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Distal leg epidermal nerve fiber density as a surrogate marker of HIV-associated sensory neuropathy risk: risk factors and change following initial antiretroviral therapy.
J Neurovirol. 2015 Oct; 21(5):525-34.JN

Abstract

Distal leg epidermal nerve fiber density (ENFD) is a validated predictor of HIV sensory neuropathy (SN) risk. We assessed how ENFD is impacted by initiation of first-time antiretroviral therapy (ART) in subjects free of neuropathy and how it is altered when mitochondrial toxic nucleoside medications are used as part of ART. Serial changes in proximal thigh and distal leg ENFD were examined over 72 weeks in 150 Thai subjects randomized to a regimen of stavudine (d4T) switching to zidovudine (ZDV) at 24 weeks vs ZDV vs tenofovir (TDF) for the entire duration of study, all given in combination with nevirapine. We found individual variations in ENFD change, with almost equal number of subjects who decreased or increased their distal leg ENFD over 72 weeks and no relationship to nucleoside backbone or to development of neuropathic signs or symptoms. Lower baseline distal leg ENFD and greater increases in mitochondrial oxidative phosphorylation complex I (CI) activity were associated with larger increases in distal leg ENFD over 72 weeks. Distal leg ENFD correlated with body composition parameters (body surface area, body mass index, height) as well as with blood pressure measurements. Assessed together with a companion cross-sectional study, we found that mean distal leg ENFD in all HIV+ subjects was lower than in HIV- subjects but similar among HIV+ groups whether ART-naïve or on d4T with/without neuropathy/neuropathic symptoms. The utility of ENFD as a useful predictor of small unmyelinated nerve fiber damage and neuropathy risk in HIV may be limited in certain populations.

Links

Publisher Full Text
ncbi.nlm.nih.gov
dx.doi.org
PMC Free PDF

Authors+Show Affiliations

Shikuma CM
University of Hawaii, Honolulu, HI, USA. shikuma@hawaii.edu. South East Asia Research Collaboration with Hawaii, Bangkok, Thailand. shikuma@hawaii.edu. Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo St. BSB Suite 231, Honolulu, HI, 96813, USA. shikuma@hawaii.edu.
Bennett K
Bennett Statistical Consulting, Inc, Ballston Lake, NY, USA.
Ananworanich J
South East Asia Research Collaboration with Hawaii, Bangkok, Thailand. US Military HIV Research Program, Walter Reed Army Institute of Research and Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Gerschenson M
University of Hawaii, Honolulu, HI, USA.
Teeratakulpisarn N
The Thai Red Cross AIDS Research Center, Bangkok, Thailand.
Jadwattanakul T
Queen Savang Vadhana Memorial Hospital, Chonburi, Thailand.
DeGruttola V
Harvard School of Public Health, Boston, MA, USA.
McArthur JC
Johns Hopkins School of Medicine, Baltimore, MD, USA.
Ebenezer G
Johns Hopkins School of Medicine, Baltimore, MD, USA.
Chomchey N
South East Asia Research Collaboration with Hawaii, Bangkok, Thailand.
Praihirunkit P
South East Asia Research Collaboration with Hawaii, Bangkok, Thailand.
Hongchookiat P
The Thai Red Cross AIDS Research Center, Bangkok, Thailand.
Mathajittiphun P
Queen Savang Vadhana Memorial Hospital, Chonburi, Thailand.
Nakamoto B
University of Hawaii, Honolulu, HI, USA. Straub Medical Center, Honolulu, HI, USA.
Hauer P
Johns Hopkins School of Medicine, Baltimore, MD, USA.
Phanuphak P
South East Asia Research Collaboration with Hawaii, Bangkok, Thailand. The Thai Red Cross AIDS Research Center, Bangkok, Thailand.
Phanuphak N
South East Asia Research Collaboration with Hawaii, Bangkok, Thailand. The Thai Red Cross AIDS Research Center, Bangkok, Thailand.
SEARCH 003 protocol team
No affiliation info available

MeSH

AdultAnti-Retroviral AgentsCross-Sectional StudiesFemaleHIV InfectionsHumansLegMalePeripheral Nervous System DiseasesRisk FactorsSensory Receptor CellsSkinStavudineTenofovirThailandZidovudine

