from the Medical Outcomes Survey SF-36v2 reported by participants included in analysis (n=1787) over cohort time in the OHTN Cohort Study (OCS), Ontario, Canada, 2007-14. Gastrointestinal symptom events (compared to not reporting the symptom) are self- reported in the AIDS Clinical Trial Group Symptom Distress Module included in the OCS.
2007 2008 2009 2010 2011 2012 2013 2014
30 32 34 36 38 40 42 44 46
Diarrhea Nausea/vomit Loss of Appetite
Bloating Weight loss/wasting
Year of Questionnaire Administration SF-36v2, Mental Componen Summary Score (Range: 0 to 100, higher is beter HRQOL)
[A]
Significant test for trend, P <0.001
2007 2008 2009 2010 2011 2012 2013 2014 30
32 34 36 38 40 42 44 46
Diarrhea Nausea/vomit Loss of Appetite
Bloating Weight loss/wasting
Year of Questionnaire Administration SF-36v2, Physical Component Summary Score (Range: 0 to 100, higher is beter HRQOL)
[B]
Significant test for trend, P <0.001
life as measured by the Medical Outcomes Survey SF-36v2, OHTN Cohort Study, Ontario, Canada, 2007-14.
Mental Component Summary (MCS) Score Physical Component Summary (PCS) Score Unadj. ^β (95% CI) Adj. ^β (95% CI) Unadj. ^β (95% CI) Adj. ^β (95% CI) GI Symptom Distress
Diarrhea or soft stool -1.02 (-1.24 to -0.81)*** -0.35 (-0.57 to -0.13)** -0.85 (-0.99 to -0.71)*** -0.53 (-0.68 to -0.38)***
0 REF REF REF REF
1 -0.53 (-1.59 to 0.54) 0.18 (0.86 to 1.24) -0.87 (-1.58 to -0.16)* -0.49 (-1.19 to 0.22) 2 -1.79 (-2.53 to -1.05)*** -0.83 (-1.56 to -0.08)* -1.17 (-1.67 to -0.68)*** -0.65 (-1.15 to -0.15)*
3 -3.37 (-4.37 to -2.37)*** -1.26 (-2.27 to -0.25)* -2.98 (-3.65 to -2.32)*** -1.86 (-2.54 to -1.18)***
4 -4.07 (-5.08 to -3.05)*** -1.15 (-2.18 to -0.11)* -3.45 (-4.12 to -2.78)*** -2.10 (-2.80 to -1.41)***
Nausea/vomiting -1.59 (0.13) -0.61 (-0.88 to -0.34)*** -1.04 (-1.21 to -0.86)*** -0.63 (-0.88 to -0.46)***
0 REF REF REF REF
1 -1.78 (-1.86 to -1.34) -1.20 (-2.93 to 0.53) -0.45 (-1.62 to 0.72) -0.16 (-1.33 to -1.00) 2 -3.43 (-3.54 to -0.03)*** -1.62 (-2.53 to -0.70)*** -2.38 (-2.99 to -1.77)*** -1.67 (-2.28 to -1.05)***
3 -5.27 (-4.35 to -2.51)*** -2.38 (-1.11 to 0.00)*** -3.24 (-4.07 to -2.40)*** -2.03 (-2.88 to -1.18)***
4 -5.83 (-6.52 to -4.02)*** -2.43 (-0.07 to 0.04)*** -3.84 (-4.72 to -2.95)*** -2.89 (-2.81 to -0.97)***
Loss of appetite -2.28 (-2.52 to -2.04)*** -1.58 (-1.83 to -1.33)*** -0.83 (-0.98 to -0.64)*** -0.46 (-0.63 to -0.29)***
0 REF REF REF REF
1 -2.30 (-3.81 to -0.79)** -1.34 (-2.84 to 0.16) -1.78 (-2.81 to -0.78)** -1.43 (-2.45 to -0.72)**
2 -4.57 (-5.46 to -3.71)*** -3.18 (-4.05 to -2.30)*** -1.95 (-2.54 to -1.36)*** -1.32 (-1.92 to -0.72)***
