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Table 4 PRO results of commonly used instruments

From: Patient reported outcome instruments used in clinical trials of HIV-infected adults on NNRTI-based therapy: a 10-year review

Study reference Treatment/dosing regimen Domain Baseline score mean (SD) Follow-up score[time, mean] Effect size Summary of PRO results
Instrument: Centre for Epidemiologic Studies – Depression Scale (CES-D)
Lake (2012) [9] Immediate switch of PI or NNRTI to RAL (continuing prior NRTI backbone) Depression NR 24 weeks, NR N/A The CES-D was administered at 0, 4, 8, 12, 18, and 24 weeks, but patient-reported depression scores were not reported in this study.
Delayed switch (at 24 weeks) of PI or NNRTI to RAL (continuing prior NRTI backbone) Depression NR 24 weeks, NR N/A
Clifford (2009) [22] ZDV/3TC/EFV Depression 12.2 (10.5) 184 weeks1, 10.1a 0.20 In participants who continued EFV-based regimens, neuropsychological performance improvement from baseline was maintained over 3 years.
ZDV/3TC/ABC Depression 11.8 (10.5) 184 weeks1, 10.4 0.13 There was statistically significant decrease in depression symptoms over the course of the study with the median score decline of 1.0 (P = 0.03).
Various regimens (± EFV) Depression 13.3 (11.1) 184 weeks1, 16.6 −0.30 In the long-term EFV-treated group, the percent with CES-D scores >16 declined from 34.1% to 22.3% over the duration of the study.
ZDV/3TC/ABC initially, then EFV added (± ABC) Depression 13.8 (12.5) 184 weeks1, 8.6 0.42
Journot (2006) [29] PI-based therapy Depression2 23% 48 weeks, 25% N/A Proportion of patients with depression was approximately 24% at BL and remained stable during the 48 week follow-up with no difference between treatment arms, P = 0.65).
EFV-based therapy Depression2 25% 48 weeks, 24% N/A
36 months, 24% N/A
Patients with a history of depression experienced depressive symptoms more frequently than those without such history (53% and 22% at week 48, respectively; P = 0.03).
Instrument: Functional Assessment of HIV Infection (FAHI)
Campo (2010) [14] Switch to EFV/3TC/ddI Total Score 130 48 weeks, 134a N/A In the overall patient population, FAHI total score increased significantly from BL to week 48 (P < 0.001) and at every other time point; changes in total score were associated with improvements in the physical and emotional well-being domains (P < 0.001 for both).
Switch PI to EFV (continuing prior NRTIs) Total Score 132 48 weeks, 138a N/A No significant between-group differences observed.
Cella (2010) [15] ETR 200 mg twice-daily3 Total Score 121.7 (23.7)5 24 weeks, 127.3a,b 0.21 The change in physical well-being, emotional well-being/living with HIV and total scores from BL to Week 24 were statistically different from zero for both groups, with statistically significant greater improvements observed in the ETR group.
Placebo3 Total Score 120.9 (26.7)5 24 weeks, 124.0a,b 0.11
Boyle (2008) [25] Continue BL ARVs (BID+ dosing) Total Score 130.4 48 weeks, NR N/A A small improvement (5% or less) for the emotional well-being and a small reduction (9% or less) for functional and global well-being were observed at some time points in both arms; however, these were not considered clinically relevant, as the effect sizes were small.
Switch to once-daily d4T/3TC/EFV Total Score 131.4 48 weeks, NR N/A No significant differences observed between arms.
Instrument: HIV Symptom Index / Symptom Distress Module (HIV-SI / SDM)
Hodder (2010) [19] EFV/FTC/TDF Dizziness 28% 4 weeks, 39%a,b N/A Simplification from PI-based or NNRTI-based regimens to EFV/FTC/TDF was associated with transient worsening or emergence of dizziness and sustained improvements in several other HIV-related symptoms: diarrhea or loose bowel movements; bloating, pain or gas in the stomach, changes in body appearance, and problems having sex.
