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)

A predominantly sensory peripheral neuropathy is common with human immunodeficiency virus (HIV) infection, but the cause is unknown. Formalin-fixed dorsal root ganglia (DRG), obtained at postmortem from patients with neuropathy and HIV infection and from control subjects, were examined for the presence of HIV DNA by using polymerase chain reaction (PCR)-amplified in situ hybridization. Viral message RNA was detected using reverse transcription in situ PCR with gag-specific primers. HIV DNA and RNA sequences were detected in many satellite cells, mononuclear cells, and occasional neurons in 5 of 5 patients with HIV and neuropathy. HIV DNA was detected only in rare interstitial and satellite cells from 3 of 4 patients with HIV infection without neuropathy and was not detected in 6 patients without HIV infection. HIV infection of DRG neurons and supporting cells may contribute to the HIV-associated sensory neuropathy.
 ...
PMID:Human immunodeficiency virus infection of dorsal root ganglion neurons detected by polymerase chain reaction in situ hybridization. 930 60

Peripheral neuropathy is associated with HIV infection. The prevalence and types of peripheral neuropathy encountered in a randomly-selected HIV infected African population at different stages of disease were investigated. HIV positive individuals were categorized into 1 of 3 groups: asymptomatic, symptomatic and AIDS. HIV negative individuals formed the control group. Nerve conduction data were obtained using standard electrophysiological procedures and CD4+ levels were measured. The type of neuropathy was determined from the history, clinical presentation and electrophysiological abnormalities. The prevalence of peripheral neuropathy was 44%: subclinical neuropathy (SCN) accounted for 56%, acute inflammatory demyelinating polyneuropathy (AIDP) for 15% and distal symmetrical polyneuropathy (DSPN) for 22% of cases of neuropathy. SCN was found in all categories whereas AIDP predominated in the symptomatic category and DSPN in individuals with AIDS. The pattern and frequency of neuropathies seen in our African population is similar to that reported from other continents.
 ...
PMID:Peripheral neuropathy in individuals with HIV infection in Zimbabwe. 932 72

Viral infections are observed with increasing frequency in HIV patients and one of the commonest viruses is cytomegalovirus. Clinical features of cytomegalovirus (CMV) encephalitis are non specific and radiology is rarely helpful. Polymerase chain reaction in cerebrospinal fluid has been shown to be useful for diagnosis of CMV encephalitis. CMV lesions in the nervous system are subdivided into six groups: Nodular encephalitis, myeloradiculitis, isolated inclusion-bearing cells, focal parenchymal necrosis, ventriculo-encephalitis and peripheral neuropathy. Clinicopathological aspects are only subdivided into four groups: Encephalitis, myelitis, myeloradiculitis and polyneuropathy. Diagnosis of cytomegalovirus encephalitis should be considered in patients with a CD4 count less than 100 cells/mm3. Recent developments in diagnostic techniques allow early recognition and more aggressive therapeutic approaches.
 ...
PMID:[Nervous system lesions due to cytomegalovirus in AIDS]. 938 5

We conducted a three-arm, randomized, phase II study to evaluate the combination of zidovudine (600 mg/day) and zalcitabine (2.25 mg/day) alone or with one of two interferon-alpha2a doses (1 mIU or 6 mIU daily). Primary study endpoints included toxicity and changes from baseline for plasma HIV-1 RNA, CD4 cells, and quantitative microculture at weeks 8 and 24. Sixty-three patients with HIV infection and <400 CD4 cells/mm3 were enrolled; four patients discontinued therapy within 2 weeks. Adverse event rates were 37%, 32%, and 60%, respectively, for the nucleoside, 1-mIU interferon, and 6-mIU interferon combination groups. Increasing doses of interferon resulted in significantly greater hematologic toxicity (p = 0.03) and peripheral neuropathy (p = 0.02). Plasma HIV-1 RNA reductions were noted across all treatment groups at week 8 (p < 0.001) but only for the nucleoside and 1-mIU interferon combination groups at week 24 (p < 0.001). Mean reductions in HIV-1 RNA at week 8 were 0.94, 1.29, and 1.40 log10, respectively, for the nucleoside, 1-mIU interferon, and 6-mIU interferon combination groups (p = 0.05); no differences were noted at week 24. No differences in CD4 cell counts were seen. The addition of interferon-alpha2a to zidovudine and zalcitabine resulted in transient enhanced decreases in viral load and increased toxicity.
 ...
PMID:Safety and antiviral activity of combination therapy with zidovudine, zalcitabine, and two doses of interferon-alpha2a in patients with HIV. AIDS Clinical Trials Group Study 197. 940 71

