Abstract
Peripheral neuropathy (PN) is associated with advanced HIV disease and may be a complication of antiretroviral therapy (ART) or anti-tuberculosis (TB) drugs, specifically isoniazid (INH). The effect of non-ART-drug-related PN on treatment outcomes is yet to be determined. We analysed prospectively collected cohort data for HIV-infected ART-naive adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa from June 2004 to June 2009. Patients who presented with signs and symptoms of numbness or dysesthesia prior to initiation of ART were defined as having PN. Cox proportional hazard models were used to estimate the effect of PN alone (HIV-related PN) or PN with a history of INH use (TB-related PN) on mortality, lost to follow-up (LTFU), persistent and recurrent PN by 12 months of follow-up. Of the 9,399 patients initiating ART, 3.9 % had HIV-related PN while a further 1.8 % had TB-related PN. Patients with PN did not have a significantly higher risk of mortality compared to those without PN (hazard ratio (HR) 1.17 95 % CI 0.92–1.49). Patients with TB-related PN were less likely to be LTFU by 12 months (HR 0.65 95 % CI 0.44–0.97) compared to those without PN. Patients with HIV-related PN were at increased risk of persistent PN at 3 months post-ART initiation. Patients with HIV-related PN had a similar risk of recurrent PN compared to those with TB-related PN (HR 1.28 95 % CI 0.72–2.27). We demonstrate that patients with PN at initiation of ART present with advanced HIV disease. Completion of TB treatment may reduce the risk of persistent PN in patients with TB-related PN. Use of HIV drugs, even neurotoxic ones, may overall limit neuropathy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Amin J, Kaye M, Skidmore S, Pillay D, Cooper DA, Dore GJ (2004) HIV and hepatitis coinfection within the CAESAR study. HIV Med 5:174–179
Boulle A, Van Cutsem G, Hilderbrand K, Carol C, Musaed A, Shaheed M et al (2010) Seven-year experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa. AIDS 24(4):563–572
Brennan AT, Maskew M, Sanne I, Fox M (2010) The importance of clinic attendance in the first six months on antiretroviral treatment: a retrospective analysis at a large public sector HIV clinic in South Africa. J Int AIDS Soc 13:49
Chow KY, Ang LW, Verghesse I, Chew SK, Leo YS (2005) Measurable predictive factors for progression to AIDS among HIV-infected patients in Singapore. Ann Acad Med Singapore 34(1):84–89
Evans SR, Ellis RJ, Chen H, Yeh T, Lee JL, Schifitto G, Wu K, Bosch RJ, McArthur JC, Simpson DM, Clifford DB (2011) Peripheral neuropathy in HIV: prevalence and risk factors. AIDS 25(7):919–928
Fairall LR, Bachmann MO, Louwagie GM, van Vuuren C, Chikobvu P, Steyn D et al (2008) Effectiveness of antiretroviral treatment in a South African program: a cohort study. Arch Intern Med 168:86–93
Fox MP, Brennan A, Maskew M, MacPhail P, Sanne I (2010) Using vital registration data to update mortality among patients lost to follow-up from ART programmes: evidence from the Themba Lethu Clinic, South Africa. Trop Med Int Health 15(4):405–413
Gao X, Nau DP, Rosenbluth SA, Scott V, Woodward C (2000) The relationship of disease severity, health beliefs and medication adherence among HIV patients. AIDS Care 12:387–398
Gonzalez-Duarte A, Cikurel K, Simpson DM (2007) Managing HIV peripheral neuropathy. Curr HIV/AIDS Rep 4(3):114–118
Kigozi IM, Dobkin LM, Martin JN, Geng EH, Muyindike W, Emenyonu NI, Bangberg DR, Hahn JA (2009) Late disease stage at presentation to an HIV clinic in the era of free antiretroviral therapy in sub-Saharan Africa. J Acquir Immune Defic Syndr 52:280
Lichtenstein KA, Armon C, Baron A, Moorman AC, Wood KC, Holmberg SD (2005) Modification of the incidence of drug-associated symmetrical peripheral neuropathy by host and disease factors in the HIV Outpatient Study cohort. Clin Infect Dis 40:148
Maritz J, Benatar M, Dave JA, Harrison TB, Badri M, Levitt NS, Heckmann JM (2010) HIV neuropathy in South Africans: frequency, characteristics and risk factors. Muscle Nerve 41(5):599–606
Mehta SA, Ahmed A, Leverty M, Holzman RS, Valentine F, Sivapalasingam S (2011) Sex difference in the incidence of peripheral neuropathy among Kenyans initiating antiretroviral therapy. Clin Infect Dis 53:490–496
Menezes CN, Maskew M, Sanne I, Crowther NJ, Raal FJ (2011) A longitudinal study of stavudine-associated toxicities in a large cohort of South African HIV infected subjects. BMC Infect Dis 11:244
Mojumdar K, Vajpayee M, Chauhan NK, Mendiratta S (2010) Late presenters to HIV care and treatment, identification of associated risk factors in HIV-1 infected Indian population. BMC Public Health 10:416
Nash D, Katyal M, Brinkhof MW, Keiser O, May M, Hughes R, Dabis F, Wood R, Sprinz E, Schechter M, Egger M (2008) Long-term immunologic response to antiretroviral therapy in low-income countries: a collaborative analysis of prospective studies. AIDS 22(17):2291–230200
National Department of Health, Republic of South Africa. The South African National Antiretroviral Treatment Guidelines (2004). http://southafrica.usembassy.gov/media/2004-doh-art-guidelines.pdf. Accessed 26 October 2010
Parboosing R, Paruk I, Lalloo UG (2008) Hepatitis C virus seropositivity in a South African Cohort of HIV co-infected, ARV naïve patients is associated with renal insufficiency and increased mortality. Med Virol 80:1530–1536
Robertson K, Kumwenda J, Supparatpinyo K, Jiang JH, Evans S, Campbell TB et al (2011) A multinational study of neurological performance in antiretroviral therapy-naïve HIV-1-infected persons in diverse resource-constrained settings. J Neurovirol 17:438–447
Sacktor N (2002) The epidemiology of human immunodeficiency virus-associated neurological disease in the era of highly active antiretroviral therapy. J Neurovirol 8:115–121
Schifitto G, McDermott MP, McArthur JC, Marder K, Sacktor N, McClernon DR, Conant K, Cohen B, Epstein LG, Kieburtz K (2005) Markers of immune activation and viral load in HIV-associated sensory neuropathy. Neurology 64:842
Simpson SM, Kitch D, Evans SR, McArthur JC, Asmuth DM, Cohen B, Goodkin K, Gerschenson M, So Y, Marra CM, Diaz-Arrastia R, Shriver S, Millar L, Clifford DB (2006) HIV neuropathy natural history cohort study. Neurology 66:1679–1687
Singh NN, Roos KL (2011) Central nervous system complications in HIV (Overview) eMedicine Drugs, Diseases & Procedures. http://emedicine.medscape.com/article/1167008--overview. Accessed 23 Mar 2012
Singh N, Squier C, Sivek C, Wagener M, Nguyen MH, Yu VL (1996) Determinants of compliance with antiretroviral therapy in patients with human immunodeficiency virus: prospective assessment with implications for enhancing compliance. AIDS Care 8:261–269
Walensky R, Wood R, Ciaranello AL, Paltiel D, Lorenzana SB, Anglaret X, Stoler AW, Freedberg KA (2010) Scaling up the 2010 World Health Organization HIV treatment guidelines in resource-limited settings: a model-based analysis. PLoS 7(1–12):e1000382
Westreich D, MacPhail P, Van Rie A, Malope-Kgokong B, Ive P, Rubel D, Boulmé R, Eron J, Sanne I (2009a) Effect of pulmonary tuberculosis on mortality in patients receiving HAART. AIDS 23:707–715
Westreich D, Sanne I, Maskew M, Malope-Kgokong B, Conradie F, Majuba P, Funk M, Kaufman JS, Van Rie A, Macphail P (2009b) Tuberculosis treatments and risk of stavudine substitution in first-line antiretroviral therapy. Clin Infect Dis 48:1617–1623
World Health Organization. Antiretroviral therapy for HIV infection in adults and adolescents. 2010 Revision. Geneva, Switzerland: World Health Organization. 2010. http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf. Accessed 7 February 2012
Wuff EA, Wang AK, Simpson DM (2000) HIV-associated peripheral neuropathy: epidemiology, pathophysiology and treatment. Drugs 59:1251–1260
Acknowledgments
We would like to acknowledge the directors and staff of Themba Lethu Clinic (TLC), CHRU and Right to Care (RTC)—a PEPFAR (US President's Emergency Plan for AIDS Relief) funded NGO. We would like to acknowledge the Gauteng Provincial and National Department of Health for providing for the care of the patients at TLC as part of the National Comprehensive Care, Management and Treatment of HIV and AIDS programme. Lastly, we would like to sincerely thank the patients attending the Themba Lethu Clinic for their continued trust in the treatment and care provided at the clinic.
Source of funding
Funding was provided by United States Agency for International Development (USAID) under the terms of agreement 674-A-00-08-00007-00 with Right to Care (RTC). Denise Evans is supported by funding from the Claude Leon Foundation and NIH/CFAR/IAS Creative and Novel Ideas in HIV Research programme (Sub-award with UAB Center for AIDS Research: P30AI027767). The opinions expressed herein are those of the authors and do not necessarily reflect the views of NIH, NIAID, USAID, the Themba Lethu Clinic or Right to Care. Right to Care provides some funding for technical and logistic support and for the provision of treatment for patients in this study.
Conflict of interest
The authors have declared that no competing interests exist. Right to Care (RTC) provided some of the funding for the current research and also supports the provision of treatment for the patients in the study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Evans, D., Takuva, S., Rassool, M. et al. Prevalence of peripheral neuropathy in antiretroviral therapy naïve HIV-positive patients and the impact on treatment outcomes—a retrospective study from a large urban cohort in Johannesburg, South Africa. J. Neurovirol. 18, 162–171 (2012). https://doi.org/10.1007/s13365-012-0093-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13365-012-0093-2