Background
Methods
Dataset
Baseline state as a latent variable
Pre-treatment model structure
Conditional distribution of ‘true’ baseline
Post-treatment model structure
Mean response to treatment
Long-term maximum
Speed of response to treatment
Residual variance structure
Differences in variability between patients
Overall model structure and interpretation
Maximum likelihood estimation
Results
Model fitting
M
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β
0
| 22.44 (22.13 to 22.74) | 22.45 (22.16 to 22.74) | 22.44 (22.15 to 22.73) | 22.26 (21.96 to 22.56) | 22.26 (21.96 to 22.56) | 22.23 (21.94 to 22.53) |
β
1
| −1.36 (−1.52 to −1.2) | −1.39 (−1.55 to −1.23) | −1.39 (−1.55 to −1.23) | −1.3 (−1.46 to −1.14) | −1.32 (−1.47 to −1.16) | −1.36 (−1.5 to −1.21) |
U
00
| 12.37 (10.64 to 14.37) | 13.39 (11.77 to 15.23) | 13.42 (11.79 to 15.28) | 14.43 (12.68 to 16.43) | 14.53 (12.77 to 16.54) | 12.92 (11.29 to 14.8) |
ρ
| −0.65 (−0.79 to −0.44) | −0.86 (−0.99 to 0.18) | −0.84 (−0.98 to −0.1) | −0.95 (−1 to 1) | −0.92 (−1 to 0.91) | −0.63 (−0.76 to −0.44) |
U
11
| 0.55 (0.33 to 0.93) | 0.25 (0.08 to 0.75) | 0.28 (0.1 to 0.75) | 0.2 (0.05 to 0.74) | 0.21 (0.06 to 0.74) | 0.49 (0.31 to 0.77) |
κ
pre
| 9.68 (8.77 to 10.68) | 5.91 (5.23 to 6.67) | 5.9 (5.22 to 6.68) | 5.99 (5.29 to 6.8) | 5.92 (5.21 to 6.72) | 5.37 (4.37 to 6.6) |
H
pre
| 0.11 (0.09 to 0.14) | 0.3 (0.25 to 0.37) | 0.3 (0.24 to 0.36) | 0.31 (0.25 to 0.37) | 0.31 (0.25 to 0.38) | 0.16 (0.13 to 0.19) |
σ
| 1.25 (1.09 to 1.42) | 1.95 (1.89 to 2.01) | 1.94 (1.87 to 2) | 1.92 (1.85 to 1.99) | 1.92 (1.86 to 1.99) | 1.32 (1.19 to 1.46) |
ϕ1 model: | ||||||
long-term | Constant for all patients | Linear for all patients | NCS for all patients | Linear for all patients | Linear for early treatment | Linear for all patients |
maximum | stratified by ART
t
| groups or NCS for late | stratified by ART
t
| |||
treatment group | ||||||
At11 | — | — | — | 7.04 (4.75 to 9.33) | 7.06 (4.77 to 9.35) | 8.44 (6.05 to 10.83) |
At12 | — | — | — | 0.9 (0.79 to 1.01) | 0.9 (0.79 to 1) | 0.84 (0.72 to 0.95) |
At21 | — | — | — | 10.73 (7.93 to 13.53) | 10.68 (7.85 to 13.51) | 12.32 (9.28 to 15.35) |
At22 | — | — | — | 0.67 (0.54 to 0.81) | 0.67 (0.53 to 0.81) | 0.64 (0.47 to 0.8) |
A
1
| 25.93 (25.49 to 26.36) | 11.42 (9.74 to 13.09) | 5.1 (0.3 to 9.9) | 14.58 (12.3 to 16.86) | 3.76 (−1.99 to 9.51) | 14.35 (12.32 to 16.38) |
A
2
| — | 0.69 (0.62 to 0.77) | 1.14 (0.84 to 1.44) | 0.55 (0.44 to 0.66) | 1.23 (0.86 to 1.6) | 0.57 (0.46 to 0.67) |
A
3
| — | — | -0.43 (−0.64 to −0.22) | — | −0.32 (−0.63 to −0.01) | — |
A
4
| — | — | 0.82 (0.43 to 1.2) | — | 0.52 (−0.07 to 1.11) | — |
ϕ2 model: | ||||||
recovery | Constant for all patients | Linear for all patients | NCS for all patients | Linear for all patients | Linear for early treatment | Linear for all patients |
speed | stratified by ART
t
| groups or NCS for late | stratified by ART
t
| |||
treatment group | ||||||
Bt11 | — | — | — | 2.66 (0.52 to 4.79) | 2.8 (0.76 to 4.84) | 5.68 (2.94 to 8.43) |
Bt12 | — | — | — | 0.02 (−0.08 to 0.11) | 0.01 (−0.08 to 0.1) | −0.14 (−0.29 to −1.98e-03) |
Bt21 | — | — | — | −0.99 (−3 to 1.02) | −0.92 (−2.97 to 1.13) | 0.23 (−1.39 to 1.86) |
Bt22 | — | — | — | 0.15 (0.05 to 0.26) | 0.15 (0.04 to 0.26) | 0.01 (−0.1 to 0.12) |
B
1
| -0.16 (−0.3 to −0.02) | −3.34 (−4.19 to −2.48) | 1.82 (−0.23 to 3.87) | −3.64 (−4.7 to −2.59) | 2.42 (0.26 to 4.58) | −2.25 (−3.3 to −1.21) |
