The advent of antiretroviral therapy (ART) has significantly enhanced the prognosis of individuals living with HIV (PLHIV), mitigating morbidity and mortality as well as improving life expectancy.This study aims to assess the impact of ART initiation on the health-related quality of life (HRQoL) of PLHIV attending a national tertiary infectious disease hospital, using a validated multidimensional assessment tool.Prospective cohort study among newly diagnosed HIV-positive adults enrolled in San Lazaro Hospital. Participants completed the WHOQOL-HIV BREF questionnaire and evaluates six domains. Data were analyzed using descriptive statistics to summarize socio-demographic and clinical characteristics and HRQoL scores.The study enrolled 68 participants, primarily young adults aged 19-29 years (52.9%), male (95.6%), single (98.5%), and employed (60.3%). Most (83.8%) had baseline CD4 counts <200 cells/mm³, indicating advanced immunocompromise.  Baseline HRQoL scores showed moderate quality of life, with the highest scores in the level of independence (mean 3.29, SD 0.505) and environment domains (mean 3.28, SD 0.387). The lowest scores were recorded in the social relationships domain (mean 2.77, SD 0.608), suggesting issues with interpersonal support and social integration.The baseline findings show that most participants were young, male, single, and employed, reflecting the typical demographic pattern seen in Philippine HIV cases. Despite being economically active, many were already in a state of advanced immunosuppression at diagnosis. High independence scores indicate that they can still perform daily activities, likely due to their young age and active employment status. The environment domain also scored well, influenced by the study setting in a national tertiary hospital where healthcare access, information, and support services were readily available. Moderate physical and psychological scores suggest common pre-treatment symptoms such as fatigue, anxiety, and emotional distress, emphasizing the need for early medical and mental health interventions. The lowest social relationships score highlights persistent stigma, fear of disclosure, and social isolation experienced by PLHIV in the Philippines.Baseline findings revealed moderate HRQoL across all domains, highlighting significant social relationship challenges. This underscores the importance of integrating psychosocial and environmental interventions with clinical care during ART initiation. Further assessments at three-month follow-up will evaluate changes and predictors of HRQoL improvements.