Residual HIV-1 disease in seminal cells of HIV-1-infected men on suppressive HAART: latency without on-going cellular infections.
BACKGROUND
HIV-1-infected men on suppressive highly active antiretroviral therapy (HAART) have a reduction of viral replication in vivo, but HIV-1 RNA is still detectable by certain ultrasensitive reverse transcriptase-PCR assays in blood plasma. Replication-competent virus can also be isolated from both peripheral blood mononuclear cells (PBMC) and seminal cells of these patients. Despite HAART, on-going in vivo infection of HIV-1-seropositive patients' PBMC was demonstrated by the detection of episomal HIV-1 moieties, known as HIV-1 two-long terminal repeat (2-LTR) DNA circles.


METHODS
The present study analyzes whether new cellular infections occur in vivo in seminal cells of HIV-1-infected men on suppressive HAART. PBMC and seminal cells were isolated from a cohort of HIV-1-seropositive men taking suppressive HAART (< 50 copies HIV RNA/ml blood plasma). Viral growth assays were performed in vitro, as well as semi-quantitative PCR to detect HIV-1 2-LTR circular DNA in PBMC and seminal mononuclear cells.


RESULTS
Viral growth in vitro was demonstrated in 16 out of 28 (57%) patients' PBMC, and in five patients' seminal cells (18%). Although 18 patients' PBMC were positive for HIV-1 2-LTR DNA circles, importantly, 2-LTR circular DNA was not detected in any semen sample, even when replication-competent HIV-1 virus had been recovered from a patient's seminal cells by viral co-culture assays.


CONCLUSIONS
The current study suggests that in HIV-1-infected men treated with suppressive HAART, new cellular infections occur in PBMC, but that new infections do not take place in seminal cells in vivo. Thus, these findings suggest that mainly latent HIV-1 occurs in seminal cells of men on suppressive HAART, which may be a compartment-specific mechanism of residual HIV-1 disease.
Nunnari
Giuseppe
G
Dorrance H. Hamilton Laboratories, Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Otero
Miguel
M
Dornadula
Geethanjali
G
Vanella
Michelle
M
Zhang
Hui
H
Frank
Ian
I
Pomerantz
Roger J
RJ
D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral / Q000032:analysis / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D012661:Semen / Q000166:cytology / Q000276:immunology / Q000821:virology*; D017735:Virus Latency
D004279:DNA, Viral; D012367:RNA, Viral