IntroductionIndonesia antiretroviral therapy guideline suggests the use of Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-based regiments as first line of HIV treatment and Protease Inhibitor to replace NNRTI when treatment failure occurred. This case-control study was aimed to study factors predicting first-line ART treatment failure among HIV positive patients aged >15 years, non-pregnant, and registered in our institution, Indonesia. MethodsDiagnosis of HIV treatment failure was made according to the standard WHO criteria. Demographic and outcome variables were recorded. The association between variables were analyzed by Chi-square test with odds ratios (OR) and 95% confidence intervals (95% CI), followed by multivariate analysis using logistic regression test. ResultsTwenty-six index cases and 26 age- and sex-matched control cases were included in the study with a mean age of 32.27 ± 8.7 years and 32.88 ± 8.15 years, respectively. Median time for switching to second-line (Lopinavir/ritonavir, LPV/r) was 46.32 ± 30.21 months. Patients presented with tuberculosis and treated by nevirapine as the first-line treatment were 26.6-folds (95% CI: 2.41–293.81, p = 0.007) and 6.7–folds (95% CI: 1.56–28.45, p = 0.011) higher risk for treatment failure, respectively. ConclusionsThe presence of tuberculosis and the use of nevirapine in first-line treatment were strong predictors for first-line ARV treatment failure, suggesting for closer clinical monitoring for patients with those conditions. A further and larger prospective cohort study is needed to confirm the findings in this study.