Effects of Sex, Existing Antibodies, and HIV-1-Related and Other Baseline Factors on Antibody Responses to Quadrivalent HPV Vaccine in Persons With HIV

Abstract

Background: We compared antibody (Ab) responses to a quadrivalent (types 6, 11, 16, and 18) human papillomavirus (HPV) vaccine between men and women with HIV-1.

Methods: A retrospective analysis of participant-level data from published clinical trials of HPV vaccine administered at study entry and at weeks 8 and 24 was conducted separately for baseline Ab undetectable and baseline Ab detectable using Ab titers and titer changes from baseline, respectively, at week 28 and year 1.5. Generalized estimating equations accounted for multiple HPV types and were adjusted for multiple baseline factors, including existing HPV antibodies before vaccination from natural exposure.

Results: We evaluated 575 participants with CD4+ count >200 cells/mm3, 323 men and 252 women: median ages 46 and 38 years, respectively. Week 28 and year 1.5 Ab titers were similar between men and women regardless of the baseline Ab detection in multivariate models. HIV-1 RNA ≥400 copies/mm3 was associated with a lower week 28 Ab response; in baseline Ab detectable, the baseline HPV Ab titer level, HPV DNA detection, and lower CD4+/CD8+ ratio were also associated with a lower response. CD4+/CD8+ ratio was a stronger predictor in the year 1.5 Ab analysis than in the week 28 analysis. Ab responses among baseline Ab detectable were only somewhat higher than those among baseline Ab undetectable (eg, type 16 week 28 median 3.46 vs 3.20 log10 mMU/mL) despite the existing baseline titer (median 1.74).

Conclusions: We did not find any sex differences of serologic response to HPV vaccine. Ab titer gain was lower in those with preexisting antibodies due to previous natural infection.

Trial registration: ClinicalTrials.gov NCT00604175 NCT00513526 NCT01461096.

Figure 1:

Log10-transformed HPV antibody titers by HPV type and sex. (A) Baseline Ab titers among participants with detectable Ab titer at baseline, (B) Week 28 Ab titers among participants with detectable Ab titer at baseline, (C) Week 28 Ab titers among participants with undetectable Ab titer at baseline, (D) Week 28 Ab titer changes from baseline among participants with detectable Ab titer at baseline, (E) Year 1.5 Ab titers among participants with detectable Ab titer at baseline, (F) Year 1.5 Ab titers among participants with undetectable Ab titer at baseline, (G) Year 1.5 Ab titer changes from baseline among participants with detectable Ab titer at baseline. The plots present medians with lower and upper quartiles (box), mean (diamond), 5th and 95th percentiles (whiskers).

Figure 2:

Forest plots of the effect sizes for the log10-transformed HPV antibody titer at Week 28 (4 weeks after the vaccination series) among participants without antibodies detected at baseline, from the GEE models including all four vaccine types. Regression coefficient estimates with 95% confidence intervals and p-values are shown: (A) full model for A5298 only, (B) full model for combined studies, and (C) final model for combined studies.

Figure 3:

Forest plots of the effect sizes for the change in log10-transformed HPV antibody titer from baseline at Week 28 (4 weeks after the vaccination series) among participants with antibodies detected at baseline, from the GEE models including all four vaccine types. Regression coefficient estimates with 95% confidence intervals and p-values are shown: (A) full model for A5298 only, (B) full model for combined studies, and (C) final model for combined studies.

Figure 4:

Forest plots of the effect sizes for the log10-transformed HPV antibody titer at 1.5 years after the vaccination series from the GEE models including all 4 vaccine types. Regression coefficient estimates with 95% confidence intervals and p-values are shown: (A) among participants without antibodies detected at baseline, full model (light color) and final model (dark color), and (B) among participants with antibodies detected at baseline, full model (light color) and final model (dark color).