September 20, 2017 SIMULATED DATA

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1 Tables and Figures for manuscript for Virologic Suppression and Mortality in Older HIV subjects in a Multisite Latin American and the Caribbean Cohort manuscript September 20, 2017 : RESULTS ARE NOT TO BE INTERPRETED SUBSTANTIVELY, BUT ARE PRO- VIDED TO MAKE OUR STUDY QUASI-REPRODUCIBLE BY ALLOWING OTHERS TO VERIFY THE ANALYSIS CODE USED FOR THE ORIGINAL REPORT ON PUBLICLY AVAILABLE. (mock-ccasanet-data ) 1

2 Table 1: Age-stratified characteristics of patients that initiated antiretroviral therapy across seven Caribbean, Central and South America sites (N=15396). Over 50(N=1583) Under(N=13813) Value Value Pvalue Age, years 53 (51-57) 36 (30-41) < Sex < Female 546(34%) 5393(39%) Male 1037(66%) 8420(61%) Route of infection < Heterosexual 135(9%) 2217(16%) MSM 240(15%) 2862(21%) IDU 149(9%) 623(5%) Other 151(10%) 1657(12%) Unknown 908(57%) 6454(47%) Clinical stage AIDS 227(14%) 2117(15%) not AIDS 393(25%) 3438(25%) Missing 963(61%) 8258(60%) Nadir CD4 count, cells/ml 168 (80-288) 154 (65-277) Missing 759(48%) 6483(47%) Baseline CD4 count, cells/ml 228 ( ) 214 ( ) Missing 966(61%) 8140(59%) Baseline viral load (log10) 4.6 ( ) 4.6 ( ) Baseline viral load (undetectable) < Yes (%) (%) No 272(17%) 3491(25%) Missing 511(32%) 5327(39%) Missing (Haiti) 800(51%) 4995(36%) Baseline ART class NNRTI 1355(86%) 11383(82%) Boosted PI 137(9%) 1458(11%) Other 91(6%) 972(7%) ART Initiation Year 2007 ( ) 2007 ( ) ART naive NA Yes 1583(100%) 13813(100%) No (%) (%) Unconfirmed (%) (%) Time from Diagnosis to HAART 2494 ( ) 1900 ( ) < Missing 351(22%) 3135(23%)

3 Table 2: Frequency of patients over and under 50 years old at each site site Percent.Over50 argentina 9.09 brazil 8.44 chile 7.94 haiti honduras 9.61 mexico 8.34 peru

4 Figure 1: Estimated proportion of ART initiators older than 50 years during the study period. Points at top and bottom of the figure correspond to the date of ART initiation for individual patients over 50 years and under 50 years, respectively. 4

5 Figure 2: Crude cumulative incidence of mortality, regimen modification, and virologic failure. 5

6 Table 3: Changes in CD4 cell count over time by age group. Over 50 Under 50 Value Value Pvalue Baseline CD4 measurement N = 617 N = 5673 CD4 measurement at 6 months (or dead) N = 202 N = 1645 CD4 measurement at 12 months (or dead) N = 173 N = 1935 CD4 measurement at 24 months (or dead) N = 232 N = 2337 Baseline VL measurement N = 272 N = 3491 VL measurement at 6 months (or dead) N = 172 N = 2471 VL measurement at 12 months (or dead) N = 185 N = 2262 VL measurement at 24 months (or dead) N = 155 N = 1928 Baseline CD4 count, cells/ml 220 ( ) 216 ( ) CD4 count at 6 months, cells/ml 286 ( ) 298 ( ) CD4 count at 12 months, cells/ml 330 ( ) 343 ( ) CD4 count at 24 months, cells/ml 392 ( ) 384 ( ) Baseline VL (undetectable) 100% 100%. VL at 6 months (undetectable) 78.7% 80.2% VL at 12 months (undetectable) 78.0% 79.7% VL at 24 months (undetectable) 73.2% 76.5%

7 Table 4: Cumulative incidence of HAART treatment change (with 95% CI) at one and five years by age group. age50 time cuminc lower upper over under over under Table 5: Cumulative incidence of virologic failure (with 95% CI) at one and five years by age group. age50 time cuminc lower upper over under over under

