We previously established that mTOR activity governs increased susceptibility to HIV-1 infection after T cell activation by up-regulating biosynthesis of macromolecules required for HIV reverse transcription (RT) and cytoplasmic transport of RT products; along with others, we find that ATP-competitive, catalytic mTOR inhibitors (mTORi) targeting both enzymatic complexes efficiently suppress HIV replication, providing support for further assessing mTOR inhibitors as an adjunct to current ART15–18. Here, MTOR is linked to HIV-1 infection.