CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

656LB INTERIM SAFETY ANALYSIS OF CITN-12: PEMBROLIZUMAB IN PATIENTS WITH HIV AND CANCER Thomas S. Uldrick 1 , Priscila H. Gonçalves 2 , Steven Fling 1 , Brinda Emu 3 , Marc S. Ernstoff 4 , Judith Kaiser 1 , Matthew Lindsley 2 , Lisa Lundgren 1 , Kathryn Lurain 2 , Rob Gorelick 5 , Frank Maldarelli 2 , Elad Sharon 2 , Robert Yarchoan 2 , Martin “Mac” A. Cheever 1 1 Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 2 National Cancer Institute, Bethesda, MD, USA, 3 Yale University, New Haven, CT, USA, 4 Roswell Park Cancer Institute, Buffalo, NY, USA, 5 National Cancer Institute, Frederick, MD, USA Background: Anti-PD-1 and anti-PD-L1 antibodies are becoming mainstays of cancer therapy. The safety of pembrolizumab, an anti-PD-1 humanized monoclonal antibody, is being evaluated in patients with HIV and cancer. The effect of anti-PD-1 therapy on HIV reservoirs is unknown. Methods: Cancer Immunotherapy Trials Network (CITN)-12 is a multicenter study of pembrolizumab in patients with HIV and advanced cancers. Three CD4 defined cohorts (C) are accruing; C1: 100-199, C2: 200-350, and C3: >350 cells/uL. Eligibility: >4 weeks antiretroviral therapy (ART), HIV viral load <200 copies/mL. Treatment: pembrolizumab 200mg intravenously every 3 weeks for up to 2 years. Primary objective: assess safety and tolerability by summarizing CTCAEv4 graded adverse events (AEs) and evaluating HIV viral load (VL) and CD4 counts. Immune mediated AEs are managed using standard guidelines. We performed an interim analysis of treatment emergent adverse events at least possibly related to pembrolizumab (rTEAEs), serious AEs, and CD4 counts on therapy. Plasma HIV VL was measured by an HIV gag single copy assay (SCA). Results: 17 patients were accrued starting April 2016 and followed through May 2017. Characteristics: 1 woman, 16 men; median age 56 years (range 43-77); Cancers: lymphoma (3), Kaposi sarcoma (1), anal (5), tonsil (1), lung (2), bladder (1), hepatocellular (1), pancreatic (1), cholangiocarcinoma (1). Safety was observed over 100 total cycles, median 4 (range 1-20). 82 rTEAEs were observed and comparable between cohorts. 93%were grade 1-2. Ten primary serious AEs were observed, 2 possibly attributable to pembrolizumab, both in the setting of progressive malignancy. Immune mediated AEs: subclinical hypothyroidism 6 (35%), pneumonitis (2) and liver test elevations (2). Median CD4 increased over time, changes did not reach statistical significance. HIV remained suppressed on ART in all patients. In a subset of 14 patients, baseline median HIV VL by SCA was 0.8 copies/mL (range: <0.3-9.9); In an evaluation of plasma HIV kinetics over the first two cycles, no significant increases from baseline were noted. Conclusion: Pembrolizumab has an acceptable safety profile to date in patients with cancer and suppressed HIV on CITN-12, with no evidence of increased HIV VL over 6 weeks of therapy. Anti-PD1 therapy is appropriate for FDA approved indications in HIV-infected patients. Studies evaluating HIV latency reversal and HIV-specific immunity are underway. 657 SUPPRESSIVE ART ASSOCIATED WITH EFFECTIVE TREATMENT OF CERVICAL PRECANCER Christina Carlander 1 , Philippe Wagner 2 , Astrid van Beirs 3 , Aylin Yilmaz 4 , Kristina Elfgren 5 , Joakim Dillner 1 , Anders Sönnerborg 1 , Pär Sparén 1 1 Karolinska Institute, Stockholm, Sweden, 2 Uppsala University, Uppsala, Sweden, 3 Linköping University, Linköping, Sweden, 4 Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden, 5 Karolinska University Hospital, Stockholm, Sweden Background: It is uncertain what effect suppressive antiretroviral therapy (ART) (HIV-RNA<50 copies/mL) has on the results of CIN2+ treatment among women living with HIV (WLWH). We conducted a matched register-based national cohort study with the aim of analyzing: 1) if WLWH in Sweden have a poorer outcome after treatment of CIN2+ than HIV-negative women 2) to identify predictors of CIN2+ treatment failure and recurrence. Methods: The Swedish National HIV Registry and the Swedish Population Registry were linked with the Swedish National Cervical Screening Registry. We identified all WLWH, living in the Counties of Stockholm and Gothenburg sometime between 1983 and 2014, with a diagnosis of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). For each WLWH we randomly selected two HIV-negative women, living in the same counties sometime between 1983 and 2014, diagnosed with CIN2+, matched for country of birth. Additional data, such as surgical method, was collected frommedical records. Treatment failure was defined as the presence of an abnormal cervical cytology/histology at initial follow-up. Recurrence was defined as the presence of CIN1+ subsequent to an initial normal follow-up. Logistic regression and Cox regression were

