Virally Suppressed People Living with HIV Who Use Opioids Have Diminished Latency Reversal.

Of the 12 million people who inject drugs worldwide, 13% live with HIV. Whether opioid use impacts HIV pathogenesis and latency is an outstanding question. To gain insight into whether opioid use influences the proviral landscape and latent HIV reservoir, we performed intact proviral DNA assays (IPDA) on peripheral blood mononuclear cells (PBMCs) from antiretroviral therapy (ART)-suppressed people living with HIV (PWH) with or without current opioid use.

Targeted Chromatinization and Repression of HIV-1 Provirus Transcription with Repurposed CRISPR/Cas9.

The major barrier to HIV-1 cure is the persistence of latent provirus, which is not eradicated by antiretroviral therapy. The "shock and kill" approach entails stimulating viral production with latency-reversing agents followed by the killing of cells actively producing the virus by immune clearance. However, this approach does not induce all intact proviruses, leaving a residual reservoir.

Targeting HIV-1 proviral transcription.

Despite the success of antiretroviral therapies, there is no cure for HIV-1 infection due to the establishment of a long-lived latent reservoir that fuels viral rebound upon treatment interruption. 'Shock-and-kill' strategies to diminish the latent reservoir have had modest impact on the reservoir leading to considerations of alternative approaches to target HIV-1 proviruses. This review explores approaches to target HIV-1 transcription as a way to block the provirus expression.