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5. Pre-print: Ex vivo expression of chemokine receptors on cells surrounding cutaneous nerves in patients with HIV-associated sensory neuropathy. DOI: 10.1097/QAD.0000000000001714

Author

Mountford, Jenjira, Octaviana, Fitri, Estiasari, Riwanti, Setiawan, Denise Dewanto, Ariyanto, Ibnu, Lee, Silvia, Gaff, Jessica, Chew, Constance, Jackaman, Connie, Kamerman, Peter, Cherry, Catherine, and Price, Patricia

Subjects
virus diseases
Abstract

Post-print copy of: Mountford J, Octaviana F, Estiasari R, Setiawan DD, Ariyanto I, Lee S, Gaff J, Chew C, Jackaman C, Kamerman P, Cherry C, Price P. Ex vivo expression of chemokine receptors on cells surrounding cutaneous nerves in patients withHIV-associated sensory neuropathy. AIDS 32: 431-441, 2018. DOI: 10.1097/QAD.0000000000001714, PMID: 29239897Abstract: Objective: HIV-associated sensory neuropathy (HIV-SN) remains common in HIV+ individuals receiving anti-retroviral therapy (ART), even though neurotoxic anti-retroviral drugs (e.g. stavudine) have been phased out of use. Accumulating evidence indicates that the neuropathy is immune-mediated. We hypothesise that chemokines produced locally in the skin promote migration of macrophages and T-cells into the tissue, damaging cutaneous nerves causing HIV- SN. Design: We assessed chemokine receptor expression on infiltrating CD14+ and CD3+ cells around cutaneous nerves in standardised skin biopsies from HIV-SN+ patients (n=5), HIV-SN- patients (n=9) and healthy controls (n=4). Methods: The AIDS Clinical Trials Group Brief Peripheral Neuropathy Screen was used to assess Indonesian HIV+ patients receiving ART without stavudine (case definition: bilateral presence of at least one symptom and at least one sign of neuropathy). Distal leg skin biopsies were stained to visualise chemokine receptors; CCR2, CCR5, CXCR3, CXCR4, CX3CR1, infiltrating CD3+ and CD14+ cells and protein-gene-product 9.5 on nerves, using immunohistochemistry and 4-colour confocal microscopy. Results: Intraepidermal nerve fibre density was variable in patients without HIV-SN and generally lower in those with HIV-SN. CX3CR1 was more evident on CD14+ cells whereas CCR2, CCR5, CXCR3 and CXCR4 were more common on CD3+ cells. Expression of CX3CR1, CCR2 and CCR5 was more common in HIV-SN+ patients than those without HIV-SN. CXCR3 and CXCR4 were upregulated in all HIV+ patients, compared with healthy controls. Conclusion: Inflammatory macrophages expressing CX3CR1 and T-cells expressing CCR2 and CCR5 may participate in peripheral nerve damage leading to HIV-SN in HIV+ patients treated without stavudine. Further characterisation of these cells is warranted.

Published
2017
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6. Brief report: Demographic and genetic associations with markers of small and large fiber sensory neuropathy in HIV patients treated without stavudine

Author

<p>Curtin University Universitas Indonesia</p>, Safri, Ahmad Yanuar, Gaff, Jessica, Octaviana, Fitri, Setiawan, Denise Dewanto, Imran, Darma, Cherry, Catherine L., Laws, Simon M., Price, Patricia, <p>Curtin University Universitas Indonesia</p>, Safri, Ahmad Yanuar, Gaff, Jessica, Octaviana, Fitri, Setiawan, Denise Dewanto, Imran, Darma, Cherry, Catherine L., Laws, Simon M., and Price, Patricia

Abstract

Safri, A. Y., Gaff, J., Octaviana, F., Setiawan, D. D., Imran, D., Cherry, C. L., ... Price, P. (2020). Brief report: Demographic and genetic associations with markers of small and large fiber sensory neuropathy in HIV patients treated without stavudine. JAIDS Journal of Acquired Immune Deficiency Syndromes, 85(5), 612-616. https://doi.org/10.1097/QAI.0000000000002503

7. Brief Report: Demographic and Genetic Associations With Markers of Small and Large Fiber Sensory Neuropathy in HIV Patients Treated Without Stavudine.

Author

Safri AY, Gaff J, Octaviana F, Setiawan DD, Imran D, Cherry CL, Laws SM, and Price P

Subjects
Adult, Alleles, Biomarkers, Female, Genetic Predisposition to Disease genetics, Humans, Male, Middle Aged, Peripheral Nervous System Diseases etiology, Peripheral Nervous System Diseases genetics, Peripheral Nervous System Diseases pathology, Risk Factors, Young Adult, Anti-HIV Agents adverse effects, Calcium-Calmodulin-Dependent Protein Kinase Kinase genetics, HIV Infections drug therapy, Peripheral Nervous System Diseases chemically induced, Stavudine adverse effects
Abstract

Neurotoxic antiretroviral therapy (ART) such as stavudine has been now replaced with safer therapies, reducing the prevalence of neuropathy from 34% to 15% in HIV+ Indonesians. However, it is unclear whether the residual cases display damage to small or large nerve fibers and whether both are influenced by known risk factors, including alleles of CAMKK2 associated with neuropathy in HIV patients. The encoded protein influences the growth and repair of nerve fibers. HIV-positive adults on ART for >12 months without exposure to stavudine were screened for neuropathy using the AIDS Clinical Trials Group Brief Peripheral Neuropathy Screen (BPNS). Large fiber neuropathy was assessed by nerve conduction (NC) and small fiber neuropathy using stimulated skin wrinkling (SSW) applied to the fingers. CAMKK2 alleles were assessed by TaqMan OpenArray technology. Neuropathy diagnoses were more common with SSW than BPNS (49/173 vs 26/185, χ; P = 0.0009), with poor alignment between these outcomes (P = 0.60). NC and BPNS diagnosed neuropathy at similar frequencies (29/151 vs 26/185; P = 0.12) and were aligned (P < 0.0001). In bivariate analyses, all diagnoses were associated with patients' age and persistent HIV replication, with minor effects from CD4 T-cell counts and time on ART. CAMKK2 alleles associated with neuropathy diagnosed with BPNS and SSW but not NC. Multivariable analyses confirmed the importance of age and HIV replication, with distinct CAMKK2 polymorphisms affecting BPNS and SSW. Paradoxically, height was protective against skin wrinkling. Overall the data link CAMKK2 genotypes with small rather than large fiber damage. SSW may reflect pathology distinct from that identified using BPNS.

Published
2020
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8. Detectable Plasma HIV RNA Is Associated With Sensory Neuropathy in Patients With HIV Treated Without Stavudine.

Author

Octaviana F, Safri AY, Setiawan DD, Estiasari R, Imran D, Ranakusuma T, Affandi J, Cherry CL, and Price P

Subjects
AIDS-Associated Nephropathy pathology, Adult, Anti-HIV Agents adverse effects, Antiretroviral Therapy, Highly Active adverse effects, Female, HIV Infections complications, HIV Infections virology, Humans, Male, Middle Aged, Young Adult, AIDS-Associated Nephropathy epidemiology, Anti-HIV Agents administration & dosage, Antiretroviral Therapy, Highly Active methods, HIV Infections drug therapy, Plasma virology, RNA, Viral blood, Viral Load
Published
2018
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