used to estimate the effect of predictors of treatment failure and recurrence respectively. All models were adjusted for age and birth region. Results: A total of 140 WLWH and 284 HIV-negative women were treated for CIN2+ and had at least one follow-up cervical cytology/histology within one year and were not treated with a hysterectomy. WLWH were three times more likely to have a treatment failure (odds ratio (OR) 3.3 (95% CI 2.1-5.2) and five times more likely to recur (hazard ratio 5.0 (95% CI 2.1-11.6) than HIV-negative women. Suppressive ART at time of treatment of CIN2+ was associated with reduced odds of treatment failure (OR 0.4 (95% CI 0.2-0.8)). Advanced immunosuppression (CD4+T-cell/μL<200) at time of treatment of CIN2+ was associated with almost nine times higher odds of treatment failure than a CD4 count ≥500 (OR 8.9 (95% CI 2.9-27.7). Conclusion: To our knowledge this is the first study to show that suppressive ART and CD4 counts ≥500 at time of treatment are both associated with an effective treatment of CIN2+. An early HIV diagnosis, immediate ART and continuum of care are all essential to reach successful CIN2+ treatment.

Poster Abstracts

658 LEEP TREATMENT OF EXTENSIVE CERVICAL INTRAEPITHELIAL NEOPLASIA IN HIV-INFECTED WOMEN

Sharon A. Greene 1 , Hillary M. Topazian 2 , Hugo De Vuyst 3 , Christine J. McGrath 1 , Barbra A. Richardson 1 , Grace John-Stewart 1 , Anthony Cagle 1 , Evans Nyongesa- Malava 1 , Nelly Yatich 1 , Catherine Kiptinness 1 , Sameh Sakr 4 , Nelly R. Mugo 1 , Michael H. Chung 1 1 University of Washington, Seattle, WA, USA, 2 Harvard University, Cambridge, MA, USA, 3 International Agency for Research on Cancer, Lyon, France, 4 Coptic Hospital, Nairobi, Kenya Background: WHO guidelines recommend loop electrosurgical excisional procedure (LEEP) in resource-limited settings for histologically confirmed cervical intraepithelial neoplasia 2/3 (CIN2+) regardless of HIV status or extent of lesion. We determined the incidence and correlates of recurrence following LEEP among HIV-infected women with CIN2+. Methods: From June 2011 to July 2014, HIV-infected women enrolled at the Coptic Hope Center for Infectious Diseases in Nairobi, Kenya underwent cervical cancer screening with Papanicolaou (Pap) smear. Women with high grade squamous intraepithelial lesions (HSIL) and CIN2+ diagnosed by colposcopy- directed biopsy or endocervical curettage (ECC) were treated with LEEP. Recurrence of pre-cancerous cervical disease was defined as HSIL+ on Pap smear taken every 6 months for 2 years. Outcomes were compared between women with biopsy-confirmed CIN2+ lesions limited to the ectocervix (ECL) and ECC-confirmed CIN2+ lesions indicating endocervical involvement (ENL) using Chi-square tests and Cox proportional hazards regression. Results: Among 275 women who received LEEP at baseline, 186 women with ECL had a median age of 37 years, [interquartile range (IQR), 31-44], 92% were on antiretroviral therapy (ART), 34% had low CD4 (<250 cells/µl) and 69%were treated for CIN3. Eighty-nine women with ENL had a median age

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