Introduction: Prior studies assessing sex differences correlated with the levels of human immunodeficiency virus (HIV) RNA and absolute CD4 cell count in adults and children, treated or untreated with antiretroviral (ARV) therapy presented conflicting results. Objective: To assess comparative HIV RNA levels and absolute CD4 cell count in men and women from a large cohort of HIV-infected long term survivors patients. Methods: 462 HIV infected patients were analyzed cross-sectionally and longitudinally after being split into three groups: 156 naïve deceased patients, median age at death 10 years, 197 ARV treated patients, median age 17 years and 109 ARV treated patients, median age 23 years followed up until 2011. HIV RNA and absolute CD4 cell count were measured in all patients enrolled in the study. Results: In cross-sectional analysis of 156 naïve patients HIV RNA median levels were lower in females comparing to males, 4.95 vs. 5.73 HIV RNA log10 (copies/ml). Female absolute CD4 cell count was slightly higher, (median 97 vs. 65.5 cells/μL; P = 0.0001). Cross-sectional analysis of 197 ARV treated patients showed a lower log10 HIV RNA level in females compared to males, (P=0.0001), and also lower median CD4 count values in women, 336 cells/μL vs 456 cells/μL in men, P=.0001. Longitudinal analysis revealed statistically significant results: mean log viral loads were lower in females (F=13.90, P= 0.0009) and absolute CD4 cell count was lower in malse (F=16.72, P<0.0001), almost across all tested ages. Conclusion: We report steady sex differences in HIV RNA levels and absolute CD4 cell count in ART-treated HIV-infected patients, a fact that may suggest a reevaluation of our current treatment strategies according to sex.