Table 2.
Factors associated with virological failure in AHOD using Cox regression
| Univariable | Multivariable model I | Multivariable model II | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Person-years of follow-up (PYFU) | virological failure (n) | IR per 100 PYFU (95% CI) | Unadjusted HR (95% CI) | P-value | Adjusted HR (95% CI) | P-value | Adjusted HR (95% CI) | P-value | |
| Overall (N=2544) | 18125.26 | 444 | 2.45 (2.23, 2.69) | ||||||
| Age at ART initiation | <0.001 | <0.001 | <0.001 | ||||||
| <=30 | 2655.35 | 111 | 4.18 (3.47, 5.03) | Ref | Ref | Ref | |||
| 31–40 | 6441.68 | 168 | 2.61 (2.24, 3.03) | 0.67 (0.53, 0.86) | 0.67 (0.53, 0.86) | 0.67 (0.52, 0.85) | |||
| 41–50 | 5366.04 | 119 | 2.22 (1.85, 2.65) | 0.58 (0.45, 0.75) | 0.59 (0.45, 0.77) | 0.58 (0.44, 0.76) | |||
| >50 | 3662.19 | 46 | 1.26 (0.94, 1.68) | 0.33 (0.24, 0.47) | 0.33 (0.23, 0.47) | 0.33 (0.23, 0.47) | |||
| Sex | |||||||||
| Male | 16144.74 | 400 | 2.48 (2.25, 2.73) | Ref | Ref | Ref | |||
| Female | 1980.51 | 44 | 2.22 (1.65, 2.99) | 0.88 (0.64, 1.20) | 0.408 | 0.73 (0.49, 1.1) | 0.13 | 0.72 (0.48, 1.08) | 0.11 |
| Country of birth | 0.298 | 0.46 | 0.46 | ||||||
| Australia & New Zealand | 11304.32 | 287 | 2.54 (2.26, 2.85) | Ref | Ref | Ref | |||
| Overseas | 4847.12 | 110 | 2.27 (1.88, 2.85) | 0.84 (0.68, 1.05) | 0.89 (0.69, 1.13) | 0.9 (0.71, 1.15) | |||
| Unknown | 1973.82 | 47 | 2.38 (1.79, 3.17) | 0.92 (0.67, 1.25) | 0.83 (0.59, 1.18) | 0.83 (0.59, 1.17) | |||
| HIV mode of acquisition | 0.008 | 0.88 | 0.88 | ||||||
| MSM | 13090.20 | 308 | 2.35 (2.10, 2.63) | Ref | Ref | Ref | |||
| Injecting drug use | 842.44 | 38 | 4.51 (3.28, 6.2) | 1.84 (1.31, 2.57) | 1.18 (0.81, 1.71) | 1.13 (0.78, 1.64) | |||
| Heterosexual | 3567.87 | 81 | 2.27 (1.83, 2.82) | 0.94 (0.73, 1.20) | 1.08 (0.78, 1.48) | 1.09 (0.79, 1.5) | |||
| Other/Unknown | 624.74 | 17 | 2.72 (1.69, 4.38) | 1.16 (0.71, 1.89) | 0.97 (0.59, 1.62) | 0.97 (0.59, 1.62) | |||
| CD4 at ART initiation, cells/mm 3 | 0.001 | 0.005 | 0.005 | ||||||
| <=200 | 3617.00 | 105 | 2.90 (2.40, 3.51) | Ref | Ref | Ref | |||
| 201–350 | 4277.51 | 84 | 1.96 (1.59, 2.43) | 0.68 (0.51, 0.91) | 0.74 (0.55, 0.99) | 0.74 (0.55, 0.99) | |||
| 351–500 | 2997.37 | 53 | 1.77 (1.35, 2.31) | 0.61 (0.44, 0.84) | 0.63 (0.44, 0.88) | 0.63 (0.44, 0.88) | |||
