Electronic Supplementary Material

Patient Reported Symptoms Over 48 Weeks in a Randomized, Open-Label, Phase 3b Non-Inferiority Trial of Adults with HIV Switching to Coformulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir DF (EVG/COBI/FTC/TDF) versus Continuation of Non-Nucleoside Reverse Transcriptase Inhibitor with Emtricitabine (FTC) and Tenofovir DF (TDF)

1Anthony Mills, MD; 2Will Garner, PhD; 3Anton Pozniak, MD; 4Juan Berenguer, MD; 5Rebecca Speck, PhD, MPH; 5Randall Bender, PhD; 2Thai Nguyen, MD

1. Assistant Professor of Clinical Medicine, UCLA, Los Angeles, CA, USA

2. Gilead Sciences, Inc., Foster City, CA, USA

3. St Stephens Centre, Chelsea & Westminster Hospital, London, UK

4. Hospital General Universitario Gregorio Marañon, Madrid, Spain

5. Evidera, Bethesda, MD, USA

Corresponding Author:

Thai Nguyen, MD

Gilead Sciences, Inc.

333 Lakeside Drive

Foster City, CA 94404

Office (650) 372-4418

Email:

Page 1

ESM Table 1. Descriptive Patient Reported Outcomes: Baseline, Week 4, and Week 48a

/ Switch Group / No-Switch Group /
/ Baseline / Week 4 / Week 48a / Baseline / Week 4 / Week 48a /
/ Mean (SD) /
Treatment adherence VAS (0-100) / n=261
98.6 (6.0) / n=243
99.2 (2.6) / n=251
98.1 (7.4) / n=126
98.9 (2.4) / n=123
99.1 (2.9) / n=108
98.7 (3.5)
Treatment satisfaction (HIVTSQ)b / n=256
52.3 (7.4) / n=252
18.7 (11.6)*** / n=243
21.7 (10.2)*** / n=123
52.1 (8.5) / n=104
13.4 (13.2)*** / n=110
15.1 (13.0)***
CES-D total depressive symptoms scorec / n=270
9.8 (9.3) / n=261
8.8 (9.2) / n=269
9.4 (11.6) / n=133
8.9 (8.6) / n=120
7.9 (8.0) / n=114
7.5 (8.5)
STAI – State anxietyd / n=222
32.8 (10.6) / n=200
32.1 (10.8) / n=221
32.8 (12.3) / n=104
30.8 (9.2) / n=90
31.2 (10.1) / n=98
31.3 (10.7)
STAI – Trait anxietyd / n=248
33.8 (11.1) / n=249
33.3 (10.5) / n=263
33.1 (12.3) / n=121
32.6 (9.6) / n=116
32.4 (10.8) / n=117
31.3 (10.1)
SF-36 PCSe / n=288
55.3 (5.9) / - / n=250
54.6 (6.5) / n=139
56.0 (4.7) / - / n=112
55.1 (6.1)
SF-36 MCSe / n=288
50.0 (10.4) / - / n=250
50.2 (12.4) / n=139
51.7 (9.0) / - / n=112
52.7 (8.6)

Note: * p<0.05; ** p < 0.01; *** p < 0.001 between the switch group and no-switch group at that data collection time point

aWeek 24 scores are shown for the HIVTSQ, as the measure was not administered at Week 48.

bHIVTSQ scale is scored from 0 to 60 at Baseline and from -30 to 30 at Weeks 4 and 24, with higher scores indicating more/improved satisfaction.

cThe CES-D total score ranges from 0 to 60, with higher scores indicated greater depression severity.

dScores for both scales of the STAI range from 20 to 80, with higher scores indicating greater anxiety severity.

eSF-36 PCS and MCS are scored from 0–100, with higher scores indicating better health.

