Journal Article

A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease

Oliver, Anthony W., Gichangi, Peter, Maranga, Innocent O., Hampson, Ian N., He, Xiaotong, Mwaniki, Alex M., Masinde, Millicent S., Stringfellow, Helen, Desai, Minaxi, Okemwa, Parmenas M., Batman, Gavin, Hampson, Lynne, Martin-Hirsch, Pierre

2016

Overview

Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC-ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy. ISRCTN Registry 48776874.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Administration, Intravaginal / Adult / Antiretroviral drugs / Antiviral Agents - therapeutic use / Antiviral drugs / Biology and Life Sciences / Biopsy / Cancer / Cancer therapies / Cellular biology / Cervical cancer / Cervix / Cervix diseases / Cervix Uteri - drug effects / Cervix Uteri - pathology / Cervix Uteri - virology / Clinical trials / Colposcopy / Complications and side effects / Cytology / Departments / Developing countries / Dosage and administration / Drug Administration Schedule / Drug Combinations / Drug therapy / Dysplasia / Family planning / Female / Genotype / Gynecology / Health risks / Health sciences / Histology / HIV / Hospitals / Human immunodeficiency virus / Human papillomavirus / Humans / Infections / Invasiveness / Kenya / Laboratories / LDCs / Lesions / Lopinavir / Lopinavir - therapeutic use / Malignancy / Medical screening / Medical treatment / Medicine and Health Sciences / Molecular Typing / Morbidity / Mortality / Oncology / Papillomaviridae - drug effects / Papillomaviridae - genetics / Papillomaviridae - growth & development / Papillomavirus Infections - drug therapy / Papillomavirus Infections - pathology / Papillomavirus Infections - psychology / Papillomavirus Infections - virology / Pathology / Patient Acceptance of Health Care - psychology / Quality / Risk factors / Ritonavir / Ritonavir - therapeutic use / Self Administration / Severity of Illness Index / Squamous Intraepithelial Lesions of the Cervix - drug therapy / Squamous Intraepithelial Lesions of the Cervix - pathology / Squamous Intraepithelial Lesions of the Cervix - psychology / Squamous Intraepithelial Lesions of the Cervix - virology / Studies / Therapy / Treatment Outcome / Vagina / Womens health