| Literature DB >> 33028546 |
Zvifadzo Matsena Zingoni1,2, Tobias Chirwa3, Jim Todd4, Eustasius Musenge3.
Abstract
OBJECTIVE: To determine the loss to follow-up (LTFU) rates at different healthcare levels after antiretroviral therapy (ART) services decentralisation among ART patients who initiated ART between 2004 and 2017 using the competing risk model in addition to the Kaplan-Meier and Cox regressions analysis.Entities:
Keywords: HIV & AIDS; epidemiology; public health
Mesh:
Substances:
Year: 2020 PMID: 33028546 PMCID: PMC7539573 DOI: 10.1136/bmjopen-2019-036136
Source DB: PubMed Journal: BMJ Open ISSN: 2044-6055 Impact factor: 2.692
Figure 1Flow chart of the inclusion criteria for analyses of adult ART patients enrolled in Zimbabwe ART Programme followed up between 2004 and 2017. ART, antiretroviral therapy; ePMS, electronic patient management system.
Figure 2Schematic illustration of the variable of importance selection steps and subsequent models fitted for sensitivity analysis of the results.
Figure 3Trend analysis of loss to follow-up outcome among patients receiving ART in Zimbabwe national ART programme on a quarterly time scale, 2004–2017.
Patients’ sociodemographic and clinical characteristics at ART initiation in Zimbabwe national ART programme, 2004–2017
| Characteristics | Categories | Primary healthcare (PHC) n=176 253 (45.1%) (n (%)) | District/mission hospitals n=192 238 (49.2%) (n (%)) | Provincial/referral hospitals n=22 280 (5.7%) (n (%)) | Total |
| Patient demographics | |||||
| Age (years) at ART initiation | 15–24 | 20 314 (11.53) | 21 057 (10.95) | 2601 (11.67) | 43 972 (11.25) |
| 25–34 | 54 416 (30.87) | 58 874 (30.63) | 6979 (31.32) | 120 269 (30.78) | |
| 35–44 | 59 284 (33.64) | 66 418 (34.55) | 7875 (35.35) | 133 577 (34.18) | |
| 45+ | 42 239 (23.96) | 45 889 (23.87) | 4825 (21.66) | 92 953 (23.79) | |
| Degree of urbanisation | Rural | 113 738 (66.92) | 137 380 (73.57) | 432 (2.01) | 251 550 (66.52) |
| Urban | 56 223 (33.08) | 49 348 (26.43) | 21 055 (97.99) | 126 626 (33.48) | |
| Sex | Female | 117 567 (66.70) | 124 141 (64.58) | 14 136 (63.45) | 255 844 (65.47) |
| Male | 58 686 (33.30) | 68 097 (35.42) | 8144 (36.55) | 134 927 (34.53) | |
| Education status at ART initiation | None | 3854 (2.19) | 4136 (2.15) | 227 (1.02) | 8217 (2.10) |
| Primary | 33 735 (19.14) | 34 062 (17.72) | 2248 (10.09) | 70 045 (17.92) | |
| Secondary | 59 181 (33.58) | 58 349 (30.35) | 6593 (29.59) | 124 123 (31.76) | |
| Tertiary | 2921 (1.66) | 4423 (2.30%) | 1177 (5.28) | 8521 (2.18) | |
| Missing | 76 562 (43.44) | 91 268 (47.48) | 12 035 (54.02) | 179 865 (46.03) | |
| Marital status at ART initiation | Single | 24 438 (13.87) | 24 489 (12.74) | 3530 (15.84) | 52 457 (13.42) |
| Married | 105 504 (59.86) | 113 953 (59.28) | 12 935 (58.06) | 232 392 (59.47) | |
| Widowed | 25 798 (14.64) | 30 994 (16.12) | 3523 (15.81) | 3523 (15.81) | |