48 weeks, 28% N/A
Remain on BL antiretroviral regimen Dizziness 27% 4 weeks, 25%b N/A
48 weeks, 28% N/A
Potard (2010) [21] EFV- or NVP-based therapy Symptom Count 11.9 (9.1) 12 months, 9.0a 0.32 Overall, there was a small improvement in HIV symptoms at 1 year (effect size 0.32).
Symptom Bother Count 7.7 (5.9) 12 months, 6.0a 0.29 An initial difference between groups in mean change in other symptoms, bothersome symptoms, and other bothersome symptoms observed at 1 month was not maintained at months 6 and 12.
Regnault (2009) [18] ZDV/3TC + MVC 300 mg twice dailyZDV/3TC + MVC 600 mg once dailyZDV/3TC + EFV 600 mg once daily Symptom Count Mean score ranged from ~5 (European Romance group) to ~10 (Bantu group) 96 weeks, NR N/A This study assessed the cross-cultural validity of the HIV-SI using pre-ARV treatment cross-sectional data of the MERIT trial.
Statistically significant differential item functioning between cultural groups was observed for 4 items: fatigue, fevers, anxiety, and headache.
Symptom Bother Count Mean score ranged from 10.08 (European Romance group) to 24.00 (Bantu group) 96 weeks, NR N/A The authors concluded that the absence of meaningful explanations for statistically significant differences between cultural groups supports the cross-cultural validity of the HIV-SI versions used in the MERIT trial.
DeJesus (2008) [26] Switch from twice-daily AZT/3TC to once-daily TDF/FTC with EFV Symptom Count NR 24 weeks, NR N/A Significant differences were observed in the percentage of patients reporting the absence of the symptom at Week 24 compared to BL for 17 of the 20 items assessed.
Symptom Bother Count NR 24 weeks, NR N/A Compared to BL, significantly more patients reported the absence of fatigue, absence of nausea and vomiting, absence of diarrhea, and absence of headache.
Instrument: Medical Outcomes Study HIV health survey (MOS-HIV)
Jayaweera (2009) [24] ddI/3TC/EFV once-daily Total Score 874 96 weeks, 924 N/A The overall MOS-HIV QoL score, which is the sum of all individual MOS-HIV scores (range: 0 to 1,100), significantly improved from BL (874) to Week 96 (924; P < 0.05).
Jayaweera (2009) [24] d4T/3TC/EFV once-daily Total Score 832 12 weeks, 880 N/A The overall MOS-HIV QoL score significantly improved from BL (832) to Week 12 (880; P < 0.05).
Lafaurie (2008) [28] PI-containing regimen PHS 56.5 (50.0-61.8)3 48 weeks, -1.044 0.24 The mean change from BL to week 48 in the PCS and MCS were −1.04 and +0.0 in the maintenance arm and −1.76 and +1.01 in the switch arm, respectively (P = 0.57 and 0.42).
MHS 40.2 (33.8-45.3)3 48 weeks, 0.004 0.00
EFV/ddI/FTC PHS 57.4 (51.5-60.4)3 48 weeks, -1.764 0.53 Specific items such as physical functioning, social functioning, and emotional functioning remained unchanged in both treatment groups during follow-up.
MHS 38.3 (33.4-43.6)3 48 weeks, 1.014 −0.27
Bucciardini (2007) [27] ddI/d4T/EFV PHS 50 (11) 3 years, 54.9 −0.45 Similar results reported for follow-up at years 1 and 2 (data not shown).
MHS 49 (10) 3 years, 49.5 −0.05
ddI/d4T/NFV PHS 46 (13) 3 years, 50.9 −0.38 During follow-up, an increase of PHS score was observed in all treatment arms (NS).
MHS 48 (10) 3 years, 53.5 −0.55
ddI/d4T/EFV/NFV PHS 48 (12) 3 years, 50.0 −0.17 The MHS score of both NNRTI- and PI-based 3-drug regimens showed a trend toward improvement but remained substantially unchanged with the four-drug combination.
