indinavir-sulfate and AIDS-Dementia-Complex

The authors describe a patient with known human immunodeficiency virus (HIV)-1 infection who presented with two generalized seizures and was found to have extensive white matter disease and a left/bilateral temporo-occipital focal slowing on electroencephalography (EEG). There were no magnetic resonance imaging (MRI) or cerebrospinal fluid (CSF) indications for opportunistic infection. Plasma viremia was controlled, whereas viral replication was uncontrolled in CSF. CSF-specific genotype-guided adaptation of the antiretroviral therapy in order to optimize central nervous system (CNS) penetration resulted in clinical improvement and normalization of MRI and EEG. Our case report illustrates the importance of individualized antiretroviral therapy in HIV infected patients with neurological complications.

Topics: Adenine; Adult; AIDS Dementia Complex; Alkynes; Anti-HIV Agents; Anticonvulsants; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Benzoxazines; Cerebrospinal Fluid; Cyclopropanes; Didanosine; HIV-1; Humans; Indinavir; Lamivudine; Male; Nelfinavir; Nevirapine; Oligopeptides; Organophosphonates; Pyridines; Ritonavir; Seizures; Stavudine; Tenofovir; Viral Load; Virus Replication; Zidovudine

The ability of highly active antiretroviral therapy (HAART) to prevent the onset of HIV-associated dementia and to prevent or reduce the neuropathological features of HIV encephalitis (HIVE) remains unclear. Using a severe combined immunodeficient (SCID) mouse model of HIVE, we determined the effects of regular HAART treatment on HIVE. Before studying HAART in infected SCID mice, nonmanipulated SCID mice were treated with a single injection of the HAART cocktail (consisting of zidovudine, lamivudine, and indinavir) to determine optimum dosage and sampling time and to measure antiretroviral levels in the brain. After these preliminary studies, SCID mice that were inoculated with either HIV-infected or uninfected human monocytes were given intraperitoneal (IP) injections of HAART three times daily over a 1- and 2-week period. All three drugs were detected in the brain using a novel drug extraction technique and a modified high-performance liquid chromatography method. HAART significantly decreased the amount of astrogliosis and viral load in treated mice compared with mice that received vehicle injections. These studies offer insight into the ability of HAART to treat HIV infection of the brain.

Topics: AIDS Dementia Complex; Animals; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Brain; Disease Models, Animal; Drug Therapy, Combination; HIV Protease Inhibitors; Humans; Indinavir; Lamivudine; Male; Mice; Mice, SCID; Monocytes; Viral Load; Zidovudine

We report a 63-year-old male with HIV encephalopathy, whose initial symptom was acutely progressing dementia. He tested positive for HIV antibody, and HIV-RNA count was 2.8 x 10(5) copy/ml. All opportunistic infections that could cause dementia were ruled out. Dementia remarkably improved after the combination antiretroviral therapy of three types of drugs, two being nucleoside analog reverse transcriptase inhibitors and one being a protease inhibitor. The combination therapy could be very effective for the treatment of HIV dementia.

Topics: AIDS Dementia Complex; Anti-HIV Agents; Drug Therapy, Combination; HIV Protease Inhibitors; Humans; Indinavir; Lamivudine; Male; Middle Aged; Treatment Outcome; Zidovudine

A 60-year-old male had tested in 1986, at age 46, positive for human immunodeficiency virus (HIV). In mid-1996 he was started on a protease inhibitor regimen, which included indinavir, lamivudine and stavudine, and remained on this therapy until his death. In April 1999 he was hospitalized after a fainting episode. Although examination focusing on cardiac disease did not disclose any remarkable findings, he died suddenly one week after being discharged from hospital. At autopsy the kidneys were enlarged, with a total weight of 500 g, patchy pale gray and pinkish. Microscopy showed leukocytic cell casts in many of the tubules and collecting ducts. In many of these casts there were clefts left by crystals. In the interstitium, both in the cortex and the medulla, there was focal inflammation and fibrosis. Death was attributed to sudden cardiac dysfunction, probably ventricular fibrillation as a consequence of severe nephropathy with electrolyte disturbances. It is likely that kidney damage developed secondary to the indinavir treatment as indinavir can cause not only nephrolithiasis but also crystal-induced acute renal failure.

Topics: Acute Kidney Injury; AIDS Dementia Complex; Antiretroviral Therapy, Highly Active; Crystallization; Death, Sudden, Cardiac; Diagnosis, Differential; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Lamivudine; Male; Middle Aged; Solubility; Stavudine; Syncope; Ventricular Fibrillation; Water-Electrolyte Imbalance

Topics: AIDS Dementia Complex; Anti-HIV Agents; Brain; Female; Follow-Up Studies; HIV-1; Humans; Indinavir; Lamivudine; Neopterin; RNA, Viral; Stavudine; Viral Load; Virus Replication; Zidovudine

A human immunodeficiency virus type 1 (HIV)-seropositive, antiretroviral-naive patient presented with significant cognitive dysfunction. Neuropsychologic, neuroradiologic, immunologic, and virologic studies confirmed HIV-associated dementia (HAD). After 12 weeks of highly active antiretroviral therapy (HAART) with ibuprofen, dramatic improvements were demonstrated in neurologic function and were sustained for > 1 year. HIV-1 RNA in cerebrospinal fluid (CSF) decreased from 10(5) to 10(4) copies/mL after 4 weeks. After 20 weeks of therapy, plasma viremia decreased from 10(6) copies/mL to undetectable (< 96 copies/mL). Assays of neurotoxins (tumor necrosis factor-alpha, quinolinic acid, and nitric oxide) in plasma and CSF were considerably elevated at presentation and significantly decreased after therapy. Baseline plasma and CSF demonstrated neurotoxic activities in vitro, which also reduced markedly. These data, taken together, support the notion that HAD is a reversible metabolic encephalopathy fueled by viral replication. HAART used with nonsteroidal antiinflammatory agents leads to the suppression of inflammatory neurotoxins and can markedly improve neurologic function in HAD.

Topics: Adult; AIDS Dementia Complex; Anti-HIV Agents; Atrophy; Brain; Female; Humans; Ibuprofen; Indinavir; Lamivudine; Magnetic Resonance Imaging; Neurons; Neurotoxins; Nitric Oxide; Quinolinic Acid; Toxicity Tests; Tumor Necrosis Factor-alpha; Zidovudine