Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antiretroviral drugs are associated with a variety of adverse effects on the central and peripheral nervous systems. The frequency and severity of neuropsychiatric adverse events is highly variable, with differences between the antiretroviral classes and amongst the individual drugs in each class. In the developing world, where the nucleoside reverse transcriptase inhibitor (NRTI) stavudine remains a commonly prescribed antiretroviral, peripheral neuropathy is an important complication of treatment. Importantly, this clinical entity is often difficult to distinguish from human immunodeficiency virus (HIV)-induced peripheral neuropathy. Several clinical trials have addressed the efficacy of various agents in the treatment of NRTI-induced neurotoxicity. NRTI-induced neurotoxicity is caused by inhibition of mitochondrial DNA polymerase. This mechanism is also responsible for the mitochondrial myopathy and lactic acidosis that occur with zidovudine. NRTIs, particularly zidovudine and abacavir, may also cause central nervous system (CNS) manifestations, including mania and psychosis. The non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is perhaps the antiretroviral most commonly associated with CNS toxicity, causing insomnia, irritability and vivid dreams. Recent studies have suggested that the risk of developing these adverse effects is increased in patients with various cytochrome P450 2B6 alleles. Protease inhibitors cause perioral paraesthesias and may indirectly increase the relative risk of stroke by promoting atherogenesis. HIV integrase inhibitors, C-C chemokine receptor type 5 (CCR5) inhibitors and fusion inhibitors rarely cause neuropsychiatric manifestations.
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PMID:Neurological and psychiatric adverse effects of antiretroviral drugs. 2436 68

Dolutegravir (DTG), a next-generation integrase strand transfer inhibitor (INSTI), was recently approved for use in the treatment of human immunodeficiency virus infection. In treatment-naive trial participants, DTG given at 50 mg once daily without pharmacologic boosting combined with a standard nucleoside backbone was shown to be noninferior or superior to first-line regimens containing efavirenz, darunavir/ritonavir, or raltegravir regardless of pretreatment viral load. This drug also exhibited efficacy in antiretroviral therapy-experienced participants and has proven to retain activity when dosed twice daily in some participants harboring resistance to the other INSTIs, raltegravir and elvitegravir. DTG has few drug interactions and is taken without regard to meals. It causes benign elevations in serum creatinine based on its inhibition of tubular creatinine secretion without affecting the glomerular filtration rate. Overall, DTG is well tolerated, with headache and insomnia being the most frequently reported adverse events.
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PMID:Dolutegravir: a next-generation integrase inhibitor for treatment of HIV infection. 2472 81

Raltegravir, as the first HIV integrase inhibitor, has been used and prospectively monitored since 2010 in our HIV outpatient centre, where over 1,200 patients are monitored. The aim of our report is to perform an interim assessment of the background, the safety profile and the clinical-laboratory monitoring of all patients treated with a combination antiretroviral therapy (cART) including raltegravir, for at least 12 months. In all, 109 pretreated patients started a raltegravir-containing cART when aged 44.8 plus or minus 19.2 years, with a history of HIV infection lasting 13.4 plus or minus 9.7 years. All subjects were monitored for at least 12 months (mean 17.2 plus or minus 10.3 months). In the vast majority of cases (93 of 109: 85.3%), multiple (3-16) prior cART changes prompted raltegravir introduction in advanced-salvage lines: 72 of 109 (66.1%) patients had even developed a concurrent triple-class resistance to anti-HIV compounds. The most frequent companion antiretroviral agents were: darunavir/ritonavir (75 cases), maraviroc (47 subjects), and etravirine (38 cases). The most common underlying conditions were: AIDS (46 patients), liver cirrhosis (31 cases), AIDS-related or other malignancies (23 cases), and major cardio-cerebro-vascular events (18 cases). A chronic HCV and HBV hepatitis were of concern in 48 and 23 patients, respectively. The adjunct of raltegravir favourably affected all clinical-laboratory markers of HIV disease progression, and those of the broad spectrum of comorbidities, except for two patients who failed the raltegravir-containing cART due to insufficient adherence. Despite the already compromised clinical situation, a minority of subjects experienced mild-transient clinical-laboratory untoward events possibly attributable to raltegravir, such that no patients discontinued raltegravir during the observation period. Only three AIDS-defining conditions became apparent during raltegravir-based cART; chemotherapy and/or radiotherapy cycles were performed as scheduled in patients suffering from cancer; chronic hepatitis B and C progressed to liver cirrhosis and/or hepatocarcinoma in only 2 and 6 patients. Otherwise, treatment with pegylated interferon-ribavirin became feasible in 25 patients of 48 with chronic HCV. During raltegravir-containing cART, neither autoimmune disorders nor novel malignancies were diagnosed. Only mild-transient gastrointestinal disorders, fatigue, dizziness, insomnia and cutaneous rash were reported, although their relationship with the study drug was difficult to assess due to multiple comorbidities and polypharmacy. Abnormal liver function testings were observed in 57 patients (52.3%), all suffering from concurrent hepato-biliary disorders. Significant increases in serum lipids and/or lipase levels versus baseline values were never registered: serum lipid levels significantly improved after raltegravir introduction. Our experience with raltegravir underlines its excellent efficacy and safety profile, which exploits a novel mechanism of action, and displays no cross-resistance with any other antiretroviral. A progressively extended prescription in naive patients and early cART lines will allow the therapeutic potential of raltegravir to be exploited.
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PMID:Raltegravir use prospectively assessed in a major HIV outpatient clinic in Italy: sample population, virological-immunological activity, and tolerability profile. 2555 44

Neuropsychiatric adverse events (NPAEs) observed with the integrase strand transfer inhibitor (INSTI) dolutegravir (DTG) are usually mild to moderate. The most prevalent symptoms are insomnia and sleep disorders, but the spectrum also includes dizziness, anxiety, depression, headache, paraesthesia, muscle-skeletal pain, poor concentration, and slow thinking. In recent cohort studies involving >6400 patients in different countries, discontinuation rates due to NPAEs were observed in around 3.5% (range, 1.4-7.2%) of subjects treated with DTG. These rates have been higher than those seen in randomized clinical trials and were also higher than with other INSTIs such as elvitegravir or raltegravir. Elderly, female patients and those who initiate abacavir simultaneously appear to be more vulnerable in some cohorts. It remains unclear if NPAEs are driven by an increased DTG exposure. With heightened awareness of health-care providers and patients, reports of NPAEs will probably increase in the future.
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PMID:Neuropsychiatric Adverse Events with Dolutegravir and Other Integrase Strand Transfer Inhibitors 3089 13