3 -7.06 (-8.20 to -5.93)*** -4.77 (-5.92 to -3.62)*** -2.41 (-3.17 to -1.64)*** -1.25 (-2.03 to -0.73)**
4 -8.97 (-10.16 to -7.87)*** -5.91 (-7.15 to -4.67)*** -3.10 (-3.91 to -2.29)*** -1.64 (-2.48 to -0.79)**
Bloating/painful abdomen -1.51 (-1.71 to -1.30)*** -1.05 (-1.26 to -0.85)*** -0.81 (-0.95 to -0.67)*** -0.55 (-0.69 to -0.42)***
0 REF REF REF REF
1 -0.86 (-2.17 to 0.45) -0.66 (-1.96 to 0.61) -0.46 (-1.33 to 0.42) -0.22 (-1.08 to 0.65) 2 -2.66 (-3.37 to -1.95)*** -1.85 (-2.56 to -1.15)*** -1.18 (-1.65 to -0.71)*** -0.71 (-1.19 to -0.23)**
3 -4.48 (-5.39 to -3.57)*** -2.83 (-3.89 to -2.07)*** -2.74 (-3.35 to -2.13)*** -1.90 (-2.58 to -1.29)***
4 -6.25 (-7.20 to -5.30)*** -4.42 (-5.38 to -3.47)*** -3.31 (-3.95 to -2.67)*** -2.26 (-2.92 to -1.62)***
Weight loss/wasting -1.67 (-1.92 to -1.43)*** -1.06 (-1.36 to -0.80)*** -0.62 (-0.79 to -0.45)*** -0.35 (-0.52 to -0.19)***
0 REF REF REF REF
1 -1.10 (-2.19 to -0.01)* -0.42 (-1.49 to 0.66) -0.92 (-1.66 to -0.19)* -0.68 (-1.41 to 0.04) 2 -2.75 (-3.86 to -1.64)*** -1.42 (-2.52 to -0.32)* -1.23 (-1.98 to -0.48)* -0.69 (-1.43 to 0.05) 3 -5.88 (-7.20 to -4.57)*** -4.04 (-5.43 to -2.74)*** -1.70 (-2.58 to -0.82)*** -0.87 (-1.17 to 0.01)*
4 -6.62 (-7.82 to -5.42)*** -4.28 (-5.48 to -3.08)*** -2.52 (-3.34 to -1.72)*** -1.43 (-2.24 to -0.62)**
Demographics
Age (each additional 10y) 2.35 (1.90 to 2.76)*** 1.47 (0.98 to 1.96) -1.24 (-1.54 to -0.94)*** -1.18 (-1.52 to -0.85)***
39 REF REF REF REF
40 to 49 1.98 (0.90 to 3.05)** 1.26 (1.13 to 1.32)* -1.66 (-1.72 to -1.53)*** -1.16 (-2.33 to 0.00)*
50 to 59 3.71 (2.53 to 4.88)*** 2.39 (2.01 to 2.50)*** -3.00 (-3.31 to -2.92)*** -1.29 (-2.55 to -0.04)*
60 7.67 (6.15 to 9.18)*** 5.27 (5.11 to 5.55)*** -3.51 (-3.66 to -3.42)*** -1.85 (-3.14 to -0.57)*
Sex Female Male: MSM Male: non-MSM
REF
2.56 (1.29 to 3.83)***
1.92 (0.36 to 3.48)*
REF
1.18 (-0.11 to 2.48) 1.42 (0.01 to 2.83)*
REF
1.40 (0.55 to 2.26)*
0.51 (-0.55 to 1.56)
REF
2.28 (-0.12 to -0.04)**
1.19 (1.09 to 3.17)***
Race/ethnicity Caucasian
African-Caribbean black Indigenous
Other
REF
-0.97 (2.20 to 0.25) -2.81 (-5.03 to -0.59)*
-1.65 (-3.16 to -0.15)*
REF
0.66 (-0.62 to 1.95) -0.89 (-2.83 to 1.03) -0.81 (-2.13 to 0.52)
REF
1.08 (0.26 to 1.92)*
-0.66 (-2.16 to 0.83) 0.73 (-0.28 to 1.75)
REF
0.47 (-0.41 to 1.35) -0.41 (-1.73 to 0.92) -0.16 (-1.07 to 0.75) Behavioral Factors
Any drug use, past 6 months None
Used drugs
REF
-1.66 (-2.65 to -0.68)***
REF
-0.46 -1.42 to 0.48)
REF
0.24 (-0.41 to 0.89)
REF
0.26 (-0.39 to 0.90)
≥6 drinks, one occasion
