Tuesday, November 24, 2015

A Randomized Trial of Time-Limited Antiretroviral Therapy in Acute/Early HIV Infection

Background
It has been proposed that initiation of antiretroviral treatment (ART) very soon after establishment of HIV infection may be beneficial by improving host control of HIV replication and delaying disease progression.

Methods
People with documented HIV infection of less than 12 months’ duration in Baltimore MD and seven Canadian sites were randomized to either a) observation and deferred ART, or b) immediate treatment with ART for 12 months. All subjects not receiving ART were followed quarterly and permanent ART was initiated according to contemporaneous treatment guidelines. The endpoint of the trial was total ART-free time from study entry until initiation of permanent ART.

Results
One hundred thirteen people were randomized, 56 to the observation arm and 57 to the immediate treatment arm. Twenty-three had acute (<2 months) infection and 90 early (2–12 months) infection. Of those randomized to the immediate treatment arm, 37 completed 12 months of ART according to protocol, 9 declined to stop ART after 12 months, and 11 were nonadherent to the protocol or lost to follow-up. Comparing those in the observation arm to either those who completed 12 months of ART or all 56 who were randomized to immediate ART, there was no significant difference between the arms in treatment-free interval after study entry, which was about 18 months in both arms.

Conclusions
This study did not find a benefit from administration of a brief, time-limited (12-month) course of ART in acute or early HIV infection.

Below:  Per-protocol survival analysis of time from randomization (Deferred Treatment arm) or cessation of immediate ART (Immediate Treatment arm) until permanent initiation of antiretroviral therapy (ART).
Results are stratified by study arm (Immediate ART vs. Deferred ART). The Immediate ART arm includes the 37 subjects who completed the study protocol, i.e., 12 months of ART followed by cessation of ART and continuation of clinical monitoring. Numbers of observations at 6-monthly time points are shown. (For the results of the same analysis including the 9 subjects in the Immediate arm who completed 12 months of ART but did not stop ART at that time, see S1 Fig).


Full article at:  http://goo.gl/UkO6Xj

By:   
Joseph B. Margolick, Linda Apuzzo
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America

Joel Singer, Hubert Wong, Terry Lee
CIHR Canadian HIV Trials Network, Vancouver, British Columbia, Canada

Joel E. Gallant
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America

Phillippe El-Helou
Department of Medicine, McMaster University, Hamilton, Ontario Canada

Mona R. Loutfy
Maple Leaf Medical Clinic, Toronto, Ontario, Canada

Anita Rachlis
Sunnybrook Health Sciences, Toronto, Ontario, Canada

Christopher Fraser
Cool Aid Community Health Center, Victoria, British Columbia, Canada

Kenneth Kasper
Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada

Cécile Tremblay
Centre de recherché du Centre Hospitalier de l’ Université de Montréal, Montréal, Quebec, Canada

Harout Tossonian, Brian Conway
Vancouver Infectious Diseases Centre, Vancouver, British Columbia, Canada
 



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