Predicting Factors of Plasma HIV RNA Undetectability after Switching to Co-Formulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Experienced HIV-1 Patients: A Multicenter Study

Round 1

Reviewer 1 Report

Summary:

The authors present a retrospective study of patients who switched to BIC/TAF/FTC to understand the predictors of suppression (either <50 or undetectable) at 24 months post switch. Among the 329 with suppression, 98 were excluded for lack of virological data 12 months before switch and 34 patients had positive HBsAG or HCV positive RNA leaving 197 in the analytical set. For patients that were always undetectable in the 12 months prior to switch, there was a greater likelihood of undetectable by 24 months than for those with at least one <50 and even less than at least one >50 copies/mL, but not more likely to be <50 copies by this same group compared to the others. CD4 nadir and INSTI were also predictive.

I do believe these findings are interesting though some of the sentences are a bit difficult to follow which can make it challenging to understand some of the more complicated nuances of the study. This can be corrected. Also, I would suggest stratifying the same outcomes by the T0 viral load as that may be the easiest to calculate.  This measure could be as predictive as the other.

Major Comments:

1.       Methods – on page 2, line 94 it should be clarified if “at least one month before switch” means the viral load could be 60 days or 90 days or more before switch or if it means “less than one month before switch” such that it could be 10 days or 15 days before the switch.  ALSO, the authors should clarify if there was more than one viral load that they used the value closest to the switch date that was still prior to the switch date.

2.       Methods – the authors should clarify if the viral load above (screening) is the same as the T0 viral load.

3.       Methods – page 3, line 106; it is not clear why the authors state that patients with HV VL <50 were “further” split into undetectable and <50 if all patients had to have <50 or be undetectable to enter the study. It should not be “further” if all are in this group. No one should be >50 copies.

4.       Methods – page 3, line 116, there could be viral loads higher than 100 copies without a follow up undetectable (i.e. not a blip). It is not clear why this was not also a reason for switch.

5.       Methods – as mentioned above in the summary, the authors should stratify the same time to event outcomes by the T0 viral load as that may be the easiest metric to calculate for a clinician to make a decision as whether they should switch now or later.

6.       Results – the authors should describe the median/IQR for the “number of VLs per patient in the 12 months prior to switch” used in the determination of belonging to one of three categories.

7.       Results – in table 2, the percentages across each row do not add up to 100 and so appear to be the percentage of the vertical groups (undetectable or detectable). This does not make sense to use those percentages when comparing across the rows such as undetectable in the prior 12 months either being undetectable at T0 or detectable at T0 (p=0.0002).

8.       Results – in table 4, only the 52 M has an actual reason for switching but the others do not describe why they switched. This should be added.

9.       Discussion – the authors could provide some summary of studies that have looked at the probability of virologic rebound for individuals having blips or low-level viremia with a focus on whether the balance of information is in favor or against the predictability of this measure.

Minor Comments:

1.       There are numerous grammatical errors and the syntax for complicated areas are somewhat difficult to understand. This can make important and nuanced points hard to follow or even missed.

2.       In line 95 of page 2, the authors could also clarify if “never HCV infected” could also be a reason of a negative HCV RNA.

3.       Page 3, line 102 – the authors should clarify what “origin” means.

4.       I would change “subjects” to “participants” or “patients” (depending on if they were consented or not respectively).

5.       Any mention of “undetectable” in the 12 months prior to switch should have the word “always” before it for this category.

6.       There are several instances of “NR” used as an abbreviation in the text and tables. It is not clear what this means but seems to be “not detectable” which would be better to use ND throughout (as was used in some instances).

7.       It would be interesting to know if the patient who switched for weight gain improved with the raltegravir regimen as that was the only medication that changed and both are INSTIs.

8.       In table 5, the 49 M is listed as therapeutic failure but the other patients with similar viral loads were considered blips. This should be explained or corrected.

Mentioned above

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Here is a start:

42: 108 had undetectable with HIV RNA? Whom is this? The INSTI-based regimen?

42-46: please rewrite this long sentence or make into 2 sentences. Not clear.  

58: delete “at now”

65: delete second “of” after and

66: add “a” before pharmacokinetic

72: delete “include” add is included

73: add “in” before patients

75: delete “demonstrated”

What is NR in the tables? Shouldn’t you use ND for not detectable

What’s a blip?

 The tables in the results need restructured. in their current state it is difficult to follow. There must be a more comprehensible way to present this data so the reader can more easily follow the various follow ups. You compare the follow ups to T0, but would it worthwhile to compare back the previous timepoint, or is there a way to do that? Could you please expand the results section so the tables are adequately described in the body of the manuscript. 

Here is a start:

42: 108 had undetectable with HIV RNA? Whom is this? The INSTI-based regimen?

42-46: please rewrite this long sentence or make into 2 sentences. Not clear.  

58: delete “at now”

65: delete second “of” after and

66: add “a” before pharmacokinetic

72: delete “include” add is included

73: add “in” before patients

75: delete “demonstrated”

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

the authors made significant improvements to the manuscript.