A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease
| Autor: | Sahasrabuddhe, Vikrant, Hampson, Lynne, Maranga, Innocent O., Masinde, Millicent S., Oliver, Anthony W., Batman, Gavin, He, Xiaotong, Desai, Minaxi, Okemwa, Parmenas M., Stringfellow, Helen, Martin=Hirsch, Pierre, Mwaniki, Alex M., Gichangi, Peter, Hampson, Ian N. |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
RNA viruses Biopsy Cancer Treatment Lopinavir/ritonavir lcsh:Medicine Self Administration Cervix Uteri Pathology and Laboratory Medicine Severity of Illness Index Cervix Lopinavir 0302 clinical medicine Immunodeficiency Viruses Medicine and Health Sciences Papillomaviridae lcsh:Science Colposcopy Cervical cancer Multidisciplinary Manchester Cancer Research Centre medicine.diagnostic_test biology Pharmaceutics HPV infection Drug Combinations Treatment Outcome Oncology Medical Microbiology 030220 oncology & carcinogenesis Viral Pathogens Viruses Female Squamous Intraepithelial Lesions of the Cervix Pathogens Anatomy Genital Anatomy medicine.drug Research Article Adult medicine.medical_specialty Dysplasia Papillomaviruses Genotype Surgical and Invasive Medical Procedures Microbiology Antiviral Agents B700 Drug Administration Schedule 03 medical and health sciences Signs and Symptoms Drug Therapy Internal medicine Retroviruses medicine Humans Adverse effect Microbial Pathogens Gynecology Ritonavir business.industry ResearchInstitutes_Networks_Beacons/mcrc Lentivirus Papillomavirus Infections lcsh:R Organisms Reproductive System Biology and Life Sciences HIV Human Papillomavirus Cell Biology Patient Acceptance of Health Care medicine.disease biology.organism_classification Kenya Clinical trial Molecular Typing Administration Intravaginal 030104 developmental biology lcsh:Q business Cytology DNA viruses |
| Zdroj: | PLoS ONE, Vol 11, Iss 1, p e0147917 (2016) PLoS ONE Hampson, L, Maranga, I, Masinde, M S, Oliver, A, Batman, G, He, X, Desai, M, Okemwa, P M, Stringfellow, HF, Martin-Hirsch, P, Mwaniki, A M, Gichangi, P & Hampson, I 2016, ' A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease ', PLoS ONE, vol. 11, no. 1, e0147917 . https://doi.org/10.1371/journal.pone.0147917 |
| ISSN: | 1932-6203 4877-6874 |
| DOI: | 10.1371/journal.pone.0147917 |
| Popis: | BACKGROUND:\ud 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.\ud \ud METHODS:\ud 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.\ud \ud RESULTS:\ud 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.\ud \ud CONCLUSIONS:\ud 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.\ud \ud TRIAL REGISTRATION:\ud ISRCTN Registry 48776874. |
| Databáze: | OpenAIRE |
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