We previously showed that the most primordial member of the nuclear factor of activated T cells (NFAT) family, NFAT5 (also known as TonEBP), binds to a site within the HIV-1 LTR that is highly conserved across all HIV-1 subtypes, and is also conserved in HIV-2 and SIV LTRs. This NFAT5 site overlaps the core NF-κB binding motifs in the LTR and is required for constitutive replication of representative HIV-1 subtype B, C, and E isolates in human primary monocyte-derived macrophages (MDM) [31]. Given that NFAT5 has previously been shown to be transcriptionally activated by the MAP kinase p38, which is downstream of MyD88 signaling, [32], we speculated that NFAT5 may also be involved in MTb-induced activation of HIV-1 replication via a TLR-mediated pathway in monocytes and peripheral blood mononuclear cells (PBMC).