Table 2.
Predictors of second-line treatment failure (n=302)
| Covariate | Number of failures | Patient years follow up | Rate per 100pt/yrs (95%CI) | Univariate HR (95%CI) | p | p overall | Multivariate¥ HR (95%CI) | p | p overall |
|---|---|---|---|---|---|---|---|---|---|
| Age (yrs)¤ | |||||||||
| <30 | 3 | 110.48 | 2.72 (0.88 - 8.42) | 1.00 | 1.00 | ||||
| 30-40 | 28 | 448.89 | 6.24 (4.31 - 9.03) | 1.78 (0.52 - 6.08) | 0.356 | 2.36 (0.65 - 8.51) | 0.190 | ||
| 41-50 | 33 | 268.18 | 12.31 (8.75 - 17.31) | 3.88 (1.15 - 13.10) | 0.029 | 5.50 (1.51 - 20.07) | 0.010 | ||
| >50 | 17 | 96.65 | 17.59 (10.93 - 28.29) | 4.98 (1.39 - 17.89) | 0.014 | <0.001† | 7.50 (1.93 - 29.19) | 0.004 | <0.001† |
| Baseline viral load (copies/ml)¤ | |||||||||
| <1,000 | 7 | 143.13 | 4.89 (2.33 - 10.26) | 1.00 | 1.00 | ||||
| 1,000-10,000 | 12 | 149.62 | 8.02 (4.55 - 14.12) | 2.30 (0.86 - 6.17) | 0.098 | 2.22 (0.79 - 6.24) | 0.130 | ||
| >10,000 | 26 | 250.23 | 10.39 (7.07 - 15.26) | 2.43 (1.00 - 5.90) | 0.050 | 0.051† | 2.90 (1.17 - 7.18) | 0.021 | 0.031† |
| Unknown | 36 | 380.55 | 9.46 (6.82 - 13.11) | - | - | ||||
| Initial second-line regimen | |||||||||
| LPV/r or ATV/r + dual NRTI | 29 | 427.00 | 6.79 (4.72 - 9.77) | 1.00 | 1.00 | ||||
| Other PI + dual NRTI | 21 | 188.33 | 11.15 (7.27 - 17.10) | 2.71 (1.40 - 5.25) | 0.003 | 3.17 (1.65 - 6.06) | 0.001 | ||
| NNRTI + dual NRTI | 21 | 232.05 | 9.05 (5.90 - 13.88) | 0.92 (0.48 - 1.76) | 0.806 | 0.96 (0.50 - 1.84) | 0.904 | ||
| Other | 10 | 76.82 | 13.02 (7.00 - 24.19) | 1.19 (0.54 - 2.62) | 0.675 | 0.018‡ | 1.94 (0.83 - 4.56) | 0.128 | 0.002 ‡ |
| Gender | |||||||||
| Male | 66 | 711.59 | 9.27 (7.29 - 11.81) | 1.00 | 1.00 | ||||
| Female | 15 | 212.60 | 7.06 (4.25 - 11.70) | 0.87 (0.47 - 1.60) | 0.647 | 0.99 (0.51 - 1.90) | 0.968 | ||
| HIV exposure | |||||||||
| Heterosexual | 62 | 665.32 | 9.32 (7.27 - 11.95) | 1.00 | 1.00 | ||||
| Homosexual | 12 | 135.16 | 8.88 (5.04 - 15.63) | 0.74 (0.34 - 1.59) | 0.434 | 1.18 (0.50 - 2.78) | 0.710 | ||
| IDU | 3 | 80.37 | 3.73 (1.20 - 11.57) | 0.89 (0.23 - 3.36) | 0.858 | 1.04 (0.25 - 4.25) | 0.958 | ||
| Other | 4 | 43.35 | 9.23 (3.46 - 24.58) | 1.07 (0.37 - 3.09) | 0.896 | 0.871‡ | 0.87 (0.28 - 2.69) | 0.816 | 0.974‡ |
| Baseline CD4 (cells/mm3) | |||||||||
| >200 | 24 | 237.00 | 10.13 (6.79 - 15.11) | 1.00 | 1.00 | ||||
| ≤200 | 41 | 409.45 | 10.01 (7.37 - 13.60) | 1.33 (0.78 - 2.29) | 0.296 | 0.96 (0.53 - 1.74) | 0.896 | ||
| Missing | 16 | 277.75 | 5.76 (3.53 - 9.40) | - | - | ||||
| AIDS prior to second-line ART | |||||||||
| None known | 45 | 583.53 | 7.71 (5.76 - 10.33) | 1.00 | 1.00 | ||||
| Yes | 36 | 340.67 | 10.57 (7.62 - 14.65) | 1.28 (0.78 - 2.09) | 0.326 | 1.19 (0.72 - 1.98) | 0.505 | ||
