The incidence of pediatric infections by penicillin resistant Streptococcus pneumoniae (PRSP) is increasing worldwide. Chronically ill and immunocompromised children are at an increased risk of S. pneumoniae infections. Some such children may have increased NP colonization with PRSP. No data are available on the prevalence of PRSP in HIV-infected children in the United States. The objective of this study was to determine the prevalence of PRSP NP carriage among HIV-infected children. NP swabs were performed in 50 HIV-exposed and 50 HIV-infected children:Streptococcus pneumoniae (SP) was isolated from 11 (22%) HIV-exposed and 2 (4%) HIV-infected children (OR: 6.65, 95%:CI: 1.34-65.3 p=.015). The prevalence of PRSP in the HIV-exposed children was 36%. The isolates from the HIV-infected children were susceptible to penicillin. The most common isolate in both groups was Moraxella catharrhalis: 31 (62%) and 19 (38%) in the HIV-exposed and HIV-infected, respectively (p=.004). Day Care attendance, prior antibiotic treatment, and the presence of upper respiratory symptoms increased the risk of pneumococcal colonization in the HIV-exposed children. A number of variables may have influenced S. pneumoniae carriage in the HIV-infected children. Of the HIV-infected children, 30 were receiving TMP/SMZ and 7 Azithromycin; also, 25 were receiving monthly IVIG and 33 had received pneumococcal vaccine. When the risk of NP carriage of S. pneumoniae was adjusted for each of these four variables in the HIV-infected group, there was a decreased risk of NP colonization in children receiving TMP/SMZ, Azithromycin, IVIG and pneumococcal vaccine.Conclusion. These results suggest that S. pneumoniae colonization is not higher and the rate of PRSP is not greater in HIV-infected children. The use of TMP/SMZ, Azithromycin, IVIG and pneumococcal vaccine may decrease NP carriage of S. pneumoniae in HIV-infected children and thereby provide protection against S. pneumococcal infections.