Genotypic Alteration of HAART-Persistent HIV-1 Reservoirs In Vivo .

Roger J. Pomerantz, Julie Sullivan, Yan Xu, Anne Malin, Miguel Otero, Sandra Calarota, Derek M. Culnan, and Joseph Kulkosky. Center for Human Virology and Biodefense, Thomas Jefferson University, Philadelphia, Pennsylvania (USA)

Three individuals infected with human immunodeficiency virus type I (HIV-1), on virally-suppressive highly active anti-retroviral therapy (HAART), were treated in vivo with intensification and stimulatory therapies in attempting to eradicate latent viral reservoirs. Afterwards, the patients ceased all anti-retroviral drugs. Sequencing of a region of the patients' viruses, coupled with techniques to detect infectious virus were performed before, during, and certain times after the clinical regimen. The results indicate: 1.) diversity in HAART-persistent viral strain complexity for individual patients,  2.) certain viruses that emerge after discontinuation of HAART may originate from peripheral blood cell proviral DNA,  3.) expression of unique or specific viruses can be induced through stimulation in vivo, which likely altered the genotype of the persistent viral reservoir,  4.) certain latent HAART-persistent viral species or quasi-species, induced to express in vivo by stimulation, may revert to latency but remain responsive to induction by the original stimulatory agents, and 5.) elimination of HAART-persistent viruses may occur over time through natural immunity aiding clearance of replication-competent viruses. Attempts to culture virus, even with the addition of cell stimulatory agents in vitro, provide no indication yet of replication-competent HIV-1 in peripheral blood cells for one patient. This finding, and the viral sequence data, suggest that elimination of certain infectious viral species could have occurred as a consequence of viral intensification and stimulation in vivo..