title: A high HIV DNA level in PBMCs at antiretroviral treatment interruption predicts a shorter time to treatment resumption, independently of the CD4 nadir.
abstract: This study aimed to evaluate the safety of antiretroviral treatment interruption (TI) in HIV-infected patients who started treatment based on earlier guidelines, and to identify baseline factors predictive of the time to reach fixed criteria for treatment resumption. Prospective, open-label, multicenter trial. Patients were eligible if they had a CD4 cell count >350/mm(3) and plasma HIV RNA <50,000 copies/ml when they first started antiretroviral therapy (ART); and if they had a CD4 count >450/mm(3) and stable plasma HIV RNA <5,000 copies/ml for at least 6 months prior to enrollment. The criteria for ART resumption were a CD4 cell count <300/mm(3) and/or a CDC stage B or C event. 116 patients had received ART for a median of 5.3 years. The median CD4 cell count and plasma HIV RNA values at inclusion were 809/mm(3) and 2.6 log copies/ml, respectively. Median HIV DNA load at inclusion was 2.3 log copies/10(6) peripheral blood mononuclear cells (PBMCs). Thirty-six months after TI, 63.9% of the patients had not yet reached the criteria for ART resumption, and 55.9% of patients had not resumed ART. In Cox multivariable analysis, a high HIV DNA level at TI, a low CD4 nadir, and pre-existing AIDS status were the only significant risk factors for reaching the criteria for ART resumption (hazards ratio: 2.15 (1.02-4.53), 4.59 (1.22-17.24), and 5.74 (1.60-20.56), respectively). Patients who started ART with a CD4 cell count above 350/mm(3) were able to interrupt treatment for long periods without a high absolute risk of either AIDS or severe non-AIDS morbidity/mortality. A high PBMC HIV DNA level at TI was a strong predictor for more rapid treatment resumption.
authors.affiliation: AP-HP, Department of Clinical Immunology, Georges Pompidou European Hospital, Paris, France. christophe.piketty@egp.aphp.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Piketty
authors.forename: Laurence
authors.initials: L
authors.lastname: Weiss
authors.forename: Lambert
authors.initials: L
authors.lastname: Assoumou
authors.forename: Marianne
authors.initials: M
authors.lastname: Burgard
authors.forename: Aurélie
authors.initials: A
authors.lastname: Mélard
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Ragnaud
authors.forename: Michele
authors.initials: M
authors.lastname: Bentata
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood*; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral