UMLS:C0019693 - FACTA Search

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

Query: UMLS:C0019693 (HIV)
170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The alkenyldiarylmethanes (ADAMs) are currently being investigated as non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) of potential value in the treatment of HIV infection and AIDS. During the course of these studies, a number of ADAM analogues have been identified that protect HIV-infected cells from the cytopathic effects of the virus by an unknown, HIV-1 RT-independent mechanism. Since the phosphodiesterase 4 family is required for HIV infection, the effect of various ADAMs on the activity of PDE4B2 was investigated in an effort to determine if the ADAMs could possibly be targeting phosphodiesterases. Six compounds representative of the ADAM class were tested for inhibition of cAMP hydrolysis by PDE4B2 enzymatic activity. Four ADAMs were found to be weak inhibitors of PDE4B2 and two of them were inactive. The experimental results are consistent with an antiviral mechanism that does not include inhibition of PDE4 isoforms.
...
PMID:Investigation of the alkenyldiarylmethane non-nucleoside reverse transcriptase inhibitors as potential cAMP phosphodiesterase-4B2 inhibitors. 1822 88

Pulmonary arterial hypertension is an idiopathic process or can be associated with another circumstances (connective tissue diseases, congenital heart disease, portal hypertension, exposure to appetite suppressants or another drugs or infectious agents such as HIV). Most patients are diagnosed as the result of an evaluation of symptoms, whereas others are diagnosed incidentally or during screening of asymptomatic populations at risk. We reviews systematic screening for the approach to diagnosing pulmonary arterial hypertension. A diagnostic algorithm can guide the evaluation but it can be modified according to specific clinical circumstances. The number of therapeutic options has increased.in the last years. We reviews the use of calcium-channel blockers, prostacyclin (and analogues), endothelin-receptor antagonists, and phosphodiesterase-5 inhibitors, and the use of combination therapy, and provides specific recommendations about the actual treatment.
...
PMID:[Diagnosis and treatment of pulmonary hypertension]. 1827 69

Pulmonary arterial hypertension (PAH) is a progressive albeit rare long-term complication of HIV infection, which has gained importance following the improved survival of HIV-infected patients with the use of HAART. The clinical and pathological findings in PAH associated with HIV infection (HIV-PAH) share many features with the idiopathic form of the disease. HIV-PAH is associated with a particularly poor prognosis and decreased survival compared with HIV-infected patients without this complication, and patients with HIV-PAH tend to die from the effects of PAH rather than as a result of their HIV infection. Prompt diagnosis and effective treatment of PAH in HIV-infected patients is therefore essential. There are currently only limited data regarding the efficacy of PAH therapies in HIV-PAH. Treatment with epoprostenol has been reported to provide benefit in some cases, but is associated with a range of problems linked to the need for continuous intravenous infusion. The dual endothelin receptor antagonist bosentan has proved to be effective in HIV-PAH without affecting the control of HIV infection, and has the benefit of oral administration. Other PAH therapies including prostacyclin analogs, phosphodiesterase type 5 inhibitors and selective endothelin receptor antagonists have yet to be trialed in this setting. Taking into account currently available data and clinical experience, a treatment algorithm for HIV-PAH based on that defined in treatment guidelines for other forms of PAH is suggested.
...
PMID:HIV-related pulmonary arterial hypertension: clinical presentation and management. 1884 23