It is a review of the most common neuropathies observed in HIV infected people. The authors present the basic clinical and neuropathological features of the: distal peripheral neuropathy, chronic inflammatory, demyelinating polyneuropathy, progressive ascending polyradiculopathy-myelopathy, mononeuropathy multiplex, and autonomic neuropathy. Mentioned are neuropathies observed as adverse reactions to drugs used for people with AIDS. HIV related myopathy is included in the review.
 ...
PMID:[Neurologic syndromes in patients with HIV infections. I. Diseases of peripheral nerves and skeletal muscles associated with HIV infection]. 944 46

Lower extremity symptoms are caused by lesions at any level of the neuraxis, from cortex to muscle. HIV affects virtually every level of the nervous system, either directly or indirectly. The presence of pathology at multiple levels and by multiple processes further complicates the bedside diagnosis of a patient with AIDS and neurologic symptoms. Many neuropathies and other conditions that affect the lower extremities can be identified with careful history and physical examination, confirmed with limited testing, and can be treated successfully. Distal symmetric polyneuropathy is the most common lower extremity disorder, but it must be distinguished from similar-appearing neuropathies caused by medications, B12 deficiency, or vasculitis. Diffuse infiltrative lymphocytosis syndrome also causes a painful peripheral neuropathy that must be distinguished from distal symmetric polyneuropathy. Inflammatory demyelinating polyneuropathies are characterized by muscle weakness. They occur in early, asymptomatic HIV infection and respond to plasmapheresis or steroids. Mononeuropathies in patients with CD4 counts more than 200 often resolve on their own. Multiple mononeuropathies, which occur in patients with CD4 counts less than 50, are often associated with cytomegalovirus infection and may follow a rapidly progressive course unless treated promptly and aggressively. Progressive polyradiculopathy occurs late in the course of AIDS, is often caused by cytomegalovirus, is rapidly progressive, and generally is fatal unless recognized and treated promptly. Muscle weakness, myalgia, and fatigue are common in HIV and have multiple causes. Lower extremity spasticity may be caused by treatable etiologies such as spinal cord abscess, tumor, disc compression, B12 deficiency, or ischemia. Gait disturbances are common but nonspecific and may be caused by treatable neurologic disorders at any level of the neuraxis.
 ...
PMID:Neurologic problems of the lower extremity associated with HIV and AIDS. 957 54

The appearance in the clinic of two to three new antiretroviral agents yearly since 1995 has permitted unprecedented advances in HIV treatment. This remarkable pace of drug development is a testimony to an extraordinary international effort involving scientists, clinicians, governments, community activists and industry dedicated to the rapid and safe development of novel therapies. New drugs present the opportunity to improve HIV therapy. They also create an enormous challenge to the clinician, who must constantly assimilate data on new drugs and incorporate this information into practical management strategies. Combination therapy has proven the most effective approach to treat HIV disease. The profound and sustained viral suppression achievable with combinations such as indinavir (IDV), lamivudine (3TC) and zidovudine (ZDV) have resulted in a dramatic shift in HIV treatment paradigms over the last year. The full potential of combination therapy with available drugs has yet to be realized as only a limited number of the possible combinations incorporating new drugs have been fully tested. Even drugs available for many years may have untapped potential. Didanosine (ddI) and stavudine (d4T), once thought to be contraindicated in combination because of their overlapping peripheral neuropathy toxicity, have proven well tolerated and effective. Combination therapy can increase antiviral suppression, prevent drug resistance, optimize drug exposure and simplify dosing, but it can also result in pharmacologic antagonism, subtherapeutic drug concentrations and unexpected toxicities. Clinical studies have confirmed in vitro studies showing pharmacologic antagonism for the combination of ZDV and d4T. Combining protease inhibitors with each other or with non-nucleoside reverse transcriptase inhibitors is complicated by effects both classes of drugs have on drug metabolism and clearance. These observations underline the importance of carefully conducted clinical studies to characterize safety, pharmacokinetics and efficacy of combination therapies. In this review, we will first summarize the clinical profile of new drugs which either became commercially available last year [nelfinavir, nevirapine, delavirdine (DLV)] or are in the late stages of clinical development (DMP-266, abacavir and 141W94). Later we will summarize new data on nucleoside, protease inhibitor and non-nucleoside reverse transcriptase combination regimens. Finally, we will briefly mention new drugs in early stages of development.
 ...
PMID:New antiretrovirals and new combinations. 963 99

