P44.10
Background: Despite the encouraging results obtained in the CAPRISA trial by using Tenofovir gel to prevent HIV-1 sexual transmission, the development of an effective microbicide remains a major priority. Among candidate new microbicides, we are investigating the phenolic phytochemical compound 5-HT (previously shown to be possess anti-HIV-1, anti-inflammatory and anti-oxidant activities in isolated cell systems) in human cervical tissue explants (CTE).
Methods: CTE established from HIV-1 seronegative women undergoing hysterectomy for benign tumors, were infected ex vivo with R5 HIV-1BaL in the presence or absence of increasing concentrations of 5-HT or, as control, of 3TC. Productive infection of HIV-1 was measured in terms of p24Gag expression in the culture supernatants. In addition, total viral DNA was quantified by RT-PCR in the different experimental conditions.
Results: A decrease of p24Gag release was observed in the culture supernatant after incubation with 200 μM of 5-HT and this effect was also associated with 50% decrease of total viral DNA, as determined on tissue blocks after 12 days of culture.
No modulation of CD4 and CCR5 or of activation markers (CD69, CD25, CD38) was observed in CD4+ lymphocytes incubated with up to 200 μM of 5-HT. Ongoing experiments are aimed at evaluating the potential effect of 5-HT on the release of pro/anti-inflammatory cytokines and chemokines in CTE culture supernatants.
Conclusions: These results confirm that 5-HT bears the potential to be developed as an anti-HIV microbicide as it inhibits HIV-1 replication in CTE, in addition to isolated cell systems, without inducing cytotoxicity or promoting T cell activation.
