir; Lopinavir; Microbial Sensitivity Tests; Mutation; Nelfinavir; Practice Guidelines as Topic; Pyrimidinones; Retroviridae; Retroviridae Infections; Reverse Transcriptase Inhibitors; Sulfonamides; Time Factors; Treatment Failure; Viral Load

Interest has recently focused on anti-HIV prophylaxis in case of sexual exposure. A circular from the French Ministry of Health (DGS/DH n(o) 97/560, 12 August 1997) envisages such treatment in certain risk situations such as sexual aggression. The toxic risk of prescribing a tritherapy or a bitherapy, even for a short period of a few weeks must be considered.. A 20-year-old rape victim with an uneventful medical history was given a prophylactic regimen including zidovudine, laminovudine and indinavir. Three months later, she developed free-bilirubin jaundice with biological signs of hemolysis.. We draw attention to the risk of severe adverse effects of short-duration anti-HIV prophylaxis in apparently healthy subjects. The protocol must included careful patient information and rigorous surveillance.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-HIV Agents; Bilirubin; Female; HIV Infections; Humans; Indinavir; Jaundice; Rape; Retroviridae Infections; Zidovudine

Topics: HIV Protease Inhibitors; Humans; Hypersensitivity; Indinavir; Retroviridae Infections; Ritonavir; Saquinavir