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26002840

Citation

Shikuma, Cecilia M., et al. "Distal Leg Epidermal Nerve Fiber Density as a Surrogate Marker of HIV-associated Sensory Neuropathy Risk: Risk Factors and Change Following Initial Antiretroviral Therapy." Journal of Neurovirology, vol. 21, no. 5, 2015, pp. 525-34.
Shikuma CM, Bennett K, Ananworanich J, et al. Distal leg epidermal nerve fiber density as a surrogate marker of HIV-associated sensory neuropathy risk: risk factors and change following initial antiretroviral therapy. J Neurovirol. 2015;21(5):525-34.
Shikuma, C. M., Bennett, K., Ananworanich, J., Gerschenson, M., Teeratakulpisarn, N., Jadwattanakul, T., DeGruttola, V., McArthur, J. C., Ebenezer, G., Chomchey, N., Praihirunkit, P., Hongchookiat, P., Mathajittiphun, P., Nakamoto, B., Hauer, P., Phanuphak, P., & Phanuphak, N. (2015). Distal leg epidermal nerve fiber density as a surrogate marker of HIV-associated sensory neuropathy risk: risk factors and change following initial antiretroviral therapy. Journal of Neurovirology, 21(5), 525-34. https://doi.org/10.1007/s13365-015-0352-0
Shikuma CM, et al. Distal Leg Epidermal Nerve Fiber Density as a Surrogate Marker of HIV-associated Sensory Neuropathy Risk: Risk Factors and Change Following Initial Antiretroviral Therapy. J Neurovirol. 2015;21(5):525-34. PubMed PMID: 26002840.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distal leg epidermal nerve fiber density as a surrogate marker of HIV-associated sensory neuropathy risk: risk factors and change following initial antiretroviral therapy. AU - Shikuma,Cecilia M, AU - Bennett,Kara, AU - Ananworanich,Jintanat, AU - Gerschenson,Mariana, AU - Teeratakulpisarn,Nipat, AU - Jadwattanakul,Tanate, AU - DeGruttola,Victor, AU - McArthur,Justin C, AU - Ebenezer,Gigi, AU - Chomchey,Nitiya, AU - Praihirunkit,Pairoa, AU - Hongchookiat,Piranun, AU - Mathajittiphun,Pornpen, AU - Nakamoto,Beau, AU - Hauer,Peter, AU - Phanuphak,Praphan, AU - Phanuphak,Nittaya, AU - ,, Y1 - 2015/05/22/ PY - 2015/01/03/received PY - 2015/04/30/accepted PY - 2015/04/20/revised PY - 2015/5/24/entrez PY - 2015/5/24/pubmed PY - 2016/8/25/medline KW - Epidermal nerve fiber density KW - HIV KW - Neuropathy KW - Stavudine SP - 525 EP - 34 JF - Journal of neurovirology JO - J Neurovirol VL - 21 IS - 5 N2 - Distal leg epidermal nerve fiber density (ENFD) is a validated predictor of HIV sensory neuropathy (SN) risk. We assessed how ENFD is impacted by initiation of first-time antiretroviral therapy (ART) in subjects free of neuropathy and how it is altered when mitochondrial toxic nucleoside medications are used as part of ART. Serial changes in proximal thigh and distal leg ENFD were examined over 72 weeks in 150 Thai subjects randomized to a regimen of stavudine (d4T) switching to zidovudine (ZDV) at 24 weeks vs ZDV vs tenofovir (TDF) for the entire duration of study, all given in combination with nevirapine. We found individual variations in ENFD change, with almost equal number of subjects who decreased or increased their distal leg ENFD over 72 weeks and no relationship to nucleoside backbone or to development of neuropathic signs or symptoms. Lower baseline distal leg ENFD and greater increases in mitochondrial oxidative phosphorylation complex I (CI) activity were associated with larger increases in distal leg ENFD over 72 weeks. Distal leg ENFD correlated with body composition parameters (body surface area, body mass index, height) as well as with blood pressure measurements. Assessed together with a companion cross-sectional study, we found that mean distal leg ENFD in all HIV+ subjects was lower than in HIV- subjects but similar among HIV+ groups whether ART-naïve or on d4T with/without neuropathy/neuropathic symptoms. The utility of ENFD as a useful predictor of small unmyelinated nerve fiber damage and neuropathy risk in HIV may be limited in certain populations. SN - 1538-2443 UR - https://www.unboundmedicine.com/medline/citation/26002840/Distal_leg_epidermal_nerve_fiber_density_as_a_surrogate_marker_of_HIV_associated_sensory_neuropathy_risk:_risk_factors_and_change_following_initial_antiretroviral_therapy_ L2 - https://dx.doi.org/10.1007/s13365-015-0352-0 DB - PRIME DP - Unbound Medicine ER -