Author's response to reviews Title:Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study Authors:

conclusions: The definition does not necessarily identify all those that progress to incident CKD, however, it can be used alongside other renal measurements to early identify and assess those at risk of developing CKD. Conclusions: Despite the weak association between our RP definition and subsequent development of CKD, perhaps due to the limited follow-up available, other studies have shown that short-term changes in eGFR relate to subsequent mortality and underline the clinical importance of RP. In future analyses, the D:A:D study group will consider this definition of RP to identify and assess potential risk factors including antiretroviral use, as a dynamic tool to be used, in addition to commonly used CKD analysis. Minor Essential Revisions: 1. Abstract: While the association of RP with CKD events is mentioned in the methods, no findings are reported in the results. As this would be of greatest interest to readers, a brief summary of these findings in the abstract should be considered for inclusion. Response: This result has now been added to the results section of the abstract as shown below. Abstract results: For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD.results: For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD. 2. Introduction: The last sentence in the first paragraph may be improved by actually describing the MDRD findings which led to the authors asserting that the MDRD study "made a strong case" for RP. Response: This sentence has now been modified (Page 4, paragraph 2) as shown below. Introduction: A study from the Modification of Diet in Renal Disease (MDRD) study group to determine baseline factors that predict the decline in GFR made a case for the rapid decline in renal function to be further investigated. They reported that the mean rate of GFR decline was not significantly related to the baseline GFR, and this suggests an approximately linear mean eGFR decline as renal disease progresses [9]. 3. Introduction: The "normal" age-related decline for eGFR cited by the authors pertains mainly to those aged >=50. This point should be clarified for accuracy. Response: The sentence has now been clarified (Page 4, paragraph 2) as shown below. Introduction: It is commonly accepted that a normal age-related eGFR decline in the general population (typically >50 years) is approximately 1 ml/min/1.73m2/year [10-12].