Painful sensory neuropathy (PSN) is the most common neurological disorder associated with HIV infection and affects up to 30% of HIV-positive individuals. PSN may develop as a consequence of HIV infection or from the toxic effect of the antiretrovirals. Although several tools have been developed to screen for PSN, their validity and reliability has yet to be established among HIV-positive patients. The Subjective Peripheral Neuropathy Screen (SPNS) is a brief self-report tool that is currently being administered in the AIDS Clinical Trials Group. The objective of this study was to establish the psychometric properties of the SPNS screening tool for the correct identification of PSN in HIV-positive individuals. Specifically the goals were to determine the reliability, the validity, and the diagnostic efficiency of the SPNS in the detection of PSN. Data were abstracted on subjects enrolled in an ongoing natural history cohort. The SPNS was administered to a convenience sample of 39 HIV-positive individuals with PSN and 44 HIV-positive controls. Results showed the SPNS to be internally consistent (Cronbach's alpha = .86). SPNS score differences assessed by t-test were significantly different for individual symptoms of parasthesias, numbness, and pain of the lower extremities, and for severity measures (the Clinical Severity Grade, and the Average Severity Score) between the HIV-positive groups (p < .05). Using Spearman's rank, significant correlations were demonstrated between the neurological exam and the Clinical Severity Grade and the Average Severity Score, the neurological exam and vibratory quantitative sensory testing (QST) only, and the severity measures and vibratory QST only. Sensitivity and specificity analysis demonstrated that numbness of the lower extremities was the symptom with the highest efficiency for correctly classifying PSN. Thus, internal consistency, construct validity, and criterion related validity were confirmed with the SPNS for the correct classification of PSN in HIV-positive individuals.
 ...
PMID:The reliability and validity of the subjective peripheral neuropathy screen. 965 64

Certain aspects of the clinical syndrome of dementia, cerebral atrophy, predominantly sensory neuropathy, and vacuolar myelopathy in AIDS resemble those seen in vitamin B12 deficiency. Pathologically, there are similarities not only in the changes in the spinal cord, but also in the brain and peripheral nerves. The pathogenesis of vacuolar myelopathy may be secondary to a combination of immune mediated myelin and oligodendrocyte injury, and simultaneous impairment of repair mechanisms due to a deficiency of S-adenosylmethionine (SAM). Products derived from macrophages may interfere directly with the methyl transfer cycle through the generation of reactive oxygen intermediates and reactions involving nitric oxide and peroxynitrite which may limit the supply of methionine for conversion to SAM, both by direct interaction as well as through inhibition of methionine synthase. Macrophage activation with secretion of cytokines and other biologically reactive substances within the nervous system is sustained in the late stages of HIV infection by the general effects of immune depletion, including loss of T cells (with concomitant reduction of macrophage regulatory molecules) and recurrent opportunistic infections, and may be further augmented by the local presence of the virus itself (or its surface glycoprotein gp120). This would account for the common, but not exclusive, occurrence of vacuolar myelopathy in AIDS. The ability of the virus and its products to stimulate macrophage and microglial activation may also explain the association between severity of vacuolar myelopathy and the presence of HIV encephalitis. A similar mechanism may underlie the pathogenesis of dementia, cerebral atrophy, and peripheral neuropathy. Local factors or differential susceptibility between the central and peripheral nervous system may determine whether myelinotoxic or neurotoxic processes predominate; the prominence of myelin involvement in the spinal cord, and axonal involvement peripherally may reflect both ends of this range, with the brain manifesting a more equal balance of both processes.
 ...
PMID:Hypothesis on the pathogenesis of vacuolar myelopathy, dementia, and peripheral neuropathy in AIDS. 1020 45

This investigation examined the effects of HIV-1 infection on speeded complex cognitive processing in a group of HIV-negative (n = 666), HIV-positive symptomatic (n = 156), and HIV-positive asymptomatic (n = 623) participants while controlling for the effects of slowed motor functioning, peripheral neuropathy, and several other putative confounds. Stroop Interference and reaction-time tasks served as anchor procedures to assess cognitive processing. The present findings suggest that HIV-1 infection is capable of compromising CNS-mediated cognitive processes (speeded processing) infringing upon their efficacy in the symptomatic stages of the disease while sparing individuals in the asymptomatic stage. The detrimental effects observed on information-processing mechanisms associated with HIV infection persisted despite the use of procedures to control for peripheral nerve integrity and other potential confounds.
 ...
PMID:Slowed information processing in HIV-1 disease. The Multicenter AIDS Cohort Study (MACS). 967 20


<< Previous 1 2 3 4 5 6 7 8 9 10