Continued evolution of HIV-1 circulating in blood monocytes with antiretroviral therapy: genetic analysis of HIV-1 in monocytes and CD4+ T cells of patients with discontinued therapy.
The role of blood monocytes in HIV-1 infection is a relatively new field of interest. What happens to HIV-1 in monocytes and their relationship to CD4+ T cells before, during, and after suppressive antiretroviral therapy (ART) is largely unstudied. Here, considering that diversity is a good indicator of continued replication over time, we evaluated the effect of ART on HIV-1 in blood monocytes and CD4+ T cells by examining the diversity of HIV-1 from 4 infected patients who underwent and stopped therapy. We determined diversity and compartmentalization of HIV-1 between blood monocytes and CD4+ T cells in each patient in relationship to their ART regimens. Our data indicate that the rate of HIV-1 diversity increase in monocytes during therapy was significantly higher than in CD4+ T cells (P<0.05), suggesting that HIV-1 present in monocytes diversify more during therapy than in CD4+ T cells. Increased rates of HIV-1 compartmentalization between monocytes and CD4+ T cells while on therapy were also observed. These results suggest that ART inhibits HIV-1 replication in CD4+ T cells more than in blood monocytes and that better treatments to combat HIV-1 in monocytes/macrophages may be needed for a more complete suppression of HIV replication.
Llewellyn
Nick
N
Department of Laboratory Medicine, University of Washington School of Medicine, Washington, USA.
Zioni
Rafael
R
Zhu
Haiying
H
Andrus
Thomas
T
Xu
Younong
Y
Corey
Lawrence
L
Zhu
Tuofu
T
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D018450:Disease Progression; D019143:Evolution, Molecular; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000821:virology*; D010802:Phylogeny; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013329:Structure-Activity Relationship; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents