|Year : 2018 | Volume
| Issue : 12 | Page : 69-74
Clinical pattern of human immunodeficiency virus-associated sensory neuropathy among adults in Kano, Northwestern Nigeria
Musbahu Rabiu1, Aliyu Ibrahim2, Ahmad Maifada Yakasai3, Muhammad Hamza4, Lukman Femi Owolabi2
1 Department of Medicine, Murtala Mohammed Specialist Hospital, Kano, Nigeria
2 Department of Medicine, Neurology Unit, Aminu Kano Teaching Hospital, Bayero University Kano, Kano, Nigeria
3 Department of Medicine, Infectious and Tropical Diseases Unit, College of Medical Sciences, Public Health and Diagnostic Institute, Yusuf Maitama Sule University Kano, Kano, Nigeria
4 Department of Medicine, Infectious and Tropical Diseases Unit, Aminu Kano Teaching Hospital, Bayero University Kano, Kano, Nigeria
|Date of Web Publication||19-Nov-2018|
Department of Medicine, Neurology Unit, Aminu Kano Teaching Hospital, Bayero University Kano, No. 1 Zaria Road, PMB 3452, Kano
Source of Support: None, Conflict of Interest: None
Background: Peripheral neuropathy has implications for drug adherence and quality of life including the physical and emotional functioning in human immunodeficiency virus (HIV)-positive individuals. The debilitating impact on the ability to carry out their daily tasks is considerable and may sometimes become longstanding. The study assessed the frequency and determinants of HIV-associated sensory neuropathy (HIV-SN) in Kano, Northwestern Nigeria, with a view to provide optimal care. Methodology: A cross-sectional survey where the brief peripheral neuropathy screening (BPNS) benign familial neonatal seizures tool was administered to 380 HIV-positive clinic attendees using systematic random sampling was carried out. Potential risk variables were subjected to multivariate analysis modeling using logistic regression statistics to determine if they are independent predictors of the HIV-SN. Results: Of the 380 study participants, 263 (69.2%) were females, with a mean age of 37.4 ± 9.9 years. The mean CD4 count and duration of the diagnosis of HIV infection of the participants were 484.5 ± 254.9 cells/mm3 and 60.9 ± 43.5 months, respectively. Using the BPNS screening (BPNS) tool, 29.2% (111/380) of the participants had HIV-SN. Independent determinants of HIV-SN in our included age >40 years (odd ratio [OR] 5.86, 95% confidential interval [CI] = 2.48–13.88, P < 0.001) and type of highly active antiretroviral therapy combination used (OR 0.36, 95% CI = 0.17–0.73, P = 0.005). Conclusion: The frequency and determinants of HIV-SN prompt the need to strengthen early screening and treatment of HIV-infected patients by physicians managing them, to improve their overall quality of life.
Keywords: Determinants, neuropathy, screening
|How to cite this article:|
Rabiu M, Ibrahim A, Yakasai AM, Hamza M, Owolabi LF. Clinical pattern of human immunodeficiency virus-associated sensory neuropathy among adults in Kano, Northwestern Nigeria. N Niger J Clin Res 2018;7:69-74
|How to cite this URL:|
Rabiu M, Ibrahim A, Yakasai AM, Hamza M, Owolabi LF. Clinical pattern of human immunodeficiency virus-associated sensory neuropathy among adults in Kano, Northwestern Nigeria. N Niger J Clin Res [serial online] 2018 [cited 2020 Oct 19];7:69-74. Available from: https://www.mdcan-uath.org/text.asp?2018/7/12/69/245791
| Introduction|| |
Human immunodeficiency virus (HIV) may affect the nervous system directly producing distinct neurological syndromes or indirectly causing immunodeficiency states with resultant susceptibility to opportunistic infections, which is associated with high morbidity and mortality., These neurological disorders may negatively impact the patients' quality of life and adherence to medical treatments. However, with the significant increase in life expectancy of HIV-positive individuals since the commencement of highly active antiretroviral therapy (HAART) has changed the disease from being a terminal illness to a chronic condition that is associated with many