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HIV infected children remain at increased risk of HPV associated malignancies as they initiate sexual activity. Though they mount a vigorous immune response to the quadrivalent human papillomavirus (QHPV-6, -11,-16, and -18; Gardasil®) vaccine, durability of the immune response is uncertain. We assessed antibody responses to HPV 6, -11, -16 and -18 for up to 48 months following administration of quadrivalent human papillomavirus vaccine in HIV-infected girls and boys ages 9–14 years in Kenya. Of 178 girls and boys who had previously received three doses of the quadrivalent HPV vaccine, 176 enrolled into extended follow up for 4 years. HPV antibodies to -6, -11, -16 and -18 were measured at 24, 36 and 48 months after the first vaccine dose using the total immunoglobulin G immunoassay (IgG LIA). We evaluated the magnitude and trend in HPV vaccine response and the effect of plasma HIV-1 RNA on HPV vaccine response from month 24 to month 48 of follow up. At re-enrollment, 24 months after initial vaccination, median age of participants was 14 years (range 11–17); 167 (95%) were receiving antiretroviral therapy and 110 (66%) had plasma HIV RNA < 40 copies/mL. The rate of HPV seropositivity at 48 months was 83% for HPV-6; 80% for HPV-11; 90% for HPV-16; and 77% for HPV-18. There was a plateau in mean log10 HPV-specific antibody titer between month 24 and 48. The mean log10 HPV-type specific antibody titer for children with undetectable HIV viral load (<40) at the time of vaccination consistently remained higher for the 48 months of follow up compared to children with detectable viral load. Children with HIV infection may retain long term antibody response following HPV immunization. Further work to define whether HIV-infected children are protected from HPV acquisition with low levels of HPV antibodies is needed. [ABSTRACT FROM AUTHOR]