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)

A study of Triangle Pharmaceuticals' non-nucleoside reverse transcriptase inhibitor, Coactinon, found that the drug significantly suppressed viral replication when used with d4T and 3TC. The manufacturer reported mild side effects, including nausea, headache, dizziness, diarrhea, and rash.
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PMID:Triangle Pharma Coactinon combo may suppress HIV. 1136 23

HIV-infected patients are at increased risk of developing adverse drug reactions such as a maculopapular rash due to antiretroviral drugs. For example, exanthema induced by non-nucleoside reverse transcriptase inhibitors leads to drug discontinuation in many patients. We present a patient with a severe pulmonary hypersensitivity reaction due to efavirenz.
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PMID:Pulmonary hypersensitivity reaction induced by efavirenz. 1137 7

A substantial body of evidence provides support (but not definitive proof of efficacy) for the use of antiretroviral agents as postexposure prophylaxis for occupational exposures to HIV in the healthcare workplace. Despite the lack of definitive evidence of the efficacy of these agents in this setting, over the past decade this intervention has become the standard of care for healthcare workers who sustain occupational exposures to HIV. Administration of these agents--even for a relatively short 28-day postexposure course--is often fraught with difficulty. All of the agents currently used for postexposure prophylaxis regimens have substantial adverse effects, and significant adverse effects occur in more than two-thirds of individuals electing prophylaxis. This manuscript reiterates current US Federal Government guidelines for the administration of postexposure prophylaxis, specifically noting that zidovudine plus lamivudine (with or without a protease inhibitor) remains the recommended regimen. The paper summarises the significant toxicities associated with nucleoside reverse transcriptase inhibitors (primarily nausea, vomiting, diarrhoea and bone marrow suppression), non-nucleoside reverse transcriptase inhibitors (rash, fever, gastrointestinal symptoms and hepatitis, including hepatic decompensation necessitating liver transplantation) and protease inhibitors (nausea, vomiting, diarrhoea, abdominal pain, hyperglycaemia, hyperlipidaemia, headache and anorexia). As a class, the antiretroviral agents have an extraordinary number of drug interactions. The non-nucleoside reverse transcriptase inhibitors and the protease inhibitors are metabolised through the cytochrome P450 pathway, and the effects of concomitant administration of protease inhibitors with other agents in the same class are discussed, as well as the effects of concomitant administration of protease inhibitors with non-nucleoside agents. The potential for numerous and medically risky drug interactions emphasises the importance of planning antiretroviral prophylaxis in consultation with practitioners or clinical pharmacists who are skilled in the use of these agents and knowledgeable about the potential for significant drug interactions that could either reduce the benefit of prophylaxis or increase the potential for toxicity. Another common problem encountered by individuals managing postexposure prophylaxis programmes relates to the administration of chemoprophylaxis to a pregnant healthcare worker who has sustained an occupational exposure to HIV. We address what is known about the potential for toxicity and emphasise the recently published warning concerning the deaths of pregnant women and their offspring from lactic acidosis while receiving regimens containing stavudine and didanosine.
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PMID:Tolerability of postexposure antiretroviral prophylaxis for occupational exposures to HIV. 1148 Apr 91

An adult wild-caught female tamarin (Saguinus mystax) housed in a biomedical research facility was found moribund and extremely dehydrated, with severe diarrhea. She initially responded to supportive therapy but died 3 days later. Necropsy findings included hyperemia of the colonic mucosa, mesenteric lymphadenopathy, acanthocephalid parasites (Prosthenorchis elegans) embedded in the mucosa of the terminal ileum and cecum, and free filarid nematodes (Dipetalonema sp.) in the abdominal cavity. Campylobacter sp. was recovered from the colon. With the exception of changes associated with the parasites, significant histologic changes were limited to the colon. Changes consistent with acute enteric viral infection were found against a background of chronic inflammation. Enterocytes were variably hypertrophied, degenerate, and attenuated. Numerous epithelial syncytial cells were present, and some affected cells (uni- as well as multinucleated) contained intranuclear inclusions. Lymphoid follicles were mildly depleted and contained rare syncytia. Measles (Morbillivirus) infection was confirmed by using immunohistochemistry, reverse transcriptase polymerase chain reaction, and Southern blot analysis. In contrast to the cutaneous rash, respiratory involvement, and low mortality characteristic of Old World monkeys with measles, severe diarrhea with high mortality occurs in New World monkeys with this disease. In addition, our case differs from previous reports of measles in New World monkeys in that syncytial cell formation apparently was limited to the colon of our animal.
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PMID:Colitis in a female tamarin (Saguinus mystax). 1148 41