Pulmonary arterial hypertension (PAH) is a rare but life-threatening complication of human immunodeficiency virus (HIV) infection. PAH can complicate the course of HIV infection regardless of the route of HIV transmission, the stage of HIV infection, and the degree of immunosuppression. The clinical presentation and underlying pathology of PAH associated with HIV infection (PAH-HIV) are similar to those encountered in other forms of PAH, although there are data suggesting a greater inflammatory component in the HIV-related form. Given the good long-term prognosis of HIV patients with highly active antiretroviral treatments and the severity of PAH in HIV-infected patients, screening for pulmonary hypertension according to a precise algorithm is warranted in HIV-infected patients presenting with dyspnea not explained by another cause. In all cases, right heart catheterization must be performed to establish the diagnosis of PAH. Beneficial effects of antiretroviral treatments on PAH-HIV still remain to be proven. Patients with PAH-HIV appear to respond well to treatment with the prostacyclin epoprostenol, although continuous intravenous infusion is associated with a range of potential complications. Treatment with the oral dual endothelin receptor antagonist bosentan has been shown to benefit patients with PAH-HIV without adversely affecting the control of HIV infection, and resulted in functional and hemodynamic normalization in approximately 20% of patients. Other PAH therapies, including prostacyclin analogs, type 5 phosphodiesterase inhibitors, and single endothelin receptor antagonists, have yet to be evaluated in PAH-HIV.
...
PMID:Pulmonary arterial hypertension and HIV infection. 1963 83

Because of the improvement in survival rates of human immunodeficiency virus (HIV)-infected patients after the introduction of combined antiretroviral therapy, pulmonary arterial hypertension (PAH) has become an important cause of morbidity. As the awareness of PAH has increased, it is more likely that this condition will be diagnosed more frequently and earlier in the course of the disease and HIV infection. The etiopathogenesis is not clear; no evidence of direct infection of the pulmonary vascular tree has been found and the current evidence seems to favor a role of dysregulated cytokine response to HIV infection. The pathological changes of plexiform arteriopathy are indistinguishable from the pathological changes of idiopathic pulmonary arterial hypertension (IPAH). Dyspnea is the most common presenting symptom. Echocardiography, though always not accurate in diagnosing PAH and estimating its severity, remains the main screening tool. Right heart catheterization is the gold standard investigation for diagnosis. New therapies like prostanoids, endothelin receptor antagonists, and phosphodiesterase inhibitors have improved the outcome of patients with HIV-associated PAH. However, the overall prognosis of HIV-infected patients who develop PAH still remains poor.
...
PMID:Pulmonary arterial hypertension in human immunodeficiency virus infection. 1982 Feb 75

This study examined relationships between use of the phosphodiesterase type-5 (PDE-5) inhibitors (erectile dysfunction medications) sildenafil (Viagra), Pfizer, New York, NY), tadalafil (Cialis), Eli Lily, Indianapolis, IN), and/or vardenafil (Levitra), Bayer, Berlin, Germany), substance use, perceptions of risk, and sexual behavior in men who have sex with men (MSM). MSM (N = 342) attending a gay pride festival completed a brief survey assessing sexual behavior, risk perceptions, and substance use, including the use and the source of PDE-5 inhibitors. More than a quarter of the sample (26.3%, n = 89) reported having ever used a PDE-5 inhibitor. Those reporting use of PDE-5 inhibitors had higher rates of sexual risk behaviors and differed in their assessment of the risk of HIV transmission for unprotected anal sex. Users who received PDE-5 inhibitors from their doctors did not report sexual behaviors that differed significantly from those who received PDE-5 inhibitors from nonphysician sources. In a sequential logistic regression analysis, recent PDE-5 inhibitor use was associated with unprotected anal sex after accounting for the influence of age, education, ethnic identity, and substance use. Many MSM users of erectile dysfunction drugs report behaviors that may place their and others' health at risk. Interventions to reduce risk among MSM PDE-5 inhibitor users should be explored.
...
PMID:Sexual risk behaviors among men who have sex with men using erectile dysfunction medications. 1990 71

