Differential effects of tipranavir plus ritonavir on atorvastatin or rosuvastatin pharmacokinetics in healthy volunteers.

To identify pharmacokinetic (PK) drug-drug interactions between tipranavir-ritonavir (TPV/r) and rosuvastatin and atorvastatin, we conducted two prospective, open-label, single-arm, two-period studies. The geometric mean (GM) ratio was 1.37 (90% confidence interval [CI], 1.15 to 1.62) for the area under the concentration-time curve (AUC) for rosuvastatin and 2.23 (90% CI, 1.83 to 2.72) for the maximum concentration of drug in serum (Cmax) for rosuvastatin with TPV/r at steady state versus alone. The GM ratio was 9.36 (90% CI, 8.02 to 10.94) for the AUC of atorvastatin and 8.61 (90% CI, 7.25 to 10.21) for the Cmax of atorvastatin with TPV/r at steady state versus alone. Tipranavir PK parameters were not affected by single-dose rosuvastatin or atorvastatin. Mild gastrointestinal intolerance, headache, and mild reversible liver enzyme elevations (grade 1 and 2) were the most commonly reported adverse drug reactions. Based on these interactions, we recommend low initial doses of rosuvastatin (5 mg) and atorvastatin (10 mg), with careful clinical monitoring of rosuvastatin- or atorvastatin-related adverse events when combined with TPV/r.

Use of ultrasonography-assisted liposuction for the treatment of human immunodeficiency virus-associated enlargement of the dorsocervical fat pad.

Enlargement of the dorsocervical fat pad (i.e., "buffalo hump") is one manifestation of the lipodystrophy syndrome associated with human immunodeficiency virus. We report our experience with the use of ultrasonography-assisted liposuction in a cohort of 10 patients with this complication.

Nevirapine-induced hepatitis: a case series and review of the literature.

Nevirapine, a nonnucleoside reverse transcriptase inhibitor used as part of combination antiretroviral therapy, can cause mild elevations in transaminase levels. Severe elevations in transaminase levels related to the use of nevirapine developed in 4 patients. Data on these patients were extracted via chart review, and a review of the literature was also completed. Nevirapine-induced hepatitis occurred shortly after drug initiation in patients with and without preexisting liver disease. Significant elevations in liver enzyme levels occurred but resolved promptly in most with discontinuation of the nevirapine. Close monitoring of liver enzyme levels in the early period after starting nevirapine is essential.

Pharmacokinetics and safety of amprenavir and ritonavir following multiple-dose, co-administration to healthy volunteers.

OBJECTIVE: To evaluate the safety and pharmacokinetic interaction between amprenavir (APV) and ritonavir (RTV). METHODS: Three open-label, randomized, two-sequence, multiple-dose studies having the same design (7 days of APV or RTV alone followed by 7 days of both drugs together) used 450 or 900 mg APV with 100 or 300 mg RTV every 12 h with pharmacokinetic assessments on days 7 and 14. Safety was monitored as clinical adverse events (AEs) and laboratory abnormalities. RESULTS: Relative to APV alone, RTV co-administration resulted in a 3.3- to 4-fold and 10.84 to 14.25-fold increase in the geometric least-square (GLS) mean area under the plasma concentration--time curve (AUC(tau,ss)) and minimum concentration (C(min,ss)), respectively. APV 900 mg with RTV 100 mg resulted in a 2.09-fold and 6.85-fold increase in the GLS mean AUC(tau,ss) and C(min,ss), respectively. On day 14, the geometric mean (95% confidence interval) for 450 mg APV AUC(tau,ss) (micro x h/mL) was 23.49 (19.32--28.57) with 300 mg RTV and 35.42 (30.46--44.42) with 100 microg RTV, and for the 900 mg APV with 100 mg RTV 47.11 (39.47--61.24). The 450 mg APV C(min,ss) (microg/ml) were 1.32 (1.05--1.67) and 2.01 (1.70--2.61), and 2.47 (2.08--3.32) for 900 mg APV. The most common AEs were mild and included diarrhea, nausea/vomiting, oral parasthesias, and rash. The triglyceride and cholesterol increased significantly from RTV exposure. CONCLUSION: Adding RTV to APV resulted in clinically and statistically significant increases in APV AUC and C(min) with variable effects on maximum concentration. The two RTV doses had similar effects on APV but AEs were more frequent with 300 mg RTV.

HAART improves prognosis in HIV-associated progressive multifocal leukoencephalopathy.

Introduction of highly active antiretroviral therapy (HAART) has been associated with many changes in the complications of human immunodeficiency virus (HIV) infection. A cohort of 25 HIV patients with progressive multifocal leukoencephalopathy (PML) treated with HAART experienced a median survival of >46 weeks. This is an improvement in prognosis compared with recent historic experience and correlated with HIV RNA viral load reductions. We conclude that current HIV therapy is important in improving the outlook of PML in the setting of HIV.

Pulmonary zygomycosis after allogeneic bone marrow transplantation.

The Zygomycetes are uncommon human pathogens. They cause illness in some patients who are immunosuppressed and can present as any of several syndromes, including rhinocerebral, pulmonary, gastrointestinal, or cutaneous disease, or as disseminated infection. Pulmonary zygomycosis can occur in any of several patterns and can mimic more common pneumonic processes. This mimicry, as well as the rarity of the disease, may delay diagnosis. We present a case of pulmonary zygomycosis that occurred in a patient who was a bone marrow transplant recipient. The case illustrates several of the common features of the disease in this patient group.

Acute uveitis associated with rifabutin use in patients with human immunodeficiency virus infection.

PURPOSE: We studied patients with a new anterior uveitis syndrome associated with rifabutin use. METHODS: Nine patients with the acquired immunodeficiency syndrome (AIDS) who developed acute anterior uveitis were identified retrospectively from institutional ophthalmology, infectious disease, and AIDS primary care practices. Five patients initially had hypopyon; in three patients hypopyon was bilateral and recurrent. The medical history, initial signs and symptoms, diagnostic examination, clinical course, and response to therapy were ascertained by a review of the medical records. RESULTS: All nine patients were being treated with rifabutin for treatment of, or prophylaxis against, Mycobacterium avium complex. In no patient was another untreated cause of uveitis found. In each patient the uveitis resolved rapidly without sequelae with treatment with topical corticosteroids alone. In eight patients uveitis resolved completely while treatment or prophylaxis for M. avium complex was maintained. CONCLUSIONS: We studied a new hypopyon uveitis syndrome in patients with AIDS who are being treated with rifabutin. The interaction of multiple drugs may contribute to this uveitis syndrome. This uveitis is remarkable because it is fulminant yet responds rapidly to topical corticosteroids. Characterization of this syndrome is important because hypopyon in the immunocompromised patient generally mandates intensive, and sometimes invasive, ophthalmic and systemic examination and therapy. Additional study is required to determine whether immune status, underlying infection, or drug-related factors contribute to the development of this uveitis syndrome. Although this syndrome remains a diagnosis of exclusion, ophthalmologists must be aware of it, so that intervention is guided appropriately.

Eastern equine encephalitis presenting as focal neuroradiographic abnormalities: case report and review.

We describe a well-documented case of Eastern equine encephalitis (EEE) in a patient who presented with fever and altered mental status and who had focal cranial lesions that were evident on both computed tomography (CT) and magnetic resonance imaging. Only 15 CT scans performed for patients with EEE have been described previously; findings on most were normal or revealed diffuse cerebral edema. It is not widely appreciated that EEE can manifest as discrete lesions on CT. We review the radiographic experience with EEE and interpret it in light of certain clinical and pathological features of the disease.