The safety and effect of an acetone-water neem leaf extract (IRAB) on CD4 cells was investigated in 60 HIV/AIDS patients as part of an ongoing study to determine the influence of neem on immunity and viral load in HIV/AIDS. Patients were confirmed as HIV I or II positive, as having CD4 cell count, less than 300 cells/microL, and as antiretrovirally naïve. They were given oral IRAB (1.0 g daily for 12 weeks). Clinical and laboratory tests were carried out at baseline and at 4 weekly intervals. Thus, the patients served as their own controls. Sixty patients completed treatment. Fifty (83.33%) were completely compliant with respect to laboratory tests. Increase in mean CD4 cells, 266 cells/microL (159%), for the 50 patients was significant (P < 0.001) between baseline and week 12. Erythrocyte sedimentation rate (64 mm/hr at baseline) was 16 mm/hr at week 12, whereas total number of incidences of HIV/AIDS-related pathologies decreased from 120 at baseline to 5. Mean bodyweight, hemoglobin concentration, and lymphocyte differential count increased significantly by 12% (P < 0.05), 24% (P < 0.0001), and 20% (P < 0.0001), respectively. There were no adverse effects and no abnormalities in kidney and liver function parameters. The results support the safety of IRAB in HIV/AIDS, and its significant influence on CD4 cells may be useful in the formulation of multidrug combination therapies for HIV/AIDS. However, its antiretroviral activity is being evaluated in our laboratory.