Database records for a total of 6442 children younger than 16 years of age were screened for eligibility for the study. Children excluded were 1134 who commenced ART within 6 months of closure of the site database, 1381 who were documented as being ART experienced, 269 who had 0 days of follow-up time and 95 for whom it could not be definitively ascertained as to whether they received support from a PA or not. Thus, 3563 ART-naïve children were included in analyzes.
There were 323 (9.1%) and 3240 (90.9%) children who received and did not receive support from a PA, respectively (). At the start of treatment, PA-supported children had a higher proportion aged below 1 year, a higher proportion treated at PHC facilities, a lower proportion who were treated at rural facilities, lower proportions from Mpumalanga and Eastern Cape provinces and a lower proportion having Zidovudine (ZDV) instead of Stavudine included in the initial regimen. Baseline clinical status variables were equivalent between the groups. Patients supported by PAs had significantly fewer missing baseline TB treatment values (2 [0.6%] vs. 276 [8.5%]; p<0.0005), as well as fewer missing baseline immunological values (44 [13.6%] vs. 766 [23.6%]; p<0.0005).
Baseline characteristics of ART-naïve children beginning antiretroviral therapy
The total observation time was 4848 person-years, with median observation times of 18.5 months per child (IQR: 8.4 to 30.2) amongst children with PAs and 15.2 months per child (IQR: 8.2 to 22.4) amongst children without PAs. Using facility-level data, amongst children with and without PAs, 4 (1.2%) and 106 (3.3%) children were ascertained as having died during the study period, respectively, and 16 (5.0%) and 195 (6.0%) were LTFU, respectively. Patient retention (I – attrition) after 3 years of ART in children with PAs was 91.5% (95% CI: 86.8% to 94.7%) vs. 85.6% (95% CI: 83.3% to 87.6%) amongst children without PAs (logrank p=0.027) (). Amongst children aged below 2 years when starting ART, retention after 3 years was 92.2% (95% CI: 76.7% to 97.6%) vs. 74.2% (95% CI: 65.4% to 81.0%) in children with and without PAs, respectively (p=0.053; n=507; 52 [10.3%] PA-supported).
Kaplan-Meier estimates of retention in care for children with and without patient advocates. ART, antiretroviral therapy, PAs, patient advocates; CI, confidence interval.
Cumulative mortality based on facility-held data after three years of ART was 1.5% (95% CI: 0.5% to 4.1%) in children with PAs vs. 4.7% (95% CI%: 3.6% to 6.2%) amongst children without PAs (logrank p=0.032). Amongst all children LTFU, 93 (44.0%) had valid civil identification numbers, of whom 36 (38.7%) were registered as having died in the national registry by November 2010. The estimates of corrected mortality based on the weighted dataset after 3 years of ART were 3.7% (95% CI: 1.9% to 7.4%) amongst children with PAs vs. 8.0% (95% CI: 6.5% to 9.8%) amongst children without PAs (logrank p=0.060) (). Corrected mortality rates on ART were 1.6 deaths per 100 child-years (95% CI: 0.7 to 4.9) vs. 4.2 deaths per 100 child-years (95% CI: 3.5 to 5.1) in children with and without PAs, respectively (p=0.060). Amongst children aged below 2 years when starting ART, corrected mortality rates were 1.5 deaths per 100 child-years (95% CI: 0.5 to 10.5) vs. 7.7 deaths per 100 child-years (95% CI: 5.3 to 11.7) in children with and without PAs, respectively (p=0.12).
Figure 2 Weighted Kaplan-Meier estimates of corrected mortality for children with and without patient advocates. For patients who were lost to follow-up with available civil identification numbers, vital status was ascertained from the national death registry. (more ...)
In multivariable analyzes adjusting for all available baseline variables (), children with PAs had an independently reduced probability of attrition, adjusted hazard ratio (AHR) 0.57 (95% CI: 0.35 to 0.94; p=0.026) and a reduced probability of mortality (based on the weighted data), AHR 0.39 (95% CI: 0.15 to 1.04; p=0.060). Other baseline factors independently associated with mortality were age under 2 years (AHR 1.70 [95% CI: 1.01 to 2.85]), WAZ-scores below −3 (AHR 3.95 [95% CI: 2.38 to 6.56]), severe immunodeficiency (AHR 2.36 [95% CI: 1.27 to 4.64]) and receiving treatment for TB (AHR 2.37 [95% CI: 1.21 to 4.64]). Mortality was higher in KwaZulu-Natal and Mpumalanga provinces compared with that of the Western Cape. Mortality and attrition were equivalent between PHC and hospital facilities.
Characteristics at the start of ART associated with mortality and attrition in multivariable Cox regression modelsa.
The improved outcomes in PA-supported children remained apparent when sensitivity analyses were performed. When death registry information was ignored and vital status based on site-level ascertainment only, PA-supported children had an independently reduced probability of death, AHR 0.26 (95% CI: 0.09 to 0.75; p=0.013, n=3563). Analyses limited to the sites at which PAs were active included 1577 (83.0%) patients who did not receive PA support. In multivariable models, attrition and corrected mortality were both independently reduced in PA-supported children at these sites; AHR 0.49 (95% CI: 0.28 to 0.87, p=0.015, n=1900) and AHR 0.24 (95% CI: 0.07 to 0.76, p=0.015, n=1848), respectively.
Analyses limited to the 32 PHC clinics included 1507 children, with 306 (20.3%) receiving PA support. After 36 months of ART, retention in care was 90.1% (95% CI: 85.9% to 94.3%) in patients with PAs vs. 80.0% (95% CI: 73.0% to 85.3%) in patients without PAs, respectively (logrank p=0.036). In multivariable models, attrition and corrected mortality were independently reduced in PA-supported children, AHR 0.57 (95% CI: 0.34 to 0.97; p=0.039) and AHR 0.37 (95% CI: 0.13 to 1.06; p=0.065), respectively.
The proportion of patients achieving virological suppression was equivalent between children with and without PA support. Virological suppression was 78.8% (95% CI: 71.7% to 85.9%; n=132) and 82.4% (95% CI: 80.4% to 84.4%; n=1409) (p=0.30) in children with and without PAs, respectively, after 6 months of ART; and after 12 months it was 80.6% (95% CI: 73.0% to 88.1%; n=108) vs. 78.5% (95% CI: 75.9% to 81.1%; n=959) (p=0.62) in children with and without PAs, respectively. Virological suppression was also equivalent between PHC and hospital facilities (p=0.10 after 6 months; p=0.85 after 12 months).
Median CD4 percentage increases were equivalent between children with and without PA support; overall increases were 8.0% (IQR: 4.0% to 12.7%; p=0.57; n=972) after six months and 11.1% (IQR: 6.8% to 17.1%; p=0.43; n=652) after 12 months of ART. Median CD4 percentage increases were also equivalent between PHC and hospital facilities (p=0.86 after 6 months; p=0.87 after 12 months).