This study confirmed whether children on the current treatment of choice for HIV infection, Highly Active Antiretroviral Treatment (HAART), exhibit better immune functioning than children on earlier forms of treatment, including sole exposure to Monotherapy/Combination Therapy (Mono-Combo) and "upgrading" from Mono-Combo to HAART (Conversion). It explored whether HAART protects areas of neuropsychological functioning previously found to be compromised in children perinatally infected with HIV more effectively than these earlier treatments. This study includes a unique population (i.e., predominantly minority, low SES status, and largely bilingual), and controls for a number of treatment variables that have not been previously considered. Using the Neurodevelopmental Model and the literature, it was hypothesized that more global functions (i.e., IQ indices besides processing speed) and functions developing earlier in life (i.e., language) would be less affected than more specific functions developing later in life (i.e., visual-motor integration and processing speed). Treatment groups included Mono-Combo, Converters, and HAART. Participants (N=161, 3 to 20 years) were assessed in language, visual-motor integration, processing speed, and IQ using standardized measures and procedures. Three MANCOVAS and an ANCOVA compared groups on immune and neuropsychological measures using age antiretroviral medications were started and years on antiretroviral medications as covariates. Results showed children on HAART have significantly better immune functioning than the Mono-Combo and Converter groups. Consistent with other studies that have controlled for demographic factors, language functioning was not affected by treatment type. Contrary to expectations, visual-motor integration was also not affected by treatment type. Interestingly, Converters were found to perform worse on processing speed than children only exposed to Mono-Combo or HAART. Consistent with expectations, the other IQ indices (i.e., VCI, POI, and FDI) were not affected by treatment type. Findings support the use of HAART globally to improve immune functioning. However, they also provide evidence that HAART does not more effectively protect areas of neuropsychological functioning previously found to be compromised than these former treatments, even when controlling for agents that cross the blood brain barrier, age medications were started, and years on medications. They also bring into question the possible effect of frequency and timing of regimen changes.