Stavudine neuropathy risk increases with patient age and height. Prioritizing older and taller patients for alternative agents would be an inexpensive strategy to reduce neuropathy rates in countries where the burden of HIV disease limits treatment options.

Objectives The aim of the study was to describe the prevalence of and risk factors for HIV‐associated sensory neuropathy (HIV‐SN) in 2006 [the era of stavudine, didanosine and zalcitabine (dNRTI)‐sparing highly active antiretroviral therapy (HAART)] and to compare our findings with data obtained in the same clinic in 1993 (pre‐HAART) and 2001 (frequent use of dNRTI‐containing HAART). Methods This was a cross‐sectional comparative study using convenience sampling. HIV‐positive adults attending a tertiary referral clinic over a 2‐week period were screened for HIV‐SN using the AIDS Clinical Trials Group screening tool. HIV‐SN was defined as present if the patient had both neuropathic symptoms and abnormal signs. Demographic, clinical, laboratory and treatment data were considered as possible risk factors for HIV‐SN, and results were compared with data obtained in the same clinic in 1993 and 2001. Results One hundred patients were screened. The prevalence of HIV‐SN was 42%, which was unchanged since 2001 (44%) despite a significant reduction in the use of dNRTIs. HIV‐SN remained much more common than in 1993 (42% vs 13%; P<0.0001). The only independent associations with HIV‐SN in 2006 were increasing patient age and a history of exposure to either stavudine or indinavir. This compares with 1993 when neuropathy was increased in those with Mycobacterium avium complex infection, and 2001 when patient age and use of stavudine and didanosine were the independent associations with HIV‐SN in this clinic. Conclusions HIV‐SN remained common among ambulatory patients in 2006 (42% prevalence) despite a significant reduction in the use of dNRTIs. In addition to patient age and stavudine exposure, indinavir use may be a risk factor for HIV‐SN.

Nucleoside analog-associated sensory neuropathy (NRTI-SN) attributed to stavudine, didanosine, or zalcitabine (the dNRTIs) and distal sensory polyneuropathy (DSP) attributed to HIV are clinically indistinguishable. As inflammatory cytokines are involved in DSP, we addressed a role for inflammation in NRTI-SN by determining the alleles of immune-related genes carried by patients with and without NRTI-SN. Demographic details associated with risk of various neuropathies were included in the analysis. Alleles of 14 polymorphisms in 10 genes were determined in Australian HIV patients with definite NRTI-SN (symptom onset Ͻ6 months after first dNRTI exposure, n ‫؍‬ 16), NRTI-SN-resistant patients (no neuropathy despite Ͼ6 months on dNRTIs, n ‫؍‬ 20), patients with late onset NRTI-SN (neuropathy onset after Ͼ6 months of dNRTIs, n ‫؍‬ 19), and HIV-negative controls. Carriage of TNFA-1031*2 was highest in NRTI-SN patients, suggesting potentiation of NRTI-SN. Carriage of IL12B (3Ј UTR)*2 was higher in NRTI-SN-resistant patients than controls or NRTI-SN patients, suggesting a protective role. BAT1 (intron 10)*2 was more common in NRTI-SN than resistant patients, but neither group differed from controls. This marks the conserved HLA-A1, B8, DR3 haplotype. Of the demographic details considered, increasing height was associated with NRTI-SN risk. A model including cytokine genotype and height predicted NRTI-SN status (p Ͻ 0.0001, R 2 ‫؍‬ 0.54). Late onset NRTI-SN patients clustered genetically with NRTI-SN-resistant patients, so these patients may be genetically "protected." In addition to patient height, cytokine genotype influenced NRTI-SN risk following dNRTI exposure, suggesting inflammation contributes to NRTI-SN. 117

A toxic sensory neuropathy associated with exposure to inexpensive nucleoside analogue reverse transcriptase inhibitors (NRTIs) [particularly stavudine (d4T)] causes dilemmas in the management of patients with HIV, especially in resource-poor settings. Here patients (n = 96) attending Pokdisus AIDS Clinic at the Cipto Mangunkusumo Hospital, Jakarta who had been treated with d4T were screened for symptomatic neuropathy. Clinical, demographic, and genetic factors were considered as possible neuropathy risk factors. DNA from saliva was used to examine alleles of TNFA-308, BAT1 (intron 10), TNFA-1031, IL1A+4845, and IL12B (3' UTR). The prevalence of neuropathy (symptoms and signs) was 34%. On multivariate analysis, neuropathy following d4T exposure was associated with increasing age, increasing height, and TNFA-1031*2 (model p = 0.0009). Isoniazid exposure (present in 56% of patients) was not associated with neuropathy in this cohort, where all patients had received pyridoxine coadministration. These data suggest that a simple algorithm based on patient age, height, and TNF genotype could be used to predict the individual's risk of symptomatic neuropathy prior to prescription of d4T.

Cytomegalovirus (CMV) has been linked with vascular pathology and is a common complication of renal transplantation. We addressed whether CMV seropositivity influences vascular pathology several years after transplant. Levels of CMV antibody increased with age, were higher in transplant recipients than healthy controls (P < 0.001), and correlated with vascular endothelial function measured by flow mediated-dilation of the brachial artery (FMD). However, the optimal general linear model predicting FMD included CMV seropositivity as a marginal effect (P = 0.068), with age (P = 0.013), gender (P < 0.0001), and transplantation (P < 0.0001). Other measures of the burden of CMV are being tested as CMV prophylaxis is feasible as an approach to reduce vascular disease. J. Med. Virol. 89:177-181, 2017. © 2016 Wiley Periodicals, Inc.