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11:00am | 25-07-2018 | Hall 10 IAS 2018 Session Title: Keep your eyes on OIs and STIs

Natural history of anogenital HPV infection and related disease among HIV-positive men: Findings from a Cohort Study in South Africa. 11:00am | 25-07-2018 | Hall 10 IAS 2018 Session Title: Keep your eyes on OIs and STIs Admire Chikandiwa. Background.

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11:00am | 25-07-2018 | Hall 10 IAS 2018 Session Title: Keep your eyes on OIs and STIs

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  1. Natural history of anogenital HPV infection and related disease among HIV-positive men: Findings from a Cohort Study in South Africa • 11:00am | 25-07-2018 | Hall 10 • IAS 2018 Session Title: Keep your eyes on OIs and STIs • Admire Chikandiwa

  2. Background • Persistent high-risk (HR) HPV causes 88% of 35 000 anal and 50% of 26 000 penile cancers globally [1] • Anal CA are increasing globally-PLWHIV & MSM [2] • HIV alters the natural history of HPV infection [3-4]

  3. Cervical HPV infection as a model Transient Infection 70-80% <1 year Normal Cervix HR-HPV Infection 2-5 years 4-5 years 9-15 years Persistent Infection 20-30% Low grade LSIL CIN-1 High grade HSIL CIN-2/3 Invasive cancer

  4. Definition of key terms

  5. Objectives • Describe persistence of anal and genital HPV infection and related disease among MLHIV • Characterize correlates of persistent anal and genital HPV infection and anal squamous intra-epithelial lesions (SILs) among MLHIV • Explore the correlates of clearance of AGW

  6. Setting Gauteng province Limpopo (formerly Northern Province) Mpuma- langa North West KwaZulu Natal Free State Northern Cape Eastern Cape Western Cape

  7. Methods Enrolled 304 HIV+ Men • Sociodemographic and medical history Month 6 279 (92%) • Blood: CD4+ and HIV Plasma Viral Load Month 12 257 (85%) Anal and genital swabs: HPV DNA testing (RLA & PCR) Month 18 244 (80%) Anal smears: Bethesda Classification

  8. Methods Enrolled 304 HIV+ Men • Sociodemographic and medical history NILM Month 6 279 (92%) • Blood: CD4+ and HIV Plasma Viral Load ASCUS ASC-H Month 12 257 (85%) Anal and genital swabs: HPV DNA testing (RLA) LSIL HSIL Month 18 244 (80%) Anal smears: Bethesda Classification

  9. Baseline-characteristics of study population

  10. Persistent anal HPV infection (n=260) n=180 n=80

  11. Persistent anal HPV infection (n=260) n=180 n=59 n=80 n=21

  12. Persistent genital HPV infection (n=259) n=67 n=192

  13. Persistent genital HPV infection (n=259) n=67 n=124 n=192 n=68

  14. Persistent HPV infection by enrolment CD4+ count P-trend for persistence by CD4 count <0.05 n=29 n=19 n=23 n=15 n=15 n=10 n=6 n=12

  15. Progression of anal SILs

  16. Progression of anal SILs n=57 n=124 n=18 n=9 n=48 n=36 n=72

  17. Effect of persistent anal HPV infection on persistent SILs n=36 aOR=6.48 (1.16-35.93) aOR=3.98 (1.05-15.11) n=5 n=7 n=31 n=29

  18. Anogenital warts • Prevalence at enrolment was 12% (36/304) • Incidence rate was 1.4 (95% CI: 0.6-3.5) per 100 PYs • 33 (91%) of participants with AGW at enrolment were followed up until clearance

  19. Effect of CD4+ count on AGW clearance

  20. Discussion • About one third of anogenital HPV infections and SILs are persistent • Persistence of infection is mainly associated with low CD4+ count • Persistent infection drives persistent anal SILs • AGW clearance strongly influenced by CD4+ count • Limitations: • testing interval for HPV infection • use of anal cytology as proxy for histology

  21. Conclusion • HPV vaccination to prevent infection seems to be the best way to prevent HPV related disease • Role for anal screening for cancer not clear and feasible at present moment • Currently available treatment for AGW does not appear to be very effective • High levels of adherence (>95%) required for immunological reconstitution are often difficult to achieve in many LMICs

  22. References • de Martel, C., et al., Worldwide burden of cancer attributable to HPV by site, country and HPV type.Int J Cancer, 2017. • Shiels, M.S., et al., Impact of the HIV Epidemic on the Incidence Rates of Anal Cancer in the United States. JNCI 2012. 104(20): p. 1591-1598. • Chin-Hong, P.V. and J.M. Palefsky, Natural history and clinical management of anal human papillomavirus disease in men and women infected with human immunodeficiency virus. Clin Infect Dis, 2002. 35(9): p. 1127-34. • Schiffman, M., et al., Human papillomavirus and cervical cancer. Lancet, 2007. 370(9590): p. 890-907.

  23. Acknowledgements Study participants Co-authors: Pedro. T. Pisa, Catherine Tamalet, Etienne. E. Muller, Pamela Michelow, Matthew. F. Chersich, Philippe Mayaudand Sinead Delany-MoretlweGraphics and editing: Melody Joubert

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