Virologic determinants of success after structured treatment interruptions of antiretrovirals in acute HIV-1 infection.
BACKGROUND
Latently infected resting memory CD4 T cells are thought to be the major reservoir that contributes to rebound viremia after cessation of antiretrovirals (ARVs). Commencing ARVs during primary HIV-1 infection (PHI) may limit the size of the latent pool and lead to improved control of viral replication during structured treatment interruption (STI).


METHODS
Individuals with PHI (n = 59) were randomized to receive ARVs with or without hydroxyurea. After STI, a good response was defined as maintenance of HIV-1 RNA <5000 copies/mL for 24 weeks off therapy. In a detailed prospective virologic substudy (n = 19), integrated HIV-1 DNA, total HIV-1 DNA, and cell-associated HIV-1 unspliced (US) RNA were quantified using a real-time polymerase chain reaction assay.


RESULTS
The plasma HIV-1 RNA 12 weeks after the initiation of ARVs was significantly lower in good responders (n = 7) compared with poor responders (n = 12) (P = 0.005). There were no significant differences between good and poor responders in integrated HIV-1 DNA, HIV-1 DNA, and HIV-1 US RNA. Integrated HIV-1 DNA before initiation of ARVs was strongly correlated with plasma HIV-1 RNA at week 12 (P = 0.006, r = 0.81).


CONCLUSIONS
HIV-1 RNA measured 12 weeks after initiation of ARV was the only virologic variable associated with viral rebound after treatment interruption in PHI.
Lewin
Sharon R
SR
Infectious Diseases Unit, Alfred Hospital, Melbourne, Australia. s.lewin@alfred.org.au
Murray
John M
JM
Solomon
Ajantha
A
Wightman
Fiona
F
Cameron
Paul U
PU
Purcell
Damian J
DJ
Zaunders
John J
JJ
Grey
Pat
P
Bloch
Mark
M
Smith
Don
D
Cooper
David A
DA
Kelleher
Anthony D
AD
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D014481:United States; D014766:Viremia; D016662:Virus Integration; D028761:Withholding Treatment
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral; D006918:Hydroxyurea