CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

of 40 (IQR 36-46), 89%were on ART, 28% had low CD4 and 81%were treated for CIN3. The rate of HSIL+ recurrence was 16.7 per 100 woman-years for ECL and rose to 27.8 for ENL. Women with ENL were significantly more likely to be ≥40 years, compared to women with ECL (53% vs 39%, P=0.034) and report younger age of sexual debut, ≤16 years (39% vs 26%, P=0.059). At the end of follow-up, women with ENL experienced significantly higher recurrence than those with ECL (40% vs 27%; P=0.030). Women treated for ENL were 56%more likely to experience recurrence than women with ECL (Hazard Ratio: 1.56, 95% confidence interval: 1.02-2.39; P=0.039). Recurrence among women with ENL was associated with age ≥40 years (P=0.031) and antecedent pathology of CIN3 (P=0.052), but not with low CD4 <250 cells/µl (P=0.364) or ART use (P=0.975). Conclusion: Pre-cancerous lesions with endocervical involvement among HIV-infected women were more likely to occur in older women and were 36% less likely to be successfully treated with LEEP compared to lesions limited to the ectocervix. Immune status and ART did not modify recurrence risk after LEEP in HIV-infected women with endocervical involvement.

identification of group-specific genes: group 1-specific genes (n=22, e.g. ITIH5, PCBP4, NANOS1, PARP1) and group 2-specific genes [n=81, e.g. PTPRD, EYA4, TNMD, SFRP5, TIGIT, CDKN1A, UHRF1, IL-21R, CDC42, EGR3, SIRPG, CCL22, NR4A3, E2F8, SELL, CTLA4, ATF3, FCRL3). No significant difference in gene expression was found in dysplastic lesions fromwomen with or without recurrence/relapse, despite a trend for enrichment of neoplasia-associated genes observed in women with recurrence/relapse following LEEP. Conclusion: An enrichment in neoplasia-associated cervical gene expression was detected as an indicator of cervical dysplasia independently of high-risk HPV type infection, or of the potential for recurrence/relapse after LEEP excision in ART-suppressed women. Background: Women in sub-Saharan Africa have high dual burden of HPV and HIV infections, which can interact to increase cervical cancer (CC) risk. The 9-valent HPV (9vHPV) vaccine has high demonstrated effectiveness against HPV types causing 90% of CC. Additionally, one dose of the 9vHPV vaccine has the potential to achieve greater coverage at lower costs than a two-dose schedule. However, the potential impact of the single-dose 9vHPV vaccine in a high HIV prevalence setting has not been estimated while accounting for HPV-HIV interactions. Methods: We adapted a dynamic HIV transmission model to include HPV acquisition and CC pathogenesis and projected the impact of a single dose 9vHPV preadolescent vaccination in KwaZulu-Natal, South Africa. We report the health impact of HPV vaccination separately for HIV-negative women and HIV- positive women stratified by HIV treatment and CD4 count status. Results: At 90% coverage of females age 9 years with 80% lifelong vaccine efficacy, single dose HPV vaccination was projected to reduce both CC incidence and mortality by 56% at 70 years after the start of the vaccination program. Mortality reductions were highest in HIV-positive females at high CD4 counts (60%). Health benefits were reduced when assuming waning protection at 20 years, with a 30% reduction in CC and a 31% reduction in CC-associated mortality. Conclusion: Single dose 9vHPV vaccination is projected to avert substantial CC burden in South Africa and similar high HIV prevalence settings. Results were dependent on assumptions of vaccine coverage, efficacy, and waning. 661 COST-EFFECTIVENESS OF CERVICAL CANCER SCREENING IN WOMEN WITH HIV IN SOUTH AFRICA Nicole G. Campos 1 , Naomi Lince-Deroche 2 , Carla J. Chibwesha 3 , Cindy Firnhaber 4 , Pamela Michelow 5 , Gesine Meyer-Rath 6 , Lise Jamieson 2 , Suzette Jordaan 7 , Vivien Tsu 8 , Jose Jeronimo 9 , Jane Kim 1 1 Harvard University, Cambridge, MA, USA, 2 Health Economics and Epidemiology Research Office, Johannesburg, South Africa, 3 University of North Carolina Chapel Hill, Chapel Hill, NC, USA, 4 Clinical HIV Research Unit, Johannesburg, South Africa, 5 National Health Laboratory Service, Cape Town, South Africa, 6 Boston University, Boston, MA, USA, 7 National Health Laboratory Service, Johannesburg, South Africa, 8 PATH, Seattle, WA, USA, 9 Global Coalition Against Cervical Cancer, Arlington, VA, USA Background: Women with HIV face increased risk of human papillomavirus (HPV) acquisition and persistence, cervical intraepithelial neoplasia, and invasive cervical cancer. WHO guidelines recommend cervical cancer screening every three years for these high-risk women, but the cost-effectiveness of different screening strategies has not been established. Methods: To evaluate the health impact and cost-effectiveness of screening among women with HIV in South Africa, we modified a mathematical model of HPV infection and cervical disease to reflect co-infection with HIV. The model was calibrated to epidemiologic data from HIV-infected women in South Africa (i.e., age-specific prevalence of HPV; proportion of HPV type-specific infections in CIN3 and cervical cancer). Clinical and economic data were drawn from in- country data sources. The model was used to project reductions in the lifetime risk of cervical cancer, discounted life expectancy, discounted lifetime costs, and incremental cost-effectiveness ratios (ICERs) of alternative Pap and HPV DNA testing algorithms beginning at HIV diagnosis. We considered screening performed at 1-, 2-, or 3-year intervals. Strategies with an ICER below South Africa’s per capita GDP (2016 US$5,270) were considered ‘cost-effective.’ 660 IMPACT OF SINGLE-DOSE NANOVALENT VACCINE FOR HIV-HPV COINFECTION IN SOUTH AFRICA Nicholas Tan , Monisha Sharma, Ruanne V. Barnabas University of Washington, Seattle, WA, USA

