PurposeDespite advancements in prevention, diagnosis, and treatment, HIV/AIDS remains a critical health concern, particularly in India. This study contributes valuable insights into HIV management strategies. This prospective and retrospective longitudinal observational study aimed to analyze the trends in CD4 cell count and viral load suppression among adult People Living with HIV (PLHIV) undergoing antiretroviral therapy (ART) and evaluate the influence of demographic factors and ART adherence on these parameters at the ART Centre of New Civil Hospital, Surat, India. Materials & methodsAdult PLHIV registered and initiated on ART between June 2017 and May 2018 at ART-NCH, Surat with Continuous follow-up until 2023 were included in the study. Data was collected and Statistical analysis was performed using Microsoft Excel and SPSS software. Other factors were evaluated for their influence on treatment outcomes. ResultsA longitudinally analyzed data from 365 adult PLHIV receiving ART with continuous follow-up until 2023 revealed significant trends, with CD4 counts increasing from 425 (1st month) to 612.67 (24th month), indicating improving immune function. Individuals on first-line ART regimens had significantly higher odds (OR: 3.5, 95 % CI: 1.1–11.3) of achieving CD4 counts ≥350 compared to those on second-line regimens. Adherence to treatment (OR: 1.98, 95 % CI: 1.1–3.4) also increased the odds of attaining CD4 counts ≥350. Viral load suppression was achieved in 353 out of 365 participants. ConclusionThis study highlights the need for tailored interventions to optimize immune recovery and viral load suppression among PLHIV. Recommendations include targeted intervention to improve long-term health outcomes.