comorbidities., There are two major types of HIV-associated sensory neuropathies: primary HIV-associated distal sensory polyneuropathy and ART toxic neuropathy, together which affect approximately 30%–67% of patients with advanced HIV disease. It is common at all stages of HIV infection, and the prevalence of the most common form of peripheral neuropathy, which is HIV-associated sensory neuropathy (HIV-SN) in the pre-HAART era was documented to be as high as 40% among patients with AIDS., The incidence of most neurological complications of HIV infection has fallen with the introduction of HAART; however, rates of peripheral neuropathy have been rising since the first effective antiretroviral drugs were developed particularly the nucleoside analog reverse transcriptase inhibitors (NRTIs).,, Recent evidences also suggest that the prevalence of peripheral neuropathy has remain high even in countries where known neurotoxic antiretroviral drugs such as stavudine and didanosine are no longer used., Other studies have highlighted that early identification, selection of less neurotoxic ART drugs, and management of the neuropathic pain symptoms are important in primary care setting to improve the overall quality of life of these patients. The brief peripheral neuropathy screening (BPNS) tool assesses both subjective and objective findings consistent with peripheral neuropathy. The tool was developed and validated by the National Institute of Health-AIDS clinical Trials group using physiologic (quantitative sensory threshold testing) and pathologic (epidermal nerve fiber density) testing as the reference standards. It is simple to administer specifically in a busy HIV/AIDS clinic settings and was used for the diagnosis in several large-scale cohort studies from low-resource settings.,, The National HIV sentinel survey of 2015 reported a National prevalence of 3.4% with Kano State having 1.3% of the HIV population. The paucity of data on the frequency and determinants of HIV-SN in this cohort of patients from Kano State with the largest population in the country prompted this study.
| Methodology|| |
The study was conducted at the HIV clinic in both Aminu Kano Teaching Hospital (AKTH) and Murtala Mohammed Specialist Hospital (MMSH), Kano, Nigeria, The former was established in 1988 and the latter in 1928, with bed capacities of 500 and 700, respectively. Kano State has an estimated population of 12,757,211 (Maternal, Newborn and Child Health in Nigeria Programme Phase 2 [MNCH2]-2013).
The study was a cross-sectional hospital-based survey on adult male and female patients with HIV infection attending the HIV clinic in both AKTH and MMSH, Kano, recruited using proportionate allocation. Eligible patients were adults aged 18 years and above, have satisfied the World Health Organization (WHO) clinical case definition for staging HIV/AIDS, and were enrolled from December 1, 2014 to November 31, 2015. The approval for the study was obtained from the Research and Ethics committees of both study centers.
We recruited 190HIV-positive HAART-naïve individuals and equivalent number on treatment, who satisfied the inclusion criteria, for both AKTH and MMSH using systematic random sampling. The researchers screened approximately four patients from the HAART naïve and treated groups at each site per week to achieve the required samples. The first person was randomly selected from the total number of potential participants booked and present on each clinic day, thereafter every nth person thereafter was then selected. (by dividing the total persons on the list [K] by the sample size to be selected per day [k], nth = K/k). Patients with other risks for peripheral neuropathy such as diabetes mellitus, chronic liver disease, chronic kidney disease, thyroid dysfunction, positive venereal diseases research laboratory test, history of chronic alcohol ingestion, on antituberculosis treatment, or patients who did not give consent were excluded from the study.