8 Table 6: Comparison of mortality (N=15396), treatment modification (N=15396), and virologic failure (N=6977) by age group for patients across seven Caribbean, Central and South America sites (N=15396). Death HAART modification Viral load failure Hazard Ratio Hazard Ratio Hazard Ratio Age group < 50 Ref Ref Ref ( ) 0.95 ( ) 0.99 ( ) All models adjusted for the following covariates: sex, clinical AIDS at baseline, nadir CD4, HAART initiation year, initial HAART class, IVDU, and time from HIV diagnosis to HAART initiation. 8

9 Table 7: Comparison of mortality (N=15396), treatment modification (N=15396), and virologic failure (N=6977) for patients over 50 years old across seven Caribbean, Central and South America sites (N=15396). Death HAART modification Viral load failure Hazard Ratio Hazard Ratio Hazard Ratio Age group < 50 Ref Ref Ref ( ) 0.95 ( ) 0.99 ( ) Sex Female Ref Ref Ref Male 1.09 ( ) 1.00 ( ) 0.99 ( ) Clinical AIDS at baseline Yes 1.01 ( ) 0.96 ( ) 0.96 ( ) Nadir CD4 count ( ) 0.99 ( ) 1.10 ( ) ( ) 0.98 ( ) 1.09 ( ) ( ) 1.00 ( ) 1.02 ( ) 350 Ref Ref Ref ART initiation year ( ) 1.03 ( ) 0.94 ( ) ( ) 0.98 ( ) 1.02 ( ) 2008 Ref Ref Ref ( ) 1.00 ( ) 1.15 ( ) ( ) 0.97 ( ) 1.43 ( ) Baseline ART class NNRTI Ref Ref Ref PI 1.17 ( ) 1.19 ( ) 1.00 ( ) Other 1.19 ( ) 2.40 ( ) 0.85 ( ) IVDU Yes 1.24 ( ) 1.17 ( ) 1.04 ( ) Time from HIV Diagnosis to HAART 0 Ref Ref Ref 6 months 1.00 ( ) 1.00 ( ) 1.00 ( ) 1 year 1.00 ( ) 1.00 ( ) 0.99 ( ) 3 years 0.99 ( ) 1.00 ( ) 0.99 ( ) 9

10 Table 8: Comparison of mortality (N=1583), treatment modification (N=1583), and virologic failure (N=532) for patients over 50 years old across seven Caribbean, Central and South America sites (N=1583). Death HAART modification Viral load failure Hazard Ratio Hazard Ratio Hazard Ratio Age 50 Ref Ref Ref ( ) 1.09 ( ) 0.84 ( ) ( ) 1.32 ( ) 0.48 ( ) ( ) 1.61 ( ) 0.28 ( ) Sex Female Ref Ref Ref Male 0.85 ( ) 1.08 ( ) 0.99 ( ) Clinical AIDS at baseline Yes 0.96 ( ) 0.92 ( ) 1.03 ( ) Nadir CD4 count ( ) 1.27 ( ) 1.08 ( ) ( ) 1.22 ( ) 1.04 ( ) ( ) 1.13 ( ) 0.98 ( ) 350 Ref Ref Ref ART initiation year ( ) 0.97 ( ) 0.66 ( ) ( ) 1.04 ( ) 1.04 ( ) 2008 Ref Ref Ref ( ) 1.06 ( ) 1.94 ( ) ( ) 1.18 ( ) 4.82 ( ) Baseline ART class NNRTI Ref Ref Ref PI 1.76 ( ) 1.05 ( ) 1.24 ( ) Other 2.06 ( ) 1.43 ( ) 0.87 ( ) IVDU No NA NA NA Yes NA NA NA Time from HIV Diagnosis to HAART 0 Ref Ref Ref 6 months 0.99 ( ) 1.00 ( ) 0.98 ( ) 1 year 0.98 ( ) 0.99 ( ) 0.95 ( ) 3 years 0.93 ( ) 0.98 ( ) 0.87 ( ) 10

