Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Some AIDS Drugs Promote Neurological Damage

07.10.2004


One group of drugs that is effective in fighting HIV may, paradoxically, also be promoting the death of sensory nerves in the skin, according to a study presented October 5, 2004, at the 129th annual meeting of the American Neurological Association in Toronto.



A team of American and Australian researchers reported that the use of certain anti-HIV drugs, called dideoxynucleosides, is highly correlated with a condition called sensory neuropathy, in which patients experience constant pain, and abnormal sensations including numbness and sensitivity, in the feet and legs. In a separate presentation, presented on October 4, the same investigators showed that simple punch skin biopsies are an effective way of identifying sensory neuropathy, possibly even before symptoms appear.

Dideoxynucleosides, members of a class of drugs called ’nucleoside reverse transcriptase inhibitors’ are common component of highly active antiretroviral therapy (HAART), the so-called AIDS "cocktails" that prevent HIV from duplicating itself. The authors noted that these drugs are frequently included in the generic HAART combinations used in Africa and India. "Because the introduction of HAART has reduced the rates of HIV-associated dementia and opportunistic infections, sensory neuropathies have become the commonest neurological disorders associated with AIDS," said lead author Justin C. McArthur, MD, of Johns Hopkins University in Baltimore, Maryland.


The factors that lead to HIV-associated sensory neuropathy are not clear. Diabetes, intravenous drug use, or hepatitis C may contribute to heightened susceptibility, along with some of the same drugs that help protect against HIV.

In the present study, McArthur and his colleagues at Johns Hopkins and at the Alfred Hospital, Burnet Institute, and Monash University in Melbourne, Australia studied the relationship between the use of three dideoxynucleosides called ddC, ddI, and d4T and the occurrence of sensory neuropathy. The researchers combined data from two diverse study populations in Baltimore and Melbourne, with significant (and preplanned) differences in terms of racial demographics and history of IV drug use, male homosexual relations, and hepatitis C co-infection. "We found a strong association between previous or current use of ddC, ddI, or d4T and the presence of symptomatic sensory neuropathy," said McArthur.

In a separate study in the same subjects, led by medical student Siva P. Raman, McArthur’s team used skin biopsies to determine whether the extent of HIV-sensory neuropathy was associated with a loss of the smallest sensory fibers in the skin, which are responsible for transmitting pain sensations. This method has been proposed as a way to measure the extent of sensory neuropathy and also to detect nerve damage that has not reached the stage where it causes pain or numbness.

Raman, McArthur, and colleagues found that the biopsy method correlates well with the extent of sensory neuropathy, and they were also able to detect nerve abnormalities in a substantial number of HIV patients who had not yet developed sensory neuropathy. They also showed that factors such as hepatitis C co-infection or vitamin B-12 deficiency, among others, were not apparently associated with the loss of small nerve fibers in the skin.

[abstracts]
323. Antiretroviral Exposure Is a Risk Factor for HIV-Associated Sensory Neuropathies, Justin C. McArthur, Jason Creighton, Richard Skolasky, Luxmi Lal, Richard Moore, Steven Wesselingh, and Katherine Cherry; Baltimore, MD and Melbourne, Victoria, Australia

Background: specific reverse transcriptase inhibitors may provoke HIV-associated sensory neuropathies (SN). Methods: 156 HIV+ adults underwent standardized clinical/physiological assessments. PGP9.5 immunostaining quantified epidermal innervation. Antiretroviral exposure was assessed with multivariate analysis.

Results: at JHU, 86% were black, 35% had a history of IDU, and 71% were HepC+. At MU, 95% were white, 92% had a history of MSM, and 11% were HepC+. HgbA1C levels were > 5.8% in 23% at JHU and 12% at MU (p=0.101). 33% were neuropathy-free, 18% had asymptomatic SN, and 49% symptomatic SN. The likelihood of having symptomatic SN was strongly associated with use of ddI (OR=2.6, p=.024), or d4T (OR=5.1, p=.002). Thermal and vibration thresholds were measured with the Case IV device and vibratory QST was relatively insensitive to symptomatic SN. More morphological abnormalities on skin biopsy were noted in SN subjects, but 23% of neuropathy-free had abnormalities. Conclusions: The frequency of SN was high and correlated strongly with anytime exposure to ddI or d4T. Hepatitis C serostatus did NOT modify the prevalence of SN at baseline. Morphological abnormalities were noted in a high proportion of neuropathy-free subjects. Quantitative sensory testing had a low diagnostic efficiency in this cohort. Study supported by NS44807

WIP4. HIV-associated sensory neuropathies: Relationship to epidermal nerve fiber densities

Siva P Raman, J Creighton, R Skolasky, TBN Cherry, R Moore, Carter K, S Wesselingh, C Cherry, JC McArthur. Baltimore, MD, USA, Melbourne, Australia.

Background: Specific nucleoside reverse transcriptase inhibitors (ddI, d4T, and ddC) provoke symptomatic HIV-associated sensory neuropathies (HIV-SN). The relationship of epidermal nerve fiber densities (ENFD) to symptoms of sensory neuropathy, and the modifying role of hepatitis C, Vitamin B12, HgbA1C, and lactate is uncertain.

Methods: 130 HIV-infected adults underwent standardized clinical and physiological assessment: skin biopsies and assays for hepatitis C (HpC), vitamin B12, hemoglobin A1C, and plasma lactate. Results: At baseline, HAART was used in 79% at JHU, and 90% at MU, with ddI and d4T used together in combination in 4% and 15% respectively. ENFD were calculated for 36 JHU subjects at the distal leg and thigh. The distribution of subjects was (JHU): neuropathy-free 30%; asymptomatic SN (asx-SN) 17%; and symptomatic SN (sx-SN) 52%. The average fiber density (distal leg and thigh) for sx-SN was 5.88, 9.38 for the neuropathy-free group, and 7.41 for the asx-SN, with a significant difference between the groups (p=0.01). There was no correlation between ENFD and Vitamin B12, lactate, Hepatitis C serostatus, or Hemoglobin A1C. Conclusions: ENFD are related to the expression of symptomatic SN, but do not appear to be modified by Hepatitis C, vitamin B12, lactate, and hemoglobin A1C, which are not correlated with fiber densities.

| newswise
Further information:
http://www.aneuroa.org

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

Im Focus: Scientists improve forecast of increasing hazard on Ecuadorian volcano

Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).

The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New thruster design increases efficiency for future spaceflight

16.08.2017 | Physics and Astronomy

Transporting spin: A graphene and boron nitride heterostructure creates large spin signals

16.08.2017 | Materials Sciences

A new method for the 3-D printing of living tissues

16.08.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>