CD4 T cell nadir independently predicts the magnitude of the HIV reservoir after prolonged suppressive antiretroviral therapy.
BACKGROUND
The level of HIV-1 integrated DNA in CD4 T cells was reported to predict the evolution of untreated HIV-1 infection independently of CD4 cell counts or plasma HIV-1 RNA levels. However, the relevance of reservoir level while on efficient antiretroviral therapy (ART) is still unknown.


OBJECTIVE
To evaluate factors that may contribute to the establishment and maintenance of HIV-1 reservoir size in ART-treated HIV-1-infected adults with complete suppression of viremia.


METHODS
35 subjects receiving ART with plasma HIV-1 RNA below the limit of detection for an average duration of 3.2 years were studied. A highly sensitive PCR was used to assess HIV-1 integrated DNA levels in sorted CD4 T cells.


RESULTS
The mean HIV-1 integrated DNA was 300±7copies/10(6) CD4 cells (range 10-1408). In univariate analysis, the levels of HIV-1 proviral DNA appeared to be independent of duration of HIV-1-infection, duration on ART, time since HIV-1 viral load was undetectable, delay between HIV-1 infection and starting ART, or viral load before starting ART. Conversely, CD4 T cell nadir, CD4/CD8 ratio and, to lesser degree, CD4 T cell counts were inversely associated with HIV-1 proviral DNA levels. In multivariate analysis, only CD4 T cell nadir significantly predicted levels of HIV-1 proviral DNA (P=0.025).


CONCLUSIONS
CD4 T cell nadir strongly predicted reservoir size independently of other factors in HIV-1-infected adults with complete suppression of viremia. Collectively, these results indicate that the extent of CD4 T cell depletion before ART drives the size of the viral reservoir after prolonged therapy.
Division of Hematology, Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, Canada. rachid.boulass@muhc.mcgill.ca
Mohamed-Rachid
MR
Boulassel
Nicolas
N
Chomont
Nitika Pant
NP
Pai
Norbert
N
Gilmore
Rafick-Pierre
RP
Sékaly
Jean-Pierre
JP
Routy
D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D004197:Disease Reservoirs / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012044:Regression Analysis; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000235:genetics / Q000821:virology; D016662:Virus Integration
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors