Seminal reservoirs during an HIV type 1 eradication trial.
Despite dramatic reduction of the levels of human immunodeficiency virus type I (HIV-1) virions in blood and seminal plasma of infected patients, highly active antiretroviral therapy (HAART) does not eradicate HIV-1. Three patients, with less than 50 copies/ml of plasma viral RNA, were enrolled in this eradication protocol. Didanosine (DDI) and hydroxyurea (HU) were added to their baseline HAART and after a month of therapy, low dose OKT3, followed by a 2-week course of interleukin 2 (IL-2), was administrated. All antiretroviral therapy was then interrupted and the three patients developed viral rebound in the peripheral blood. The V3 loop region of the HIV-1 gp120 from cell-free viral RNA and proviral DNA in blood and seminal compartments was sequenced in one patient. The two major viral isolates in semen cells were macrophage- tropic (R5) and dual-tropic (R5X4), and these isolates were also present in the PBMCs. Six months after the viral rebound, we demonstrated a shift toward dual tropism in semen cell-associated HIV-1 proviral DNA, with the first appearance of a T-lymphotropic (X4) provirus solely in this compartment. The virus responsible for the blood plasma viral rebound was never found in the semen microenvironment. This study suggests viral compartmentalization of the semen microenvironment after an intensification and stimulatory HIV-1 eradication protocol, with evidence of viral evolution.
Nunnari
Giuseppe
G
Institute for Human Virology and Biodefense, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. Giuseppe.Nunnari@jefferson.edu
Leto
Daniela
D
Sullivan
Julie
J
Xu
Yan
Y
Mehlman
Ketti E
KE
Kulkosky
Joseph
J
Pomerantz
Roger J
RJ
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral; D016049:Didanosine / Q000627:therapeutic use; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D008297:Male; D008969:Molecular Sequence Data; D016853:Muromonab-CD3 / Q000627:therapeutic use; D019384:Nucleic Acid Synthesis Inhibitors / Q000627:therapeutic use; D010446:Peptide Fragments / Q000235:genetics*; D010802:Phylogeny; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral; D012661:Semen / Q000821:virology*; D016415:Sequence Alignment; D016896:Treatment Outcome; D014766:Viremia; D028761:Withholding Treatment
D019380:Anti-HIV Agents; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016853:Muromonab-CD3; D019384:Nucleic Acid Synthesis Inhibitors; D010446:Peptide Fragments; D012367:RNA, Viral; D016049:Didanosine; D006918:Hydroxyurea