High-risk vaccine-specific HPV infection in HIV-infected and HIV-uninfected, vaccine-naïve Asian female adolescents (Abstract no. MOAB0206) Sricharoenchai S, Bunupuradah T, Hansudewechakul R, Le HD, Ngoc HD T, Kerr S, Chalermchockcharoenkit A, Teeratakulpisarn N, Achalapong J, Ngoc DY, Termrungruanglert W, Chaithongwongwatthana S, Singtoroj T, Pankam T, Phanuphak N, Sohn AH, Chokephaibulkit K  TREAT Asia/ amfAR - The Foundation for AIDS Research Thailand: Faculty of Medicine Siriraj Hospital, Mahidol University, HIV Netherlands-Australia-Thailand Research Collaboration (HIV-NAT), Chiangrai Prachanukroh Hospital, Thai Red Cross AIDS Research Centre, Faculty of Medicine, Chulalongkorn University Vietnam: Hung Vuong Hospital, Children’s Hospital 1

Disclosures None to report

Background & Objectives Human papillomavirus (HPV) vaccine uptake has been inconsistent in resource-limited settings. It is unclear how well current vaccines would cover common HPV genotype infections among perinatally HIV-infected and HIV-uninfected adolescents and young adult (AYA) females in Southeast Asia. We studied high-risk vaccine-specific HPV types in the nonavalent vaccine, neutralizing antibody (NAb) to HPV-16 or 18, and factors associated with orogenital HPV infection in HPV vaccine-naïve AYA.

Methods Study design From 2013 to 2015 Prospective cohort study Study design From 2013 to 2015 At 5 sites in Vietnam (2) and Thailand (3) Perinatally HIV +ve & HIV- ve females Study population Age 12-24 years, sexually active and naïve to HPV vaccine No pregnancy and symptomatic STI at enrollment Matching criteria Age group Number of lifetime sex partners

Study procedures HPV infection Behavioral risks STI HPV genotyping (samples: oral rinse, swabs from cervical, vaginal, anal sites) Serum neutralizing Ab - HPV 16 & 18 HPV infection ACASI (audio-computer -assisted self-interview) Behavioral risks Cervical: C. trachomatis, N. gonorrhoeae, herpes simplex virus-2 Serum VDRL: Syphilis STI

Statistical analysis Participant characteristics Descriptive statistics Fisher’s exact test, Mann-Whitney U test HPV 16,18,31, 33,45,52, 58 HPV 6, 11 High-risk vaccine-specific genotypes (HRVS-9) 7 of 9 included in the vaccine Excluded: types associated with genital warts Associations with orogenital HPV infection, HRVS-9 genotypes at any site, positive NAb to HPV-16 or -18 Multiple logistic regression

Participant characteristics Characteristics at enrollment HIV-positive (n=93) N (%) or median (IQR) HIV-negative (n=99) P-value Age (years) 19 (17 to 20) 19 (18 to 20) 0.27 Lifetime sex partners, range (min-max) 2 (1-3), 1-22 2 (1-3), 1-50 0.76 Age at first sex 16 (15-17) 15 (14-17) 0.05 Asymptomatic STI C. trachomatis 24 (26%) 20 (20%) 0.39 N. gonorrhoeae 5 (5%) 0 (0%) 0.03 HSV-2 3 (3%) 0.25 Syphilis 2 (2%) 1.00 Always use condom when having sex? 31 (35%) 12 (12%) <0.001 STI: sexually transmitted infection; HSV: herpes simplex virus

Prevalence of HPV infection by HRVS-9 & HPV-16,18 NAb 49 (53%) 49 (49%) 43 (46%) 39 (39%) 26 (28%) 19 (22%) P=0.34 P=0.30 P=0.66 HRVS-9 genotypes Positive HPV-16,18 NAb HRVS-9 genotypes or Positive HPV-16,18 NAb

Prevalence of HPV infection by HRVS-9 & HPV-16,18 NAb stratified by AGE 20 (61%) 19 (58%) 28 (52%) 50 (48%) 42 (40%) 21 (39%) 17 (33%) 9 (27%) 19 (20%) P=0.16 P=0.18 P=0.42 HRVS-9 genotypes Positive HPV-16,18 NAb HRVS-9 genotypes or Positive HPV-16,18 NAb

Prevalence of HPV infection by HRVS-9 stratified by anatomical site 37 (41%) 34 (37%) 26 (28%) 29 (30%) 23 (23%) 17 (17%) 3 (3%) 3 (3%) Oral rinse Anus Cervix Vagina

Multivariate analysis Factors associated with infection with HRVS-9 at any site or NAb to HPV 16,18 Covariate Univariate analysis Multivariate analysis OR (95% CI) P-value aOR (95% CI) >1 asymptomatic STI 3.95 (1.93-8.05) <0.001 3.39 (1.56-7.39) 0.002 Ever used amphetamine-type stimulant 2.83 (1.05-7.58) 0.03 1.79 (0.60-5.35) 0.30 Ever been pregnant 0.63 (0.35-1.23) 0.12 0.54 (0.28-1.04) 0.06 Number of lifetime sex partners 1 2 ≥3 Ref. 2.58 (1.17-5.70) 4.63 (2.33-9.19) 1.83 (0.79-4.27) 3.34 (1.59-7.04) 0.006 Subgroup: HIV-positive HIV RNA >40 copies/ml 2.88 (1.91-6.96) 5.85 (1.97-17.39) 0.02 0.001 2.57 (1.01-6.52) 5.39 (1.78-16.33) 0.05 0.003 STI: sexually transmitted infection

Limitations Cross-sectional analysis, and age at HPV acquisition not known Recently acquired vs. persistent infection undistinguishable Neutralizing antibody was not measured against other vaccine types

Conclusions Half of all HPV vaccine-naïve female AYA in our study had evidence of prior vaccine-preventable HPV orogenital infection While HIV-uninfected AYA were more likely to engage high-risk behaviors, perinatally HIV-infected AYA had similar prior HPV infection and more cervical infection with HRVS-9 types In perinatally HIV-infected AYA, HIV-RNA >40 copies/mL and any non-HPV STI independently predicted increased HPV risk Greater access to HPV vaccination is needed in early adolescence in the region to prevent future cancer risk

Acknowledgements All patients, study staff, and participating sites in Thailand and Vietnam Eunice Kennedy Shriver National Institute of Child Heath and Human Development, National Institutes of Health, USA (R01HD073972) Joel Palefsky, University of California, San Francisco

Prevalence of HPV infection by each vaccine-specific genotype 23% 8% 22% 18% 10% 13% 10% 13% 11% 11% 5% 6 % 4% 0% 3% 2% 2% 1% HPV6 HPV11 HPV16 HPV18 HPV31 HPV33 HPV45 HPV52 HPV58