| 500+ | 2796.21 | 67 | 2.40 (1.89, 3.04) | 0.78 (0.57, 1.06) | 0.83 (0.6, 1.15) | 0.84 (0.6, 1.17) | |||
| Missing | 4437.17 | 135 | 3.04 (2.57, 3.6) | 1.02 (0.79, 1.31) | 1.16 (0.84, 1.62) | 1.18 (0.85, 1.63) | |||
| HIV RNA at ART initiation, copies/mL | 0.596 | 0.24 | 0.24 | ||||||
| <=100,000 | 8446.14 | 189 | 2.24 (1.94, 2.58) | Ref | Ref | Ref | |||
| >100,000 | 4010.69 | 115 | 2.87 (2.39, 3.44) | 1.29 (1.02, 1.62) | 1.08 (0.85, 1.38) | 1.1 (0.87, 1.4) | |||
| Missing | 5668.43 | 140 | 2.47 (2.09, 2.91) | 1.11 (0.89, 1.38) | 0.85 (0.63, 1.15) | 0.84 (0.62, 1.12) | |||
| Documented treatment interruption duration * | <0.001 | <0.001 | <0.001 | ||||||
| No interruption | 11065.04 | 148 | 1.34 (1.14, 1.57) | Ref | Ref | Ref | |||
| 1-<14 days | 2327.51 | 29 | 1.25 (0.87, 1.79) | 1.03 (0.69, 1.53) | 1.10 (0.73, 1.66) | 0.74 (1.67, 1.66) | |||
| 14 days – 3 months | 926.15 | 27 | 2.92 (2.00, 4.25) | 2.29 (1.52, 3.45) | 2.42 (1.58, 3.69) | 1.61 (3.76, 3.69) | |||
| 3 months – 6 months | 398.22 | 29 | 7.28 (5.06, 10.48) | 5.64 (3.79, 8.39) | 6.9 (4.47, 10.64) | 4.19 (9.98, 10.64) | |||
| > 6 months | 3408.34 | 211 | 6.19 (5.41, 7.08) | 4.88 (3.95, 6.03) | 6.23 (4.82, 8.05) | 4.81 (8.05, 8.05) | |||
| HBV surface antigen positivity | 0.013 | 0.001 | 0.001 | ||||||
| Negative | 14841.18 | 379 | 2.55 (2.31, 2.82) | Ref | Ref | Ref | |||
| Positive | 517.79 | 20 | 3.86 (2.49, 5.99) | 1.45 (1.02, 2.27) | 1.75 (1.11, 2.78) | 1.80 (1.13, 2.85) | |||
| Unknown | 2766.28 | 45 | 1.63 (1.21, 2.18) | 0.61 (0.45, 0.83) | 0.60 (0.4, 0.88) | 0.62 (0.42, 0.91) | |||
| HCV antibody positivity | 0.03 | 0.06 | 0.054 | ||||||
| Negative | 15035.41 | 355 | 2.36 (2.13, 2.62) | Ref | Ref | Ref | |||
| Positive | 1497.29 | 50 | 3.34 (2.53, 4.41) | 1.41 (1.05, 1.89) | 0.99 (0.72, 1.37) | 1.02 (0.74, 1.41) | |||
| Unknown | 1592.56 | 39 | 2.45 (1.79, 3.35) | 0.98 (0.71, 1.37) | 1.73 (1.14, 2.62) | 1.66 (1.1, 2.51) | |||
| Number of VL measurement (per 5-unit increase) | 1.11 (1.06, 1.16) | <0.001 | 1.09 (1.03, 1.16) | 0.004 | 1.1 (1.03, 1.17) | 0.004 | |||
| ART type commenced | <0.001 | 0.03 | 0.03 | ||||||
| NRTI+NNRTI | 9658.96 | 193 | 2 (1.74, 2.3) | Ref | Ref | Ref | |||
| NRTI+PI | 5028.11 | 169 | 3.36 (2.89, 3.91) | 1.67 (1.36, 2.06) | 1.34 (1.08, 1.67) | 1.35 (1.08, 1.68) | |||
| NRTI+INSTI | 2267.34 | 40 | 1.76 (1.29, 2.41) | 0.71 (0.50, 1.00) | 1.21 (0.8, 1.84) | 1.21 (0.80, 1.83) | |||
