title: A Pilot Study of Raltegravir Plus Combination Antiretroviral Therapy in Early Human Immunodeficiency Virus Infection: Challenges and Lessons Learned.
abstract: Availability of integrase strand transfer inhibitors created interest in determining whether their use would decrease persistently infected cell numbers. This study hypothesized that adding raltegravir (RAL) to standard antiretroviral therapy (ART) would decrease human immunodeficiency virus (HIV)-infected CD4(+) T cells more than standard combination ART. This was a pilot, randomized study comparing open-label standard triple ART to standard triple ART plus RAL over 96 weeks in ART-naive adults with early HIV infection. The primary objective was to compare quantity and trajectory of HIV DNA. Eighty-two persons were referred. A diverse set of reasons precluded the enrollment of all but 10. Those who enrolled and completed the study had an estimated median duration of HIV infection of 74 days at ART start. The groups had similar baseline characteristics. The RAL group had more rapid first phase plasma HIV RNA decay (0.67 log10 copies/mL/day) than with combination ART (0.34 log10copies/mL/day), p = 0.037. Second phase HIV RNA decay, residual viremia, cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circle levels did not differ between groups. Among those with entry plasma HIV RNA levels above the median, 2LTR circles were significantly lower over time than in those with lower entry HIV RNA levels (p = 0.02). Our results suggest homogeneity of responses in cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circles with early HIV in both ART groups. The kinetics of 2LTR DNA did not reflect the kinetics of plasma HIV RNA decline following ART initiation.
authors: Division of Infectious Diseases, Department of Medicine, University of Washington , Seattle, Washington.
authors: Ann C
authors: AC
authors: Collier
authors: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
authors: Tae-Wook
authors: TW
authors: Chun
authors: Division of Infectious Diseases, Department of Medicine, University of Washington , Seattle, Washington.
authors: Janine
authors: J
authors: Maenza
authors: Division of Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington.; Department of Laboratory Medicine, University of Washington, Seattle, Washington.
authors: Robert W
authors: RW
authors: Coombs
authors: Department of Global Health, University of Washington , Seattle, Washington.
authors: Kenneth
authors: K
authors: Tapia
authors: Department of Laboratory Medicine, University of Washington , Seattle, Washington.
authors: Ming
authors: M
authors: Chang
authors: Department of Neurology, University of Washington , Seattle, Washington.
authors: Claire E
authors: CE
authors: Stevens
authors: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
authors: J Shawn
authors: JS
authors: Justement
authors: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
authors: Danielle
authors: D
authors: Murray
authors: Division of Infectious Diseases, Department of Medicine, University of Washington , Seattle, Washington.
authors: Joanne D
authors: JD
authors: Stekler
authors: Division of Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington.; Department of Laboratory Medicine, University of Washington, Seattle, Washington.; Department of Microbiology, University of Washington, Seattle, Washington.
authors: James I
authors: JI
authors: Mullins
authors: Program in Biostatistics and Biomathematics, Division of Fred Hutch, Department of Biostatistics, University of Washington , Seattle, Washington.
authors: Sarah E
authors: SE
authors: Holte
keywords: antiretroviral therapy; integrase inhibitor; primary HIV; reservoir