O2-17. Suppressive antiretroviral therapy is associated with effective treatment of high-grade cervical intraepithelial neoplasia

Christina Carlander [1,2], Philippe Wagner [2], Astrid van Beirs [3], Aylin Yilmaz [4], Kristina Elfgren [5], Joakim Dillner [6], Anders Sönnerborg [1,6] Pär Sparén [7]
Affiliates: [1] Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden. [2] Centre for Clinical Research, Västmanland County Hospital, Västerås, Sweden. [3] Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden. [4] Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. [5] CLINTEC, Department of Obstetrics and Gynaecology, Karolinska University Hospital Huddinge, Stockholm, Sweden. [6] Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. [7] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Background
Treatment failure and recurrence of cervical lesions after surgical treatment of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) are more common in women living with HIV (WLWH) than in HIV-negative women. It is yet uncertain what effect suppressive antiretroviral therapy (ART) has on the results of CIN2+ treatment. We conducted a population-based register study with the aim of analysing: 1) if WLWH in Sweden have a poorer outcome after treatment of CIN2+ than HIV-negative women of the same country of birth and 2) to identify predictors of treatment failure and recurrence among WLWH.

Methods
The Swedish National InfCareHIV Registry was 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, grade 3 or adenocarcinoma in situ or cervical cancer (CIN2+). For each WLWH (n=179) we randomly selected two HIV-negative women, living in the same counties sometime between 1983 and 2014, diagnosed with CIN2+, matched on country of birth (n=321). Additional data, such as surgical method, was collected from medical records. Treatment failure was defined as the presence of an abnormal (atypical squamous cells of undetermined significance or worse) cervical cytology/biopsy at initial follow-up, within one year of treatment. Recurrence was defined as the presence of CIN1+ subsequent to an initial normal cervical cytology/biopsy at 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 288 HIV-negative women were treated for CIN2+ and had at least one follow-up cervical cytology/biopsy within one year and were not treated with a hysterectomy (Fig1). Both treatment failure (n=63 (45%) vs. n=57 (20%); p<0.001) and recurrence (n=13(17%) vs. n=11(5%); p<0.001) were more common in WLWH than in HIV-negative women. WLWH were more than three times more likely to have a treatment failure (OR 3.38 (95% CI 2.16-5.28) and four times more likely to recur (HR 4.77 (95% CI 2.08-10.92) than HIV-negative women. Suppressive ART (HIV-RNA< 50 copies/ml) at time of treatment of CIN2+ was associated with reduced odds of treatment failure (OR 0.42(95% CI 0.21-0.84)). 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 8.89(95% CI 2.85-27.70) and associated with recurrence (trend for continuous CD4+T-cell/ μL; p=0.036). There was no association between suppressive ART and risk of recurrence, which may have been due to the small number of events.

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+. Similar to earlier studies, treatment failure and recurrence were clearly more common in WLWH than in HIV-negative women. An early HIV diagnosis, immediate ART and continuum of care are all essential to reach successful CIN2+ treatment.