The demographic characteristics information collected on the questionnaire includes gender, age, educational status and health status information regarding their HAART use (current regimen combination and duration), height, weight, and CD4 count. The primary outcome of interest, which is the presence of HIV-SN, defined using the BPNS as the combination of a subjective neuropathy greater than Grade 0 (symptoms do not have to be bilateral to be graded as ≥1) and at least one bilateral objective finding. HIV-SN is when at least one subjective symptom with either an abnormal perception of vibrations using a 128 Hz tuning fork on the great toe and/or deep ankle reflexes bilaterally is present. Patients were asked to describe the presence or absence of neuropathic symptoms, which included pain, aching, or burning in feet and or legs; “pins and needles,” and or numbness in feet and/or legs. Their responses were documented as yes or no. Of the symptoms listed in the screening tool, the presence of numbness had the greatest diagnostic efficiency for identifying those with neuropathy. Vibration perception was evaluated using a 128 Hz tuning fork. The fork was maximally struck and applied on the great toe distal to the interphalengeal joint of each foot. Vibration sense was defined as normal when felt for >10 s, and abnormal when felt for <10 s or not at all. Ankle reflexes were determined using a flexible tendon hammer with the foot passively positioned and dorsiflexed slightly to obtain optimal stretch of the muscle and the Achilles tendon percussed directly. Reflexes were graded as absent, depressed (present only with reinforcement), and normal.
All data extracted were analyzed using IBM SPSS version 20.0 for Windows (SPSS Inc., Chicago, IL, USA). Information about each participant's demographic and clinical characteristics which included age, sex, educational status, weight, height, basal metabolic index, duration of diagnosis of HIV infection, WHO stage, current CD4 count, HAART status, duration of HAART use, symptoms, and signs of peripheral neuropathy were extracted from the completed questionnaire forms. Variables were further cross-tabulated and subjected to test of significance (Pearson's Chi-square test), and a P = 0.05 was considered statistically significant. Multivariate logistic regression was applied to further establish association with HIV-SN, while controlling for possible confounding variables.
| Results|| |
During the study period, 380 consenting adult outpatients with clinical diagnosis of HIV infection were enrolled. Two hundred and sixty three (69.2%) were females with a male-to-female ratio of 1:2.3 and 248 (65.3%) had nonformal type of education (mainly Arabic knowledge). The mean standard deviation (SD) age of the participants in the study was 37.4 ± 9.9 years, with a mean (SD) weight of 64.55 ± 14.29 kg, height of 1.65 ± 0.08 m, and BMI of 23.74 ± 5.07 kg/m2. The mean duration of diagnosis of HIV infection of the patients and exposure to HAART was 60.9 ± 43.5 and 31.6 ± 44.8 months, respectively. The study also showed that 167 (88.8%) and 23 (12.2%) were on first and second-line HAART, respectively [Table 1]. The overall mean CD4 count for all the participants was 484.5 ± 254.9 cells/mm3 (HAART exposed – 528.2 ± 226.5 cells/mm3 and HAART naïve – 440.7 ± 254.9 cells/mm3) with a mean CD4 count of 444.6 ± 287.7 cells/mm3 and 348.5 ± 254.8 cells/mm3 for those on first- and second-line HAART, respectively (P = 0.263).
Using the BPNS, 111 (29.2%) of the participants had clinical diagnosis of HIV-SN. The frequency of HIV-SN in the HAART experienced group was 42.1% (80/190) and 16.3% (31/190) in the HAART naive group (odds ratio [OR], 3.73, 95% confidential interval [CI]: 2.25–6.21, P < 0.0001). The variables associated with HIV-SN after variate analysis included; gender, age of patient, educational status, HAART treatment, duration of HAART usage, weight, height, and CD4 count [Table 2]. These variables were further subjected to multivariate logistic regression analysis considering that they can affect the nerves simultaneously. Type of HAART combination (OR: 0.34, 95% CI = 0.16–0.71, P < 0.004) and older age of the patients (OR: 5.54, 95% CI: 2.33–13.17, P < 0.001) were shown to be significant determinants of HIV-SN with the former being protective and the latter a risk [Table 3].
|Table 2: Clinical characteristics associated with human immune deficiency virus-associated sensory neuropathy using univariate analysis|
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|Table 3: Determinants of human immune deficiency virus-associated sensory neuropathy using multivariate logistic regression|
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| Discussion|| |
The overall frequency of HIV-SN from this study was found to be 29.2%. This was comparable to figures from Gabon and South-Africa, which reported 27.4% and 30%, respectively., It was, however, lower than figures reported in earlier studies from Nigeria, Tanzania, Rwanda, and India.,,, Possible explanation for these differences may include the earlier enrollment of patients on neurotoxic HAART regimen in the older studies and majority of their patients had a more advanced WHO staging with more likelihood of comorbidities necessitating the use of other neurotoxic drugs such as antituberculous therapy. Furthermore, nutritional and vitamin deficiencies associated with advanced WHO staging may have increased their predisposition to the development of peripheral neuropathy.