Over 1.4 million of the worlds' children are infected with HIV-1, mostly acquired in the perinatal period. Antiviral therapeutic options for children with HIV-1 infection have lagged behind those for infected adults. However, we now know that prevention of perinatal HIV-1 transmission to children is possible and that combination therapy for the management of infected children is efficacious. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are developing a more prominent role in combination therapy regimens, particularly as alternatives to protease inhibitors. They also have a role in preventing perinatal transmission, where it has been shown that only 2 doses of the NNRTI nevirapine can significantly reduce mother-to-child transmission of HIV-1. This has major therapeutic implications, particularly in areas where combination therapy is not readily available. Palatable paediatric formulations of NNRTIs are available or are being developed. Whilst pharmacokinetic data regarding the use of antiretrovirals in children remain scarce, published clinical trials have demonstrated the efficacy of NNRTIs when used as part of combination regimens in the management of HIV-1 infected children. The toxicity profile of NNRTIs is relatively favourable; however, severe skin rash, hepatotoxicity and central nervous system adverse effects with various NNRTIs can lead to treatment cessation. The development of class resistance with single step mutations in the reverse transcriptase gene remains a major therapeutic problem with this class of antiretrovirals. Novel NNRTIs under development are of interest either because of improved pharmacodynamics, reduced toxicity profiles or because of action against NNRTI-mutation containing resistant virus. There are no data available yet on the use of these drugs in the paediatric population.
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PMID:The role of non-nucleoside reverse transcriptase inhibitors in children with HIV-1 infection. 1168 99

Nevirapine (Viramune, Boehringer Ingelheim) is a non-nucleoside reverse transcriptase (RT) inhibitor (NNRTI) effective in the treatment of HIV-1 infected antiretroviral-naive and -experienced patients. Some recent studies have suggested that nevirapine-based regimens may have an efficacy similar to protease inhibitor (PI)-based regimens, at least in naive patients with CD4+ > 200 microl, while it lacks the drawbacks inherent in PI-containing regimens, such as lipodystrophy and metabolic alterations. Switching from a PI-containing regimen to a nevirapine-containing regimen seems to retain the virological response to therapy and it may also limit or reverse the development of some metabolic disorders induced by PIs. Nevirapine is also effective in preventing mother-to-child transmission of HIV-1 disease and in the treatment of HIV-1 infected children. Nevirapine is well-tolerated, rash being the most common severe adverse effect observed. Hepatotoxicity may also appear with nevirapine, mainly in patients with chronic hepatitis C and/or altered liver function tests. This side effect may occasionally be life-threatening but it can be safely managed in most patients.
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PMID:The role of nevirapine in the treatment of HIV-1 disease. 1182 35

Data on the efficacy and tolerability of antiretrovirals in children are limited as, in contrast to adult studies, large paediatric cohort studies are lacking. Thus, data pertaining to adults are often extrapolated to children despite the acknowledgement that children are not little adults. This review summarises information gathered from existing reports and focuses on the tolerabilities of antiretrovirals in children infected with HIV-1. The efficacy of antiretrovirals is not included in the scope of the discussion. Taste of antiretrovirals should be an important factor when considering the tolerability of antiretrovirals in children. However, antiretroviral options are often limited in young children as only some of the antiretrovirals are available as paediatric formulations. All antiretrovirals have been associated with toxicities in children, but in general, they are relatively well tolerated. The gastrointestinal system including hepatic system is most prone to being affected by these drugs. Skin rashes and hypersensitivity reactions are also associated with antiretroviral use, particularly with the non-nucleoside reverse transcriptase inhibitors. Mitochondrial toxicities that lead to impairment of liver function, pancreatic function and lactic acidosis are associated with most of the nucleoside analogues. Haematological toxicity is often a dose limiting adverse effect especially of the nucleoside analogues, in particular zidovudine. The protease inhibitors are associated with gastrointestinal intolerance (diarrhoea) and metabolic derangements that can lead to hypercholesterolaemia and hypertriglyceridaemia, which in turn and can lead to changes in body habitus. The renal system is also affected by several drugs, the most important of which is indinavir, which has been associated with renal stones and damage to the renal tubules. Fortunately, with lower incidence of major toxicity and with the range of drugs now available for paediatric use, toxicities are usually not a barrier to effect antiretroviral therapy in children.
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PMID:Tolerabilities of antiretrovirals in paediatric HIV infection. 1240 30

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

A 3-month-old girl who developed severe measles encephalitis after neonatal measles is reported. Her mother had measles when she was ten days old and she was admitted to our hospital with low grade fever, Koplik spot, and mild exanthema seventeen days after birth, and she recovered in 7 days without any complication. At three months of age, she was readmitted because of intractable seizures. The levels of IgM and IgG antibodies against measles in the cerebrospinal fluid were elevated. The measles virus genome, amplifying the region encoding the nucleocapsid protein, was detected from the brain specimen by reverse transcriptase-polymerase chain reaction. Magnetic resonance imaging showed a focal destructive lesion and diffuse cerebral atrophy. The electroencephalogram did not show periodic synchronous discharges. Although the neonatal measles was believed to be relatively mild in severity, the possible development of measles encephalitis should be carefully monitored in an infant who had neonatal measles.
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PMID:Severe infantile measles encephalitis occurred three months after neonatal measles. 1253 72

There have been recent increases in the number of female participants in HIV clinical trials and the number of studies addressing the influence of sex on HIV infection. The findings of some studies indicate a potential sex differences in the frequency and severity of adverse reactions to antiretroviral drugs. This article reviews the available data on the incidence and characteristics of potential sex differences in adverse reactions to certain nucleoside and nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Adverse effects for which a sex difference has been reported include lactic acidosis, rash, elevation in liver enzymes, dyslipidemia, and insulin resistance. The reasons for these sex differences in adverse drug events are unclear but may include differences between men and women in body mass index and fat composition, hormonal effects on drug metabolism, or the effects of genomic constitutional differences on the levels of various enzymes. These differences warrant further study.
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PMID:Sex differences in adverse reactions to antiretroviral drugs. 1271 43


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