Background:   Specific NRTI (ddI, d4T, and ddC) inhibit mitochondrial DNA polymerase g 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.

Keywords: Neuropathy; Hepatitis C; Sensory