Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(1) Lactic acidosis is a serious, often fatal adverse reaction to nucleoside HIV reverse transcriptase inhibitors. (2) The presenting symptoms are non specific, and include gastrointestinal upset, fatigue, fever, and breathlessness. They appear gradually after several weeks or months of antiretroviral treatment. (3) Moderate hyperlactataemia, with few if any symptoms, is common in patients taking nucleoside inhibitors, and is not predictive of severe lactic acidosis. (4) Cases of lactic acidosis were reported in newborns whose mothers were given nucleoside inhibitors to reduce the risk of mother to child transmission of HIV. (5) In practice, hyperlactataemia should be suspected in patients taking antiretroviral drugs who present with unexplained symptoms, and especially breathlessness. Elevated lactataemia (especially above 5 mmol/l) requires rapid withdrawal of antiretroviral treatment.
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PMID:Lactic acidosis and anti-retroviral drugs. 1220 Dec 94

Stavudine administered once daily is a nucleoside analogue reverse transcriptase inhibitor. The efficacy (reduction in viral load and increase in CD4+ lymphocyte counts from baseline) of stavudine once daily-containing triple therapy was similar to that of stavudine immediate release (IR)-containing triple therapy in the treatment of antiretroviral-naive patients with HIV infection in two 48-week, randomised, double-blind trials. In the largest trial (n = 783), 80% of patients receiving stavudine 75 or 100mg once daily in combination with lamivudine 150mg twice daily and efavirenz 600mg once daily, and 75% of patients receiving stavudine IR 30 or 40mg twice daily-containing combination therapy, had HIV RNA levels reduced to below the limit of quantification at 48 weeks (<400 copies/ml; intent-to-treat analysis). These findings are supported by those from the smaller trial in 150 patients. Stavudine once daily triple therapy was well tolerated, with the incidence of adverse events being similar to that with stavudine IR. Grades 2-4 treatment related adverse events occurring in > or =3% of patients in either group were dizziness, rash, abnormal dream, headache, insomnia, fatigue and peripheral neurological symptoms. Peripheral neurological symptoms occurred in 3% of patients receiving long-term treatment with stavudine once daily and 6% of patients receiving stavudine IR in a combined analysis.
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PMID:Stavudine once daily. 1246 9

The difference between adherence to non- nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI)-based regimens was investigated. Better adherence was found in NNRTI-treated patients, especially when efavirenz was included in the regimen, compared with single PI-treated patients and in those with CD4 cell counts less than 200 x 10(6)/l. By contrast, younger age, self-report of active drug use, fatigue or vomiting negatively affected adherence. Self-reported sexual dysfunction was significantly associated with non-adherence only in PI-treated individuals.
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PMID:Adherence to highly active antiretroviral therapy is better in patients receiving non-nucleoside reverse transcriptase inhibitor-containing regimens than in those receiving protease inhibitor-containing regimens. 1270 Apr 67

The triple combination tablet containing lamivudine (150 mg), zidovudine (300 mg) and abacavir (300 mg, as abacavir sulfate) is a new formulation of three nucleoside analogue reverse transcriptase inhibitors. Two studies in treatment-naive patients (one double-blind, one nonblind) have reported that lamivudine/zidovudine (dual combination tablet) plus abacavir showed efficacy similar to that of lamivudine/zidovudine plus indinavir. In both studies, similar numbers of patients in each treatment group had plasma HIV RNA levels </=400 copies/mL at week 48 (51% vs 51% and 64% vs 50%). In treatment-experienced patients with baseline plasma HIV RNA levels <50 copies/mL, switching to lamivudine/zidovudine/abacavir (triple combination tablet) was as effective as remaining on highly active antiretroviral treatment (mainly protease inhibitor [PI]-based). Virological failure, the primary endpoint, defined as two consecutive plasma HIV RNA values >400 copies/mL, was reported in 22% of patients in both treatment groups at week 48. Treatment-naive patients receiving lamivudine/zidovudine/abacavir combination therapy experienced several adverse events, including nausea, malaise/fatigue and vomiting.
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PMID:Lamivudine/zidovudine/abacavir: triple combination tablet. 1274 41

