Introduction: Discordant immuno-viral response, defined as a failure in increasing more than 100 CD4+ cells/μl T lymphocytes with an undetectable viral load at one year after initiation of a highly active antiretroviral therapy (HAART), is associated with an increase in mortality in people living with HIV (PLWH). This study explored a cohort of HIV-positive patients in a Peruvian hospital to determine factors associated with discordant immuno-viral response. Material and methods: A retrospective, analytical, cross-sectional single-site study was conducted, including PLWH receiving HAART with regular follow-up visits. In total, 310 PLWH, out of which 47 with a discordant response (DIR) and 263 with concordant immune response (CIR) fulfilled inclusion criteria for the study. Results: Main characteristics of our population were: age of onset of HAART around 35 years, male and heterosexual. Moreover, age over 65 years, from different hospital, co-infection, opportunistic infections, and baseline CD4+ > 250 cells/μl were significantly associated with DIR. Multivariate regression analysis showed basal CD4+ > 250 cells/μl and opportunistic infections associated with DIR. Conclusions: In our cohort, factors associated with the development of DIR are baseline CD4+ over 250 cells/μl and opportunistic infections.