MHS 50 (9) 3 years, 53.4 −0.38
Portsmouth (2005) [30] Continue twice-daily regimen of d4T(IR)/3TC/EFV or ZDV/3TC/EFV Total Score NR 24 weeks, NR N/A There were no significant differences in quality of life between the IR and PRC arms based on overall (sum of 11 domains) change from BL to week 24.
Cognitive Function NR 24 weeks, NRa N/A Both arms showed significant improvement in the cognitive function domain (P < 0.001) during the course of the study, based on BL cognitive scores at weeks 12 and 24.
Switch to once-daily d4T(PRC)/3TC/EFV Total Score NR 24 weeks, NR N/A Differences between groups were not observed.
Cognitive Function NR 24 weeks, NRa N/A
Casado (2004) [31] ZDV/3TC/NFV PHS 54.16 (8.97) 12 months, 52.79 −0.15 In the ZDV/3TC/NVP arm, there were statistically significant changes in the PHS score (P < 0.01) and a trend toward statistically significant change in the MHS score (P = 0.07).
MHS 45.72 (11.10) 12 months, 49.20 0.31
ZDV/3TC/NVP PHS 50.95 (11.37) 12 months, 56.73a 0.51
MHS 43.78 (9.92) 12 months, 48.22 0.45 There were no statistically significant changes over time in the ZDV/3TC/NFV arm in both summary scores.
Negredo (2004) [32] Continue twice-daily ARV therapy (PI- or NNRTI-based) General Health NR NR N/A Although quality of life tended to increase in both groups, no significant differences were found during the study in general health and health transition scales.
Health Transition NR NR N/A
Switch to once-daily ddI/TDF/NVP General Health NR NR N/A
Health Transition NR NR N/A
van Leth (2004) [33] d4T/3TC/EFV PHS 50.5 48 weeks, 53.9 N/A PHS and MHS BL values were comparable in all 3 treatment groups (P = 0.883 and P = 0.937, respectively).
MHS 46.9 48 weeks, 53.9 N/A
d4T/3TC/NVP PHS 51.0 48 weeks, 54.9 N/A No significant differences between the 3 treatment groups in increases in dimension scores.
MHS 46.7 48 weeks, 52.8 N/A After adjusting for all significantly associated variables, the increase of PHS was 4.6 for NVP, 4.8 for EFV and 3.8 for NVP + EFV (P = 0.790); the adjusted increase of MHS was 6.1, 7.3 and 3.8, respectively (P = 0.093).
d4T/3TC/EFV/NVP PHS 50.9 48 weeks, 53.8 N/A
MHS 47.1 48 weeks, 51.0 N/A
  1. Abbreviations: 3 TC lamivudine, ABC abacavir, ARV antiretroviral, AZT zidovudine, BL baseline, CF cognitive functioning, d4T stavudine, ddI didanosine, DRV/r darunavir/ritonavir, EFV efavirenz, ENF enfuvirtide, EWB emotional well-being, ETR etravirine, FGWB functional global well-being, FTC emtricitabine, HAART highly-active antiretroviral therapy, IQR interquartile range, IR immediate release, MCS mental component score, MHS mental health summary, N/A not available, NFV nelfinavir, NNRTI non-nucleoside reverse transcriptase inhibitor, NRTI nucleoside/nucleotide reverse transcriptase inhibitor, NS not significant, NVP nevirapine, PCS physical component score, PHS physical health summary, PI protease inhibitor, PRC prolonged-release capsule, PRO patient-reported outcome, PWB physical well-being, SD standard deviation, SWB social well-being, TDF tenofovir, ZDV zidovudine.
  2. 1184 weeks, or study discontinuation; 2Score ≥17 for men and ≥23 for women; 3Median (IQR); 4Mean change; 5Standard deviation estimated from IQR.
  3. aSignificant change over time (P < 0.05); bSignificant change between groups (P < 0.05).