Immunologic and Virologic Responses to Nevirapine Based Antiretroviral Therapy (ART) Among HIV-Tuberculosis Co-Infected Ugandan Children on Rifampicin Based Anti-Tubercular Treatment
DOI:
https://doi.org/10.17140/HARTOJ-2-104Keywords:
Nevirapine and rifampicin co-administration, HIV TB co-infected children, Immunologic and virologic outcomesAbstract
Background: Children co-infected with Human Immunodeficiency Virus (HIV) and Tuberculosis (TB) require concurrent treatment with anti-tuberculosis drugs and Antiretroviral therapy (ART). Drug interaction between nevirapine and rifampicin leads to decreased nevirapine levels. The impact of this drug-drug interaction on virologic and immunologic outcomes in the treatment of HIV - TB co-infected children has not been fully studied. A retrospective analysis was conducted to compare the response to nevirapine-based ART regimen among HIV- infected Ugandan children on a rifampicin containing anti-TB regimen for TB disease versus those only on ART.
Methods: We analyzed data from HIV infected children aged 6 months to 12 years attending a Paediatric HIV clinic in Kampala, Uganda who between October 2004-June 2006 were enrolled into an ART program based on the 2002 World Health Organization (WHO) ART guide lines for Resource Limited Settings. In this retrospective analysis, children were divided into two groups; those on nevirapine based ART and rifampicin containing anti-TB treatment (TB group) and those on ART alone (no TB group). CD4 cell percent and viral load data obtained at baseline and thereafter 12 weekly until 48 weeks was compared using Wilcoxon rank sum test. Kaplan Meir plots were used to compare virologic success between the two groups over the 48 week follow up period.
Results: The analysis included a total of 127 children of whom 20% (26/127) were in the TB group. Median log10 HIV RNA (Interquatile range-IQR) at baseline was 5.69 (5.19-6.19) in the TB group versus 5.59 (4.86-6.32) in the no TB group; p=0.576. Median viral load was undetectable for all children by 12 weeks post ART initiation and this was sustained through 48 weeks irrespective of receiving rifampicin. Baseline median CD4% was not significantly different between the two groups. The median CD4% (IQR) during follow- up for the TB group versus the no TB group was: 17.0 (8.0-26) versus 20.9 (8.0- 33.8), p=0.147 by 12 weeks; 26.0 (12.7-39.3) versus 22.9 (7.5-38.3), p=0.472 by 24 weeks; 26.6 (13.6-39.6) versus 26.4 (12.3 40.5), p=0.927 by 36 weeks and 29.0 (20.0-38) versus 28.9 (16.8-41), p=0.931 by 48 weeks respectively.
Conclusion: HIV/TB co-infected children receiving rifampicin demonstrated satisfactory immunologic and virologic responses to nevirapine based ART, similar to children not on anti- TB treatment. These findings provide evidence that nevirapine based ART may remain effective among HIV positive children co-infected with TB who receiverifampicin-based anti-TB treatment.
References
WHO. Global update on the health sector response to HIV 2014, World Health Organization. Website: http://www.who.int/ hiv/en/. 2015; Accessed 2015.
WHO. Global tuberculosis report 2013; , World Health Orga-nization. Website: http://apps.who.int/iris/handle/10665/91355. 2013; Accessed 2015.
WHO. Consolidated guidelines for use of antiretroviral drugs for treating and preventing HIV infection; recommendations for a public health approach. Website: http://www.who.int/hiv/pub/ guidelines/arv2013/en/. 2013; Accessed 15 Feb 2014.
Prasitsuebsai W, Cressey T, Capparelli E, et al. Pharmacoki-netics of nevirapine when co administered with rifampicin in HIV infected Thai children with tuberculosis in 16th Confer-ence on Retroviruses and Opportunistic Infections. Montreal, Canada. 2009.
Barlow-Mosha L, Musoke P, Ajuna P, et al. Early effective-ness of Triomune in HIV infected Ugandan children. in 3rd IAS Conference on HIV Pathogenesis and Treatment. Rio de Janeiro, Brazil. 2005.
Oudijk JM, McIlleron H, Mulenga V, et al. Pharmacokinetics of nevirapine in HIV-infected children under 3 years on rifampi-cin-based antituberculosis treatment. AIDS. 2012; 26(12): 1523- 1528. doi: 10.1097/QAD.0b013e3283550e20
Manosuthi W, Sungkanuparph S, Tantanathip P, et al. A ran-domized trial comparing plasma drug concentrations and effi-cacies between 2 nonnucleoside reverse-transcriptase inhibitor-based regimens in HIV-infected patients receiving rifampicin: the N2R Study. Clinical Infectious Diseases. 2009; 48(12): 1752-1759. doi: 10.1086/599114
Cohen, K, van Cutsem G, Boulle A, et al. Effect of rifampicin-based antitubercular therapy on nevirapine plasma concentra-tions in South African adults with HIV-associated tuberculosis. Journal of antimicrobial chemotherapy. 2008; 61(2): 389-393. doi: 10.1093/jac/dkm484
WHO. Scaling up antiretroviral therapy in resource-limited set-tings: guidelines for a public health approach: executive summary. Website: http://www.who.int/hiv/pub/prev_care/ScalingUp_E. pdf. 2002; Accessed 2015.
