title: Favorable outcome of ex-vivo purging of monocytes after the reintroduction of treatment after interruption in patients infected with multidrug resistant HIV-1.
abstract: In multidrug resistant patients treatment interruptions allow the selection of archived wild-type drug-susceptible viruses that compete for the less fit drug-resistant strains. However, the selection of viruses with increased replicative capacity is often followed by a loss of CD4+ T cells. In addition, drug resistant variants later re-emerge limiting the overall clinical benefit of treatment interruption. Blood monocytes are a key component of the HIV reservoir and can be partially removed by a system for purging of myeloid cells (MYP). This study tested the safety and efficacy of MYP on multidrug resistant patients who underwent treatment interruption. Twelve patients were randomized to receive or not six cycles of MYP during treatment interruption. An optimized antiretroviral regimen was reintroduced after the reappearance of a drug susceptible genotype. Following therapy reintroduction, a long lasting increase in CD4+ T cell counts was observed only in the treatment interruption + MYP patients but not in the control patients. Five/six treatment interruption + MYP patients never experienced virological rebound during a median follow up period of 98 weeks. In contrast, 4/6 patients who did not receive MYP never reached complete viral suppression and had a virological rebound after a median of 16.5 weeks after treatment reintroduction. The difference between the two groups in the time to virological rebound was statistically significant (P = 0.021). A consistent decrease of HIV DNA load in CD14+ purified cells was observed only in treatment interruption + MYP patients. These data suggest that MYP can improve the immunological and virological response to treatment interruption.
authors.affiliation: San Raffaele Scientific Institute, Infectious Diseases Clinic, Milano, Italy.
authors.forename: Hamid
authors.initials: H
authors.lastname: Hasson
authors.forename: Barbara
authors.initials: B
authors.lastname: Mantelli
authors.forename: Priscilla
authors.initials: P
authors.lastname: Biswas
authors.forename: Mauro
authors.initials: M
authors.lastname: Malnati
authors.forename: Nicola
authors.initials: N
authors.lastname: Gianotti
authors.forename: Andrea
authors.initials: A
authors.lastname: Vecchi
authors.forename: Silvia
authors.initials: S
authors.lastname: Nozza
authors.forename: Massimo
authors.initials: M
authors.lastname: Cernuschi
authors.forename: Enzo
authors.initials: E
authors.lastname: Boeri
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Alberto
authors.initials: A
authors.lastname: Beretta
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome
chemical_list: D012367:RNA, Viral