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

PLoS One. 2016 Jan 29;11(1):e0147917. doi: 10.1371/journal.pone.0147917. eCollection 2016.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: ISRCTN Registry 48776874.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravaginal
  • Adult
  • Antiviral Agents / therapeutic use*
  • Cervix Uteri / drug effects*
  • Cervix Uteri / pathology
  • Cervix Uteri / virology
  • Colposcopy
  • Drug Administration Schedule
  • Drug Combinations
  • Female
  • Genotype
  • Humans
  • Kenya
  • Lopinavir / therapeutic use*
  • Molecular Typing
  • Papillomaviridae / drug effects
  • Papillomaviridae / genetics
  • Papillomaviridae / growth & development
  • Papillomavirus Infections / drug therapy*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / psychology
  • Papillomavirus Infections / virology
  • Patient Acceptance of Health Care / psychology
  • 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
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Drug Combinations
  • lopinavir-ritonavir drug combination
  • Lopinavir
  • Ritonavir

Associated data

  • ISRCTN/ISRCTN48776874

Grants and funding

This study was primarily funded by Mr. Ken Cholerton from the Janice Cholerton Research Fund/East Africa Medical Trust (EAMT) and the Caring Cancer Trust, http://www.caringcancertrust.com/. Other contributors were: The Cancer Prevention Research Trust (http://www.cancerprevention-research.co.uk/), Quest Cancer Research, The Humane Research Trust (http://www.humaneresearch.org.uk/), and United-in-Cancer Charitable Trust. The authors would also like to thank the following: Hologic Inc for the loan of diagnostic equipment plus set-up maintenance and running costs; Central Manchester Foundation NHS Trust for the donation of two electro-diathermy units; Lancashire Teaching Hospitals NHS Trust for the donation of two colposcopes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.