title: A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease.
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.
  
  
  BACKGROUND
  ISRCTN Registry 48776874.
authors.affiliation: University of Manchester Viral Oncology Laboratories, Institute of Cancer Sciences, Research Floor 5, St Mary's Hospital, Oxford Road, Manchester M13 9WL, United Kingdom.
authors.forename: Lynne
authors.initials: L
authors.lastname: Hampson
authors.affiliation: Kenyatta National Hospital, Department of Reproductive Health, PO Box 20723-00202, Nairobi, Kenya.|University of Nairobi, College of Health Sciences, Departments of Gynaecology and Pathology, PO Box 19676-00202, Nairobi, Kenya.
authors.forename: Innocent O
authors.initials: IO
authors.lastname: Maranga
authors.affiliation: University of Nairobi, College of Health Sciences, Departments of Gynaecology and Pathology, PO Box 19676-00202, Nairobi, Kenya.
authors.forename: Millicent S
authors.initials: MS
authors.lastname: Masinde
authors.affiliation: University of Manchester Viral Oncology Laboratories, Institute of Cancer Sciences, Research Floor 5, St Mary's Hospital, Oxford Road, Manchester M13 9WL, United Kingdom.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Oliver
authors.affiliation: University of Manchester Viral Oncology Laboratories, Institute of Cancer Sciences, Research Floor 5, St Mary's Hospital, Oxford Road, Manchester M13 9WL, United Kingdom.
authors.forename: Gavin
authors.initials: G
authors.lastname: Batman
authors.affiliation: University of Manchester Viral Oncology Laboratories, Institute of Cancer Sciences, Research Floor 5, St Mary's Hospital, Oxford Road, Manchester M13 9WL, United Kingdom.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: He
authors.affiliation: Cytology Laboratories, PO Box 208, Clinical Sciences Building 2, Central Manchester University Hospital NHS Trust, Oxford Rd, Manchester M13 9WW, United Kingdom.
authors.forename: Minaxi
authors.initials: M
authors.lastname: Desai
authors.affiliation: University of Nairobi, College of Health Sciences, Departments of Gynaecology and Pathology, PO Box 19676-00202, Nairobi, Kenya.
authors.forename: Parmenas M
authors.initials: PM
authors.lastname: Okemwa
authors.affiliation: Department of Pathology, Royal Preston Hospital, Sharoe Green Lane, Fulwood, Preston, PR2 9HT, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Stringfellow
authors.affiliation: Department of Obstetrics & Gynaecology, Royal Preston Hospital, Sharoe Green Lane, Fulwood, Preston, PR2 9HT, United Kingdom.
authors.forename: Pierre
authors.initials: P
authors.lastname: Martin-Hirsch
authors.affiliation: University of Nairobi, College of Health Sciences, Departments of Gynaecology and Pathology, PO Box 19676-00202, Nairobi, Kenya.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Mwaniki
authors.affiliation: University of Nairobi, College of Health Sciences, Departments of Gynaecology and Pathology, PO Box 19676-00202, Nairobi, Kenya.
authors.forename: Peter
authors.initials: P
authors.lastname: Gichangi
authors.affiliation: University of Manchester Viral Oncology Laboratories, Institute of Cancer Sciences, Research Floor 5, St Mary's Hospital, Oxford Road, Manchester M13 9WL, United Kingdom.
authors.forename: Ian N
authors.initials: IN
authors.lastname: Hampson
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002584:Cervix Uteri / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D003127:Colposcopy; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005838:Genotype; D006801:Humans; D007630:Kenya; D061466:Lopinavir / Q000627:therapeutic use*; D058889:Molecular Typing; D027383:Papillomaviridae / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D030361:Papillomavirus Infections / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology / Q000821:virology; D010342:Patient Acceptance of Health Care / Q000523:psychology; D019438:Ritonavir / Q000627:therapeutic use*; D012646:Self Administration; D012720:Severity of Illness Index; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology / Q000821:virology; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004338:Drug Combinations; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; D019438:Ritonavir
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