| Divorced | 13 429 (7.62) | 14 732 (7.66) | 1677 (7.53) | 29 838 (7.64) | |
| Missing | 7084 (4.02) | 8070 (4.20) | 615 (2.76) | 15 769 (4.04) | |
| Calendar time of starting ART | 2004–2007 | 6635 (3.76) | 8942 (4.65) | 2962 (13.29) | 18 539 (4.74) |
| 2008–2011 | 38 990 (22.12) | 61 321 (31.85) | 7899 (35.45) | 108 120 (27.67) | |
| 2012–2014 | 67 759 (38.44) | 90 582 (47.12) | 9472 (42.51) | 167 813 (42.94) | |
| 2015–2017 | 62 869 (35.67) | 31 483 (16.38) | 1947 (8.74) | 96 299 (24.64) | |
| Clinical factors | |||||
| WHO staging at ART initiation | I/II | 82 203 (46.64) | 69 629 (36.22) | 7690 (34.52) | 159 519 (40.82) |
| III/IV | 79 279 (44.98) | 118 113 (61.44) | 14 425 (64.74) | 211 817 (54.20) | |
| Missing | 14 771 (8.38) | 4499 (2.34) | 165 (0.74) | 19 435 (4.97) | |
| Baseline CD4 (cell/µL) at ART initiation | Above 500 | 4783 (2.71) | 4950 (2.57) | 601 (2.70) | 10 334 (2.64) |
| 351–500 | 8227 (4.67) | 8790 (4.57) | 940 (4.22) | 17 957 (4.60) | |
| 200–350 | 17 908 (10.16) | 24 895 (12.95) | 2866 (12.86) | 45 669 (11.69) | |
| Below 200 | 23 796 (13.50) | 35 020 (18.22) | 4982 (22.36) | 63 798 (16.33) | |
| Missing | 121 539 (68.96) | 118 583 (61.69) | 12 891 (57.86) | 253 013 (64.75) | |
| Treatment regimen at the time of data extraction | First line | 170 662 (98.29) | 184 321 (97.37) | 20 724 (94.32) | 375 704 (97.65) |
| D4T(30)+3TC+NVP | 625 (0.35) | 2942 (1.53) | 629 (2.82) | 4196 (1.07) | |
| D4T(30)+3TC+EFV | 42 (0.02) | 155 (0.08) | 20 (0.09) | 217 (0.06) | |
| AZT+3TC+NVP | 1349 (0.77) | 1933 (1.01) | 349 (1.57) | 3631 (0.93) | |
| AZT+3TC+EFV | 212 (0.12) | 425 (0.22) | 56 (0.25) | 693 (0.18) | |
| TDF+3TC+NVP | 6541 (3.71) | 16 334 (8.50) | 2923 (13.12) | 25 798 (6.60) | |
| TDF+3TC+EFV | 161 288 (91.51) | 162 006 (84.27) | 16 628 (4.63) | 339 922 (86.99) | |
| Other first lines | 3236 (1.84) | 3474 (1.81) | 428 (1.92) | 7138 (1.83) | |
| Second line | 2960 (1.68) | 4969 (2.58) | 1247 (5.60) | 9176 (2.35) | |
| Tuberculosis status at ART initiation | Negative | 156 072 (88.55) | 170 869 (88.88) | 20 218 (90.75) | 347 159 (88.84) |
| Positive | 2092 (1.19) | 2423 (1.26) | 301 (1.35) | 4816 (1.23) | |
| Not assessed | 15 743 (8 93) | 16 387 (8.52) | 1347 (6.05) | 33 477 (8.57) | |
| Missing | 2346 (1.33) | 2559 (1.33) | 414 (1.86) | 5319 (1.36) | |
| Body functional status at ART initiation | Working | 162 710 (92.32) | 180 417 (93.85) | 20 024 (89.87) | 363 151 (92.93) |
| Ambulatory | 11 789 (6.69) | 10 454 (5.44) | 2089 (9.38) | 24 332 (6.23) | |
| Bed ridden | 331 (0.19) | 452 (0.24) | 28 (0.13) | 811 (0.21) | |
| Missing | 1423 (0.81) | 915 (0.48) | 139 (0.62) | 2477 (0.63) | |
Missing category refers to information that is unavailable in the dataset for that particular variable.
ART, antiretroviral therapy; AZT, zidovudine; D4T, stavudine; EFV, efavirenz; NVP, nevirapine; 3TC, lamivudine; TDF, tenofovir.
