Lopimune
Lopimune is an oral HIV Protease Inhibitor (PI) comprising of Lopinavir and Ritonavir. Pre-clinical and early trial results in the locoregional therapy for CIN have been promising 53. PIs have anti-cancer activity against HPV- related cervical disease, in addition to their anti-HIV action 54 and Lopinavir is the most effective. It exerts its activity by blocking the HPV16 E6 protein from producing proteasomal degradation of p53 in cultured cervical carcinoma cells 100 and upregulation of the antiviral protein, ribonuclease L, and this has been subsequently confirmed in HPV16 E6/E7 immortalized keratinocytes 54 and at doses used for oral HIV therapy, which are more than ten times the concentration achieved in cervico-vaginal fluid 101, Lopinavir shows high selective toxicity for E6/E7 expressing cells102. Lopimune is formulated as an oral gelatine capsule for HIV treatment.
In a single-arm non-randomized proof-of-concept clinical trial done in Kenya, 23 high risk HPV positive women with CIN2+ used Lopimune capsules as a self-applied twice daily vaginal pessary for a period of two weeks53. Cytology was done at 12 weeks which was confirmed by histology, and showed that in 77.8% there was either complete resolution of dysplasia or there had been a change from CIN2+ to CIN1/2, and HPV was no longer detected in 52.2% of women. Treatment with Lopimune was well tolerated, and nausea was the only reported adverse reaction. Systemic exposure of the drug was limited, reaching plasma levels of 10ng/ml which is much less than the levels of 2.8-6.6 μgml-1 that is reported with oral delivery in HIV therapy 101. However, this could be partly due to the sub-optimal dosage used in the trial, which resulted in some women showing a transient change in HPV status or cytology which reverted back to baseline after 12 weeks. The authors surmised that since HPV is DNA-based and therefore more stable than RNA-based HIV, it is possible to repeat treatment multiple times with less chance of developing resistance, as a way of addressing treatment failure. In contrast to 5 FU, Lopimune is a non-cytotoxic drug which can be safely used in women of child-bearing age. Additionally, it is currently licensed for systemic treatment of HIV infected pregnant women and children103.