Abbreviations: CES-D, Center for Epidemiological Studies Depression; HIV-SI, HIV Symptom Index; HIVTSQ, HIV Treatment Satisfaction Questionnaire; SD, Standard deviation; SF-36 MCS, Short Form 36 Mental Component Summary; SF-36 PCS, Short Form 36 Physical Component Summary; STAI, State Trait Anxiety Inventory; VAS, Visual Analog Scale

ESM Table 2. Unadjusted and Adjusteda Associations between Treatment and Bothersome Symptoms at Week 4 and
Week 48

Symptom Description / Week 4 / Week 48 /
Unadjusted / Adjustedc / Unadjusted / Adjustedd /
OR (95% CI) p-valueb /
Nightmare / 0.51 (0.28–0.96), 0.035 / 0.28 (0.12–0.64) 0.003d,h,i,j / 0.52 (0.27–1.04), 0.060 / 0.27 (0.11–0.64) 0.004d,i
Vivid dreams / 0.58 (0.34–0.98), 0.039 / 0.37 (0.18–0.75) 0.006d, / 0.56 (0.32–0.99), 0.045 / 0.43 (0.21–0.88) 0.020a,d,f
Weird/intense dreams / 0.66 (0.39–1.14), 0.13 / 0.34 (0.16–0.74) 0.006c,d,h,j / 0.60 (0.33–1.11), 0.099 / 0.45 (0.20–1.00) 0.049d,f,j
Nervous/anxious / 0.65 (0.40–1.07), 0.086 / 0.41 (0.20–0.81) 0.011d,g,j / 1.34 (0.77–2.39), 0.31 / 0.94 (0.46–2.01) 0.87d,h
Dizzy/lightheadedness / 0.51 (0.29–0.90), 0.019 / 0.33 (0.16–0.66) 0.002d / 0.74 (0.41–1.36), 0.31 / 0.40 (0.19–0.85) 0.018d
Fatigue/loss of energy / 0.72 (0.47–1.13), 0.15 / 0.50 (0.28–0.91) 0.023d,g,k / 0.90 (0.57–1.45), 0.66 / 0.66 (0.37–1.19), 0.16d,f,k
Pain/numbness/tingling in hands/feet / 0.75 (0.43–1.30), 0.29 / 0.45 (0.21–0.94) 0.034a,c,d,e,g / 0.74 (0.43–1.28), 0.27 / 0.49 (0.25–0.97) 0.039d
Nervous/anxious / 0.65 (0.40–1.07), 0.086 / 0.41 (0.20–0.81) 0.011d,g,j / 1.34 (0.77–2.39), 0.31 / 0.94 (0.46–2.01) 0.87d,h
Drowsy / 0.61 (0.36–1.03), 0.062 / 0.37 (0.18–0.76) 0.007d,g / 1.51 (0.86–2.76), 0.16 / 1.15 (0.58–2.37) 0.70d
Difficulty sleeping / 0.87 (0.56–1.37), 0.55 / 0.61 (0.34–1.11) 0.10d,i,l / 1.01 (0.63–1.65), 0.95 / 0.88 (0.50–1.58) 0.67a,b,d
Diarrhea/loose bowels / 0.80 (0.48–1.34), 0.39 / 0.67 (0.36–1.25) 0.20d / 0.99 (0.57–1.77), 0.97 / 0.68 (0.35–1.34) 0.26a,c,d
Bloating/pain/gas in stomach / 1.37 (0.82–2.34), 0.24 / 1.08 (0.56–2.12) 0.82d,i,k / 1.54 (0.86–2.91), 0.16 / 1.20 (0.60–2.50) 0.61a,d,i,j
Trouble remembering / 0.77 (0.45–1.33), 0.34 / 0.44 (0.21–0.91) 0.028d / 1.08 (0.63–1.91), 0.77 / 0.84 (0.43–1.67) 0.61d,f
Feeling off balance / 0.80 (0.42–1.56), 0.49 / 0.38 (0.16–0.90) 0.029d,g,i / 1.03 (0.50–2.25), 0.94 / 0.70 (0.29–1.79) 0.45d
Changes in body composition / 0.64 (0.39–1.06), 0.081 / 0.41 (0.21–0.77) 0.006d,j / 1.12 (0.66–1.93), 0.68 / 0.76 (0.40–1.43) 0.39d,f,k
Problems with sex / 1.28 (0.77–2.17), 0.36 / 1.23 (0.65–2.40) 0.53d,g,i / 1.13 (0.68–1.94), 0.64 / 0.98 (0.53–1.86) 0.94d,k,l
Skin problems/rash/itching / 0.80 (0.48–1.35), 0.39 / 0.55 (0.29–1.03) 0.061d / 1.68 (0.97–3.03), 0.070 / 1.68 (0.86–3.43) 0.14d,k
Muscle aches/joint pain / 1.05 (0.61–1.85), 0.87 / 0.57 (0.29–1.15) 0.12a,d,i,k / 1.30 (0.76–2.27), 0.35 / 1.05 (0.53–2.14) 0.89d,h,k
Fevers/chills/sweats / 0.55 (-0.27–1.49), 0.21 / 1.60 (0.59–4.95) 0.38d / 0.90 (0.43–1.98), 0.77 / 0.43 (0.16–1.10) 0.077d,e
Headaches / 1.26 (0.71–2.32), 0.44 / 1.16 (0.58–2.39) 0.68d / 1.13 (0.61–2.21), 0.70 / 0.88 (0.42–1.88) 0.73d,k
Hair loss/changes / 0.54 (0.26–1.14), 0.10 / 0.42 (0.16–1.11) 0.077c,f,j / 0.94 (0.46–1.99), 0.86 / 0.63 (0.26–1.59) 0.32c
Nausea / 1.50 (0.76–3.20), 0.26 / 1.31 (0.57–3.25) 0.54d / 0.80 (0.36–1.85), 0.59 / 0.76 (0.26–2.31) 0.61d
Cough/trouble breathing / 1.35 (0.68–2.90), 0.41 / 1.12 (0.46–2.88) 0.81d / 1.04 (0.49–2.36), 0.92 / 0.77 (0.29–2.13) 0.59d,k
Loss of appetite/food taste / 1.03 (0.48–2.33), 0.95 / 0.60 (0.20–1.82) 0.35d / 1.11 (0.51–2.62), 0.79 / 0.48 (0.17–1.35) 0.16l
Unsteady walking / 1.04 (0.47–2.46), 0.93 / 0.46 (0.16–1.32) 0.14d,i / 2.11 (0.77–7.42), 0.19 / 1.05 (0.29–4.55) 0.94d
Weight loss/wasting / 0.51 (0.24–1.13), 0.090 / 0.42 (0.15–1.15) 0.092c,k,l / 0.72 (0.30–1.87), 0.48 / 0.59 (0.21–1.77) 0.33
Vomiting / 0.64 (0.20–2.21), 0.46 / 0.68 (0.17–2.90) 0.58 / 1.06 (0.29–4.96), 0.94 / 0.43 (0.06–2.92) 0.38h