Never ≥6 drinks Once a month or less More than once a month
1.61 (0.78 to 2.43)***
-0.17 (-1.35 to 1.00) 0.55 (-0.42 to 1.52)
0.96 (0.12 to 1.75)*
0.42 (-0.53 to 1.36) 0.20 (-0.94 to 1.33)
1.05 (0.50 to 1.60)**
1.50 (0.85 to 2.15)***
2.09 (1.30 to 2.88)***
0.65 (0.11 to 1.18)*
0.99 (0.35 to 1.64)**
1.68 (0.91 to 2.44)***
Cannabis use Never Former Current
REF
-0.57 (-1.34 to 0.19) -1.56 (-2.52 to -0.59)*
REF
-0.56 (-1.32 to 0.19) -0.51 (-1.45 to 0.44)
REF
0.07 (-0.44 to 0.59) -0.79 (-1.44 to -0.14)*
REF
-0.59 (-1.24 to 0.05) -0.12 (-0.63 to 0.39) Clinical Factors
CD4+ T-cell/mm3 ≥500
200-499 <200
REF
-0.61 (-1.26 to 0.05) -2.21 (-3.50 to -0.92)**
REF
-0.78 (-2.01 to 0.45) -0.21 (-0.83 to 0.42)
REF
-0.11 (-0.54 to 0.33) -1.74 (-2.60 to -0.88)***
REF
-0.22 (-0.64 to 0.21)**
-1.35 (-2.18 to -0.52)***
Viral load Undetectable Detectable
REF
-1.76 (-2.81 to -0.99)***
REF
0.37 (-1.17 to 0.43)
REF
-0.55 (-1.05 to -0.05)*
REF
-0.64 (-1.17 to -0.10)*
Current ARV backbone Not on ARV
Any new agent (EI or InI)
REF
3.71 (2.21 to 5.19)***
REF
2.06 (00.58 to 3.56)*
REF
-1.69 (-2.67 to -0.71)**
REF
-0.71 (-1.71 to 0.29)
NNRTI NRTI alone PI and NNRTI PI alone
2.54 (1.15 to 3.91)**
-0.05 (-4.10 to 4.01) 1.99 (0.38 to 3.59)*
1.62 (0.27 to 2.95)*
0.87 (-0.49 to 2.23) -1.30 (-5.08 to 2.47) 0.86 (-0.70 to 2.42) 0.84 (-0.47 to 2.17)
1.27 (0.36 to 2.19)**
-0.93 (-3.60 to 1.75) -0.99 (-2.05 to 0.06) -0.57 (-1.45 to 0.32)
1.03 (0.11 to 1.95)*
0.27 (-2.27 to 2.80) -0.02 (-1.07 to 1.03) 0.13 (-0.76 to 1.02) HCV co-infection
Never HCV+
Ever HCV+
REF
-2.56 (-4.20 to -0.92)*
REF
-1.27 (-2.78 to 0.24)
REF
-3.43 (-4.52 to -2.33)***
REF
-2.13 (-3.16 to -1.09)***
Each additional 5 years since
HIV diagnosis 0.99 (0.69 to 1.30)*** 0.19 (-0.13 to 0.52) -0.82 (-1.02 to -0.62)*** -0.42 (-0.64 to -0.19)***
<1 REF REF REF REF
1 to <5 3.69 (1.92 to 5.46) 0.21 (0.00 to 0.29) -0.75 (-1.93 to 0.43) -1.37 (-2.08 to -0.66)***
5 to <10 5.32 (3.42 to 7.26)* 0.84 (-0.97 to 0.91) -1.41 (-2.67 to -0.15)* -2.66 (-3.49 to -1.83)***
≥10 5.83 (3.94 to 7.72)*** 1.61 (-0.98 to 0.47) -2.63 (-3.89 to -1.37)*** -3.51 (-4.56 to -2.45)***
Psychosocial Scales CES-D Score
<16 16-22 ≥23
REF
-0.72 (-1.25 to -0.18)**
-0.59 (-1.11 to -0.06)*
REF
-0.05 (-0.58 to 0.48) -0.78 (0.23 to 1.29)**
^Unadjusted and adjusted general linear mixed models with spatial power covariance structures; ***P <0.001 **P <0.01 *P <0.05
human immunodeficiency virus; HCV, hepatitis C virus; InI, integrase inhibitor; IQR, interquartile range; MSM, men having sex with men;
NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; Unadj, unadjusted.