B
2
| — | 0.24 (0.2 to 0.28) | −0.11 (−0.24 to 0.02) | 0.23 (0.17 to 0.29) | −0.15 (−0.29 to −0.02) | 0.13 (0.07 to 0.19) |
B
3
| — | — | 0.28 (0.19 to 0.38) | — | 0.19 (0.04 to 0.33) | — |
B
4
| — | — | −0.52 (−0.71 to −0.33) | — | −0.28 (−0.58 to 0.02) | — |
P
| 11.09 (8.76 to 14.03) | 2.97 (2.09 to 4.23) | 3.05 (2.13 to 4.38) | 3.07 (2.19 to 4.31) | 3.31 (2.39 to 4.59) | 2.72 (1.71 to 4.31) |
κ
post
| 7.59 (6.79 to 8.49) | 3.09 (2.46 to 3.89) | 3.17 (2.53 to 3.98) | 3.36 (2.7 to 4.18) | 3.3 (2.66 to 4.11) | 4.33 (3.5 to 5.36) |
H
post
| 0.08 (0.07 to 0.1) | 0.42 (0.32 to 0.52) | 0.4 (0.3 to 0.5) | 0.38 (0.29 to 0.48) | 0.39 (0.3 to 0.5) | 0.13 (0.11 to 0.16) |
Differences in variability | ||||||
between patients | No | No | No | No | No | Yes |
d
f
pre
| — | — | — | — | — | 3.84 (3.06 to 4.82) |
d
f
post
| — | — | — | — | — | 4.28 (3.4 to 5.38) |
ρ
Moran
| — | — | — | — | — | 0.37 (0.19 to 0.52) |
n
pars
| 13 | 15 | 19 | 23 | 27 | 26 |
ℓ
| −31954.8 | −31724.6 | −31708.9 | −31664.5 | −31656.5 | −31299.7
a
|
BIC
| 64032.85 | 63591.41 | 63597.94 | 63547.06 | 63568.98 | 62845.9
a
|
Model parameter
|
Description
| |||||
---|---|---|---|---|---|---|
β
0
| Pre-treatment mean intercept | |||||
β
1
| Pre-treatment mean slope | |||||
U
00
| Pre-treatment intercept subject-specific random effect variance | |||||
ρ
| Correlation between pre-treatment intercept and slope subject-specific random effects | |||||
U
11
| Pre-treatment slope subject-specific random effect variance | |||||
σ
| Standard deviation of residual error term for each measurement, shared by pre- and post-treatment parts of model | |||||
κ
pre
| Scale parameter for pre-treatment fBM process | |||||
H
pre
| Hurst index for pre-treatment fBM process | |||||
ϕ1 model | These parameters relate to the long-term maximum value of the response variable after treatment initiation | |||||
At11,At12 | Intercept and slope terms in relationship with \(u_{i}^{+}\) for patients treated within 6 months of seroconversion | |||||
At21,At22 | Intercept and slope terms in relationship with \(u_{i}^{+}\) for patients treated beyond 6 months but within 1 year of seroconversion | |||||
A1,A2 | Intercept and slope terms in relationship with \(u_{i}^{+}\) for linear or NCS models
a
| |||||
A3,A4 | Third and fourth coefficients for NCS models
a
| |||||
ϕ2 model | These parameters relate to the rate of recovery of the response variable after treatment initiation | |||||
Bt11,Bt12 | Intercept and slope terms in relationship with \(u_{i}^{+}\) for patients treated within 6 months of seroconversion | |||||
Bt21,Bt22 | Intercept and slope terms in relationship with \(u_{i}^{+}\) for patients treated beyond 6 months but within 1 year of seroconversion | |||||
B1,B2 | Intercept and slope terms in relationship with \(u_{i}^{+}\) for linear or NCS models
a
| |||||
B3,B4 | Third and fourth coefficients for NCS models
a
| |||||
P
| Residual variance for long-term maximum (ϕ1:i) not explained by \(u_{i}^{+}\) | |||||
κ
post
| Scale parameter for post-treatment fBM process | |||||
H
post
| Hurst index for post-treatment fBM process | |||||
d
f
pre
| Degrees of freedom parameter for pre-treatment stochastic process | |||||
d
f
post
| Degrees of freedom parameter for post-treatment stochastic process | |||||
ρ
Moran
| Correlation parameter for latent scaling variables of pre- and post-treatment stochastic processes |