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.