Following 2 weeks acclimation to the running wheel in the home cages, an i.p. injection of a synthetic double-stranded RNA, polyriboinosinic:polyribocytidylic acid (poly I:C, 3 mg/kg), was performed to produce the immunologically induced fatigue in rats. The daily amounts of spontaneous running wheel activity decreased to about 40-60% of the preinjection level until day 9 with normal circadian rhythm, then gradually returned to the baseline level by day 14. Rats given a heat exposure (36 degrees C for 1 h) for the consecutive 3 days showed an increase in activity except for the first day. In the open field test, the total moving distance and the number of rearing of the poly I:C-injected rats decreased on day 1, but they were not different from the saline-injected group on day 7, suggesting that the poly I:C-induced fatigue on day 7 was not due to the peripheral problems such as muscle/joint pain, but involved the CNS. Quantitative analysis of mRNA levels using a real-time capillary reverse transcriptase-polymerase chain reaction (RT-PCR) method revealed that interferon-alpha (IFN-alpha) mRNA contents in the cortex, hippocampus, hypothalamic medial preoptic, paraventricular, and ventromedial nuclei were higher in the poly I:C group than those in the saline and heat-exposed groups on day 7, although the amount of interleukin-1 beta mRNA showed no differences. Serum adrenocorticotropic hormone and catecholamine levels were not significantly different between groups. The present results indicate that the prolonged fatigue induced by poly I:C, which is evaluated by the spontaneous running wheel activity, can be used as an animal model for the immunologically induced fatigue associated with viral infection, and suggest that brain IFN-alpha may play a role in this model.
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PMID:Prolonged effects of polyriboinosinic:polyribocytidylic acid on spontaneous running wheel activity and brain interferon-alpha mRNA in rats: a model for immunologically induced fatigue. 1289 23

Fibromyalgia and chronic hepatitis C infection share many clinical features including prominent somatic complaints such as musculoskeletal pain and fatigue. There is a growing body of evidence supporting a link between cytokines and somatic complaints. This review discusses alterations of cytokines in fibromyalgia, including increased serum levels of interleukin (IL)-2, IL-2 receptor, IL-8, IL-1 receptor antagonist; increased IL-1 and IL-6 produced by stimulated peripheral blood mononuclear cell in patients with FM for longer than 2 years; increased gp130, which is a neutrophil cytokine transducing protein; increased soluble IL-6 receptor and soluble IL-1 receptor antagonist only in patients with fibromyalgia who are depressed; and IL-1 beta, IL-6, and TNF-a by reverse transcriptase-polymerase chain reaction in skin biopsies of some patients with fibromyalgia. In addition, this review describes the mechanism by which alterations in cytokines in fibromyalgia and chronic hepatitis C infection can produce hyperalgesia and other neurally mediated symptoms through the presence of cytokine receptors on glial cells and opiate receptors on lymphocytes and the influence of cytokines on the hypothalamus-pituitary-adrenal axis such as IL-1, IL-6, and TNF-a activating and IL-2 and IFN-a down-regulating the HPA axis, respectively. The association between chronic hepatitis C infection and fibromyalgia is discussed, including a description of key cytokine changes in chronic hepatitis C infection. Future studies are encouraged to further characterize these immunologic alterations with potential pathophysiologic and therapeutic implications.
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PMID:Fibromyalgia, hepatitis C infection, and the cytokine connection. 1294 86

Enfuvirtide is a novel antiretroviral that blocks HIV-1 cell fusion and viral entry. This Phase II, controlled, open-label, randomized, multicentre dose-ranging trial explored the safety, antiviral activity and pharmacokinetics of enfuvirtide, administered by subcutaneous (s.c.) injection, in 71 HIV-1-infected, protease inhibitor-experienced, non-nucleoside reverse transcriptase inhibitor (NNRTI)-naive adults for 48 weeks. Study participants were randomized to receive enfuvirtide at a deliverable dose of 45, 67.5 or 90 mg twice daily; the 45 mg twice daily dose required 2 injections/day, while the higher doses required 4 injections/day. A background oral antiretroviral (ARV) regimen of abacavir (300 mg twice daily), amprenavir (1200 mg twice daily), ritonavir (200 mg twice daily) and efavirenz (600 mg once daily) was provided with enfuvirtide. A control group received the background ARV regimen alone. All potential participants underwent an HIV genotype at screen to ensure a homogenous population and to exclude patients with evidence of genotypic resistance to NNRTIs. Overall, the tolerability of the combination of abacavir, amprenavir, ritonavir, efavirenz and enfuvirtide was generally comparable to control through 48 weeks. No enfuvirtide dose-dependent adverse events (AEs) were observed across treatment groups. Injection site reactions (ISRs) occurred at least once in 68.5% of the enfuvirtide-treated population, and most ISRs were mild to moderate in severity, with no apparent dose relationship. Excluding ISRs, the most common treatment-emergent AEs were nausea, diarrhoea, dizziness and fatigue; with no clinically significant differences in the incidence of AEs observed between the control and enfuvirtide groups. Each treatment group benefited from ARV therapy, with a trend of increasing antiviral and immunological activity associated with increasing enfuvirtide dose. At 48 weeks, the median HIV-1 RNA change from baseline for the ITT population was -2.24 log10 copies/ml for the combined enfuvirtide groups compared with -1.87 log10 copies/ml for the control group. In addition, 54.9% of patients in the enfuvirtide group achieved HIV-1 RNA < or = 400 copies/ml versus 36.8% of patients in the control group. These results indicate that enfuvirtide has a favourable safety profile and is a promising new antiviral agent for HIV-infected patients who have been on previously failing ARV regimens.
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PMID:A controlled Phase II trial assessing three doses of enfuvirtide (T-20) in combination with abacavir, amprenavir, ritonavir and efavirenz in non-nucleoside reverse transcriptase inhibitor-naive HIV-infected adults. 1451 96

