Prevalent neuropathy in a cohort of HIV-infected Kenyan sex workers using antiretroviral drugs

Ndakala, Frank; Oyugi, Julius; Oluka, Margaret; Kimani, Joshua; Jablonka, Alexandra; Behrens, Georg M. N.

doi:10.11604/pamj.2016.25.14.9699

Cited by 8 publications

(12 citation statements)

References 46 publications

(72 reference statements)

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“…At the same time, ART has been associated with the development of DSP symptoms in some individuals despite reducing viral load. 30,31 Studies using animal models exposed to tenofovir disoproxil fumarate support a role for ART in DSP. 32 However, more work is needed to understand how DSP manifests despite reduced viral loads.…”

Section: Discussionmentioning

confidence: 99%

Predictors of worsening neuropathy and neuropathic pain after 12 years in people with HIV

Ellis

Diaz

Sacktor

et al. 2020

Ann Clin Transl Neurol

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Objective: Distal sensory polyneuropathy (DSP) and neuropathic pain are important clinical concerns in virally suppressed people with HIV. We determined how these conditions evolved, what factors influenced their evolution, and their clinical impact. Methods: Ambulatory, community-dwelling HIV seropositive individuals were recruited at six research centers. Clinical evaluations at baseline and 12 years later determined neuropathy signs and distal neuropathic pain (DNP). Additional assessments measured activities of daily living and quality of life (QOL). Factors potentially associated with DSP and DNP progression included disease severity, treatment, demographics, and co-morbidities. Adjusted odds ratios were calculated for follow-up neuropathy outcomes. Results: Of 254 participants, 21.3% were women, 57.5% were non-white. Mean baseline age was 43.5 years. Polyneuropathy prevalence increased from 25.7% to 43.7%. Of 173 participants initially pain-free, 42 (24.3%) had incident neuropathic pain. Baseline risk factors for incident pain included unemployment (OR [95% CI], 5.86 [1.97, 17.4]) and higher baseline body mass index (BMI) (1.78 [1.03, 3.19] per 10-units). Participants with neuropathic pain at follow-up had significantly worse QOL and greater dependence in activities of daily living than those who remained pain-free. Interpretation: HIV DSP and neuropathic pain increased in prevalence and severity over 12 years despite high rates of viral suppression. The high burden of neuropathy included disability and poor life quality. However, substantial numbers remained pain-free despite clear evidence of neuropathy on exam. Protective factors included being employed and having a lower BMI. Implications for clinical practice include promotion of lifestyle changes affecting reversible risk factors.

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Section: Discussionmentioning

confidence: 99%

Predictors of worsening neuropathy and neuropathic pain after 12 years in people with HIV

Ellis

Diaz

Sacktor

et al. 2020

Ann Clin Transl Neurol

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“…Several African studies have investigated the incidence of HIV‐SN and factors associated with its development . However, none of these studies assessed the incidence of SN in a cohort where all individuals were exposed only to TDF‐based cART.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the assessments used within these studies to assess SN status are methodologically questionable. For example, one study only assessed symptoms, while other studies did not state the method used to screen for SN …”

Section: Introductionmentioning

confidence: 99%

“…Several African studies have investigated the incidence of HIV-SN and factors associated with its development. [13][14][15][16][17][18][19][20] However, none of these studies assessed the incidence of SN in a cohort where all individuals were exposed only to TDF-based cART. Instead, these studies included individuals who had been exposed to several ART regimens (including stavudine) or who were on cART regimens that did not include TDF (globally, the most common cART initiation regimen).…”

mentioning

confidence: 99%

“…Furthermore, the assessments used within these studies to assess SN status are methodologically questionable. For example, one study only assessed symptoms, 15 while other studies did not state the method used to screen for SN. 13,14,17 Consequently, we investigated the 6-month incidence of SN, using methods recommended for the assessment and grading of peripheral neuropathy for research and clinical purposes, [21][22][23] in ART naive South African people living with HIV/AIDS (PLWHA) and who were initiating TDF-based cART.…”

mentioning

confidence: 99%

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Clinical diagnosis of sensory neuropathy in HIV patients treated with tenofovir: A 6‐month follow‐up study

