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SUPPLEMENTAL DIGITAL CONTENT

Datasets

We obtained demographic, laboratory, diagnosis, and utilization data from the Veterans Affairs (VA) Corporate Data Warehouse (CDW), including medical SAS datasets for inpatient and outpatient encounters, CDW’s raw pharmacy data, and Decision Support Systems and CDW’s laboratory data. To conduct the analyses, datasets were housed in the VA Informatics and Computing Infrastructure environment, which enables access to data and tools for reporting and analysis in a secure workspace to ensure veterans’ privacy and data security.

Exposures

For regimens with separate dosage forms, the third agent must have overlapped with the backbone within 30 days. For boosted or enhanced regimens (EVG/c and RTV-boosted PIs), the third agent must have also overlapped with the booster/enhancer for the patient to be classified as taking the regimen. Discontinuation of the regimen was defined as having a gap of at least 30 days for either the third agent or the backbone; patients who discontinued their regimen were censored on the first day of the first 30-day gap following the end of the prior days’ supply received by the patient.

TABLE S1. Diagnosis Codes for HIV Infection

|Category |Codes |

|Valid ICD-9 diagnosis codes |042*, V08*, or 795.71 |

|Valid ICD-10 diagnosis codes |B20* |

|Diagnostic-related group codes |488–490 |

ICD-9, International Classification of Diseases, 9th Revision; ICD-10, International Classification of Diseases, 10th Revision.

TABLE S2. Renal Adverse Outcomes Defined by Diagnosis Codes1

Proteinuria

• Valid ICD-9 diagnosis codes: DX 593.6, 791.0

• Valid ICD-10 diagnosis codes: DX D51.1, N06.0, N06.2, N06.3, N06.4, N06.5, N06.6, N06.7, N06.8, N06.9, O12.10, O12.12, O12.13, O12.20, O12.21, O12.22, O12.23, R80.0, R80.1, R80.2, R80.3, R80.8, R80.9

o Abbreviated list of ICD-10 diagnosis codes: D51.1, N06.*, O12.1*, O12.2*, R80.*

Chronic Kidney Disease (CKD) Diagnosis1-4

• Valid ICD-9 diagnosis codes: DX 016.00, 016.01, 016.02, 016.03, 016.04, 016.05, 016.06, 095.4, 189.0, 189.9, 223.0, 223.99, 236.90, 236.91, 236.99, 249.40, 249.41, 250.40, 250.41, 250.42, 250.43, 271.4, 274.10, 283.11, 403.00, 403.01, 403.10, 403.11, 403.90, 403.91, 404.00, 404.01, 404.02, 404.03, 404.10, 404.11, 404.12, 404.13, 404.90, 404.91, 404.92, 404.93, 440.1, 442.1, 572.4, 580.0, 580.4, 580.81, 580.89, 580.9, 581.0, 581.1, 581.2, 581.3, 581.81, 581.89, 581.9, 582.0, 582.1, 582.2, 582.4, 582.81, 582.89, 582.9, 583.0, 583.1, 583.2, 583.4, 583.6, 583.7, 583.81, 583.89, 583.9, 584.5, 584.6, 584.7, 584.8, 584.9, 585.1, 585.2, 585.3, 585.4, 585.5, 585.6, 585.9, 586, 587, 588.0, 588.1, 588.81, 588.89, 588.9, 591, 753.12, 753.13, 753.14, 753.15, 753.16, 753.17, 753.19, 753.20, 753.21, 753.22, 753.23, 753.29, 794.4

o Note: 223.99 (benign neoplasm of unspecified urinary organ), 236.90 (neoplasm of uncertain behavior of unspecified urinary organ), and 236.99 (neoplasm of uncertain behavior of other/unspecified urinary organs) were not included in the CMS list. However, given that the analogous malignant neoplasms of these unspecified sites were included, we have decided to include them here. Also, 403.*0 codes (malignant/benign/unspecified stage I–IV hypertensive chronic kidney disease) and 404.*0 and 404.*1 (malignant/benign/unspecified stage I–IV chronic kidney disease and hypertensive heart disease with/without heart failure) were not included in the CMS list, only the similar codes for stage V or end-stage renal disease (ESRD). This must have been an oversight (especially given that the CKD stage I–IV codes are included) and we have included them here.