Figures reported from the Cameroun of 21% were lower, despite similar geographic and sociocultural characteristics between the two HIV populations. Probable explanation includes possible inherent selection bias in the design, where consecutive patients were enrolled in the study. Other postulates may include yet unidentified genes affecting mitochondrial function and genes involved in the regulation of inflammatory response that modify the risk for HIV-SN among patients exposed to neurotoxic ARTs and HIV infection, respectively.,
Age above 40 years was an independent predictor for the development of HIV-SN, similar to previous studies, which showed that advancing age was strongly associated with the occurrence of HIV-SN. This is consistent with known vulnerability of the ageing peripheral nervous system seen in most types of polyneuropathies, in addition to the use of HAART and other neurotoxic drugs.,,,,
The frequency of HIV-SN among HAART-naïve participants was comparable to earlier reports with similar study design., However, it was lower than previous figures from studies conducted in Nigeria, which may be partly explained by the use of another assessment tool and the significantly lower CD4 count in more than half of the HAART-naïve participants, reflecting the degree of immunosuppression, which is directly related to higher risk of peripheral neuropathy. In comparison to our study, figures reported from Ethiopia were lower, which may be explained by genetic differences in the mitochondrial haplogroup and possibly by the clades type of the HIV.,
The use of HAART for >12 months was significantly associated with the occurrence of HIV-SN in this study, which was similar to findings where longer duration of HAART use was documented to be an important risk factor for peripheral neuropathy. This may possibly be explained by the fact that these patients were more likely to have presented with more advanced disease, which may predispose them to the development of peripheral neuropathy. However, it contrasts with earlier findings reported from Nigeria and Rwanda, which did not show any association.,
The pathology of length-dependent degeneration of large peripheral nerve fibers makes taller individuals more prone to the development of SN, which led to the preposition that height measurements represent an effective way of identifying individuals at higher risk for neuropathy and prioritizing them to alternative HAART therapy, rather than neurotoxic HAART. Height was, however, not found to be a significant risk factor for the occurrences of HIV-SN from this study, possibly because most of the patients are of average height, in contrast to studies conducted in Australia and Indonesia that have documented height as an independent risk factor.,,
This study also revealed that 16.4% of the study patients with CD4 count below 200 cells/mm3 and HAART exposed were found to be associated with occurrence of HIV-SN, similar to report by earlier studies.,,,, Possible reasons proposed, included residual axonal injury even with restoration of immune function, immune reconstitution disorders, or the presence of other confounding neurotoxins associated with nutritional and vitamin deficiencies. However, an earlier study though using a different tool of assessment from Nigeria showed no association between low CD4 count and the increased risk of SN. The HAART category was observed to have a protective effect for HIV-SN consistent with similar reports linking better outcomes to the restorative immune function and lesser inflammatory response when compared to use of first-generation NRTIs.
Results of this study may be generalizable within the context that it was conducted on HIV-infected populations with similar clinical and demographic profiles. In addition, selection of more than one study site and randomization during the screening may have reduced the selection bias. Our findings should, however, be interpreted within the limitations of being cross-sectional in design, limiting our ability to assess the temporal relationship between the presence of cause or exposure (i.e., risk factors) and effect (i.e., presence of HIV-SN). The baseline screening parameters for HIV-SN before initiation of those on ART was also not available. Furthermore, description of subjective neuropathic symptoms by the study patients may lead to underreporting or overreporting bias.
There is the need for larger population-based prospective studies to assess the magnitude of HIV-SN and its risk factors, which should aim toward developing a national guideline for diagnosis and optimal management, consistent with our local needs and resources.
| Conclusion|| |
The frequency and determinants of HIV-SN from the study prompt the need to adopt strategies of careful screening that would enable its early detection, careful selection of HAART, and timely change in management to maintain good quality of life, particularly in older HIV-infected patients, which will improve overall care in our environment.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Morgello S, Estanislao L, Simpson D, Geraci A, DiRocco A, Gerits P, et al.
HIV-associated distal sensory polyneuropathy in the era of highly active antiretroviral therapy: The Manhattan HIV Brain Bank. Arch Neurol 2004;61:546-51.
Sani MU, Mohammed AZ, Adamu B, Yusuf SM, Samaila AA, Borodo MM, et al.
AIDS mortality in a tertiary health institution: A four-year review. J Natl Med Assoc 2006;98:862-6.
Justin CM, Bruce JB, Avi N. Neurological complications of HIV infection. Lancet Neurol 2005;4:543-55.
Hogg R, Fraser S, Lima V, Sterne JA, Grabar S, Bonarek M, et al
. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: A collaborative analysis of 14 cohort studies. Lancet 2008;372:293-9.
Habib AG, Yakasai AM, Owolabi LF, Ibrahim A, Habib ZG, Gudaji M, et al.
Neurocognitive impairment in HIV-1-infected adults in Sub-Saharan Africa: A systematic review and meta-analysis. Int J Infect Dis 2013;17:e820-31.
Cherry CL, Skolasky RL, Lal L, Creighton J, Hauer P, Raman SP, et al.
Antiretroviral use and other risks for HIV-associated neuropathies in an international cohort. Neurology 2006;66:867-73.
Schifitto G, McDermott MP, McArthur JC, Marder K, Sacktor N, Epstein L, et al.
Incidence of and risk factors for HIV-associated distal sensory polyneuropathy. Neurology 2002;58:1764-8.
Schütz SG, Robinson-Papp J. HIV-related neuropathy: Current perspectives. HIV AIDS (Auckl) 2013;5:243-51.
Evans SR, Ellis RJ, Chen H, Yeh TM, Lee AJ, Schifitto G, et al.
Peripheral neuropathy in HIV: Prevalence and risk factors. AIDS 2011;25:919-28.
Dubey TN, Raghuvanshi SS, Sharma H, Saxena R. HIV neuropathy in pre-HAART patients and it's correlation with risk factors in central India. Neurol India 2013;61:478-80. [Full text]
Cherry CL, McArthur JC, Hoy JF, Pettersen JA, Jones G, Worthington C, et al
. Sensory neuropathy in human immunodeficiency virus/acquired immunodeficiency syndrome patients: Protease inhibitor-mediated neurotoxicity. Ann Neurol 2006;59:816-24.
Cherry CL, McArthur JC, Hoy JF, Wesselingh SL. Nucleoside analogues and neuropathy in the era of HAART. J Clin Virol 2003;26:195-207.
Vermaak JR, Dave JA, Levitt N, Heckmann JM. Sensory neuropathy and metabolic risk factors in human immune deficiency virus infected South Africans receiving protease inhibitors. AIDS Res Ther 2015;12:30.
Smyth K, Affandi JS, McArthur JC, Bowtell-Harris C, Mijch AM, Watson K, et al.
Prevalence of and risk factors for HIV-associated neuropathy in Melbourne, Australia 1993-2006. HIV Med 2007;8:367-73.
Haanpää ML, Backonja MM, Bennett MI, Bouhassira D, Cruccu G, Hansson PT, et al.
Assessment of neuropathic pain in primary care. Am J Med 2009;122:S13-21.
Cherry CL, Wesselingh SL, Lal L, McArthur JC. Evaluation of a clinical screening tool for HIV-associated sensory neuropathies. Neurology 2005;65:1778-81.
Mehta SA, Ahmed A, Kariuki BW, Said S, Omasete F, Mendillo M, et al.