Pillay

Wadley

Cherry

et al. 2019

J Peripheral Nervous Sys

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Background Sensory neuropathy (SN) is a common and often painful neurological condition associated with HIV‐infection and its treatment. However, data on the incidence of SN in neuropathy‐free individuals initiating combination antiretroviral therapies (cART) that do not contain the neurotoxic agent stavudine are lacking. Aims We investigated the 6‐month incidence of SN in ART naïve individuals initiating tenofovir (TDF)‐based cART, and the clinical factors associated with the development of SN. Methods 120 neuropathy‐free and ART naïve individuals initiating cART at a single center in Johannesburg, South Africa were enrolled. Participants were screened for SN using clinical signs and symptoms at study enrolment and approximately every 2‐months for a period of ~6‐months. Diagnostic criteria for symptomatic SN was defined by the presence of at least one symptom (pain/burning, numbness, paraesthesias) and at least two clinical signs (reduced vibration sense, absent ankle reflexes or pin‐prick hypoaesthesia). Diagnostic criteria for asymptomatic SN required at least two clinical signs only (as above). Results A total of 88% of the cohort completed three visits within the 6‐month period. The 6‐month cumulative incidence of neuropathy was 140 cases per 1000 patients (95% CI: 80‐210) at an incidence rate of 0.37 (95% CI: 0.2‐0.5) per person year. Height and active tuberculosis (TB) disease were independently associated with the risk of developing SN (P < .05). Interpretation We found that within the first 6 months of starting cART, incident SN persists in the post‐stavudine era, with 11 (9%) of individuals developing asymptomatic SN, and 9 (8%) developing symptomatic SN.

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Tenofovir disoproxil fumarate induces peripheral neuropathy and alters inflammation and mitochondrial biogenesis in the brains of mice

Fields

Swinton

Carson

et al. 2019

Sci Rep

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Mounting evidence suggests that antiretroviral therapy (ART) drugs may contribute to the prevalence of HIV-associated neurological dysfunction. The HIV envelope glycoprotein (gp120) is neurotoxic and has been linked to alterations in mitochondrial function and increased inflammatory gene expression, which are common neuropathological findings in HIV+ cases on ART with neurological disorders. Tenofovir disproxil fumarate (TDF) has been shown to affect neurogenesis in brains of mice and mitochondria in neurons. In this study, we hypothesized that TDF contributes to neurotoxicity by modulating mitochondrial biogenesis and inflammatory pathways. TDF administered to wild-type (wt) and GFAP-gp120 transgenic (tg) mice caused peripheral neuropathy, as indicated by nerve conduction slowing and thermal hyperalgesia. Conversely TDF protected gp120-tg mice from cognitive dysfunction. In the brains of wt and gp120-tg mice, TDF decreased expression of mitochondrial transcription factor A (TFAM). However, double immunolabelling revealed that TFAM was reduced in neurons and increased in astroglia in the hippocampi of TDF-treated wt and gp120-tg mice. TDF also increased expression of GFAP and decreased expression of IBA1 in the wt and gp120-tg mice. TDF increased tumor necrosis factor (TNF) α in wt mice. However, TDF reduced interleukin (IL) 1β and TNFα mRNA in gp120-tg mouse brains. Primary human astroglia were exposed to increasing doses of TDF for 24 hours and then analyzed for mitochondrial alterations and inflammatory gene expression. In astroglia, TDF caused a dose-dependent increase in oxygen consumption rate, extracellular acidification rate and spare respiratory capacity, changes consistent with increased metabolism. TDF also reduced IL-1β-mediated increases in IL-1β and TNFα mRNA. These data demonstrate that TDF causes peripheral neuropathy in mice and alterations in inflammatory signaling and mitochondrial activity in the brain.

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Prevalent neuropathy in a cohort of HIV-infected Kenyan sex workers using antiretroviral drugs

Cited by 8 publications

References 46 publications

Predictors of worsening neuropathy and neuropathic pain after 12 years in people with HIV

Predictors of worsening neuropathy and neuropathic pain after 12 years in people with HIV

Clinical diagnosis of sensory neuropathy in HIV patients treated with tenofovir: A 6‐month follow‐up study

Tenofovir disoproxil fumarate induces peripheral neuropathy and alters inflammation and mitochondrial biogenesis in the brains of mice

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