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 characterization of these cells is warranted.
Lower limb neuropathic pain in HIV patients is a common manifestation of sensory neuropathy (HIV-SN), but can be seen in patients who do not meet standard definitions of HIV-SN. The drug stavudine is a risk factor for HIV-SN, but some patients treated without stavudine experience HIV-SN, and the prevalence and risk factors influencing neuropathic pain in this setting are unknown. A cross sectional study at Cipto Mangunkusumo Hospital Jakarta tested 197 HIV patients treated for >12 months without stavudine. HIV-SN was defined using the AIDS Clinical Trial Group Brief Peripheral Neuropathy Screening Test (ACTG-BPNST). A validated Indonesia translation of Douleur Neuropathique en 4 (DN4) questionnaire was used to assess lower limb neuropathic pain. Nerve conduction studies assessed large nerve fiber function and Stimulated Skin Wrinkle (SSW) tests were performed to assess small nerve fibers. The prevalence of neuropathic pain was 6.6%. BPNST + HIV-SN was diagnosed in 14.2% of the cohort and 38.5% of patients with pain. Use of protease inhibitors and ART duration <2 years associated with neuropathic pain in univariate (p=0.036, p=0.002, resp.) and multivariable analyses (model p<0.001). SSW tests were abnormal in 53.8% of subjects with neuropathic pain and only 25.5% without pain (p=0.05). Patients with pain without BPNST + HIV-SN had begun ART more recently than those with both diagnoses. Overall this preliminary study showed that neuropathic pain associated with protease inhibitors and a shorter duration of ART in Indonesian HIV patients, and may be an early symptom of small fiber neuropathy in this context.
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, χ2; 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.