Impact of the Timing of Initiation of Antiretroviral Therapy During Primary HIV-1 Infection on the Decay of Cell-Associated HIV-DNA.
BACKGROUND
Combined antiretroviral therapy (cART) initiation during primary human immunodeficiency virus (HIV) infection (PHI) yields a larger decrease in cell-associated HIV-DNA (CA-HIV-DNA) than initiation during the chronic phase. Our objective was to model the short and long-term decay of CA-HIV-DNA blood reservoir in patients initiating cART during PHI and to assess the impact of the timing of cART initiation on CA-HIV-DNA decay.


METHODS
We included patients enrolled during PHI in the Agence Nationale de Recherche sur le Sida PRIMO cohort, treated within the month following enrollment and achieving sustained virologic response. The decay of CA-HIV-DNA over time while on successful cART was modeled with a 3-slope linear mixed-effects model according to the delay between estimated date of infection and cART initiation.


RESULTS
Three hundred twenty-seven patients were included, accounting for 1305 CA-HIV-DNA quantifications. Median time between infection and cART initiation was 41 days (interquartile range, 33-54 days). Median follow-up under cART was 2.3 years (range, 0.4-16.6 years). The timing of cART initiation had significant impact on the first slope of decrease: The earlier cART was initiated after HIV infection, the faster CA-HIV-DNA level decreased during the first 8 months of cART: -0.171, -0.131, and -0.068 log10 copies/10(6) peripheral blood mononuclear cells (PBMCs) per month when cART was initiated 15 days, 1 month, and 3 months after infection, respectively (P < .0001). The predicted mean CA-HIV-DNA level achieved after 5 years of successful cART was 1.62 and 2.24 log10 copies/10(6) PBMCs when cART was initiated 15 days and 3 months after infection, respectively (P = .0006).


CONCLUSIONS
This study provides strong arguments in favor of cART initiation at the earliest possible time point after HIV infection.
INSERM, Centre for Research in Epidemiology and Population Health, U1018, Paris-Sud University Assistance publique-Hôpitaux de Paris (AP-HP), Department of Epidemiology and Public Health, Bicêtre Hospital, Le Kremlin-Bicêtre.
Moussa
M
Laanani
AP-HP, Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Hôtel Dieu University Hospital Paris Descartes University, EA 7327, Sorbonne-Paris-Cité
Jade
J
Ghosn
INSERM, Centre for Research in Epidemiology and Population Health, U1018, Paris-Sud University.
Asma
A
Essat
AP-HP, Virology Department, Necker Hospital, Paris.
Adeline
A
Melard
INSERM, Centre for Research in Epidemiology and Population Health, U1018, Paris-Sud University Assistance publique-Hôpitaux de Paris (AP-HP), Department of Epidemiology and Public Health, Bicêtre Hospital, Le Kremlin-Bicêtre.
Rémonie
R
Seng
AP-HP, Virology Department, Necker Hospital, Paris.
Marine
M
Gousset
INSERM, Centre for Research in Epidemiology and Population Health, U1018, Paris-Sud University.
Henri
H
Panjo
AP-HP, Department of Internal Medicine, Louis-Mourier Hospital, Colombes.
Emmanuel
E
Mortier
AP-HP, Hôpital Saint-Antoine, Service des Maladies Infectieuses et tropicales Sorbonne Universités, Université Pierre et Marie Curie INSERM, UMR_S1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris.
Pierre-Marie
PM
Girard
INSERM, Centre for Research in Epidemiology and Population Health, U1018, Paris-Sud University AP-HP, Department of Internal Medicine, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
Cécile
C
Goujard
INSERM, Centre for Research in Epidemiology and Population Health, U1018, Paris-Sud University Assistance publique-Hôpitaux de Paris (AP-HP), Department of Epidemiology and Public Health, Bicêtre Hospital, Le Kremlin-Bicêtre.
Laurence
L
Meyer
Paris Descartes University, EA 7327, Sorbonne-Paris-Cité AP-HP, Virology Department, Necker Hospital, Paris.
Christine
C
Rouzioux
D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D004279:DNA, Viral / Q000032:analysis* / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D044966:Anti-Retroviral Agents; D004279:DNA, Viral
HIV-1 DNA reservoir; cohort; primary HIV infection; remission; slopes of HIV-DNA decay