Detectable Plasma HIV RNA Is Associated With Sensory Neuropathy in Patients With HIV Treated Without Stavudine

Octaviana, Fitri; Safri, Ahmad Yanuar; Setiawan, Denise Dewanto; Estiasari, Riwanti; Imran, Darma; Ranakusuma, Teguh; Affandi, Jacquita S.; Cherry, Catherine L.; Price, Patricia

doi:10.1097/qai.0000000000001836

Cited by 8 publications

(9 citation statements)

References 13 publications

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“…Despite the discontinuation of stavudine, HIV-SN remains a common neurological complication of HIV disease, impacting 14% of Indonesians surveyed in the 2016 cross-sectional study [10] and 38% of Africans in this study. We describe associations between HIV-SN and demographic variables, clinical variables and SNP and haplotypes in the TNF-block which have previously been linked with HIV-SN in Caucasians, Asians and Africans.…”

Section: Discussionmentioning

confidence: 84%

“…We compared the prevalence of HIV-SN assessed with the AIDS Clinical Trial Group Brief Peripheral Neuropathy Screening Tool in HIV+ patients treated at an inner-city clinic in Jakarta, Indonesia with stavudine in 2006 and without stavudine in 2016 [10]. A patient's height and age were associated with HIV-SN among patients receiving stavudine, and 34% experienced neuropathy [5].…”

Section: Introductionmentioning

confidence: 99%

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TNF-Block Genotypes Influence Susceptibility to HIV-Associated Sensory Neuropathy in Indonesians and South Africans

Gaff

Octaviana

Pillay

et al. 2020

IJMS

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HIV-associated sensory neuropathy (HIV-SN) is a disabling complication of HIV disease and antiretroviral therapies (ART). Since stavudine was removed from recommended treatment schedules, the prevalence of HIV-SN has declined and associated risk factors have changed. With stavudine, rs1799964*C (TNF-1031) associated with HIV-SN in Caucasians and Indonesians but not in South Africans. Here, we investigate associations between HIV-SN and rs1799964*C and 12 other polymorphisms spanning TNF and seven neighboring genes (the TNF-block) in Indonesians (n = 202; 34/168 cases) and South Africans (n = 75; 29/75 cases) treated without stavudine. Haplotypes were derived using fastPHASE and haplotype networks built with PopART. There were no associations with rs1799964*C in either population. However, rs9281523*C in intron 10 of BAT1 (alternatively DDX39B) independently associated with HIV-SN in Indonesians after correcting for lower CD4 T-cell counts and >500 copies of HIV RNA/mL (model p = 0.0011, Pseudo R 2 = 0.09). rs4947324*T (between NFKBIL1 and LTA) independently associated with reduced risk of HIV-SN and shared haplotype 1 (containing no minor alleles) associated with increased risk of HIV-SN after correcting for greater body weight, a history of tuberculosis and nadir CD4 T-cell counts (model: p = 0.0003, Pseudo R 2 = 0.22). These results confirm TNF-block genotypes influence susceptibility of HIV-SN. However, critical genotypes differ between ethnicities and with stavudine use.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

TNF-Block Genotypes Influence Susceptibility to HIV-Associated Sensory Neuropathy in Indonesians and South Africans

Gaff

Octaviana

Pillay

et al. 2020

IJMS

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“…The prevalence in Melbourne was up to 42%, whereas in Kuala Lumpur and Jakarta, the reported level was lower, 19 and 34%, respectively [7]. Stavudine is no longer in first-line therapy, and the prevalence of HIV-SN is almost halved (14.2%) compared to data from the same clinic in Indonesia when patients received stavudine [8].…”

Section: Introductionmentioning

confidence: 87%

“…• CAMKK2 (affecting neuronal repair) not disappeared. The risk factors of HIV-SN in patients on ART without stavudine are almost the same as in the pre-ART era-high plasma viral load and older age [8]. Isoniazid is widely used as therapy for tuberculosis and has been recognized as a risk factor for neuropathy for a long time.…”

Section: Clinical Factors Influence the Risk Of Hiv-snmentioning

confidence: 99%

HIV-Associated Sensory Neuropathy

Octaviana¹,

Safri²,

Imran³

et al. 2019

Demystifying Polyneuropathy - Recent Advances and New Directions

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As advances in the treatment of HIV are now allowing patients a longer life span, further comorbidities become apparent. This includes sensory neuropathy (HIV-SN) which can affect a patient's quality of life. Here, we review factors influencing HIV-SN in patients receiving antiretroviral therapy that promotes this condition and in the modern era when these therapies have been withdrawn. This has halved the incidence of HIV-SN, but the condition remains significant in the lives of many sufferers. Genetic polymorphisms that influence pathogenesis of HIV-SN have indicated likely mechanisms, but studies of skin biopsies and animal models are needed to confirm the roles of the encoded proteins.

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“…In our studies assessing HIV-SN by AIDS Clinical Trial Group Brief Peripheral Neuropathy Screening Tool (ACTG-BPNST), the prevalence of HIV-SN halved between 2006 when all patients received stavudine (observed associations with HIV-SN were increasing age and height) and 2016 when this drug was no longer used. HIV-SN was then associated with ongoing HIV replication (5).…”

Section: Introductionmentioning

confidence: 99%

Neuropathic pain in HIV patients receiving ART without stavudine in an Indonesia Referral Hospital

Octaviana

Safri

Setiawan

et al. 2019

Journal of the Neurological Sciences

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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.

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Detectable Plasma HIV RNA Is Associated With Sensory Neuropathy in Patients With HIV Treated Without Stavudine

Cited by 8 publications

References 13 publications

TNF-Block Genotypes Influence Susceptibility to HIV-Associated Sensory Neuropathy in Indonesians and South Africans

TNF-Block Genotypes Influence Susceptibility to HIV-Associated Sensory Neuropathy in Indonesians and South Africans

HIV-Associated Sensory Neuropathy

Neuropathic pain in HIV patients receiving ART without stavudine in an Indonesia Referral Hospital

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