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11th Conference on Retroviruses and Opportunistic InfectionsSan Francisco, California - February 8 - 11, 2004 |
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Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11:abstract no. 27
J C McArthur
1, J Creighton1, R Skolasky1, L Lal2, R Moore1, K Carter1, S Wesselingh2,4, K Cherry2,4, and Johns Hopkins Neuroscience Group
1Johns Hopkins Univ., Baltimore, MD, USA; 2Macfarlane Burnet Inst. for Med. Res. and Publ. Hlth., Melbourne, Australia; 2Macfarlane Burnet Inst. for Med. Res. and Publ. Hlth., Melbourne, Australia; and 4Monash Univ., Melbourne, NSW, Australia
BACKGROUND: Specific NRTI (ddI, d4T, and ddC) inhibit mitochondrial DNA polymerase gamma and provoke symptomatic HIV-associated sensory neuropathies (HIV-SN). Risk factors include age, higher viral set-point, and lower CD4 count, however, the modifier role of hepatitis C is uncertain.
METHODS: We assessed 130 HIV-infected adults by: Case IV quantitative sensory testing, skin biopsies and assays for hepatitis C, vitamin B12, hemoglobin A1C, and plasma lactate. The 2 sites (JHU and MU) were selected to provide contrasting demographics and hepatitis C seroprevalence. ART assessments included cumulative exposure to neurotoxic RTI (ntx-DDX). Epidermal innervation was assessed using PGP9.5 immunostaining. mtDNA was quantified in subcutaneous fat using real-time PCR.
RESULTS: At JHU, of 47 subjects, 78% were male, 83% black, 70% had a history of IDU, mean CD4 count was 289, and hepatitis C seroprevalence was 71%. At MU, of 83 subjects, 95% were white, 96% male, 92% had a history of MSM, mean CD count was 356, and hepatitis C seroprevalence was 11%. At baseline, HAART was used in 79% at JHU, and 90% at MU. Ntx-DDx agents were used in 21% at JHU, and 53% at MU, with ddI and d4T used together in combination in 4% and 15%, respectively. The distribution of subjects was (JHU/MU): neuropathy-free 30%/36%; asymptomatic SN (asx-SN) 17%/7%; and symptomatic SN (sx-SN) 52%/56%, with no inter-center differences. Thermal and vibration thresholds were measured with the Case IV device and were abnormal in 26% of those with asx-SN, and 45% with sx-SN. From 62 completed biopsies in 31 subjects at JHU, morphology was concordant with SN status in 61%, and 50% of neuropathy-free subjects had morphological abnormalities. Neither age, CD4 counts, plasma lactate, B12 levels, mtDNA in SC fat, nor hepatitis C serology were associated with symptomatic SN at baseline.
CONCLUSIONS: The frequency of asymptomatic and symptomatic sensory neuropathies was remarkably high at both sites, with only 32% of subjects neuropathy-free at baseline. Hepatitis C serostatus did not appear to influence the prevalence of SN at baseline, however, longitudinal study will disclose its modifier role. Morphological abnormalities were noted in a high proportion of neuropathy-free subjects, and longitudinal follow-up may disclose a high transition rate to confirmed neuropathy.
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Copyright © 2004 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.
