Genotypic alteration of HAART-persistent HIV-1 reservoirs in vivo.
Three HIV-1-infected individuals, on virally-suppressive highly active anti-retroviral therapy (HAART), were treated in vivo with anti-retroviral inhibitor intensification and cell stimulatory therapies in attempting to eradicate latent viral reservoirs. Afterwards, the patients ceased all anti-retroviral drugs. Sequences of the V3 region of HIV-1 envelope protein (ENV) from patient peripheral blood mononuclear cell (PBMC) proviral DNA, patient blood plasma viral RNA and virion-associated RNA from viruses amplified by patient cell co-culture, were obtained before, during, and certain times after the clinical regimen. As anticipated, the V3 loop sequencing results indicate diversity in viral strain complexity among the individual patients. However, the detection of unique V3 ENV signature sequences or V3 signatures of low frequency, relative to those observed prior to therapy, indicate that the expression of specific viruses, or viruses of low abundance, can be induced through stimulation in vivo. Furthermore, this stimulation or general immune activation therapy (IAT) approach, consisting of administration of the anti-T-cell receptor antibody, OKT3, and IL-2 in vivo, appeared to have subsequently altered the genotype of the persistent viral reservoir in peripheral blood cells for two of the three patients.
Kulkosky
Joseph
J
The Dorrance H. Hamilton Laboratories, Center for Human Virology and Biodefense, Division of Infectious Diseases and Environmental Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. KulkoskyJ@chc.edu
Sullivan
Julie
J
Xu
Yan
Y
Malin-Markham
Anne
A
Otero
Miguel
M
Calarota
Sandra
S
Zielinski
Jennifer
J
Culnan
Derek M
DM
Pomerantz
Roger J
RJ
D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D004197:Disease Reservoirs; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D007156:Immunologic Memory; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood; D017422:Sequence Analysis, DNA; D017735:Virus Latency
D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D012367:RNA, Viral