o Abbreviated list of ICD-9 diagnosis codes: 016.0*, 095.4, 189.0, 190.0, 223.0, 223.9, 236.9*, 249.4*, 250.4*, 271.4, 274.10, 283.11, 403.**, 404.**, 440.1, 442.1, 572.4, 580.* through 588.* and 580.** through 588.**, 591, 753.12 through 753.29, 794.4 and V42.0

• Valid ICD-9 procedure codes: 39.951, 54.981

• Valid ICD-10 diagnosis codes: DX A18.11, A52.75, B52.0, C64.1, C64.2, C64.9, C68.9, D30.00, D30.01, D30.02, D30.9, D41.00, D41.01, D41.02, D41.9, D59.3, E08.21, E08.22, E08.29, E09.21, E09.22, E09.29, E10.21, E10.22, E10.29, E11.21, E11.22, E11.29, E13.21, E13.22, E13.29, I12.0, I12.9, I13.0, I13.10, I13.11, I13.2, I70.1, I72.2, K76.7, M10.30, M10.311, M10.312, M10.319, M10.321, M10.322, M10.329, M10.331, M10.332, M10.339, M10.341, M10.342, M10.349, M10.351, M10.352, M10.359, M10.361, M10.362, M10.369, M10.371, M10.372, M10.379, M10.38, M10.39, M32.14, M32.15, M35.04, N00.0, N00.1, N00.2, N00.3, N00.4, N00.5, N00.6, N00.7, N00.8, N00.9, N01.0, N01.1, N01.2, N01.3, N01.4, N01.5, N01.6, N01.7, N01.8, N01.9, N02.0, N02.1, N02.2, N02.3, N02.4, N02.5, N02.6, N02.7, N02.8, N02.9, N03.0, N03.1, N03.2, N03.3, N03.4, N03.5, N03.6, N03.7, N03.8, N03.9, N04.0, N04.1, N04.2, N04.3, N04.4, N04.5, N04.6, N04.7, N04.8, N04.9, N05.0, N05.1, N05.2, N05.3, N05.4, N05.5, N05.6, N05.7, N05.8, N05.9, N06.0, N06.1, N06.2, N06.3, N06.4, N06.5, N06.6, N06.7, N06.8, N06.9, N07.0, N07.1, N07.2, N07.3, N07.4, N07.5, N07.6, N07.7, N07.8, N07.9, N08, N13.1, N13.2, N13.30, N13.39, N14.0, N14.1, N14.2, N14.3, N14.4, N15.0, N15.8, N15.9, N16, N17.0, N17.1, N17.2, N17.8, N17.9, N18.1, N18.2, N18.3, N18.4, N18.5, N18.6, N18.9, N19, N25.0, N25.1, N25.81, N25.89, N25.9, N26.1, N26.9, Q61.02, Q61.11, Q61.19, Q61.2, Q61.3, Q61.4, Q61.5, Q61.8, Q62.0, Q62.10, Q62.11, Q62.12, Q62.2, Q62.31, Q62.32, Q62.39, R94.4

o Note: The codes for neoplasms of uncertain behavior of the left/right/unspecified renal pelvis and ureter were included in the CMS list (including D41.1* and D41.2*). However, given that the analogous codes were excluded from all other lists (including malignant/benign neoplasms in the ICD-10 list and malignant/benign/uncertain behavior in the ICD-9 list) we have decided to exclude them here. In addition, E08.65 (diabetes mellitus due to underlying condition with hyperglycemia), E10.65 (Type I diabetes mellitus with hyperglycemia), and E11.65 (Type II diabetes mellitus with hyperglycemia) are included in the CMS list. This must be erroneous and we have excluded them here.

o Note: D30.9 (benign neoplasm of unspecified urinary organ) and D41.9 (neoplasm of uncertain behavior of unspecified urinary organ) were not included in the CMS list. However, given that the analogous malignant neoplasms of these unspecified sites were included, we have decided to include them here. Also, I12.9, I13.0, and I13.10 (unspecified stage I–IV hypertensive chronic kidney disease with and without hypertensive heart disease) were not included, only the similar codes for stage V or ESRD. This must have been an oversight and we have included them here.

