Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis
Tóm tắt
This cross-sectional study took place in the integrated tuberculosis (TB) clinic of a large outpatient clinic for HIV-infected patients in Kampala, Uganda. The purpose of this study was to describe the proportion of TB/HIV co-infected adults with virological failure, type and frequency of HIV drug resistance-associated mutations, and the proportion of patients with suboptimal efavirenz levels. HIV-1 plasma viral loads, CD4 cell count measurements, and efavirenz serum concentrations were done in TB/HIV co-infected adults. Genotypic resistance testing was performed in case of confirmed virological failure. After a median time on ART of 6 months, virological failure was found in 22/152 patients (14.5%). Of 147 participants with available efavirenz serum concentration, 26 (17.6%) had at least one value below the reference range, including 20/21 (95.2%) patients with confirmed virological failure. Genotypic resistance testing was available for 16/22 (72.7%) patients, of which 15 (93.8%) had at least one major mutation, most commonly M184V (81.2%) and K103NS (68.8%). We found a high proportion of TB/HIV co-infected patients with virological failure, the majority of which had developed relevant resistance-mutations after a median time on anti-retroviral treatment (ART) of 6 months. Virological monitoring should be prioritized in TB/HIV co-infected patients in resource-limited settings.
Tài liệu tham khảo
WHO. Global Tuberculosis Report. 2014.
Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC, et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med. 2003;163(9):1009–21.
Cohen K, Meintjes G. Management of individuals requiring antiretroviral therapy and TB treatment. Curr Opin HIV AIDS. 2010;5(1):61–9.
Shankar EM, Vignesh R, Ellegard R, Barathan M, Chong YK, Bador MK, et al. HIV-Mycobacterium tuberculosis co-infection: a ‘danger-couple model’ of disease pathogenesis. Pathog Dis. 2014;70(2):110–8.
Naidoo P, Peltzer K, Louw J, Matseke G, McHunu G, Tutshana B. Predictors of tuberculosis (TB) and antiretroviral (ARV) medication non-adherence in public primary care patients in South Africa: a cross sectional study. BMC Public Health. 2013;13:396.
Castelnuovo B, Nsumba M, Musomba R, Kaimal A, Lwanga I, Kambugu A, et al. Strengthening the “viral failure pathway”: clinical decision and outcomes of patients with confirmed viral failure in a large HIV care clinic in Uganda. J Acquir Immune Defic Syndr. 2015;70(5):e174–6.
WHO. Consolidated Guidelines ARV, chapter 7. 2013.
Rutherford GW, Anglemyer A, Easterbrook PJ, Horvath T, Vitoria M, Penazzato M, et al. Predicting treatment failure in adults and children on antiretroviral therapy: a systematic review of the performance characteristics of the 2010 WHO immunologic and clinical criteria for virologic failure. AIDS. 2014;28(Suppl 2):S161–9.
Bell LC, Breen R, Miller RF, Noursadeghi M, Lipman M. Paradoxical reactions and immune reconstitution inflammatory syndrome in tuberculosis. Int J Infect Dis. 2015;32:39–45.
Ezeamama AE, Mupere E, Oloya J, Martinez L, Kakaire R, Yin X, et al. Age, sex, and nutritional status modify the CD4 + T-cell recovery rate in HIV-tuberculosis co-infected patients on combination antiretroviral therapy. Int J Infect Dis. 2015;35:73–9.
Gupta RK, Brown AE, Zenner D, Rice B, Yin Z, Thomas HL, et al. CD4 + cell count responses to antiretroviral therapy are not impaired in HIV-infected individuals with tuberculosis co-infection. AIDS. 2015;29(11):1363–8.
Havlir DV, Kendall MA, Ive P, Kumwenda J, Swindells S, Qasba SS, et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med. 2011;365(16):1482–91.
Hermans SM, Castelnuovo B, Katabira C, Mbidde P, Lange JM, Hoepelman AI, et al. Integration of HIV and TB services results in improved TB treatment outcomes and earlier prioritized ART initiation in a large urban HIV clinic in Uganda. J Acquir Immune Defic Syndr. 2012;60(2):e29–35.
WHO. Guidelines for treatment of tuberculosis. 4th ed. 2010.
Rajesh L, Karunaianantham R, Narayanan PR, Swaminathan S. Antiretroviral drug-resistant mutations at baseline and at time of failure of antiretroviral therapy in HIV type 1-coinfected TB patients. AIDS Res Hum Retroviruses. 2009;25(11):1179–85.
Sinha S, Raghunandan P, Chandrashekhar R, Sharma SK, Kumar S, Dhooria S, et al. Nevirapine versus efavirenz-based antiretroviral therapy regimens in antiretroviral-naive patients with HIV and tuberculosis infections in India: a pilot study. BMC Infect Dis. 2013;13:482.
von Braun A, Scherrer AU, Sekaggya C, Kirangwa J, Ssemwanga D, Kaleebu P, Günthard H, Kambugu A, Castelnuovo B, Fehr J. High rates of multi class drug resistance in HIV-1 infected individuals monitored with CD4 count in Uganda. HIV Glasgow: Abstract; 2016.
Maggiolo F. Efavirenz: a decade of clinical experience in the treatment of HIV. J Antimicrob Chemother. 2009;64(5):910–28.
Breen RA, Swaden L, Ballinger J, Lipman MC. Tuberculosis and HIV co-infection: a practical therapeutic approach. Drugs. 2006;66(18):2299–308.
Manosuthi W, Sukasem C, Lueangniyomkul A, Mankatitham W, Thongyen S, Nilkamhang S, et al. CYP2B6 haplotype and biological factors responsible for hepatotoxicity in HIV-infected patients receiving efavirenz-based antiretroviral therapy. Int J Antimicrob Agents. 2014;43(3):292–6.
Barter DM, Agboola SO, Murray MB, Barnighausen T. Tuberculosis and poverty: the contribution of patient costs in sub-Saharan Africa—a systematic review. BMC Public Health. 2012;12:980.
Lee GQ, Bangsberg DR, Muzoora C, Boum Y, Oyugi JH, Emenyonu N, et al. Prevalence and virologic consequences of transmitted HIV-1 drug resistance in Uganda. AIDS Res Hum Retroviruses. 2014;30(9):896–906.