Pulmonary hypertension is a heterogeneous hemodynamic and pathophysiological state that is observed in a number of clinical conditions, which have been divided into six diagnostic groups. Although the increase in pulmonary pressure observed in these clinical groups may be similar, underlying disease mechanisms, diagnostic methods, and prognostic and therapeutic consequences are completely different. Pulmonary arterial hypertension is associated with several rare conditions that have comparable clinical and hemodynamic characteristics and exhibit virtually identical anatomical and pathological alterations in the lung microcirculation. These conditions include idiopathic and familial forms of the disease and disease forms associated with connective tissue disease, congenital heart defects involving systemic-to-pulmonary arterial shunts, portal hypertension, and HIV infection. It has been shown that treatment with specific drugs (e.g. prostanoids, endothelin-receptor antagonists and phosphodiesterase type-5 inhibitors) is effective in these patients and that these drugs can also be administered in various combinations. An evidence-based treatment algorithm has been developed for these patients. In patients with pulmonary hypertension due to left heart disease or lung disease, treatment focuses on the underlying condition and there is no convincing evidence that agents approved for pulmonary arterial hypertension are effective. For patients with chronic thromboembolic pulmonary hypertension, the treatment of choice is pulmonary endarterectomy. However, drugs intended specifically for the treatment of pulmonary arterial hypertension may be considered in inoperable cases or after suboptimal surgery.
...
PMID:Current therapeutic approaches to pulmonary arterial hypertension. 2051 28

In recent years, the pathogenic role of human immunodeficiency virus (HIV) and the clinical manifestations of HIV-associated pulmonary arterial hypertension (HIV-PAH), which currently represents one of the most severe complications of HIV infection, have received more attention HIV-PAH occurs at all stages of the disease, and does not seem to be related to the degree of immune deficiency. Many of the symptoms in HIV-PAH result from right ventricular dysfunction: the first clinical manifestation is effort intolerance and exertional dyspnoea that will progress to the point of breathlessness at rest. Echocardiography is an extremely useful tool for the diagnosis of HIV-PAH, and Doppler echocardiography can be used to estimate systolic pulmonary artery pressure. Assessment of haemodynamic measures by catheterization remains, however, the best test for evaluating the response to therapy. Cardiac catheterization is mandatory to definitively diagnose the disease and exclude any underlying cardiac shunt as the aetiology. Recently, effective therapies for pulmonary arterial hypertension (PAH) have been available, including prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors, allowing amelioration of symptoms and a better prognosis. However, HIV-PAH remains a progressive disease for which treatment is often unsatisfactory and there is no cure. As new efficient antiretroviral treatment is introduced, clinicians should expect to encounter an increasing number of cases of PAH in HIV-infected patients in the future.
...
PMID:Pulmonary hypertension and human immunodeficiency virus infection: epidemiology, pathogenesis, and clinical approach. 2054 62