aAdjusted logistic regression model includes treatment (switch group) as the independent variable and the bothersome HIVSI item as the dependent variable, adjusted for age, sex, race, Baseline HIV-SI count, Baseline VACS Index, time since HIV diagnosis, time since first ARV therapy, NNRTI (non-EFV), serious mental illness, Baseline CES-D score, Baseline SF-36 PCS, Baseline SF-36 MCS.

bp value for treatment effect (switch group); bolding indicates significant treatment effect in one or more of the models.

cR-squared values were <0.10 for hair loss/changes, vomiting; 0.10-0.19 for nightmares, vivid dreams, dizzy/lightheadedness, diarrhea/loose bowels, feeling off balance, changes in body composition, skin problems/rash/itching, muscle aches/joint pain, fevers/chills/sweats, headaches, nausea, cough/trouble breathing, loss of appetite, unsteady walking, weight loss/wasting; 0.20-0.29 for weird/intense dreams, fatigue/loss of energy, pain/numbness/tingling in hands/feet, trouble remembering, nervous/anxious, drowsy, difficulty sleeping, bloating/pain/gas in stomach, problems with sex.

dR-squared values were <0.10 for hair loss/changes, nausea, weight loss/wasting, vomiting; 0.10-0.19 for nightmares, vivid dreams, weird/intense dreams, dizzy/lightheadedness, pain/numbness/tingling in hands/feet, drowsy, difficulty sleeping, diarrhea/loose bowels, bloating/pain/gas in stomach, trouble remembering, feeling off balance, changes in body composition, problems with sex, skin problems/rash/itching, fevers/chills/sweats, headaches, cough/trouble breathing, loss of appetite, unsteady walking; 0.20-0.29 for fatigue/loss of energy, nervous/anxious, muscle aches/joint pain.

The following covariates were statistically significant (p<0.05) in the model: aAge; bSex; cRace; dBaseline HIV-SI count; eBaseline VACS Index; fTime since HIV diagnosis; gTime since first ARV therapy; hNNRTI (non-EFV); iSerious mental illness; jBaseline CES-D score; kBaseline SF-36 PCS; lBaseline SF-36 MCS

Page 2

ESM Table 3. Longitudinal Models for Modified HIV-SI Bothersome Symptoms

Nightmare / Vivid Dreams / Weird/Intense Dreams / Dizzy/Lightheadedness
Coefficient (95% CI), p-valuea
Treatment (Switch group) / -1.31 (-2.18,-0.44) 0.003 / -1.37 (-2.26,-0.49) 0.002 / -1.23 (-2.06,-0.40) 0.004 / -1.30 (-2.17,-0.42), 0.004
Time / -0.052 (-0.096,-0.0088) 0.019 / -0.066 (-0.11,-0.026) 0.001 / -0.034 (-0.072,0.0039) 0.078 / -0.013 (-0.043,0.016) 0.38
Time x Treatment / -0.013 (-0.046,0.021) 0.46 / -0.0068 (-0.039,0.025) 0.68 / -0.0053 (-0.034,0.023) 0.72 / 0.0023 (-0.025,0.030) 0.87
Age / 0.038 (-0.004,0.079) 0.077 / 0.049 (0.0036,0.095) 0.035 / 0.037 (-0.006,0.080) 0.089 / 0.026 (-0.014,0.066) 0.20
Race (non-White) / 0.20 (-0.62,1.02) 0.63 / 0.029 (-0.96,1.02) 0.95 / 0.44 (-0.42,1.30) 0.32 / 0.38 (-0.38,1.13) 0.32
Sex / 0.44 (-0.86,1.73) 0.51 / -0.014 (-1.45,1.43) 0.99 / 0.65 (-0.73,2.03) 0.35 / 0.28 (-0.70,1.25) 0.58
Baseline HIV-SI bothersome symptom / 1.98 (0.86,3.10) 0.0005 / 2.69 (1.70,3.68) <0.0001 / 2.68 (1.67,3.70) <0.0001 / 2.16 (1.26,3.05) <0.0001
Baseline HIV-SI bothersome symptom count / 0.17 (0.079,0.27) 0.0003 / 0.22 (0.11,0.32) <0.0001 / 0.13 (0.047,0.22) 0.003 / 0.084 (0.016,0.15) 0.016
Baseline VACS Index / -0.020 (-0.055,0.016) 0.28 / 0.22 (-0.068,0.030) <0.0001 / -0.022 (-0.058,0.013) 0.21 / -0.016 (-0.053,0.021) 0.40
Years since HIV diagnosis / 0.10 (0.012,0.19) 0.027 / 0.040 (-0.065,0.15) 0.45 / 0.083 (-0.016,0.18) 0.099 / 0.027 (-0.056,0.11) 0.52
Years since first ARV therapy / 0.0072 (-0.21,0.23) 0.95 / -0.033 (-0.27,0.20) 0.79 / -0.038 (-0.26,0.18) 0.73 / -0.14 (-0.33,0.040) 0.13
NNRTI (non-EFV) / 0.12 (-0.62,0.86) 0.75 / 0.21 (-0.67,1.08) 0.64 / 0.24 (-0.49,0.98) 0.52 / 0.099 (-0.61,0.81) 0.78
Serious mental illness / -1.67 (-3.00,-0.33) 0.015 / -0.63 (-1.71,0.45) 0.25 / -0.43 (-1.30,0.44) 0.33 / 0.46 (-0.45,1.37) 0.32
Baseline CES-D score / 0.070 (0.024,0.12) 0.003 / 0.053 (0.001,0.10) 0.046 / 0.051 (0.0031,0.099) 0.037 / 0.034 (-0.006,0.073) 0.096
Baseline SF-36 PCS / 0.0016 (-0.054,0.057) 0.96 / 0.040 (-0.033,0.11) 0.28 / -0.0063 (-0.066,0.054) 0.84 / -0.064 (-0.12,-0.008) 0.025
Baseline SF-36 MCS / 0.0067 (-0.042,0.055) 0.79 / 0.023 (-0.032,0.079) 0.41 / -0.017 (0.061,0.027) 0.45 / -0.034 (-0.076,0.009) 0.12
Unadjusted/adjusted BIC / 1084.16/951.93 / 1353.09/1170.56 / 1386.71/1213.54 / 1474.61/1296.54

ESM Table 3. Longitudinal Models for Modified HIV-SI Bothersome Symptoms (continued)

Fatigue/Loss of Energy / Pain/Numbness/Tingling in Hands/Feet / Nervous/Anxious / Felt Drowsy
Coefficient (95% CI), p-valuea
Treatment (Switch group) / -1.10 (-1.75,-0.44 ), 0.001 / -0.86 (-1.73,-0.0027), 0.049 / -1.56 (-2.36,-0.76) 0.0001 / -1.27 (-2.13,-0.41) 0.004
Time / -0.016 (-0.036,0.0044) 0.12 / -0.024 (-0.058,0.0087) 0.15 / -0.031 (-0.053,-0.0096) 0.005 / -0.028 (-0.053,-0.0033) 0.027
Time x Treatment / 0.010 (-0.013,0.033) 0.39 / 0.0003 (-0.029,0.029) 0.98 / 0.041 (0.017,0.066) 0.0007 / 0.032 (0.0068,0.058) 0.013
Age / -0.026 (-0.060,0.0075) 0.13 / 0.045 (0.001,0.089) 0.045 / 0.00009 (-0.036,0.036) 0.99 / -0.015 (-0.057,0.028) 0.50
Race (non-White) / -0.50 (-1.09,0.081) 0.09 / 0.32 (-0.53,1.17) 0.46 / -0.045 (-0.71,0.62) 0.90 / -0.19 (-0.95,0.57) 0.62
Sex / -0.031 (-1.03,0.97) 0.95 / 0.43 (-0.90,1.76) 0.52 / 0.0088 (-1.14,1.16) 0.99 / -0.089 (-1.15,0.97) 0.87
Baseline HIV-SI bothersome symptom / 1.96 (1.28,2.64) <0.0001 / 3.43 (2.39,4.47) <0.0001 / 3.32 (2.32,4.32) <0.0001 / 2.26 (1.18,3.34) <0.0001
Baseline HIV-SI bothersome symptom count / 0.11 (0.038,0.18) 0.003 / 0.11 (0.013,0.20) 0.025 / 0.016 (-0.073,0.11) 0.72 / 0.099 (-0.006,0.20) 0.063
Baseline VACS Index / -0.007 (-0.037,0.023) 0.64 / 0.11 (-0.081,-0.0033) 0.025 / -0.016 (-0.049,0.017) 0.34 / -0.024 (-0.062, 0.014) 0.22
Years since HIV diagnosis / 0.077 (0.0029,0.15) 0.042 / 0.090 (-0.006,0.19) 0.066 / 0.067 (-0.022,0.16) 0.14 / 0.13 (0.046,0.21) 0.002
Years since first ARV therapy / -0.15 (-0.30,0.0018) 0.053 / -0.31 (-0.52,-0.092) 0.005 / -0.11 (-0.31,0.083) 0.26 / -0.18 (-0.38,0.021) 0.079
NNRTI (non-EFV) / 0.13 (-0.48,0.74) 0.68 / -0.30 (-1.07,0.46) 0.44 / 0.14 (-0.58,0.85) 0.71 / 0.11 (-0.62,0.83) 0.77
Serious mental illness / 0.34 (-0.40,1.09) 0.36 / 0.071 (-0.83,0.97) 0.88 / 1.13 (0.34,1.92) 0.005 / 0.75 (-0.21,1.72) 0.13
Baseline CES-D score / 0.051 (0.012,0.091) 0.01 / 0.0026 (-0.041,0.046) 0.91 / 0.059 (0.012,0.11) 0.013 / 0.036 (-0.010,0.083) 0.13
Baseline SF-36 PCS / 0.11 (-0.18,-0.046) 0.0009 / -0.036 (-0.11,0.035) 0.33 / -0.062 (-0.12,-0.0009) 0.047 / -0.14 (-0.21,-0.077) <0.0001
Baseline SF-36 MCS / -0.037 (-0.074,-0.0009) 0.045 / -0.057 (-0.10,-0.009) 0.019 / -0.056 (-0.099,-0.012) 0.012 / -0.037 (-0.083,0.0084) 0.11
Unadjusted/adjusted BIC / 2277.35/1884.31 / 1549.69/1264.91 / 1766.35/1440.89 / 1662.93/1410.23

ESM Table 3. Longitudinal Models for Modified HIV-SI Bothersome Symptoms (continued)

Difficulty Sleeping / Diarrhea/Loose Bowels / Bloating/Pain/Gas in Stomach / Trouble Remembering
Coefficient (95% CI), p-valuea
Treatment (Switch group) / -1.17 (-1.94,-0.39) 0.003 / -1.05 (-1.91,-0.20) 0.016 / 0.82 (0.052,1.59) 0.036 / -0.35 (-1.23,0.52) 0.43
Time / -0.016 (-0.038,0.0059) 0.15 / -0.026 (-0.059,0.0071) 0.12 / 0.0026 (-0.020,0.025) 0.82 / -0.019 (-0.47,0.0082) 0.17
Time x Treatment / 0.011 (-0.014,0.035) 0.39 / 0.0035 (-0.024,0.031) 0.80 / -0.016 (-0.038,0.0066) 0.17 / 0.011 (-0.017,0.039) 0.44
Age / 0.024 (-0.020,0.068) 0.29 / -0.023 (-0.064,0.018) 0.28 / 0.0085 (-0.029,0.046) 0.66 / -0.031 (-0.073,0.010) 0.14
Race (non-White) / 0.85 (0.060,1.63) 0.035 / -0.48 (-1.30,0.35) 0.26 / 0.82 (0.11,1.53) 0.024 / 0.37 (-0.44,1.18) 0.37
Sex / -0.26 (-1.51,0.99) 0.68 / -0.34 (-1.69,1.01) 0.62 / -0.31 (-1.51,0.89) 0.61 / -0.57 (-2.06,0.93) 0.46
Baseline HIV-SI bothersome symptom / 3.45 (2.46,4.44) <0.0001 / 3.27 (2.47,4.07) <0.0001 / 1.96 (1.13,2.78) <0.0001 / 3.02 (1.84,4.19) <0.0001
Baseline HIV-SI bothersome symptom count / 0.016 (-0.083,0.12) 0.75 / 0.091 (0.0044,0.18) 0.039 / 0.11 (0.033,0.20) 0.006 / 0.16 (0.063,0.26) 0.001
Baseline VACS Index / -0.053 (-0.090,-0.016) 0.005 / -0.018 (-0.062,0.026) 0.43 / -0.023 (-0.062,0.016) 0.25 / -0.005 (-0.046,0.035) 0.80
Years since HIV diagnosis / 0.083 (-0.014,0.18) 0.094 / 0.051 (-0.042,0.14) 0.28 / 0.031 (-0.050,0.11) 0.45 / 0.11 (0.014,0.20) 0.023
Years since first ARV therapy / -0.16 (-0.35,0.028) 0.095 / -0.061 (-0.27,0.15) 0.57 / -0.095 (-0.27,0.076) 0.28 / -0.070 (-0.27,0.13) 0.48
NNRTI (non-EFV) / 0.16 (-0.59,0.90) 0.68 / -0.16 (-0.99,0.68) 0.71 / 0.29 (-0.39,0.97) 0.41 / -0.23 (-1.03,0.56) 0.56
Serious mental illness / 0.68 (-0.22,1.58) 0.14 / -0.27 (-1.24,0.71) 0.59 / 0.51 (-0.25,1.27) 0.19 / 0.11 (-0.76,0.99) 0.80
Baseline CES-D score / 0.024 (-0.025,0.073) 0.33 / 0.032 (-0.011,0.074) 0.14 / 0.037 (-0.0047,0.078) 0.082 / 0.058 (0.010,0.11) 0.018
Baseline SF-36 PCS / -0.12 (-0.20,-0.31) 0.007 / -0.025 (-0.098,0.048) 0.50 / -0.078 (-0.13,-0.026) 0.003 / -0.082 (-0.15,-0.016) 0.016
Baseline SF-36 MCS / -0.082 (-0.14,-0.029) 0.003 / -0.020 (-0.067,0.026) 0.39 / -0.029 (-0.071,0.013) 0.18 / -0.0076 (-0.055,0.040) 0.75
Unadjusted/adjusted BIC / 2071.63/1711.11 / 1626.71/1400.77 / 1830.24/1558.06 / 1685.81/1390.26

ESM Table 3. Longitudinal Models for Modified HIV-SI Bothersome Symptoms (continued)