Doravirine, Lamivudine, and Tenofovir Disoproxil Fumarate belong to the class of anti-viral drugs and have been widely used in the treatment of HIV-I infection. Doravirine is a novel non-nucleoside reverse transcriptase inhibitor used in the combination of Lamivudine and Tenofovir Disoproxil Fumarate to effectively treat HIV/AIDS by overcoming the common resistance mutations without any possible drug interactions when co-administered. A literature review has reported few methods for the simultaneous estimation of Doravirine, Lamivudine, and Tenofovir Disoproxil Fumarate in combination with other antiviral drugs. The present investigation aimed to develop a simple, rapid, economical and stable indicating RP-HPLC method for the simultaneous estimation of Doravirine, Lamivudine and Tenofovir Disoproxil Fumarate in the pharmaceutical dosage form. The chromatographic separation was achieved on Kromasil C18 column with the dimensions of 250 x 4.6 mm, 5µm particle size, and maintained at 30 ˚C at a wavelength of 260nm. A combination of buffer (0.1% OPA) and Acetonitrile as mobile phase has optimized the method for efficient separation of drugs. Doravirine, Lamivudine and Tenofovir Disoproxil Fumarate were eluted at 2.431, 3.187min, and 4.338, respectively, with good resolution. The linear regression coefficient for Doravirine, Lamivudine and Tenofovir Disoproxil Fumarate was 0.999 across the concentration range of 12.5-75µg/mL (Doravirine), 37.5-225 µg/mL (Lamivudine and Tenofovir Disoproxil Fumarate respectively). The proposed drugs were subjected to forced degradation studies and further validated as per ICH Guidelines. No interferences were observed, and the peak purity index was found to be within limits.INTRODUCTION: Doravirine 1, 4 (DOR, MK-1439) is a novel non-nucleoside reverse transcriptase inhibitor helpful in the treatment of HIV-I infection. DOR was first approved by the US Food and Drug Administration (FDA) in two formulationsas a complete once-daily dose regimen in combination with two NRTIs,