title: Intensification of antiretroviral therapy accelerates the decay of the HIV-1 latent reservoir and decreases, but does not eliminate, ongoing virus replication.
abstract: This study evaluated whether intensification of standard antiretroviral therapy with abacavir, with or without efavirenz, leads to better viral suppression and acceleration of the rate of HIV-1 decay. Ten HIV-1-infected individuals were enrolled in a prospective, open-label study and received standard, combination antiretroviral therapy with either 3 or 4 agents. The rate of decay of the HIV-1 latent reservoir and the frequency of intermittent viremia were compared between 5 patients who underwent treatment intensification and 5 control subjects with comparable baseline characteristics. When compared with control patients, the median half-life (t1/2) of the latent reservoir decreased from 31 to 10 months (P = 0.016) in subjects who had treatment intensification. The frequency of intermittent viremia/year also decreased in 4 of 5 individuals following intensification (2.4/y vs. 0.8/y). These data suggest that ongoing virus replication during standard antiretroviral therapy is due, in part, to the inadequate antiviral potency of current regimens. Despite better viral suppression, treatment intensification did not completely block viral replication, as evidenced by continuing intermittent viremia in some individuals. Additional studies are needed to understand the host- and pathogen-related determinants of incomplete pharmacologic control of HIV-1 replication.
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY, USA. BRamratnam@Lifespan.org
authors.forename: Bharat
authors.initials: B
authors.lastname: Ramratnam
authors.forename: Ruy
authors.initials: R
authors.lastname: Ribeiro
authors.forename: Tian
authors.initials: T
authors.lastname: He
authors.forename: Chris
authors.initials: C
authors.lastname: Chung
authors.forename: Viviana
authors.initials: V
authors.lastname: Simon
authors.forename: Jeroen
authors.initials: J
authors.lastname: Vanderhoeven
authors.forename: Arlene
authors.initials: A
authors.lastname: Hurley
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
authors.forename: David D
authors.initials: DD
authors.lastname: Ho
authors.forename: Martin
authors.initials: M
authors.lastname: Markowitz
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000254:growth & development; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000008:administration & dosage; D010865:Pilot Projects; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage; D019562:Viral Load; D017735:Virus Latency; D014779:Virus Replication; D000099227:Abacavir
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D010078:Oxazines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C098320:efavirenz