We describe in this paper that the dolabellane diterpene 8,10,18-trihydroxy-2,6-dolabelladiene (3), isolated from the marine algae Dictyota pfaffii, inhibits the HIV-1 infection in human primary cells and tumor cell lines. We initially observed that compound 3 inhibited the activity of a purified HIV-1 enzyme reverse transcriptase (RT) in a dose-dependent manner, with an IC (50) value of 16.5 +/- 4.3 microM. Next, we found that compound 3 inhibited HIV-1 infection by an R5-tropic isolate in peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner with an EC (50) value of 8.4 +/- 2.8 microM. The replication of HIV-1 isolates presenting distinct tropism for chemokine receptors was also inhibited, as analyzed in PBMCs or U87 cells infected with R5-, X4- or R5X4-tropic isolates. Likewise, compound 3 blocked HIV-1 infection in macrophages by R5 and R5X4 viruses in a dose-dependent manner with EC (50) values of 1.7 +/- 0.6 microM and 1.85 +/- 0.75 microM, respectively. Compound 3 sustained antiretroviral activity even when added to HIV-1-infected Sup-T1 cells at 12 h after infection, suggesting that, as well as inhibiting HIV-1 RT, it also blocks HIV-1 replication at a post transcriptional step. Our results support further investigations on compound 3 pharmacokinetics and we propose that this diterpene could be considered as a potential compound for HIV-1 therapy.