| Other | 1170.85 | 42 | 3.59 (2.65, 4.85) | 1.75 (1.25, 2.44) | 1.38 (0.97, 1.97) | 1.42 (1, 2.02) | |||
| Year of ART initiation | <0.001 | <0.001 | <0.001 | ||||||
| <=2005 | 7509.33 | 222 | 2.96 (2.59, 3.37) | Ref | Ref | Ref | |||
| 2006–2010 | 5663.17 | 129 | 2.28 (1.92, 2.71) | 0.76 (0.61, 0.95) | 0.54 (0.37, 0.77) | 0.56 (0.38, 0.8) | |||
| 2011–2015 | 4229.26 | 82 | 1.94 (1.56, 2.41) | 0.54 (0.42, 0.70) | 0.31 (0.19, 0.49) | 0.32 (0.2, 0.51) | |||
| 2016–2022 | 723.5 | 11 | 1.52 (0.84, 2.75) | 0.33 (0.18, 0.60) | 0.19 (0.08, 0.44) | 0.20 (0.09, 0.46) | |||
| Duration of ART (per 5-year increase) | 0.53 (0.43, 0.60) | <0.001 | 0.50 (0.42, 0.59) | <0.001 | 0.50 (0.43, 0.59) | <0.001 | |||
| Participant care setting | 0.08 | 0.014 | 0.013 | ||||||
| Sexual health services | 8395.00 | 226 | 2.69 (2.36, 3.07) | Ref | Ref | Ref | |||
| GP | 6526.71 | 134 | 2.05 (1.73, 2.43) | 0.79 (0.64, 0.98) | 0.71 (0.56, 0.89) | 0.71 (0.56, 0.90) | |||
| Hospital | 3203.55 | 84 | 2.62 (2.12, 3.25) | 0.99 (0.77, 1.27) | 0.98 (0.74, 1.29) | 0.98 (0.74, 1.29) | |||
| Viral blip * | |||||||||
| No | 11590.68 | 154 | 1.33 (1.13, 1.56) | Ref | Ref | ||||
| Yes | 6534.58 | 290 | 4.45 (3.97, 4.99) | 3.39 (2.79, 4.12) | <0.001 | 2.78 (2.23, 3.46) | <0.001 | ||
| Low level viremia * | |||||||||
| No | 16543.37 | 350 | 2.12 (1.91, 2.35) | Ref | Ref | ||||
| Yes | 1581.89 | 94 | 6.02 (4.92, 7.37) | 2.78;(2.21, 3.49) | <0.001 | 1.69 (1.32, 2.17) | <0.001 | ||
| Viremia group ** | <0.001 | <0.001 | |||||||
| Viral suppression | 11511.2 | 147 | 1.28 (1.09, 1.5) | Ref | Ref | ||||
| Blip | 5052.08 | 203 | 4.02 (3.5, 4.61) | 3.20 (2.59, 3.95) | 2.89 (2.31, 3.61) | ||||
| LLV | 1561.98 | 94 | 6.02 (4.92, 7.37) | 4.61 (3.56, 5.98) | 4.46 (3.38, 5.89) |
*
Time-updated variables
**
Viremia group was included as a time-updated covariate and reclassification was allowed only for a higher VL group.
All analyses were adjusted by site to account for the heterogeneity of healthcare systems.
Global p-values are tested for heterogeneity excluding missing values.
Abbreviations: ART, antiretroviral therapy; MSM, male to male sex; VL, viral load, NRTI, nucleoside/nucleotide reverse transcriptase inhibitors; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; INSTI, integrase strand transfer inhibitor; PYS, person-years follow up; IR, incidence rate; HR, hazard ratio.