INTRODUCTION: Human immunodeficiency virus (HIV) infects cells expressing CD4 molecules that are main receptors for the virus. HIV targets CD4+ (cluster of differentiation -4) T-lymphocyte cells resulting into their depletion. CD4+ T-lymphocyte cell counts usually fall as HIV disease progresses. Antiretroviral drugs suppress viral replication and prevent the virus from infecting more CD4+ T-lymphocyte cells. Highly active antiretroviral therapy (HAART) may vary in ability to suppress viral load and rebound of CD4+ T-lymphocyte cell count in people infected by different HIV-1 subtypes, possibly due to differences in resistance development. Extensive studies have been conducted on subtype B and showed higher baseline CD4+ T-lymphocyte cell counts and maintain this advantage throughout therapy; however, limited data is available on the immunological response to HAART among patients infected by the prevalent non-B subtypes in Tanzania. OBJECTIVE: The aim of this study was to compare the rate of CD4+ T-lymphocyte cells rebound among AIDS patients infected by different HIV-1 subtypes on antiretroviral drugs therapy. METHODOLOGY: A longitudinal study was conducted at the infectious disease clinic (IDC) and Child Centered Family Care Clinic (CCFCC) of the KCMC. Ethical clearance was applied for from the Ethics committee of KCM College and a permission to conduct this study was granted by the Executive Director of KCMC. Consenting AIDS patients eligible to start first-line antiretroviral drugs therapy and those switching to the second line antiretroviral drugs therapy were enrolled in this study. For those aged below 18 years consent forms were signed by their parents or guardians. Whole blood samples were collected during enrollment and at 3 months after initialization of treatment. CD4+ T-lymphocyte cells were estimated and plasma was separated out and stored at -80°C. HIV-1 subtyping was performed employing peptide-binding enzyme immunoassay (PEIA) on plasma samples using synthetic peptides representing HIV-1 genotypes A-E derived from consensus gp120 V3 sequences RESULTS: A total of 104 participants were enrolled in this study at IDC and CCFCC of KCMC. Among them 59.6% were females and males were 40.4%. The mean age was 39.3 years (range from 17 to 74 years). Among the participants receiving ARVs, 85.7% females were on first line ARV and 8.9% females were on second line ARV, 87.2% males were on first line ARV and 12.8% males were on second line ARV. Of 63 samples that were subtyped, 46.0% were subtype A, 36.5% were subtype C, 15.9% were subtype D, 1.6% was subtype B. The remaining samples 39.4% did not react to any of the peptides. At enrollment, there was a difference in mean CD4+ T- lymphocyte cells count among the HIV-1 subtypes. A significant difference was observed between subtypes A and D. The same findings were observed at three months of treatment whereby individuals with subtypes A and D showed a significant difference. In conclusion, there was an increase in CD4+ T-lymphocyte cells count among AIDS patients infected by different HIV-1 subtypes at three months on ART in Moshi, Kilimanjaro. DISSEMINATION OF RESULTS: The results of the present study will be published in peer reviewed journals, presented at various scientific conferences and the report will be submitted to KCM College and Ministry of Health and Social Welfare.