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THE EARLIER cART IS INITIATED DURING PHI,
THE MORE INTRACELLULAR HIV-DNA DECREASES
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Reported by Jules Levin
CROI 2015 Feb 23-26, Seattle, WA
M. LAANANI1*, J. GHOSN2,3*, A. ESSAT1, A. MELARD4, R. SENG1, E. MORTIER5, C. GOUJARD1,6, L. MEYER1,6, and C. ROUZIOUX3,4, for the ANRS PRIMO cohort study group
1. CESP Inserm U1018, Epidemiology of HIV and STI, APHP, Bicetre Hospital, Le Kremlin-Bicetre, France / 2. Unite Fonctionnelle de Therapeutique en Immuno-Infectiologie, APHP, Hotel Dieu University Hospital, Paris, France / 3. Paris Descartes University, EA 7327, Sorbonne-Paris-Cite, Paris, France / 4. Virology Department, APHP, Necker Hospital, Paris, France / 5. Internal Medicine Department, APHP, Louis Mourier Hospital, Colombes, France / 6. Univ Paris-Sud, Le Kremlin-Bicetre, France
from Jules: another theme out of CROI 2015 is the benefit of early ART, very early ART, during acute infection, in fact 2 studies looked at ART evaluated ART when started Feibig 1/2 or Feibig 3/4, a difference in days since infection with Feibig i/II earlier. Estimates of the number of days in each stage have varied & recently new estimates have been suggested.
Another very interesting study (report coming next) out of the Aaron Diamond AIDS Research Center found "Initiation of ARTduring primary HIV infection correlated with normalization or improvement in several markers of immune senescence"
CROI: ART in Acute Infection, Inflammation/Activation "Largely Disappear" - (03/18/15) in this study ART started during Feibig stages 1/2, based on estimate within 10-20 days of infection vs Feibgig 3/4 the next 10 days results in better reservoir HIV reduction - lower HIV DNA in the colon - total DNA in PBMC - greater reduction in cytokines & inflammation - reduced CD8 activation - total HIV DNA in the plasma blood - and less HIV in the brain/CSF
This study at CROI:
CROI: Inflammation Persists Despite Early ART in Acute HIV - (03/16/15) In this interesting study they found biomarker of enterocyte death, microbial translocation, inflammation, coagulation & fibrosis increase early in acute HIV infection, that very early ART, within days of infection, decreased inflammation & activation markers but inflammation & activation still persists, and compared to those who started ART in chronic infection inflammation/activation markers were often lower for those who started during early acute infection, and mostly the markers were elevated compared to HIV-uninfected, but D-Dimer normalized for patients treated during acute infection in this study; IL-6 was the lowest for those treated during stage 1 of infection. Authors said: "most biomarkers of microbial translocation, inflammation, coagulation & fibrosis decrease during early ART treatment to lower levels during following chronic infection compared to patients who start ART during chronic infection.....IFABP, biomarkers for intestinal damage/microbial translocation increase & remain elevated during infection despite suppressive ART suggesting ongoing enterocyte damage". Subjects were diagnosed with acute HIV infection and initiated ART within 0-5 days per RV254 protocol. Twenty subjects were diagnosed in 4th generation (4thG) stage 1 (median 12 days post-acquisition), 15 in stage 2 (16 days) and 43 in stage 3 (18 days). All week 0 biomarker levels were significantly higher in HIV+ than HIV- subjects (see table)
CROI: Rates of Non-confounded HIV-Associated Neurocognitive Disorder after Early cART..... "Our findings suggest substantial neuroprotective benefit of initiating cART during primary infection" - (03/03/15)
CROI: Early ART and sustained virological suppression limits HIV-1 Proviral DNA reservoir: CHER evidence (mortality increased 76% with early ART) - (03/16/15)
CROI:ART soon after infection linked to better CD4 recovery through 10 years - (03/09/15)
CROI: Early ART and IPT in HIV-Infected African Adults With High CD4 Count (Temprano Trial)...."Early ART >500 CD4s Significantly reduced Severe HIV Morbidity" - (03/06/15)
(Ref 3) CROI/2014: ART in Acute Infection Limits Viral Reservoirs in Three-Group Monkey Comparison....Okoye A, Rohankhedkar M, Reyes M, et al. Treatment in Acute SIV Infection Limits the Size and Distribution of the Viral Reservoir. 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014)....http://www.natap.org/2014/CROI/croi_79.htm
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