11 Table 9: Comparison of mortality (N=13813), treatment modification (N=13813), and virologic failure (N=6445) for patients under 50 years old across seven Caribbean, Central and South America sites (N=13813). Death HAART modification Viral load failure Hazard Ratio Hazard Ratio Hazard Ratio Age 50 Ref Ref Ref ( ) 1.04 ( ) 1.22 ( ) ( ) 1.00 ( ) 1.04 ( ) ( ) 1.02 ( ) 1.09 ( ) Sex Female Ref Ref Ref Male 1.15 ( ) 1.01 ( ) 1.00 ( ) Clinical AIDS at baseline Yes 1.01 ( ) 0.95 ( ) 0.96 ( ) Nadir CD4 count ( ) 0.96 ( ) 1.09 ( ) ( ) 0.95 ( ) 1.09 ( ) ( ) 0.99 ( ) 1.03 ( ) 350 Ref Ref Ref ART initiation year ( ) 1.07 ( ) 0.95 ( ) ( ) 0.97 ( ) 1.01 ( ) 2008 Ref Ref Ref ( ) 0.98 ( ) 1.09 ( ) ( ) 0.91 ( ) 1.25 ( ) Baseline ART class NNRTI Ref Ref Ref PI 1.11 ( ) 1.22 ( ) 0.98 ( ) Other 1.12 ( ) 2.13 ( ) 0.85 ( ) IVDU Yes Ref Ref Ref Time from HIV Diagnosis to HAART 0 Ref Ref Ref 6 months 1.00 ( ) 1.00 ( ) 1.00 ( ) 1 year 1.00 ( ) 1.00 ( ) 1.00 ( ) 3 years 1.01 ( ) 1.01 ( ) 1.00 ( ) 11

12 Table 10: Comparison of imputed values (from the first replication of a multiple imputation procedure) and non-imputed values for four covariates with missing values included in adjusted analyses. Original Data Imputed Data Value Value Route of infection IDU 657(9%) 772(10%) Other 6705(91%) 7262(90%) Clinical stage AIDS 2994(32%) 2344(38%) not AIDS 6227(68%) 3831(62%) Nadir CD4 count, cells/ml 149 (67-268) 155 (67-278) Time from Diagnosis to HAART 3113 ( ) 1953 ( ) 12

13 Table 11: Comparison of mortality (N=2521), treatment modification (N=2521), and virologic failure (N=2119) for patients across seven Caribbean, Central and South America sites using a complete case analysis. Death HAART modification Viral load failure Hazard Ratio Hazard Ratio Hazard Ratio Age group < 50 Ref Ref Ref ( ) 0.77 ( ) 0.97 ( ) Sex Female Ref Ref Ref Male 0.75 ( ) 0.99 ( ) 0.99 ( ) Clinical AIDS at baseline Yes 0.91 ( ) 1.12 ( ) 0.93 ( ) Nadir CD4 count ( ) 0.84 ( ) 1.18 ( ) ( ) 0.84 ( ) 1.19 ( ) ( ) 0.96 ( ) 1.04 ( ) 350 Ref Ref Ref ART initiation year ( ) 1.01 ( ) 1.02 ( ) ( ) 1.02 ( ) 1.13 ( ) 2008 Ref Ref Ref ( ) 1.03 ( ) 1.13 ( ) ( ) 1.07 ( ) 1.41 ( ) Baseline ART class NNRTI Ref Ref Ref PI 1.36 ( ) 1.17 ( ) 0.96 ( ) Other 1.32 ( ) 2.61 ( ) 0.80 ( ) IVDU Yes 0.61 ( ) 1.18 ( ) 0.89 ( ) Time from HIV Diagnosis to HAART 0 Ref Ref Ref 6 months 0.99 ( ) 1.01 ( ) 0.99 ( ) 1 year 0.98 ( ) 1.03 ( ) 0.97 ( ) 3 years 0.93 ( ) 1.09 ( ) 0.93 ( ) 13