Supplementary Material Table 2. Association^ between gastrointestinal symptoms and physical and mental health related quality of life as measured by the Medical Outcomes Survey SF-36v2, excluding participants lost to follow-up (n=53) or died (n=215) in the OHTN Cohort Study, Ontario, Canada, 2007-14.
Mental Component Summary (MCS) Score Physical Component Summary (PCS) Score Unadj. ^β (95% CI) Adj. ^β (95% CI)‡ Unadj. ^β (95% CI) Adj. ^β (95% CI)‡
GI Symptom Distress
Diarrhea or soft stool -1.08 (-1.18 to -0.88)*** -0.37 (-0.54 to -0.11)** -0.88 (-0.97 to -0.69)*** -0.51 (-0.70 to -0.40)***
0 (‘does not have symptom’) REF REF REF REF
1 (‘symptom doesn’t bother me’) -0.51 (-1.58 to 0.55) 0.18 (0.83 to 1.25) -0.90 (-1.561 to -0.16)* -0.47 (-1.21 to 0.29) 2 (‘symptom bothers me a little’) -1.75 (-2.51 to -1.06)*** -0.82 (-1.52 to -0.05)* -1.21 (-1.72 to -0.72)*** -0.63 (-1.19 to -0.10)*
3 (‘symptom bothers me’) -3.33 (-4.36 to -2.37)*** -1.23 (-2.25 to -0.24)* -3.01 (-3.68 to -2.38)*** -1.90 (-2.59 to -1.12)***
4 (‘symptom bothers me a lot’) -4.01 (-5.06 to -3.06)*** -1.14 (-2.15 to -0.10)* -3.55 (-4.18 to -2.82)*** -2.14 (-2.88 to -1.34)***
Nausea/vomiting -1.59 (-1.67 to -0.15)** -0.59 (-0.85 to -0.37)*** -1.09 (-1.25 to -0.88)*** -0.60 (-0.92 to -0.40)***
0 (‘does not have symptom’) REF REF REF REF
1 (‘symptom doesn’t bother me’) -1.71 (-1.87 to -1.35)*** -1.18 (-2.90 to 0.56) -0.49 (-1.65 to 0.75) -0.12 (-1.38 to 0.95) 2 (‘symptom bothers me a little’) -3.40 (-3.55 to -0.04)*** -1.59 (-2.50 to -0.75)*** -2.42 (-3.04 to -1.79)*** -1.62 (-2.34 to -1.10)***
3 (‘symptom bothers me’) -5.22 (-4.32 to -2.52)*** -2.35 (-1.08 to 0.04)*** -3.28 (-4.10 to -2.44)*** -2.10 (-2.92 to -1.22)***
4 (‘symptom bothers me a lot’) -5.80 (-6.50 to -4.04)*** -2.40 (-0.02 to 0.05)*** -3.89 (-4.75 to -2.98)*** -2.92 (-2.85 to -0.93)***
Loss of appetite -2.30 (-2.50 to -2.04)*** -1.55 (-1.79 to -1.37)*** -0.85 (-1.04 to -0.66)*** -0.49 (-0.65 to -0.22)***
0 (‘does not have symptom’) REF REF REF REF
1 (‘symptom doesn’t bother me’) -2.27 (-3.80 to -0.80)** -1.33 (-2.80 to 0.18) -1.80 (-2.88 to -0.81)** -1.38 (-2.50 to -0.74)**
