HIV-infected patients are at increased risk of human papillomavirus (HPV) acquisition and HPV-associated diseases. This study set out to determine whether a two-dose (2D) HPV vaccination schedule was sufficient in HIV-infected adolescents with immune reconstitution (IR) following antiretroviral treatment. Participants aged 9–15 years who had CD4 cell counts > 500 cells/mm3
and HIV-1 RNA < 40 copies/mL for at least one year were assigned to the 2D schedule, while older participants or those without IR received a three-dose (3D) schedule. Antibodies to HPV-16 and -18 were measured using a pseudovirion-based neutralization assay. A total of 96 subjects were enrolled; 31.3% and 68.7% received the 2D and 3D schedule, respectively. Of these, 66.7% and 57.6% of the 2D and 3D participants, respectively, were male. The seroconversion rates for HPV-16 and HPV-18 were 100% in all cases, except for HPV-18 in males who received the 3D schedule (97.4%). In males, the anti-HPV-16 geometric mean titers (GMTs) were 6859.3 (95% confidence interval, 4394.3–10,707.1) and 7011.1 (4648.8–10,573.9) in the 2D and 3D groups (p
= 0.946), respectively, and the anti-HPV-18 GMTs were 2039.3 (1432.2–2903.8) and 2859.8 (1810.0–4518.4) in the 2D and 3D (p
= 0.313) groups, respectively. In females, the anti-HPV-16 GMTs were 15,758.7 (8868.0–28,003.4) and 26,241.6 (16,972.7–40,572.3) in the 2D and 3D groups (p
= 0.197), respectively, and the anti-HPV-18 GMTs were 5971.4 (3026.8–11,780.6) and 9993.1 (5950.8–16,781.1) in the 2D and 3D groups (p
= 0.271), respectively. In summary, a 2D schedule is as immunogenic in young adolescents with IR as a 3D schedule in older subjects and those without IR.