Implementation of a validated peripheral neuropathy screening tool in patients receiving antiretroviral therapy in Mombasa, Kenya. Am J Trop Med Hyg 2010;83:565-70.
Philomène KN, Thierry A, Landry O, James I, Yvonne AZ, Martine MM, et al
. Distal sensory polyneuropathy among HIV patients in Libreville in Gabon. Neurosci Med 2015;6:84-9.
Maritz J, Benatar M, Dave JA, Harrison TB, Badri M, Levitt NS, et al.
HIV neuropathy in South Africans: Frequency, characteristics, and risk factors. Muscle Nerve 2010;41:599-606.
Nigeria National Agency for the Control of AIDS, 2014. Global AIDS Response Country Progress Report, Nigeria; 2014.
Oshinaike O, Akinbami A, Ojo O, Ogbera A, Okubadejo N, Ojini F, et al.
Influence of age and neurotoxic HAART use on frequency of HIV sensory neuropathy. AIDS Res Treat 2012;2012:961510.
Mullin S, Temu A, Kalluvya S, Grant A, Manji H. High prevalence of distal sensory polyneuropathy in antiretroviral-treated and untreated people with HIV in Tanzania. Trop Med Int Health 2011;16:1291-6.
Tumusiime DK, Venter F, Musenge E, Stewart A. Prevalence of peripheral neuropathy and its associated demographic and health status characteristics, among people on antiretroviral therapy in Rwanda. BMC Public Health 2014;14:1306.
Luma HN, Tchaleu BC, Doualla MS, Temfack E, Sopouassi VN, Mapoure YN, et al.
HIV-associated sensory neuropathy in HIV-1 infected patients at the Douala general hospital in Cameroon: A cross-sectional study. AIDS Res Ther 2012;9:35.
Onwuegbuzie G, Ogunniyi A, Isamade E, Idoko J. Prevalence of distal symmetrical polyneuropathy among drug naïve HIV/AIDS patients in Jos. AJNS 2009;28:61-6.
Kamerman PR, Wadley AL, Cherry CL. HIV-associated sensory neuropathy: Risk factors and genetics. Curr Pain Headache Rep 2012;16:226-36.
Saylor D, Nakigozi G, Nakasujja N, Robertson K, Gray RH, Wawer MJ, et al.
Peripheral neuropathy in HIV-infected and uninfected patients in Rakai, Uganda. Neurology 2017;89:485-91.
Shurie JS, Deribew A. Assessment of the prevalence of distal symmetrical polyneuropathy and its risk factors among HAART-treated and untreated HIV infected individuals. Ethiop Med J 2010;48:85-93.
Robinson-Papp J, Gelman BB, Grant I, Singer E, Gensler G, Morgello S, et al.
Substance abuse increases the risk of neuropathy in an HIV-infected cohort. Muscle Nerve 2012;45:471-6.
Cherry CL, Affandi JS, Imran D, Yunihastuti E, Smyth K, Vanar S, et al.
Age and height predict neuropathy risk in patients with HIV prescribed stavudine. Neurology 2009;73:315-20.
Wadley AL, Cherry CL, Price P, Kamerman PR. HIV neuropathy risk factors and symptom characterization in stavudine-exposed South Africans. J Pain Symptom Manage 2011;41:700-6.
Lichtenstein KA, Armon C, Baron A, Moorman AC, Wood KC, Holmberg SD, et al.
Modification of the incidence of drug-associated symmetrical peripheral neuropathy by host and disease factors in the HIV outpatient study cohort. Clin Infect Dis 2005;40:148-57.
Obiako OR, Ogoina D, Abubakar SA, Muktar HM, Sheikh TL, Tabi-Ajayi E, et al.
The frequency and outcome of neuropathies among HIV/AIDS adults treated at a tertiary hospital in Kaduna State, Nigeria. Niger Postgrad Med J 2014;21:319-26. [Full text]
[Table 1], [Table 2], [Table 3]
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