Effects of Tadalafil and Sildenafil on HIV infection in vitro
Abstract
Background: Tadalafil (Cialis, Lilly ICOS) and Sildenafil citrate (Viagra, Pfizer) are by far the most popular and widely used drugs for enhancing male erectile function. Recent studies have suggested that Tadalafil administration increases the expression of CXCR4 in human endothelial progenitor cells (EPC). CXCR4 is also a major co-receptor for HIV (Human Immunodeficiency Virus) infection of human CD4 T cells. In addition, the viral tropism switch to CXCR4 is associated with rapid disease progression in patients. Findings: We investigated whether Tadalafil and Sildenafil increased CXCR4 expression on human CD4 T cells, which may potentially facilitate HIV infection and transmission. We found that both drugs transiently increase CXCR4 expression on CD4 T cells. We further used an HIV-1 Rev-dependent reporter cell (Rev-CEM-Luc-GFP) to evaluate possible drug enhancement of viral replication in vitro. We also found that no significant impact of viral replication was observed, when cells were transiently exposed to these drugs. In contrast, both drugs inhibited HIV-1 infection when cells were treated for extended periods of time, likely resulting from interference with intracellular signaling environment involved in HIV-1 infection. Conclusion: These results suggest that although both drugs enhance CXCR4 expression, they may not enhance HIV replication and increase HIV transmission.
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