title: Cellular HIV-1 DNA quantitation in patients during simplification therapy with protease inhibitor-sparing regimens.
abstract: Simplified regimens containing protease-inhibitors (PI)-sparing combinations were used in patients with virological suppression after prolonged highly active antiretroviral therapy. This study evaluated the total HIV-1 DNA quantitation as a predictor of long-term success for PI-sparing simplified therapy. Sixty-two patients were enrolled in a prospective non-randomized cohort. All patients have been receiving a triple-therapy regimen, two nucleoside reverse transcriptase inhibitors (NRTIs) plus one PI, for at least 9 months and were characterized by undetectable plasma HIV-1 RNA levels (<50 cp/ml) for at least 6 months. Patients were changed to a simplified PI-sparing regimen to overcome PI-associated adverse effects. HIV-DNA levels in peripheral blood mononuclear cells (PBMCs) were evaluated at baseline and at the end of follow-up. Patients with proviral DNA levels below the median value (226 copies/10(6) PBMCs) had a significant higher CD4 cell count at nadir (P = 0.003) and at enrolment (P = 0.001) with respect to patients with HIV-DNA levels above the median value. At month 18, 53 out of 62 (85%) patients on simplified regimen showed virological success, 4 (6.4%) patients experienced virological failure and 5 (8%) patients showed viral blip. At logistic regression analysis, HIV-DNA levels below 226 copies/10(6) PBMCs at baseline were associated independently to a reduced risk of virological failure or viral blip during simplified therapy (OR 0.002, 95% CI 0.001-0.46, P = 0.025). The substitution of PI with NRTI or non-NRTIs may represent an effective treatment option. Indeed, treatment failure or viral blip were experienced by 6% and 8% of the patients on simplified therapy, respectively. In addition, sustained suppression of the plasma viral load was significantly correlated with low levels of proviral DNA before treatment simplification.
authors.affiliation: Department of Public Health and Cellular Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Sarmati
authors.forename: Saverio Giuseppe
authors.initials: SG
authors.lastname: Parisi
authors.forename: Emanuele
authors.initials: E
authors.lastname: Nicastri
authors.forename: Gabriella
authors.initials: G
authors.lastname: d'Ettorre
authors.forename: Carolina
authors.initials: C
authors.lastname: Andreoni
authors.forename: Luca
authors.initials: L
authors.lastname: Dori
authors.forename: Francesca
authors.initials: F
authors.lastname: Gatti
authors.forename: Marco
authors.initials: M
authors.lastname: Montano
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Buonomini
authors.forename: Caterina
authors.initials: C
authors.lastname: Boldrin
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vullo
authors.forename: Massimo
authors.initials: M
authors.lastname: Andreoni
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood* / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification
chemical_list: D004279:DNA, Viral; D017320:HIV Protease Inhibitors