The mechanisms responsible for the deterioration in glucose tolerance associated with protease inhibitorcontaining regimens in HIV infection are unclear. Insulin resistance has been implicated as a major factor, but the affected tissues have not been identified. Furthermore, ␤-cell function has not been evaluated in detail. The present study was therefore undertaken to assess the effects of protease inhibitor-containing regimens on hepatic, muscle, and adipose tissue insulin sensitivity as well as pancreatic ␤-cell function. We evaluated ␤-cell function in addition to glucose production, glucose disposal, and free fatty acid (FFA) turnover using the hyperglycemic clamp technique in combination with isotopic measurements in 13 HIV-infected patients before and after 12 weeks of treatment and in 14 normal healthy volunteers. ␤-Cell function and insulin sensitivity were also assessed by homeostasis model assessment (HOMA). Treatment increased fasting plasma glucose concentrations in all subjects (P < 0.001). Insulin sensitivity as assessed by HOMA and clamp experiments decreased by ϳ50% (P < 0.003). Postabsorptive glucose production was appropriately suppressed for the prevailing hyperinsulinemia, whereas glucose clearance was reduced (P < 0.001). ␤-Cell function decreased by ϳ50% (P ‫؍‬ 0.002), as assessed by HOMA, and firstphase insulin release decreased by ϳ25%, as assessed by clamp data (P ‫؍‬ 0.002). Plasma FFA turnover and clearance both increased significantly (P < 0.001). No differences at baseline or in responses after treatment were observed between drug naïve patients who were started on a nucleoside reverse transcriptase inhibitor (NRTI) plus a protease inhibitor and patients who had been on long-term NRTI treatment and had a protease inhibitor added. The present study indicates that protease inhibitor-containing regimens impair glucose tolerance in HIV-infected patients by two mechanisms: 1) inducement of peripheral insulin resistance in skeletal muscle and adipose tissue and 2) impairment of the ability of the ␤-cell to compensate. Diabetes 52: 918 -925, 2003 U se of protease inhibitors has remarkably improved long-term survival after HIV infection (1,2). However, up to 60% of HIV-infected patients treated with these agents develop either impaired glucose tolerance (IGT) or type 2 diabetes (3-6), and it now appears to be well established that regimens including protease inhibitors are associated with insulin resistance (2,5,7,8). Noor et al. (9,10) have shown that acute and 4-week protease inhibitor exposure of normal volunteers reduces glucose disposal during euglycemichyperinsulinemic clamp experiments. Moreover, in vitro studies have demonstrated that protease inhibitors reduce insulin-stimulated glucose uptake in adipocytes and skeletal muscle (11,12).Knowledge of the mechanisms responsible for deterioration in glucose tolerance during protease inhibitorcontaining regimens is still incomplete. It is unclear whether protease inhibitors adversely affect pancreatic ␤-cell function (4,8) and what effec...

Histoplasmosis is the most common endemic mycosis in individuals with AIDS, occurring in 2%-5% of this population. Infection is more likely to be disseminated than in immunocompetent individuals and generally presents insidiously with nonspecific symptoms. The gastrointestinal tract is involved in 70%-90% of cases of disseminated histoplasmosis, yet gastrointestinal histoplasmosis per se is infrequently encountered in patients with AIDS. The diagnosis of gastrointestinal histoplasmosis is often not suspected, particularly in areas of nonendemicity, and a delay in diagnosis may lead to increased morbidity and risk of death. Since antifungal therapy improves outcome for >80% of AIDS patients with histoplasmosis, it is essential that caregivers be aware of the varied presentations of gastrointestinal histoplasmosis in order to diagnose and to treat this potentially life-threatening infection effectively.

Use of ciprofloxacin as an alternative to vancomycin for treatment of methicillin-resistant Staphylococcus aureus infection has been paralleled by the emergence of resistant strains. This phenomenon has also been noticed in our hospital. To confirm our observation, methicillin and ciprofloxacin susceptibilities were tested by disk diffusion and broth microdilution techniques. We studied 83 methicillin-resistant Staphylococcus aureus isolates obtained from various sources over a 4-month period. Ciprofloxacin resistance (MIC, >2 ,Ig/ml) was detected in 69 isolates (83%). Prior use of ciprofloxacin was reported for 24 of 69 patients with ciprofloxacinresistant strains and 0 of 14 patients with ciprofloxacin-susceptible strains. The day of detection during the hospital stay and the location of the source patient were not significantly different between resistant and susceptible strains. Bacteriophage typing showed a higher occurrence of nontypeable strains among ciprofloxacin-resistant strains (54%). Review of our microbiology register showed a progressive increase in the rate of resistance to ciprofloxacin during the first year of use, with initial rates being about 10% and recent rates being higher than 80%. On the other hand, methicillin-susceptible S. aureus remained uniformly susceptible to ciprofloxacin (98.4%). We conclude that prior use of ciprofloxacin is an important factor for the selection of ciprofloxacin-resistant strains and that ciprofloxacin has limited usefulness against methicillin-resistant S. aureus.

AIDS wasting is associated with a GH resistant state that results in low levels of serum IGF-I, IGF-II and IGFBP-3, elevated levels of phosphorylated IGFBP-1, and a reduced ability to form the IGFBP-3 ternary complex.

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