title: Long-term antiretroviral therapy initiated during primary HIV-1 infection is key to achieving both low HIV reservoirs and normal T cell counts.
abstract: OBJECTIVE
  To characterize viro-immunological outcomes following long-term combined antiretroviral therapy (cART) initiated during primary HIV infection (PHI) or chronic HIV infection (CHI) and to identify factors predictive of optimal viro-immunological responder (OVIR) status.
  
  
  METHODS
  This was a prospective, single-centre cohort study of HIV-1-infected patients on effective cART. Total cell-associated HIV DNA levels and T cell counts before and during treatment were used to identify factors predictive of OVIR status {i.e. low HIV DNA level [<2.3 log10 copies/10(6) peripheral blood mononuclear cells (PBMCs)], together with normalization of the absolute/relative CD4+ T cell counts and CD4+/CD8+ ratio}.
  
  
  RESULTS
  A total of 307 patients were enrolled, of whom 35 started cART during PHI (<4 months post-infection) and 272 during CHI. HIV DNA decay was modelled with a non-linear mixed-effects model that showed two phases of HIV DNA decay, both of which were significantly more pronounced in the PHI group. At the end of follow-up, after a median of 4 years of viral suppression (<50 copies/mL), HIV DNA levels were lower in the PHI group than in the CHI group (median = 2.15 versus 2.84 log10 copies/10(6) PBMCs; P< 0.0001). Immune reconstitution was more rapid and sustained in the PHI group (median = 883 versus 619 CD4+ cells/mm(3); 41% versus 31% CD4+; CD4+/CD8+ 1.31 versus 0.77; all P< 0.0001). Finally, OVIR status was obtained in 19/35 (54%) and 7/272 (3%) patients in the PHI and CHI groups (P< 0.0001), respectively. In a logistic regression analysis, cART initiation during PHI (OR = 16, 95% CI = 3.5-72.3) and HIV DNA level <3.3 log10 before treatment (OR = 4.8, 95% CI = 1.2-19.3) were independently predictive of OVIR status.
  
  
  CONCLUSIONS
  Initiating cART during PHI represents a major opportunity to reduce HIV reservoirs and achieve optimal immune reconstitution.
authors: Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Régional, Orléans, France. laurent.hocqueloux@chr-orleans.fr
authors: Laurent
authors: L
authors: Hocqueloux
authors: Véronique
authors: V
authors: Avettand-Fènoël
authors: Sophie
authors: S
authors: Jacquot
authors: Thierry
authors: T
authors: Prazuck
authors: Eric
authors: E
authors: Legac
authors: Adeline
authors: A
authors: Mélard
authors: Mohamadou
authors: M
authors: Niang
authors: Catherine
authors: C
authors: Mille
authors: Gwenaël
authors: G
authors: Le Moal
authors: Jean-Paul
authors: JP
authors: Viard
authors: Christine
authors: C
authors: Rouzioux
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral