title: Effect of treatment, during primary infection, on establishment and clearance of cellular reservoirs of HIV-1.
abstract: Patients in whom virologic suppression is achieved with highly active antiretroviral therapy (HAART) retain long-lived cellular reservoirs of human immunodeficiency virus type 1 (HIV-1); this retention is an obstacle to sustained control of infection. To assess the impact that initiating treatment during primary HIV-1 infection has on this cell population, we analyzed the decay kinetics of HIV-1 DNA and of infectivity associated with cells activated ex vivo in 27 patients who initiated therapy before or <6 months after seroconversion and in whom viremia was suppressed to <50 copies/mL. The clearance rates of cellular reservoirs could not be distinguished by these techniques (median half-life, 20 weeks) during the first year of HAART. The clearance of HIV-1 DNA slowed significantly during the subsequent 3 years of treatment (median half-life, 70 weeks), consistent with heterogeneous cellular reservoirs being present. Total cell-associated infectivity (CAI) after 1 year of treatment was undetectable (<0.07 infectious units/million cells [IUPM]) in most patients initiating treatment during primary infection either before (9/9) or <6 months after (6/8) seroconversion. In contrast, all 17 control patients who initiated HAART during chronic infection retained detectable CAI after 3-6 years of treatment (median reservoir size, 1.1 IUPM; P<.0005). These results suggest that treatment <6 months after seroconversion may facilitate long-term control of cellular reservoirs that maintain HIV-1 infection during treatment.
authors.affiliation: Department of Physics, University of California at San Diego, La Jolla, California, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Strain
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Little
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Diane V
authors.initials: DV
authors.lastname: Havlir
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Gunthard
authors.forename: Ruby Y
authors.initials: RY
authors.lastname: Lam
authors.forename: Otto A
authors.initials: OA
authors.lastname: Daly
authors.forename: Juin
authors.initials: J
authors.lastname: Nguyen
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Ignacio
authors.forename: Celsa A
authors.initials: CA
authors.lastname: Spina
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wong
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D006679:HIV Seropositivity; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification*; D006801:Humans; D007700:Kinetics; D013997:Time Factors
chemical_list: D004279:DNA, Viral