o Abbreviated list of ICD-10 diagnosis codes: A18.11, A52.74, B52.0, C64.*, C68.9, D30.0*, D30.9, D41.0*, D41.9, D59.3, E08.2*, E09.2*, E10.2*, E11.2*, E13.2*, I12.*, I13.0, E13.1*, E13.2, I70.1, I72.2, K76.7, M10.30, M10.31* through M10.37*, M10.3*, M32.14, M32.15, M35.04, N0*.*, N08, N13.1, N13.2, N13.3*, N14.*, N15.*, N16, N17.*, N18.*, N19, N25.0, N25.1, N25.8*, N25.9, N26.1, Q61.02, Q61.1*, Q61.2 through Q61.8, Q62.0, Q62.1*, Q62.0, Q62.1*, Q62.2, Q62.3*, R94.4

End-Stage Renal Disease

• Valid ICD-9 diagnosis codes: DX 403.01, 403.11, 403.91, 404.02, 404.03, 404.12, 404.13, 404.92, 404.93, 585.5, 585.6, V42.0

o Abbreviated list of ICD-9 diagnosis codes: 403.*1, 404.*2, 404.*3, 585.5, 585.6, V42.0

• Valid ICD-9 procedure codes: 39.951, 54.981, 55.6, 55.6*

• Valid ICD-10 diagnosis codes: DX I12.0, I13.11, I13.2, N18.5, N18.6

Kidney Dialysis5-7

• Valid ICD-9 diagnosis codes: DX 458.21, 792.5, 996.56, 996.68, 996.73, E87.91, V45.11, V45.12, V56.0, V56.1, V56.2, V56.31, V56.32, V56.8

o Abbreviated list of ICD-9 diagnosis codes: 458.21, 792.5, 996.56, 996.68, 996.73, E87.91, V45.1*, V456.

• Valid CPT-4 codes: 90935, 90937, 90945, 90947, 90951, 90952, 90953, 90954, 90955, 90956, 90957, 90958, 90959, 90960, 90961, 90962, 90963, 90964, 90965, 90966, 90967, 90968, 90969, 90970, 90989, 90997, 90999

o Abbreviated list of CPT-4 codes: 90935-90999

• Valid HCPCS codes: G0257, G8575, G8714, G8715, G8956

• Valid ICD-9 procedure codes: 38.95, 39.26, 39.42, 39.43, 39.95, 39.951, 39.952, 39.953, 54.98, 54.981, 54.982, 54.983

o Abbreviated list of ICD-9 procedure codes: 38.95, 39.27, 39.42, 39.43, 39.95, 39.95*, 54.98, 54.98*

• Valid ICD-10 diagnosis codes: DX I95.3, R88.0, T81.502A, T81.502D, T81.502S, T81.512A, T81.512D, T81.512S, T81.522A, T81.522D, T81.522S, T81.532A, T81.532D, T81.532S, T81.592A, T81.592D, T81.592S, T82.41XA, T82.41XD, T82.41XS, T82.42XA, T82.42XD, T82.42XS, T82.43XA, T82.43XD, T82.43XS, T82.49XA, T82.49XD, T82.49XS, T85.611A, T85.611D, T85.611S, T85.621A, T85.621D, T85.621S, T85.631A, T85.631D, T85.631S, T85.691A, T85.691D, T85.691S, T85.71XA, T84.71XD, T85.71XS, Y84.1, Z49.01, Z49.02, Z99.2

o Abbreviated list of ICD-10 diagnosis codes: I95.3, R88.0, T81.502*, T81.512*, T81.522*, T81.532*, T81.592*, T82.4***, T85.611*, T85.621*, T85.631*, T85.691*, T85.698*, Y84.1, Z49.0*, Z99.2

• Valid ICD-10 procedure codes: 5A1D00Z, 5A1D60Z

o Abbreviated list of ICD-9 procedure codes: 38.95, 39.27, 39.42, 39.43, 39.95, 39.95*, 54.98, 54.98*