(1) The current first-line treatment for HIV infection is a combination of at least two nucleoside (or nucleotide) inhibitors of HIV reverse transcriptase, and one non nucleoside inhibitor or at least one HIV protease inhibitor. (2) Emtricitabine is the eighth nucleoside/nucleotide inhibitor to be marketed in France. It has a similar chemical structure to lamivudine. (3) Evaluation of emtricitabine use in adults contains data from four comparative trials, two in treatment-naive patients and two in patients who were already receiving a virologically effective treatment. Emtricitabine combination therapy was no more effective than lamivudine combination therapy on either viral load or the CD4+ lymphocyte count. (4) Only non comparative trials are available in children. (5) In clinical trials, the adverse effects of emtricitabine were similar to those of lamivudine, including headache, pain, fatigue, fever, abdominal pain, nausea, vomiting, and diarrhea. (6) Viral strains resistant to emtricitabine are also resistant to lamivudine, and vice versa. (7) Emtricitabine, like other nucleoside inhibitors (lamivudine, didanosine, tenofovir), can be taken once a day by mouth. (8) In practice, emtricitabine is indistinguishable from lamivudine and does not offer any advance for patients living with HIV/AIDS.
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PMID:Emtricitabine: new preparation. An antiretroviral very similar to lamivudine. 1587 41

Efavirenz is a non-nucleoside reverse transcriptase inhibitor that is used in the treatment of the HIV-1 variant. Adverse central nervous system side effects such as headache, dizziness, insomnia, fatigue, severe depression and suicidal ideation are noted in patients receiving efavirenz. In this study, the effects of efavirenz on changes in behaviour and on some pro- and anti-inflammatory cytokines in Wistar rats were studied to assess whether efavirenz causes depressive symptoms via the cytokine network and, if so, whether antidepressant therapy known to attenuate the effects of pro-inflammatory cytokines could prevent these changes. The efavirenz-treated rats displayed spatial memory deficits in the Morris water maze. These rats also appeared to be more susceptible to stress than the other groups as seen by an increase in the latency to emerge in the home cage emergence test following the stress of the Morris water maze. The concentrations of pro-inflammatory cytokines interleukin-1 beta and tumour necrosis factor-alpha were also significantly higher in the efavirenz group. The antidepressant paroxetine reduced the susceptibility to stress and prevented such an increase in pro-inflammatory cytokines. It is concluded that efavirenz induces depressive-like behaviour in the rat and a susceptibility to stress, which are accompanied by an increase in pro-inflammatory cytokines. These symptoms are partially alleviated by chronic treatment with paroxetine.
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PMID:Efavirenz induces depressive-like behaviour, increased stress response and changes in the immune response in rats. 1616 8

Patients with HIV (human immunodeficiency virus) experience multiple signs and symptoms that accompany the progress of HIV-related diseases. HIV-related symptoms are associated with side effects and HAART (highly active antiretroviral therapy) complications. The purposes of this study were to estimate the frequency and intensity of HIV-related signs and symptoms in patients with HIV infection and to explore relationships between HIV-related symptoms and the HAART regimen. Data on a total of 172 HIV-positive patients enrolled in an HIV case management program were analyzed for this study. Participants experienced an average of 9.73+/-7.27 symptoms, with fatigue, dry mouth and weakness the most frequently reported. Average mean symptom intensity among participants was 13.24+/-11.48. Insomnia, depression and disorientation were the most severe symptoms. No differences were recorded between HIV-related symptoms and disease progression. Fatigue intensity showed significant differences between NRTI (nucleoside reverse transcriptase inhibitors), +NNRTI (non-nucleoside reverse transcriptase inhibitors) and NRTI+PI (protease inhibitors) based regimens (p=.03). In addition, cluster symptoms of confusion/distress among participants without HAART had a significantly higher mean intensity than those with HAART (t=2.0, df=1, p=.04). Our study indicated that symptom management for fatigue and early detection of psychological distress is needed to improve quality of life for people living with HIV/AIDS.
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PMID:[HIV-related symptoms in patients with HIV infection enrolled in an HIV case management program in Taiwan]. 1922 99


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