2 (‘symptom bothers me a little’) -4.54 (-5.44 to -3.72)*** -3.17 (-4.01 to -2.35)*** -1.96 (-2.57 to -1.40)*** -1.30 (-1.99 to -0.69)***
3 (‘symptom bothers me’) -7.00 (-8.19 to -5.94)*** -4.75 (-5.87 to -3.65)*** -2.40 (-3.20 to -1.69)*** -1.27 (-2.08 to -0.70)**
4 (‘symptom bothers me a lot’) -8.91 (-10.15 to -7.88)*** -5.89 (-7.10 to -4.70)*** -3.09 (-3.94 to -2.33)*** -1.65 (-2.20 to -0.74)**
Bloating/painful abdomen -1.50 (-1.70 to -1.31)*** -1.02 (-1.22 to -0.88)*** -0.79 (-0.99 to -0.72)*** -0.59 (-0.72 to -0.38)***
0 (‘does not have symptom’) REF REF REF REF
1 (‘symptom doesn’t bother me’) -0.84 (-2.15 to 0.46) -0.61 (-1.91 to 0.64) -0.48 (-1.37 to 0.44) -0.27 (-1.11 to 0.69) 2 (‘symptom bothers me a little’) -2.64 (-3.35 to -1.95)*** -1.82 (-2.54 to -1.18)*** -1.22 (-1.69 to -0.73)*** -0.74 (-1.21 to -0.19)**
3 (‘symptom bothers me’) -4.44 (-5.37 to -3.58)*** -2.81 (-3.89 to -2.09)*** -2.79 (-3.40 to -2.16)*** -1.94 (-2.60 to -1.22)***
4 (‘symptom bothers me a lot’) -6.23 (-7.19 to -5.30)*** -4.40 (-5.35 to -3.50)*** -3.35 (-3.99 to -2.70)*** -2.30 (-2.94 to -1.59)***
1 (‘symptom doesn’t bother me’) -1.12 (-2.18 to -0.01)* -0.40 (-1.45 to 0.66) -0.92 (-1.70 to -0.21)* -0.70 (-1.44 to 0.01) 2 (‘symptom bothers me a little’) -2.75 (-3.85 to -1.65)*** -1.40 (-2.51 to -0.35)* -1.28 (-2.00 to -0.50)* -0.73 (-1.46 to 0.02) 3 (‘symptom bothers me’) -5.87 (-7.18 to -4.58)*** -4.01 (-5.43 to -2.76)*** -1.71 (-2.62 to -0.84)*** -0.91 (-1.18 to 0.00)*
4 (‘symptom bothers me a lot’) -6.62 (-7.80 to -5.42)*** -4.27 (-5.47 to -3.10)*** -2.53 (-3.34 to -1.72)*** -1.44 (-2.27 to -0.60)**
^Unadjusted and adjusted general linear mixed models with spatial power covariance structures; ***P <0.001 **P <0.01 *P <0.05 Abbreviations: Adj, adjusted; CI, confidence interval; HIV, human immunodeficiency virus
‡Both models adjusted for demographic (age; sex; HIV acquisition risk factors; race/ethnicity), behavioral (any drug use in past 6 months;
number of times per month consuming ≥6 alcoholic drinks; cannabis use), and clinical (CD4 cell count; viral load; current ARV backbone;
hepatitis C co-infection; time since HIV diagnosis) variables. PCS model was also adjusted for Center for Epidemiologic Studies Depression (CES-D) survey score.