Kidney Transplant

• Valid ICD-9 diagnosis codes: DX 996.81, V42.0

• Valid ICD-9 procedure codes: 55.69, 55.691, 55.692, 55.6, 55.6*

• Valid CPT-4 codes: 00868, 50360, 50365, 50366, 50370, 50380, 76776, 76778,

o Abbreviated list of CPT-4 codes: 00868, 50360-50380, 76776, 76778

• Valid ICD-10 diagnosis codes: DX T86.10, T86.11, T86.12, T86.13, T86.19, Z48.22, Z94.0

o Abbreviated list of ICD-10 diagnosis codes: T86.1*, Z48.22, Z94.0

• Valid ICD-10 procedure codes: 0TY00Z0, 0TY00Z1, 0TY00Z2, 0TY10Z0, 0TY10Z1, 0TY10Z2

o Abbreviated list of ICD-10 procedure codes: 0TY****

CMS, Centers for Medicare and Medicaid Services; CPT, Current Procedural Terminology; HCPCS, Healthcare Common Procedure Coding System; ICD-9, International Classification of Diseases, 9th Revision; ICD-10, International Classification of Diseases, 10th Revision.

References

1. Center for Medicare and Medicaid Services Chronic Conditions Data Warehouse. CMS Chronic Conditions Data Warehouse (CCW) CCW Condition Algorithms. Updated July 2016. Available at: . Accessed 03 October 2016.

2. Collins AJ, Chen SC, Gilbertson DT, et al. CKD surveillance using administrative data: Impact on the health care system. Am J Kidney Dis. 2009;53(3 Suppl 3):S27–S36.

3. Foley RN, Murray AM, Li S, et al. Chronic kidney disease and the risk of cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol. 2005;16:489–495.

4. Winkelmayer WC, Schneeweiss S, Mogun H, et al. Identification of individuals with CKD from Medicare claims data: a validation study. Am J Kidney Dis. 2005;46:225–232.

5. Center for Medicare and Medicaid Services. End Stage Renal Disease (ESRD) and Dialysis-related Services Fact Sheet. Updated September 2014. Available at: . Accessed 07 October 2016.

6. United Healthcare. Administrative Policy: Dialysis services. Updated January 2016. Available at: . Accessed 10 October 2016.

7. Center for Medicare & Medicaid Services (CMS) Department of Health & Human Services (DHHS). Medicare Carriers Manual Part 3 – Claims Process: Transmittal 1810. Updated July 2003. Available at: . Accessed 10 October 2016.

TABLE S3. Covariate Definitions and Codes

|Covariate |Description |

| |EFV |Non-EFV† |EVG/c |RPV |RTV-Boosted PI |

| |(n = 4172) |(n = 3050) |(n = 233) |(n = 173) |(n = 2644) |

|Age, years, mean ± SD |50 ± 10 |49 ± 9.8 |49 ± 13 |48 ± 13 |50 ± 9.3 |

|Male |4033 (96.7) |2925 (95.9) |222 (95.3) |163 (94.2) |2540 (96.1) |

|BMI, kg/m2, mean ± SD |26 ± 5.0 |25 ± 5.1 |26 ± 5.6 |27 ± 5.3 |25 ± 5.1 |

|Married |340 (8.1) |224 (7.3) |26 (11.2) |20 (11.6) |178 (6.7) |

|Race | | | | | |

|White |1256 (30.1) |923 (30.3) |74 (31.8) |48 (27.7) |801 (30.3) |

|Black |2509 (60.1) |1773 (58.1) |124 (53.2) |106 (61.3) |1543 (58.4) |

|Hispanic |262 (6.3) |209 (6.9) |19 (8.2) |10 (5.8) |180 (6.8) |

|Asian |34 (0.8) |28 (0.9) |5 (2.1) |2 (1.2) |21 (0.8) |

|Other |22 (0.5) |28 (0.9) |2 (0.9) |2 (1.2) |24 (0.9) |

|CD4+ count, cells/mm3 | | | | | |

|150 mg/g) or ACRs (>30 mg/g) occurring at least 90 days apart during the follow-up period or presence of a diagnosis code for proteinuria during the follow-up period.

§Defined as ≥2 eGFR measures ................
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