Reversal of Latency as Part of a Cure for HIV-1

Here, the use of pharmacological agents to reverse HIV-1 latency will be explored as a therapeutic strategy towards a cure. However, while clinical trials of latency-reversing agents LRAs) have demonstrated their ability to increase production of latent HIV-1, such interventions have not had an effect on the size of the latent HIV-1 reservoir. Plausible explanations for this include insufficient host immune responses against virus-expressing cells, the presence of escape mutations in archived virus, or an insufficient scale of latency reversal. Importantly, these early studies of LRAs were primarily designed to investigate their ability to perturb the state of HIV-1 latency; using the absence of an impact on the size of the HIV-1 reservoir to discard their potential inclusion in curative strategies would be erroneous and premature.

TrendsPharmacologically induced expression of latent virus is investigated as part of a cure for HIV-1 infection.Recent data from clinical trials show that short-term administration of a latency-reversing agent (LRA) may increase HIV-1 transcription and plasma HIV-1 RNA.So far, reversal of HIV-1 latency by histone deacetylase inhibitors has not been associated with a reduction in the size of the latent reservoir.Possible explanations for the lack of an effect on the size of the latent HIV-1 reservoir include insufficient immune response against virus-expressing cells, the presence of cytotoxic T lymphocyte (CTL) escape variants, and/or an insufficient degree of latency reversal achieved with current approaches.