title: Intensifying Antiretroviral Therapy With Raltegravir and Maraviroc During Early Human Immunodeficiency Virus (HIV) Infection Does Not Accelerate HIV Reservoir Reduction.
abstract: Background.  Persistent human immunodeficiency virus (HIV) within the CD4(+) T-cell reservoir is an obstacle to eradication. We hypothesized that adding raltegravir and maraviroc to standard combination antiretroviral therapy (cART) during early HIV infection could substantially reduce viral reservoirs as a step towards eradication. Methods.  A prospective, randomized, double-blinded, placebo-controlled pilot trial enrolled 32 participants with documented early (<6 months) HIV infection to either standard cART (emtricitabine/tenofovir/lopinavir/ritonavir) or intensive cART (standard regimen + raltegravir/maraviroc). Human immunodeficiency virus reservoirs were assessed at baseline and at 48 weeks by (1) proviral DNA, (2) cell-associated RNA, and (3) replication-competent virus, all from purified blood CD4(+) T cells, and (4) gut proviral DNA. A multiassay algorithm (MAA) on baseline sera estimated timing of infection. Results.  Thirty individuals completed the study to the 48-week endpoint. The reduction in blood proviral burden was -1.03 log DNA copies/10(6) CD4(+) T cells versus -.84 log in the standard and intensive groups, respectively (P = .056). Overall, there was no significant difference in the rate of decline of HIV-associated RNA, replication-competent virus in blood CD4(+) T cells, nor proviral gut HIV DNA to 48 weeks. Individuals who presented with more recent HIV infection had significantly lower virus reservoirs, and cART tended to reduce their reservoirs to a greater extent. Conclusions.  Intensive cART led to no additional reduction in the blood virus reservoir at 48 weeks compared with standard cART. Human immunodeficiency virus reservoir size is smaller earlier in HIV infection. Other novel treatment strategies in combination with early cART will be needed to eliminate the HIV latent reservoir.
authors.affiliation: Departments of Immunology ; Medicine , University of Toronto ; Keenan Research Centre for Biomedical Science of St. Michael's Hospital , Toronto, Ontario , Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Ostrowski
authors.affiliation: Maple Leaf Clinic.
authors.forename: Erika
authors.initials: E
authors.lastname: Benko
authors.affiliation: Medicine , University of Toronto.
authors.forename: Feng Yun
authors.initials: FY
authors.lastname: Yue
authors.affiliation: Medicine , University of Toronto.
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Medicine , University of Toronto.
authors.forename: Sanja
authors.initials: S
authors.lastname: Huibner
authors.affiliation: University of British Columbia ; CIHR Canadian HIV Trials Network , Vancouver, British Columbia , Canada.
authors.forename: Terry
authors.initials: T
authors.lastname: Lee
authors.affiliation: University of British Columbia ; CIHR Canadian HIV Trials Network , Vancouver, British Columbia , Canada.
authors.forename: Joel
authors.initials: J
authors.lastname: Singer
authors.affiliation: University of British Columbia ; CIHR Canadian HIV Trials Network , Vancouver, British Columbia , Canada.
authors.forename: Jim
authors.initials: J
authors.lastname: Pankovich
authors.affiliation: Laboratory of Immunoregulation , National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda ; Johns Hopkins University , Baltimore, Maryland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.affiliation: Departments of Immunology ; Medicine , University of Toronto.
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
authors.affiliation: Medicine , University of Toronto ; Keenan Research Centre for Biomedical Science of St. Michael's Hospital , Toronto, Ontario , Canada.
authors.forename: Gabor
authors.initials: G
authors.lastname: Kandel
authors.affiliation: Medicine , University of Toronto ; Maple Leaf Clinic.
authors.forename: Colin
authors.initials: C
authors.lastname: Kovacs
keywords: HIV; acute; early; intensive cART; reservoir