Rates per 100 person-years of LTFU and log-rank tests for ART patients’ baseline characteristics in Zimbabwe national ART programme, 2004–2017
| Characteristics | Category | LTFU cases | Person-years | Rate per 100 person-years | 95% CI of rate | Log-rank p value |
| Health facility level | Primary healthcare | 34 958 | 6200 | 5.6502 | 5.5913 to 5.7097 | <0.001* |
| District/mission hospitals | 48 188 | 8100 | 5.9169 | 5.8643 to 5.9700 | ||
| Provincial/referral hospitals | 5598 | 1100 | 5.0273 | 4.8973 to 5.1608 | ||
| Age (years) at ART initiation | 15–24 | 32 790 | 4500 | 7.3252 | 7.2463 to 7.4049 | <0.001* |
| 25–34 | 12 617 | 1500 | 8.4301 | 8.2843 to 8.5785 | ||
| 35–44 | 27 504 | 5500 | 4.9671 | 4.9087 to 5.0261 | ||
| 45+ | 15 833 | 3900 | 4.0242 | 3.9620 to 4.0874 | ||
| Degree of urbanisation | Rural | 52 629 | 10 000 | 5.2756 | 5.2307 to 5.3209 | <0.001* |
| Urban | 36 115 | 5500 | 6.6039 | 6.5362 to 6.6724 | ||
| Sex | Females | 59 695 | 10 000 | 5.8703 | 5.8234 to 5.9175 | <0.001* |
| Male | 29 049 | 5300 | 5.5063 | 5.4433 to 5.5700 | ||
| Education status at ART initiation | None | 1470 | 354 | 4.1582 | 3.9509 to 4.3762 | <0.001* |
| Primary | 14 786 | 2800 | 5.3558 | 5.2702 to 5.4429 | ||
| Secondary | 32 629 | 4700 | 6.9961 | 6.9206 to 7.0725 | ||
| Tertiary | 1803 | 409 | 4.4097 | 4.2108 to 4.6180 | ||
| Missing | 38 056 | 7300 | 5.2435 | 5.1911 to 5.2965 | ||
| Marital status at ART initiation | Single | 13 078 | 1900 | 6.9036 | 6.7863 to 7.0230 | <0.001* |
| Married | 7548 | 1100 | 6.6112 | 6.4637 to 6.7620 | ||
| Widowed | 9375 | 2900 | 3.1872 | 3.1233 to 3.2524 | ||
| Divorced | 55 985 | 8800 | 6.3313 | 6.2790 to 6.3839 | ||
| Missing | 2758 | 625 | 4.416 | 4.2543 to 4.5840 | ||
| Calendar time of starting ART | 2004–2007 | 790 | 1900 | 0.4255 | 0.3968 to 0.4562 | <0.001* |
| 2008–2011 | 4572 | 6900 | 0.6593 | 0.6405 to 0.6787 | ||
| 2012–2014 | 43 565 | 5300 | 8.1802 | 8.1038 to 8.2574 | ||
| 2015–2017 | 39 817 | 1300 | 29.9903 | 29.6972 to 30.2863 | ||
| WHO staging at ART initiation | I/II | 47 410 | 5100 | 9.208 | 9.1255 to 9.2912 | <0.001* |
| III/IV | 38 919 | 9500 | 4.0957 | 4.0552 to 4.1366 | ||
| Missing | 2415 | 794 | 3.0432 | 2.9242 to 3.1671 | ||
| Baseline CD4 (cell/uL) at ART initiation | Above 500 | 4341 | 257 | 16.919 | 16.4231 to 17.4299 | <0.001* |
| 351–500 | 7614 | 455 | 16.7362 | 16.3645 to 17.1164 | ||
| 200–350 | 11 556 | 1700 | 6.7428 | 6.6210 to 6.8669 | ||
| Below 200 | 15 271 | 2700 | 5.7338 | 5.6436 to 5.8254 | ||
| Missing | 49 962 | 10 000 | 4.8245 | 4.7823 to 4.8669 | ||
| Treatment regimen at the time of data extraction | First line | 88 050 | 15 000 | 5.9066 | 5.8677 to 5.9457 | <0.001* |
| D4T(30)+3TC+NVP | 2685 | 168 | 15.9847 | 15.3914 to 16.6009 | ||
| D4T(30)+3TC+EFV | 141 | 10 | 14.7353 | 12.4932 to 17.3797 | ||
| AZT+3TC+NVP | 448 | 184 | 2.4374 | 2.2218 to 2.6738 | ||
| AZT+3TC+EFV | 158 | 30 | 5.3159 | 4.5484 to 6.2129 | ||
| TDF+3TC+NVP | 9652 | 1100 | 9.1737 | 8.9925 to 9.3586 | ||
| TDF+3TC+EFV | 71 378 | 13 000 | 5.371 | 5.3318 to 5.4106 | ||
| Other first lines | 3588 | 175 | 20.559 | 19.8972 to 21.2429 | ||
| Second line | 694 | 538 | 1.29 | 1.1985 to 1.3908 | ||
| Tuberculosis status at ART initiation | Negative | 81 119 | 14 000 | 5.9418 | 5.9010 to 5.9828 | <0.001* |
| Positive | 2235 | 131 | 17.0906 | 16.3966 to 17.8141 | ||
| Not assessed | 4188 | 1400 | 2.9328 | 2.8453 to 3.0230 | ||
| Missing | 1202 | 234 | 5.1455 | 4.8627 to 5.4447 | ||
| Body functional status at ART initiation | Working | 81 122 | 14 000 | 5.6445 | 5.6057 to 5.6834 | <0.001* |
| Ambulatory | 7059 | 930 | 7.5897 | 7.4147 to 7.7688 | ||
| Bed ridden | 215 | 26 | 8.4201 | 7.3666 to 9.6243 | ||
| Missing | 348 | 117 | 2.9723 | 2.6758 to 3.3015 |
*Significant at 5%. Missing category refers to information that is unavailable in the dataset for that particular variable.
ART, antiretroviral therapy; AZT, zidovudine; D4T, stavudine; EFV, efavirenz; LTFU, loss to follow-up; NVP, nevirapine; 3TC, lamivudine; TDF, tenofovir.
Figure 4The cumulative incidence probability of mortality and loss to follow-up (A), and Kaplan-Meier curves for loss to follow-up stratified by baseline age categories (B), gender (C), level of urbanisation of the health facilities (D), baseline tuberculosis infection status (E) and baseline WHO clinical stages for ART patients from the Zimbabwe national ART programme electronic patient monitoring data, 2004–2017. ART, antiretroviral therapy.
Multiple regression models results of LTFU among ART patients in Zimbabwe national ART programme, 2004–2017, for different models
| Characteristics | Category | Cox proportional hazard | Parametric Gompertz model | Weibull model with random effects | Competing risk model of mortality on LTFU | |||
| CC+MLE (model 1) | MI+MLE | CC+BE | CC+MLE | MI+MLE | CC+MLE | CC+MLE | ||
| Health facility level | Primary healthcare | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| Secondary hospitals* | 1.48 (1.46–1.50) | 1.51 (1.49–1.53) | 1.53 (1.51–1.54) | 1.53 (1.51–1.55) | 1.57 (1.54–1.59) | 1.48 (1.45–1.51) | 1.47 (1.45–1.50) | |
| Tertiary hospitals† | 1.17 (1.14–1.21) | 1.23 (1.20–1.27) | 1.23 (1.21–1.25) | 1.23 (1.20–1.27) | 1.30 (1.26–1.34) | 1.10 (1.06–1.14) | 1.22 (1.18–1.26) | |
| Age (years) at ART initiation | 15–24 | 1.16 (1.13–1.19) | 1.17 (1.14–1.19) | 1.12 (1.11–1.14) | 1.13 (1.10–1.15) | 1.14 (1.12–1.17) | 1.23 (1.20–1.27) | 1.19 (1.16–1.21) |
| 25–34 | 1.18 (1.17–1.20) | 1.19 (1.17–1.21) | 1.18 (1.16–1.19) | 1.18 (1.16–1.20) | 1.19 (1.17–1.20) | 1.24 (1.21–1.27) | 1.19 (1.17–1.21) | |
| 35–44 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | |
| 45+ | 0.88 (0.87–0.89) | 0.87 (0.86–0.89) | 0.88 (0.87–0.89) | 0.88 (0.86–0.90) | 0.87 (0.85–0.88) | 0.86 (0.84–0.88) | 0.87 (0.85–0.89) | |
| Degree of urbanisation | Rural | 1 (reference) | 1(reference) | 1 (reference) | 1 (reference) | 1(reference) | 1 (reference) | 1(reference) |
| Urban | 1.70 (1.68–1.72) | 1.67 (1.65–1.27) | 1.67 (1.65–1.69) | 1.67 (1.65–1.70) | 1.64 (1.61–1.66) | 2.06 (2.01–2.10) | 1.61 (1.59–1.63) | |
| Calendar time of starting ART | 2004–2007 | 0.04 (0.04–0.05) | 0.04 (0.04–0.05) | 0.02 (0.02–2.02) | 0.02 (0.01–0.02) | 0.02 (0.01–0.02) | 0.01 (0.01–0.01) | 0.09 (0.09–0.10) |
| 2008–2011 | 0.07(.0.7–0.08) | 0.07 (0.07–0.08) | 0.04 (0.04–0.04) | 0.04 (0.0–0.04) | 0.05 (0.04–0.05) | 0.02 (0.02–0.02) | 0.11 (0.10–0.11) | |
| 2012–2014 | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | |
| 2015–2017 | 8.48 (8.34–8.63) | 8.40 (8.26–8.54) | 5.95 (5.90–6.00) | 5.97 (5.88–6.06) | 5.90 (5.81–5.99) | 16.09 (15.56–16.63) | 6.02 (5.91–6.12) | |
