No effect of raltegravir intensification on viral replication markers in the
blood of HIV-1-infected patients receiving antiretroviral therapy.
Author(s): Gandhi RT, Coombs RW, Chan ES, Bosch RJ, Zheng L, Margolis DM, Read S, Kallungal
B, Chang M, Goecker EA, Wiegand A, Kearney M, Jacobson JM, D'Aquila R, Lederman
MM, Mellors JW, Eron JJ; AIDS Clinical Trials Group (ACTG) A5244 Team.
Collaborators: Leavitt R, Coffin J, Palmer S, Pettinelli C, Martinez A, Demeter
LM, Philpotts B, Donoval BA, Levaro R, Alatrakchi N, Medvik K, Janik J, Sprenger
H, Jennings A, Luetkemeyer A, Volinski J, Currin D, Marcus C, Robertson M,
Creamer-Alabama R, Sbrolla A, Burgett-Yandow N, Norris J, Valle S, McMahon D,
McNulty S, Spitz T, Frain J, Taiwo B, Coleman K, Vasquez M, Aberg JA, Stroberg T,
Hughes V, Albrecht M, Youmans A, Ray M, Johnson SC, Luque A, Adams M, Thielman
NM, Silberman M.
Affiliation(s): Division of Infectious Diseases and Ragon Institute, Massachusetts General
Hospital, Boston, MA 02114, USA. rgandhi@partners.org
Publication date & source: 2012, J Acquir Immune Defic Syndr. , 59(3):229-35
BACKGROUND: Controversy continues regarding the extent of ongoing viral
replication in HIV-1-infected patients on effective antiretroviral therapy (ART).
Adding an additional potent agent, such as raltegravir, to effective ART in
patients with low-level residual viremia may reveal whether there is ongoing
HIV-1 replication.
METHODS: We previously reported the outcome of a randomized placebo-controlled
study of raltegravir intensification in patients on ART with HIV-1 RNA <50 copies
per milliliter that showed no effect on residual viremia measured by single copy
assay. We now report the effects of raltegravir intensification in that trial on
other potential measures of ongoing HIV-1 replication as follows: 2-LTR HIV-1
circles, total cellular HIV-1 DNA, and T-cell activation.
RESULTS: Of 50 patients tested, 12 (24%) had 2-LTR circles detected at baseline.
Patients who were 2-LTR-positive had higher plasma HIV-1 RNA and HIV-1 DNA levels
than 2-LTR-negative individuals. At week 12 of raltegravir intensification, there
was no change from baseline in 2-LTR circles, in total HIV-1 DNA or in the ratio
of 2-LTR circles to total HIV-1 DNA. There was also no change in markers of
T-cell activation.
CONCLUSIONS: In HIV-1-infected individuals on effective ART, we find no evidence
of ongoing viral replication in the blood that is suppressible by raltegravir
intensification. The results imply that raltegravir intensification alone will
not eradicate HIV-1 infection.
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