Poster Abstracts

659 GENE PROFILE INFORMS HPV GRADE BUT NOT RELAPSE AFTER LEEP IN ART-SUPPRESSED HIV+HPV+ Emmanouil Papasavvas 1 , Andrew V. Kossenkov 1 , Livio Azzoni 1 , Nicola M. Zetola 2 , Agnieszka Mackiewicz 1 , Brian Ross 1 , Matthew Fair 1 , Surya Vadrevu 1 , Doreen Ramogola-Masire 2 , Cindy Firnhaber 3 , Luis Montaner 1 1 Wistar Institute, Philadelphia, PA, USA, 2 Botswana–UPenn Partnership, Gaborone, Botswana, 3 University of the Witwatersrand, Johannesburg, South Africa Background: No intrinsic human papillomavirus (HPV)-associated gene expression signature able to distinguish between high risk (HR) HPV infection, cervical histopathology, or recurrence following loop electrosurgical excision of the transition zone of cervix (LEEP) has been identified. Human immunodeficiency virus 1 (HIV-1) infection alters the course of HPV-associated oncogenesis, while the role of antiretroviral therapy (ART) in this process is controversial. We performed a cross-sectional study to assess the impact of the transcriptional profile of the cervical microenvironment on cervical histopathology, and on recurrence/relapse of pre-malignant lesions following LEEP in ART-suppressed HIV+HPV+ women. Methods: Gene array analysis was performed on RNA isolated from paraffin- embedded cervical tissue collected from ART-suppressed HIV+HPV+ women from: A) South Africa: 55 women recruited in three groups: HR (-) (group 1, n=16) and HR (+) (group 2, n=15) HPV with negative cervical histopathology, and HR (+) (group 3, n=24) HPV with Cervical Intraepithelial Neoplasia (CIN) grade 1/2/3. B) Botswana: 28 women with CIN2/3 lesion grade who underwent LEEP, recruited in two groups based on a 12-month follow-up: women with (n=13) and without (n=15) lesion recurrence/relapse. Tissue in this cohort was collected at the time of LEEP. All gene groups identified had false discovery rate (FDR) <15%, and fold change >1.5. Results: Neoplasia-associated genes (n=272 genes) were a feature of dysplasia independently of the presence of HR types, as suggested by enrichment in cervical CIN 1/2/3 dysplasia for MCM2, SMC1B, CXCL6, MMP12, POU4F1, IL-1A, IL-8, and TCAM1 among other genes. This finding was also supported by the

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