| WHO staging at ART initiation | I/II | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| III/IV | 0.73 (0.72–0.74) | 0.74 (0.73–0.75) | 0.73 (0.73–0.74) | 0.73 (0.72–0.75) | 0.74 (0.73–0.75) | 0.67 (0.65–0.68) | 0.74 (0.73–0.75) | |
| Treatment regimen at the time of data extraction | D4T(30)+3TC+NVP | 5.96 (5.72–6.21) | 6.00 (5.77–6.25) | 6.065.92–6.22) | 6.09 (5.84–6.34) | 6.06 (5.82–6.30) | 15.05 (13.98–16.21) | 5.47 (5.52–5.75) |
| D4T(30)+3TC+EFV | 8.55 (7.21–10.12) | 8.34 (7.09–9.90) | 8.71 (8.21–9.20) | 8.47 (7.16–10.03) | 8.29 (7.01–9.79) | 19.88 (15.23–25.87) | 7.98 (6.41–9.94) | |
| AZT+3TC+NVP | 0.73 (0.67–0.80) | 0.72 (0.66–0.79) | 0.74 (0.71–0.78) | 0.74 (0.67–0.81) | 0.72 (0.65–0.79) | 0.74 (0.66–0.83) | 0.75 (0.68–0.83) | |
| AZT+3TC+EFV | 1.19 (1.02–1.40) | 1.19 (1.01–1.39) | 1.19 (1.16–1.23) | 1.21 (1.03–1.42) | 1.21 (1.03–1.40) | 1.27 (1.03–1.56) | 1.09 (0.91–1.30) | |
| TDF+3TC+NVP | 2.41 (2.36–2.47) | 2.46 (2.40–2.51) | 2.46 (2.42–2.50) | 2.45 (2.40–2.51) | 2.50 (2.44–2.55) | 3.58 (3.45–3.70) | 2.29 (2.23–2.34) | |
| TDF+3TC+EFV | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | |
| Other first lines | 1.97 (1.90–2.04) | 1.97 (1.91–2.04) | 1.88 (1.83–1.93) | 1.89 (1.82–1.95) | 1.89 (1.83–1.96) | 2.44 (2.32–2.57) | 1.61 (1.54–1.68) | |
| Second line | 0.46 (0.42–0.49) | 0.45 (0.42–0.49) | 0.45 (0.43–0.47) | 0.44 (0.41–0.48) | 0.44 (0.41–0.47) | 0.39 (0.36–0.42) | 0.48 (0.44–0.52) | |
| Tuberculosis status at ART initiation | Negative | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| Positive | 2.14 (2.05–2.24) | 2.13 (2.04–2.23) | 2.03 (1.99–2.09) | 2.02 (1.94–2.11) | 2.01 (1.93–2.10) | 2.66 (2.50–2.83) | 1.53 (1.45–1.62) | |
| Not assessed | 0.58 (0.56–0.59) | 0.59 (0.57–0.61) | 0.60 (0.59–0.60) | 0.60 (0.58–0.62) | 0.61 (0.59–0.63) | 0.51 (0.49–0.53) | 0.60 (0.58–0.62) | |
| Body functional status at ART initiation | Working | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) | 1 (reference) |
| Ambulatory | 1.22 (1.19–1.24) | 1.23 (1.20–1.26) | 1.23 (1.21–1.26) | 1.23 (1.20–1.27) | 1.25 (1.22–1.28) | 1.28 (1.23–1.32) | 1.08 (1.05–1.11) | |
| Bed ridden | 1.34 (1.17–1.53) | 1.33 (1.16–1.52) | 1.32 (1.29–1.35) | 1.34 (1.16–1.53) | 1.32 (1.15–1.51) | 1.42 (1.18–1.72) | 0.64 (0.54–0.75) | |
| AIC | 196 416.4 | 379 948.9 | 445 559.7 | |||||
| BIC | 380 197.6 | 445 819.3 | ||||||
| DIC | 379 925.9 | |||||||
Bold face=low values of the information criterion.
*District and mission hospitals.
†Provincial and referral hospitals.
AIC, Akaike’s information criterion; ART, antiretroviral therapy; AZT, zidovudine; BE, Bayesian estimation; BIC, Bayesian information criterion; CC, complete case; DIC, deviance information criterion; D4T, stavudine; EFV, efavirenz; MI, multiple imputation; MLE, maximum likelihood estimation; NVP, nevirapine; 3TC, lamivudine; TDF, tenofovir.