Adverse drug reactions to antiretroviral therapy (ARVs): incidence, type and risk factors in Nigeria

BackgroundData on adverse drug reactions (ADRs) related to antiretroviral (ARV) use in public health practice are few indicating the need for ART safety surveillance in clinical care.ObjectivesTo evaluate the incidence, type and risk factors associated with adverse drug reactions (ADRs) among patients on antiretroviral drugs (ARV).MethodsPatients initiated on ARVs between May 2006 and May 2009 were evaluated in a retrospective cohort analysis in three health facilities in Nigeria. Regimens prescribed include nucleoside backbone of zidovudine (AZT)/lamivudine (3TC), stavudine (d4T)/3TC, or tenofovir (TDF)/3TC in combination with either nevirapine (NVP) or efavirenz (EFV). Generalized Estimating Equation (GEE) model was used to identify risk factors associated with occurrence of ADR.Results2650 patients were followed-up for 2456 person-years and reported 114 ADRs (incidence rate = 4.6/100 person-years).There were more females 1706(64%) and 73(64%) of the ADRs were reported by women. Overall, 61(54%) of ADRs were reported by patients on AZT with 54(47%) of these occurring in patients on AZT/NVP. The commonest ADRs reported were pain 25(30%) and skinrash 10(18%). Most ADRs were grade 1(39%) with only 1% being life threatening (grade 4). Adjusted GEE analysis showed that ADR was less likely to occur in patients on longer duration of ART compared to the first six months on treatment; 6-12 months AOR 0.38(95% CI:0.16-0.91) and 12-24 months AOR 0.34(95% CI:0.16-0.73) respectively. Compared to patients on TDF, ADR was less likely to occur in patients on d4T and AZT AOR 0.18(95% CI 0.05-0.64) and AOR 0.24(95% CI:0.7-0.9) respectively. Age, gender and CD4 count were not significantly associated with ADRs.ConclusionADRs are more likely to occur within the first six months on treatment. Close monitoring within this period is required to prevent occurrence of severe ADR and improve ART adherence. Further research on the tolerability of tenofovir in this environment is recommended.

[1]  I. Shah.  Adverse effects of antiretroviral therapy in HIV-1 infected children. , 2006, Journal of tropical pediatrics.

[2]  D. Dieterich,et al.  Drug-induced liver injury associated with the use of nonnucleoside reverse-transcriptase inhibitors. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[3]  Andrew Phillips,et al.  Hepatotoxicity in HIV-1-infected patients receiving nevirapine-containing antiretroviral therapy , 2001, AIDS.

[4]  P. Kissinger,et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. , 1998, The New England journal of medicine.

[5]  A. Mc,et al.  The necessity for a health systems reform in Nigeria. , 2004 .

[6]  H. Bang,et al.  Early versus standard antiretroviral therapy for HIV-infected adults in Haiti. , 2010, The New England journal of medicine.

[7]  R. Salamon,et al.  Incidence of and risk factors for adverse drug reactions in a prospective cohort of HIV-infected adults initiating protease inhibitor-containing therapy. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  R. Salamon,et al.  Haematological Changes in Adults Receiving a Zidovudine-Containing Haart Regimen in Combination with Cotrimoxazole in Côte D'ivoire , 2005, Antiviral therapy.

[9]  J. Beijnen,et al.  Case series of acute hepatitis in a non-selected group of HIV-infected patients on nevirapine-containing antiretroviral treatment , 2003, AIDS.

[10]  J. Hitti,et al.  Antiretroviral-Associated Toxicity Among HIV-1-Seropositive Pregnant Women in Mozambique Receiving Nevirapine-Based Regimens , 2007, Journal of acquired immune deficiency syndromes.

[11]  C. Coyle.  How Providers Treat HIV: An Analysis of Provider Opinion and Adoption of the 2012 DHHS Guidelines for the use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents , 2013 .

[12]  J. J. Henning,et al.  Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, January 28, 2000 , 1998, HIV clinical trials.

[13]  R. Hogg,et al.  Improved survival among HIV-infected patients after initiation of triple-drug antiretroviral regimens. , 1999, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[14]  F. Parazzini,et al.  Incidence of adverse reactions in HIV patients treated with protease inhibitors: a cohort study. Coordinamento Italiano Studio Allergia e Infezione da HIV (CISAI) Group. , 2000 .

[15]  N. Ives,et al.  Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy , 2002, AIDS.

[16]  B. Stilwell,et al.  Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach. 2006 revision. , 2006 .

[17]  R. Chaisson,et al.  Highly Active Antiretroviral Therapy in a Large Urban Clinic: Risk Factors for Virologic Failure and Adverse Drug Reactions , 1999, Annals of Internal Medicine.

[18]  M. Kamya,et al.  First-line antiretroviral therapy in Africa--how evidence-base are our recommendations? , 2005, AIDS reviews.

[19]  Matthias Egger,et al.  Electronic medical record systems, data quality and loss to follow-up: survey of antiretroviral therapy programmes in resource-limited settings. , 2008, Bulletin of the World Health Organization.

[20]  A Muñoz,et al.  Effectiveness of potent antiretroviral therapy on time to AIDS and death in men with known HIV infection duration. Multicenter AIDS Cohort Study Investigators. , 1998, JAMA.

[21]  S L Zeger,et al.  Regression analysis for correlated data. , 1993, Annual review of public health.

[22]  D. Mayers,et al.  A Comprehensive Hepatic Safety Analysis of Nevirapine in Different Populations of HIV Infected Patients* , 2003, Journal of acquired immune deficiency syndromes.

[23]  W. El-Sadr,et al.  Nevirapine‐associated toxicity in HIV‐infected Thai men and women, including pregnant women , 2007, HIV medicine.

[24]  R. Pollard,et al.  Safety profile of nevirapine, a nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus infection. , 1998, Clinical therapeutics.

[25]  E. Delaporte,et al.  Tolerability and effectiveness of first-line regimens combining nevirapine and lamivudine plus zidovudine or stavudine in Cameroon. , 2008, AIDS research and human retroviruses.

[26]  R. Johann-Liang,et al.  Hepatotoxicity associated with nevirapine use. , 2004, Journal of acquired immune deficiency syndromes.

[27]  N. Ford,et al.  Renal Safety of a Tenofovir-Containing First Line Regimen: Experience from an Antiretroviral Cohort in Rural Lesotho , 2011, PloS one.

[28]  C. Gilks,et al.  Glomerular Dysfunction and associated Risk Factors following Initiation of ART in Adults with HIV Infection in Africa: a subanalysis in the DART Trial. , 2006 .

[29]  British HIV Association (BHIVA) guidelines for the treatment of HIV‐infected adults with antiretroviral therapy , 2000 .

[30]  S. Zeger,et al.  Longitudinal data analysis using generalized linear models , 1986 .

[31]  J. Montaner,et al.  Adverse effects of antiretroviral therapy for HIV infection. , 2004, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[32]  P. Wright,et al.  Antiretroviral therapy in a thousand patients with AIDS in Haiti. , 2005, The New England journal of medicine.

[33]  T. Flanigan,et al.  Adverse effects of highly active antiretroviral therapy in developing countries. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[34]  R. Chaisson,et al.  Hepatotoxicity associated with nevirapine or efavirenz‐containing antiretroviral therapy: Role of hepatitis C and B infections , 2002, Hepatology.

[35]  B. Gazzard.  British HIV Association guidelines for the treatment of HIV‐1‐infected adults with antiretroviral therapy 2008 , 2005, HIV medicine.

[36]  G. Satten,et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. , 1998, The New England journal of medicine.

[37]  F. Parazzini,et al.  Incidence of Adverse Reactions in HIV Patients Treated With Protease Inhibitors: A Cohort Study , 2000, Journal of acquired immune deficiency syndromes.

[38]  J. Brooks,et al.  Clinical Toxicity of Highly Active Antiretroviral Therapy in a Home-Based AIDS Care Program in Rural Uganda , 2007, Journal of acquired immune deficiency syndromes.