Etravirine (formerly TMC125) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against wild-type and NNRTI-resistant strains of HIV-1. Etravirine has been approved in several countries for use as part of highly active antiretroviral therapy in treatment-experienced patients. In vivo, etravirine is a substrate for, and weak inducer of, the hepatic cytochrome P450 (CYP) isoenzyme 3A4 and a substrate and weak inhibitor of CYP2C9 and CYP2C19. Etravirine is also a weak inhibitor of P-glycoprotein. An extensive drug-drug interaction programme in HIV-negative subjects has been carried out to assess the potential for pharmacokinetic interactions between etravirine and a variety of non-antiretroviral drugs. Effects of atorvastatin, clarithromycin, methadone, omeprazole, oral contraceptives, paroxetine, ranitidine and sildenafil on the pharmacokinetic disposition of etravirine were of no clinical relevance. Likewise, etravirine had no clinically significant effect on the pharmacokinetics of fluconazole, methadone, oral contraceptives, paroxetine or voriconazole. No clinically relevant interactions are expected between etravirine and azithromycin or ribavirin, therefore, etravirine can be combined with these agents without dose adjustment. Fluconazole and voriconazole increased etravirine exposure 1.9- and 1.4-fold, respectively, in healthy subjects, however, no increase in the incidence of adverse effects was observed in patients receiving etravirine and fluconazole during clinical trials, therefore, etravirine can be combined with these antifungals although caution is advised. Digoxin plasma exposure was slightly increased when co-administered with etravirine. No dose adjustments of digoxin are needed when used in combination with etravirine, however, it is recommended that digoxin levels should be monitored. Caution should be exercised in combining rifabutin with etravirine in the presence of certain boosted HIV protease inhibitors due to the risk of decreased exposure to etravirine. Although adjustments to the dose of clarithromycin are unnecessary for the treatment of most infections, the use of an alternative macrolide (e.g. azithromycin) is recommended for the treatment of Mycobacterium avium complex infection since the overall activity of clarithromycin against this pathogen may be altered when co-administered with etravirine. Dosage adjustments based on clinical response are recommended for clopidogrel, HMG-CoA reductase inhibitors (e.g. atorvastatin) and for phosphodiesterase type-5 inhibitors (e.g. sildenafil) because changes in the exposure of these medications in the presence of co-administered etravirine may occur. When co-administered with etravirine, a dose reduction or alternative to diazepam is recommended. When combining etravirine with warfarin, the international normalized ratio (INR) should be monitored. Systemic dexamethasone should be co-administered with caution, or an alternative to dexamethasone be found as dexamethasone induces CYP3A4. Caution is also warranted when co-administering etravirine with some antiarrhythmics, calcineurin inhibitors (e.g. ciclosporin) and antidepressants (e.g. citalopram). Co-administration of etravirine with some antiepileptics (e.g. carbamazepine and phenytoin), rifampicin (rifampin), rifapentine or preparations containing St John's wort (Hypericum perforatum) is currently not recommended as these are potent inducers of CYP3A and/or CYP2C and may potentially decrease etravirine exposure. Antiepileptics that are less likely to interact based on their known pharmacological properties include gabapentin, lamotrigine, levetiracetam and pregabalin. Overall, pharmacokinetic and clinical data show etravirine to be well tolerated and generally safe when given in combination with non-antiretroviral agents, with minimal clinically significant drug interactions and no need for dosage adjustments of etravirine in any of the cases, or of the non-antiretroviral agent in the majority of cases studied.
...
PMID:Pharmacokinetic interactions between etravirine and non-antiretroviral drugs. 2114 66

HIV infection is associated with sexual dysfunction. Using validated instruments, we investigated the relationship between HIV/AIDS and sexual function in a contemporary cohort of men who have sex with men (MSM). An anonymous Internet-based survey was disseminated to MSM via organizations and social networking sites that cater to this population. Information on ethnodemographic variables, health status (including HIV status, disease stage, and other health conditions), and sexual behavior was collected. Men were categorized as HIV-negative, HIV-positive/AIDS-negative, or HIV-positive /AIDS-positive. A modified validated version of the International Index of Erectile Function (IIEF) for use in MSM and the Premature Ejaculation Diagnostic Tool (PEDT) were used to stratify risk of sexual dysfunction. The study cohort included 1361 men (236 of whom were HIV-positive) who provided complete data on HIV status, IIEF, and PEDT. There was a significant trend toward greater prevalence of erectile dysfunction (ED) in men with progressive HIV infection 40-59 years of age relative to age matched HIV-negative men (p=0.02). In a logistic regression model controlling for other variables, HIV infection without AIDS was not associated with greater odds of ED; however, HIV infection with AIDS was associated with greater odds of ED (p=0.006). In a separate logistic regression model, HIV infection with or without AIDS was not significantly associated with greater odds of premature ejaculation (p>0.05). Use of phosphodiesterase 5 (PDE5) inhibitor drugs was much more common in HIV-infected men. HIV infection is a risk factor for poorer sexual function primarily due to higher risk of erectile dysfunction in men with AIDS.
...
PMID:Sexual dysfunction, HIV, and AIDS in men who have sex with men. 2150 Oct 95

<< Previous 1 2 3 4 5 6 7 Next >>