| HBV status | |||||||||
| Negative | 57 | 700.37 | 8.14 (6.28 - 10.55) | 1.00 | 1.00 | ||||
| Positive | 6 | 70.81 | 8.47 (3.81 - 18.86) | 0.85 (0.36 - 2.05) | 0.724 | 1.06 (0.42 - 2.62) | 0.907 | ||
| Not tested | 18 | 153.02 | 11.76 (7.41 - 18.67) | - | - | ||||
| HCV status | |||||||||
| Negative | 57 | 636.51 | 8.96 (6.91 - 11.61) | 1.00 | 1.00 | ||||
| Positive | 2 | 75.00 | 2.67 (0.67 - 10.66) | 0.48 (0.11 - 2.06) | 0.323 | 0.34 (0.08 - 1.51) | 0.158 | ||
| Not tested | 22 | 212.69 | 10.34 (6.81 - 15.71) | ||||||
| First-line regimen | |||||||||
| NNRTI | 53 | 637.85 | 8.31 (6.35 - 10.88) | 1.00 | 1.00 | ||||
| PI | 23 | 237.79 | 9.67 (6.43 - 14.56) | 0.89 (0.47 - 1.67) | 0.709 | 1.51 (0.38 - 6.04) | 0.561 | ||
| Other | 5 | 48.56 | 10.30 (4.29 - 24.74) | 0.48 (0.17 - 1.34) | 0.161 | 0.373‡ | 0.53 (0.13 - 2.19) | 0.383 | 0.243‡ |
| Time on first-line ART (yrs) | |||||||||
| <2 | 34 | 342.87 | 9.92 (7.09 - 13.88) | 1.00 | 1.00 | ||||
| 2-4 | 26 | 388.40 | 6.69 (4.56 - 9.83) | 0.92 (0.54 - 1.58) | 0.770 | 1.02 (0.58 - 1.81) | 0.934 | ||
| >4 | 21 | 192.93 | 10.89 (7.10 - 16.69) | 1.10 (0.62 - 1.95) | 0.747 | 0.796† | 1.08 (0.59 - 1.97) | 0.797 | 0.801† |
| Time from failure to second-line ART (mths) | |||||||||
| <6 | 26 | 329.73 | 7.89 (5.37 - 11.58) | 1.00 | 1.00 | ||||
| 6-18 | 19 | 223.29 | 8.51 (5.43 - 13.34) | 1.05 (0.56 - 1.98) | 0.884 | 1.19 (0.59 - 2.41) | 0.631 | ||
| >18 | 36 | 371.17 | 9.70 (7.00 - 13.45) | 0.96 (0.56 - 1.67) | 0.896 | 0.879† | 1.17 (0.64 - 2.12) | 0.614 | 0.641† |
| Year of second-line ART start | |||||||||
| Before 2007 | 44 | 466.68 | 9.43 (7.02 - 12.67) | 1.00 | 1.00 | ||||
| 2007-2010 | 34 | 399.67 | 8.51 (6.08 - 11.91) | 1.12 (0.66 - 1.89) | 0.669 | 1.31 (0.73 - 2.37) | 0.371 | ||
| After 2010 | 3 | 57.84 | 5.19 (1.67 - 16.08) | 0.49 (0.15 - 1.67) | 0.258 | 0.591† | 0.57 (0.15 - 2.12) | 0.401 | 0.953† |
| Adherence during second-line* | |||||||||
| >95% | 18 | 554.61 | 3.25 (2.04 - 5.15) | 1.00 | 1.00 | ||||
| <95% | 2 | 31.42 | 6.36 (1.59 - 25.45) | 1.61 (0.34 - 7.65) | 0.551 | 1.67 (0.33 - 8.59) | 0.537 | ||
| Unknown | 61 | 337.50 | 18.07 (14.06 - 23.23) | - | - |
All models stratified by site.
¤
Included in final model
¥
Adjusted for predictors of failure included in the fina model (age, baseline viral load, and initial second-line regimen)
*
Time updated
†
p overall for linear trend
‡
p overall for heterogeneity. ART = antiretroviral therapy; IDU = intravenous drug use; NRTI = nucleoside reverse transcriptase inhibitor; NNRTI = non-nucleoside reverse transcriptase inhibitor based therapy; PI = protease inhibitor based therapy; LPV/r = ritonavir-boosted lopinavir; ATV/r = ritonavir-boosted atazanavir; HBV = Hepatitis B virus; HCV = Hepatitis C virus.