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Abstract

Patients with advanced human immunodeficiency virus (HIV) disease have a high risk of mortality, with tuberculosis (TB) being one of the leading causes. Empiric antituberculosis therapy could be considered as a strategy to reduced mortality although there is no strong evidence. This study aims to review the efficacy of empiric antituberculosis therapy in patient with advanced HIV disease compared to isoniazid prophylaxis therapy and assessed with mortality as outcome. A 46- year old male patient with advanced HIV disease on antiretroviral therapy (ARV) and liver cirrhosis was admitted to hospital due to difficulties in sleeping and walking. During hospitalization he had seizure followed by decreased consciousness hence TB meningitis was suspected. Latest laboratory results showed CD4 count of 132 cells/mm3 and negative TB examinations. He was given empiric antituberculosis therapy but later died during hospitalization. A systematic literature searching was conducted in PubMed, ScienceDirect, Scopus, Cochrane, and EMBASE using keywords according to clinical question resulting in 69 studies. Study selection was conducted according to eligibility criteria and two studies with open-label randomized trial design were selected. Eligible studies were critically appraised using the Oxford Center for Evidence-Based Medicine Critical Appraisal Worksheet. Both studies had good validity. In patients with advanced HIV disease, mortality at week 24 was 5.2% (95%CI 3.5-7.8%) in empiric antituberculosis therapy group and 5.2% (95%CI 3.4-7.8%) in isoniazid prophylaxis therapy group, with an absolute risk difference of -0.06% (95%CI −3.05-2.94%; p=0.97). Meanwhile, mortality at week 96 was 10.1% (95%CI: 7.5- 13.6%) in empiric antituberculosis therapy group and 10.5% (95%CI 7.9-13.9%) in isoniazid prophylaxis therapy group, with absolute risk difference of 0.4% (95%CI −3.8-4.6%; p=0.86). Based on critical appraisal on both studies, it can be concluded that empiric antituberculosis therapy is not effective in significantly reducing mortality compared to isoniazid prophylaxis therapy in patients with advanced HIV disease.

Bahasa Abstract

Pasien dengan penyakit human immunodeficiency virus (HIV) stadium lanjut memiliki risiko mortalitas yang tinggi, dengan salah satu penyebab utama mortalitas ialah tuberkulosis (TB). Terapi antituberkulosis empirik dapat dipertimbangkan sebagai strategi untuk mengurangi mortalitas namun belum memiliki bukti yang kuat. Laporan ini disusun untuk meninjau efektivitas terapi antituberkulosis empirik pada pasien dengan penyakit HIV stadium lanjut dibandingkan terapi profilaksis isoniazid dan dinilai dengan luaran mortalitas. Pasien laki-laki berusia 46 tahun dengan penyakit HIV stadium lanjut yang rutin mengonsumsi terapi antiretrovirus (ARV) dan sirosis hati dirawat di rumah sakit karena sulit tidur dan sulit berjalan. Dalam perawatan pasien mengalami kejang diikuti penurunan kesadaran yang dicurigai akibat meningitis TB. Hasil laboratorium terbaru jumlah CD4 132 sel/mm3 dan pemeriksaan TB negatif. Pasien diberikan terapi antituberkulosis empirik namun kemudian meninggal dunia dalam perawatan. Pencarian literatur secara sistematis dilakukan di PubMed, ScienceDirect, Scopus, Cochrane, dan EMBASE dengan kata kunci sesuai pertanyaan klinis dan menghasilkan 69 studi. Pemilihan studi dilakukan sesuai kriteria eligibilitas yang ditentukan, sehingga didapatkan dua studi terpilih dengan desain studi uji klinis acak terbuka. Telaah kritis terhadap studi terpilih menggunakan panduan dari Oxford Centre for Evidence- Based Medicine Critical Appraisal Worksheet. Kedua studi terpilih memiliki validitas yang cukup baik. Pada pasien dengan penyakit HIV stadium lanjut didapatkan mortalitas minggu ke-24 sebesar 5,2% (IK95% 3,5 – 7,8%) pada kelompok terapi antituberkulosis empirik dan 5,2% (IK95% 3,4 – 7,8%) pada kelompok terapi profilaksis isoniazid, dengan perbedaan risiko absolut -0,06% (IK95% −3,05 – 2,94%; p=0,97). Sementara itu, mortalitas pada minggu ke-96 sebesar 10,1% (IK95% 7,5 -13,6%) pada kelompok terapi antituberkulosis empirik dibandingkan dengan 10,5% (IK95% 7,9 – 13,9%) pada kelompok terapi profilaksis isoniazid, dengan perbedaan risiko absolut 0,4% (IK95% −3,8 – 4,6%; p=0,86). Berdasarkan telaah kritis terhadap kedua studi dapat disimpulkan terapi antituberkulosis empirik tidak terbukti efektivitasnya dalam menurunkan mortalitas secara signifikan dibandingkan terapi profilaksis isoniazid pada pasien dengan penyakit HIV stadium lanjut.

Kata Kunci: antituberkulosis empirik, penyakit HIV stadium lanjut

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