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Referee Comments: Referee 1

Posted by PLOS_ONE_Group on 28 Apr 2008 at 18:09 GMT

Referee 1's Review:

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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.
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Introduction: Second paragraph, a similar (increased) trend in cardiovascular events cannot be shown in a single arm study (no comparison for ?increase) AND there were only 4 cardiovascular events not 5 (according to the reference given). - Would remove this sentence

Methods: The times of fasting metabolic testing needs to be added - I can see from the protocol when they were done, but it needs to be added to the report.

Results: A table showing no significant difference between the randomized arms in the lipids and glucose should be added, to support the grouping of all data into one arm.

Paragraph 3 gives results of absolute changes in the various lipids, then refers to figure 1 which shows percentage changes - need to be consistent, either show the absolute changes or give the results of the % changes. The figure shows large interquartile ranges. The first sentence of this paragraph states there was "a rapid and dramatic decrease in cholesterol" however, this change is described as "modest" in the large paragraph of the discussion - the description needs to be consistent.

There is no data to support the statement that all lipid changes occurred before return of detectable plasma HIV RNA. There are no results for HIV RNA in the paper.

There is also no data provided to support the statement that increase in CD8+ T cell activation occurred faster amongst those that received ART alone prior to the treatment interruption - suggest another table is added for the randomization of ART and ART + IL2 or delete altogether as it probably does not added much to the conclusions.

Discussion: Cannot say that the lipoprotein changes are unlikely to be related to HIV replication as this data was not shown. Last sentence is accurate but it does not apply to this study as there no assessment of the relationship between viremia and immune activation and inflammatory markers - why wasn't this data provided in this paper? It would strengthen it and should be included.