Background: Acquired Immunodeficiency syndrome (AIDS) has been considered as a global major concem and one of the most serious problems where it claimed the life of more than 25 million people worldwide since its discovery three decades ago. Fortunately, the introduction of Highly Active Anti-Retroviral Therapy (HAART) has changed the normal history of AIDS into a chronic disease that require long time of treatment. Regrettably, a proportion of AIDS patients do not immunologically respond to HAART and their CD4 cells never hit the normal level despite that the viral replication is fully controlled by the treatment. This variation in the immunological response has been attributed to some host genes including those which encode Human Leukocyte Antigens (HLA). Study Objectives: To determine the frequency of HLA Class I and II alleles among Omani AIDS patients and compare it with healthy Omani individuals. It is also, to determine the frequency of HLA Class I and II alleles among good and poor AIDS responders to HAART and to investigate whether an association exists between a particular HLA allele and immunological response to treatment. Methods: A total of 102 healthy individuals and 81 AIDS male and female patients, attending Sultan Qaboos University Hospital (SQUH), aged between 22.5 and 69 years, were HLA genotyped using SSP-PCR technique. The frequencies of HLA alleles were compared between AIDS patients and the healthy individuals as well as between "good" and "poor" immunological responders to HAART. Viral load measurement and CD4 cells count for AIDS patients were performed according to standard techniques and results were obtained from the SQUH information System. Mean at 95% confidence, standard deviation and the median were computed for the quantitative data, whereas Relative risk (RR%) associated with the presence of particular allele as well as the etiological fraction (EFe%) and preventive fraction (PFe%) were used to describe the qualitative data. The Statistical Package for Social Sciences (SPSS version 19) was used for data processing and analysis. Results: The frequency of HLA-A30, HLA-B40, HLA-B44 and HLA-DQ6 were found to be higher among AIDS patients, while HLA-B6l and HLA-DR17 were most frequently observed among Omani healthy individuals. HLA Class I alleles which were detected at high prevalence among healthy and AIDS Omanis are HLA-AI, HLA-A2, HLA-AII, HLA-A32, HLA-B35, HLA-B51, HLA-B52, HLA-B58, HLA-Cw3, HLACw4 and HLA-Cw7. HLA-DR3, HLA-DR16, HLA-DQ2, and HLA-DOS, were the most frequent HLA Class II alleles detected among healthy and AIDS Omanis. Only two alleles, HLA-A68 and HLA-B15, were found to be responsible for more than 50% of the poor response to HAART. Both alleles belong to the HLA class 1 and none of them were encountered among the prevalent HLA alleles among Omani healthy individuals. Conclusion: Two HLA alleles from class I, HLA-A68 and HLA-B15, were found to be significantly correlated with more than 50% of the poor response to HAART. The results of this study are indicative and should be confirmed on a larger sample size.