Ngo MH, Pankrac J, Ho RCY, Ndashimye E, Pawa R, Ceccacci R, Biru T, Olabode AS, Klein K, Li Y, Kovacs C, Assad R, Jacobson JM, Canaday DH, Tomusange S, Jamiru S, Anok A, Kityamuweesi T, Buule P, Galiwango RM, Reynolds SJ, Quinn TC, Redd AD, Prodger JL, Mann JFS, Arts EJ. Effective and targeted latency reversal in CD4+ T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection. Emerg Microbes Infect. 2024 Mar 6:2327371. doi: 10.1080/22221751.2024.2327371. Epub ahead of print. PMID: 38444369.
Abstract
To date, an affordable, effective treatment for an HIV-1 cure remains only a concept with most "latency reversal" agents (LRAs) lacking specificity for the latent HIV-1 reservoir and failing in early clinical trials. We assessed HIV-1 latency reversal using a multivalent HIV-1-derived virus-like particle (HLP) to treat samples from 32 people living with HIV-1 (PLWH) in Uganda, US and Canada who initiated combined antiretroviral therapy (cART) during chronic infection. Even after 5 to 20 years on stable cART, HLP could target CD4+ T cells harboring latent HIV-1 reservoir resulting in 100-fold more HIV-1 release into culture supernatant than by common recall antigens, and 1000-fold more than by chemotherapeutic LRAs. HLP induced release of a divergent and replication-competent HIV-1 population from PLWH on cART. These findings suggest HLP provides a targeted approach to reactivate the majority of latent HIV-1 proviruses among individuals infected with HIV-1.