14 Table 12: Comparison of mortality (N=15396), treatment modification (N=15396), and virologic failure (N=6977) for patients over 50 years old across seven Caribbean, Central and South America sites (N=15396) WITHIN FIRST 3 YEARS. Death HAART modification Viral load failure Hazard Ratio Hazard Ratio Hazard Ratio Age group < 50 Ref Ref Ref ( ) 0.96 ( ) 1.02 ( ) Sex Female Ref Ref Ref Male 1.18 ( ) 1.00 ( ) 1.03 ( ) Clinical AIDS at baseline Yes 1.07 ( ) 0.96 ( ) 0.96 ( ) Nadir CD4 count ( ) 0.99 ( ) 1.09 ( ) ( ) 0.98 ( ) 1.07 ( ) ( ) 1.00 ( ) 1.02 ( ) 350 Ref Ref Ref ART initiation year ( ) 1.05 ( ) 0.94 ( ) ( ) 0.97 ( ) 1.02 ( ) 2008 Ref Ref Ref ( ) 0.99 ( ) 1.14 ( ) ( ) 0.93 ( ) 1.41 ( ) Baseline ART class NNRTI Ref Ref Ref PI 1.00 ( ) 1.20 ( ) 1.02 ( ) Other 1.24 ( ) 2.06 ( ) 0.86 ( ) IVDU No NA NA NA Yes 1.19 ( ) 1.16 ( ) 1.03 ( ) Time from HIV Diagnosis to HAART 0 Ref Ref Ref 6 months 1.00 ( ) 1.00 ( ) 1.00 ( ) 1 year 1.00 ( ) 1.00 ( ) 0.99 ( ) 3 years 0.99 ( ) 1.00 ( ) 0.98 ( ) 14

15 Table 13: Comparison of mortality (N=9001), treatment modification (N=6009), and virologic failure (N=9115) for patients over 50 years old across seven Caribbean, Central and South America sites AFTER FIRST 3 YEARS. Death HAART modification Viral load failure Hazard Ratio Hazard Ratio Hazard Ratio Age group < 50 Ref Ref Ref ( ) 0.85 ( ) 0.77 ( ) Sex Female Ref Ref Ref Male 0.63 ( ) 1.01 ( ) 0.76 ( ) Clinical AIDS at baseline Yes 0.63 ( ) 0.99 ( ) 0.96 ( ) Nadir CD4 count ( ) 0.98 ( ) 1.21 ( ) ( ) 0.97 ( ) 1.19 ( ) ( ) 0.99 ( ) 1.08 ( ) 350 Ref Ref Ref ART initiation year ( ) 0.93 ( ) 0.92 ( ) ( ) 1.10 ( ) 1.05 ( ) 2008 Ref Ref Ref ( ) 1.48 ( ) 1.59 ( ) ( ) 2.21 ( ) 2.58 ( ) Baseline ART class NNRTI Ref Ref Ref PI 2.37 ( ) 1.10 ( ) 0.86 ( ) Other 0.78 ( ) 6.74 ( ) 0.77 ( ) IVDU No NA NA NA Yes 1.59 ( ) 1.27 ( ) 1.13 ( ) Time from HIV Diagnosis to HAART 0 Ref Ref Ref 6 months 0.99 ( ) 0.99 ( ) 1.00 ( ) 1 year 0.99 ( ) 0.98 ( ) 1.01 ( ) 3 years 0.96 ( ) 0.94 ( ) 1.02 ( ) 15

16 Figure 3: Crude cumulative incidence of regimen modification across different time periods. 16

17 1 Appendix - R/Package Versions R version ( ), x86_64-apple-darwin Base packages: base, datasets, graphics, grdevices, grid, methods, stats, stats4, utils Other packages: Formula 1.2-1, ggplot , Hmisc 4.0-2, knitr , lattice , MASS , Matrix , mi 1.0, plyr 1.8.4, rms 5.1-0, SparseM 1.74, survey , survival , timereg 1.9.0, xtable Loaded via a namespace (and not attached): abind 1.4-5, acepack 1.4.1, arm 1.9-3, assertthat 0.1, backports 1.0.5, base64enc 0.1-3, checkmate 1.8.2, cluster 2.0.5, coda , codetools , colorspace 1.3-2, data.table , digest , evaluate 0.10, foreign , gridextra 2.2.1, gtable 0.2.0, htmltable 1.9, htmltools 0.3.5, htmlwidgets 0.8, latticeextra , lava 1.5, lazyeval 0.2.0, lme , magrittr 1.5, MatrixModels 0.4-1, minqa 1.2.4, multcomp 1.4-6, munsell 0.4.3, mvtnorm 1.0-5, nlme , nloptr 1.0.4, nnet , numderiv , polspline , quantreg 5.29, RColorBrewer 1.1-2, Rcpp , rpart , sandwich 2.3-4, scales 0.4.1, splines 3.3.2, stringi 1.1.2, stringr 1.1.0, TH.data 1.0-8, tibble 1.2, tools 3.3.2, zoo