Musoke PM, Barlow-Mosha L, Bagenda D, et al. Response to antiretroviral therapy in HIV-infected Ugandan children ex-posed and not exposed to single-dose nevirapine at birth. JAIDS. 2009; 52(5): 560-568. doi: 10.1097/QAI.0b013e3181b93a5a
Barlow-Mosha L, Bagenda D, Mudiope P, et al. The long-term effectiveness of generic adult fixed-dose combination an-tiretroviral therapy for HIV-infected Ugandan children. African health sciences. 2013; 12(3): 249-258.
WHO. Antiretroviral therapy of HIV infection in infants and children: towards universal access: recommendations for a pub-lic health approach. Website: http://www.who.int/hiv/pub/guide-lines/art/en/. 2006; Accessed 2015.
Towler WI, Barlow-Mosha L, Church JD, et al. Analysis of drug resistance in children receiving antiretroviral therapy for treatment of HIV-1 infection in Uganda. AIDS research and human retroviruses. 2010; 26(5): 563-568. doi: 10.1089/ aid.2009.0164
Harries AD, Maher D, Graham S. TB/HIV: a clinical manual. 2004: World Health Organization. Website: http://www.who.int/ maternal_child_adolescent/documents/9241546344/en/. 2004; Accessed 2015.
Manosuthi W, Tantanathip P, Chimsuntorn S, et al. Treatment outcomes of patients co-infected with HIV and tuberculosis who received a nevirapine-based antiretroviral regimen: a four-year prospective study. International Journal of Infectious Diseases. 2010; 14(11): e1013-e1017. doi: 10.1016/j.ijid.2010.06.016
Shipton L, Wester C, Stock S, et al. Safety and efficacy of nevirapine-and efavirenz-based antiretroviral treatment in adults treated for TB-HIV co-infection in Botswana. The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease. 2009; 13(3): 360.
Bonnet M, Bhatt N, Baudin E, et al. Nevirapine versus efa-virenz for patients co-infected with HIV and tuberculosis: a ran-domised non-inferiority trial. The Lancet infectious diseases. 2013; 13(4): 303-312. doi: 10.1016/S1473-3099(13)70007-0
Venturini E, Turkova A, Chiappini E, et al. Tuberculosis and HIV co-infection in children. BMC infectious diseases. 2014. 14(Suppl 1): S5. doi: 10.1186/1471-2334-14-S1-S
Niemi M, Backman JT, Fromm MF, et al. Pharmacokinetic interactions with rifampicin. Clinical pharmacokinetics. 2003; 42(9): 819-850. doi: 10.2165/00003088-200342090-00003
Manosuthi W, Sungkanuparph S, Thakkinstian A, et al. Plasma nevirapine levels and 24-week efficacy in HIV-infected patients receiving nevirapine-based highly active antiretroviral therapy with or without rifampicin. Clinical infectious diseases. 2006; 43(2): 253-255. doi: 10.1086/505210
Sinha S, Dhooria S, Kumar S, et al. The antiretroviral effi-cacy of highly active antiretroviral therapy and plasma nevirap-ine concentrations in HIV-TB co-infected Indian patients receiv-ing rifampicin based antituberculosis treatment. AIDS Res Ther. 2011; 8(1): 41. doi: 10.1186/1742-6405-8-41
Ribera E, Pou L, Lopez RM, et al. Pharmacokinetic interac-tion between nevirapine and rifampicin in HIV-infected patients with tuberculosis. Journal of acquired immune deficiency syn-dromes (1999). 2001; 28(5): 450-453. doi: 10.1097/00126334- 200112150-00007
Matteelli A, Saleri N, Villani P, et al. Reversible reduction of nevirapine plasma concentrations during rifampicin treatment in patients coinfected with HIV-1 and tuberculosis. JAIDS. 2009; 52(1): 64-69. doi: 10.1097/QAI.0b013e3181b0328f
Ramachandran G, Hemanthkumar AK, Rajasekaran S, et al. Increasing nevirapine dose can overcome reduced bioavailabil-ity due to rifampicin coadministration. JAIDS. 2006; 42(1): 36- 41. doi: 10.1097/01.qai.0000214808.75594.73
Ira S, Soumya S, Geetha R, et al. Serum nevirapine and efa-virenz concentrations and effect of concomitant rifampicin in HIV infected children on antiretroviral therapy. Indian Pediat-rics. 2011; 48(12): 943-947. doi: 10.1007/s13312-011-0153-3
O’Brien DP, Sauvageot D, Zachariah R, et al. In re-source-limited settings good early outcomes can be achieved in children using adult fixed-dose combination antiretrovi-ral therapy. AIDS. 2006; 20(15): 1955-1960. doi: 10.1097/01. aids.0000247117.66585.ce
Wamalwa DC, Farquhar C, Obimbo EM, et al. Early response to highly active antiretroviral therapy in HIV-1- –infected Kenyan children. Journal of acquired immune de-ficiency syndromes (1999). 2007;. 45(3): 311. doi: 10.1097/ QAI.0b013e318042d613
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