Objective: To evaluate the efficiencies of the standard α thalassemia screening regimen in human immunodeficiency virus (HIV) infected patients and improve the efficiencies of this screening regimen using new cutoff values.Material and Methods: A screening process using the osmotic fragility (OF) test, the old cutoff values of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) at <80 fL and <22 pg, and the new cutoff values at <87 fL and <29 pg was performed in 300 HIV infected patients. After which, a genetic study was performed to detect common α thalassemia 1 genes deletions composed of Southeast Asian and THAI deletions and also for hemoglobin constant spring and hemoglobin Pakse mutations for α thalassemia 2 carriers. Screening efficiency was estimated by sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).Results: Sensitivity, specificity, PPV, and NPV of the original regimen for thalassemia screening in HIV infected patients were at 50.0%, 95.0%, 39.0% and 96.8%, respectively, demonstrating a high false positivity in HIV-1 infected populations. Therefore, new cutoff values for MCV and MCH were proposed at <87 fL and <29 pg, due to the highest value found in α thalassemia 1 carriers with HIV-1 infection. These new cutoff values showed higher sensitivity, specificity, PPV, and NPV at 100.0 92.6%, 46.2%, and 100.0%, respectively, and thus enhanced thalassemia screening efficiency in HIV-1 infected patients.Conclusion: Incorporation of the OF test and the new cutoff values for MCV and MCH improve the efficiencies of α thalassemia 1 screening in HIV-1 infected patients. This helps reduce the cost of confirming positive test results in α thalassemia screening.