5-Hydroxytyrosol inhibits HIV-1 replication in primary cells of the lower and upper female reproductive tract

- 5-HT was tested as candidate anti-HIV microbicide to prevent or limit HIV-1 replication in primary human CTE and EAL.
- Nontoxic concentrations of 5-HT (<200 μM) inhibited R5 HIV-1 replication in both CTE and EAL.
- 5-HT also decreased the levels of CD4+ and CD8+ T lymphocytes infiltrating the CTE and coexpressing CD38.
- 5-HT should be tested either alone or in combination with other anti-HIV microbicides to prevent sexual HIV transmission.

We investigated the potential anti-HIV-1 activity of the candidate microbicide 5-hydroxytyrosol (5-HT) both in primary human cervical tissue explants (CTE), established from tissues of women undergoing histerectomy, and in endometrium-associated leukocytes (EAL). CTE were exposed to either the laboratory-adapted HIV-1BaL or to primary viral isolates in the presence or absence of 5-HT or 3TC/lamivudine as control and were then monitored for 12 days in terms of HIV-1 p24 Gag antigen production in culture supernatants. HIV-1BaL replication was also evaluated in EAL by reverse transcriptase (RT) activity. The highest nontoxic concentrations of 5-HT (200 and 100 μM for CTE and EAL, respectively) exerted a significant inhibitory effect on virus replication in both primary cell systems. 5-HT did not cause significant alterations of the activation profile of CD4+ and CD8+ T cells, in terms of CD4, CCR5, CD25, CD69 and HLA-DR expression, although it decreased the percentage of CD38+CD8+ T cells. Thus, 5-HT deserves consideration as a potential candidate microbicide for preventing HIV-1 transmission or curtailing its replication in the female reproductive tract.

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