This study describes the implementation and treatment outcomes of a paediatric HIV care network linking public sector provincial and community ART programs in northern Thailand. Findings suggest that despite difficulties associated with the administration of ART for HIV-infected children, it is possible to achieve and sustain beneficial outcomes in a decentralized ART program in resource-limited settings by strengthening a network of tertiary- and community-based care providers. This is demonstrated by high retention rates and clinical and immunological improvements, despite the fact that most children initiated ART only at the advanced disease stage.
The study cohort represents a first group of children with perinatally acquired HIV-infection in Thailand before the national PMTCT was implemented in 2000 (86% born before 2000). The older age and severe immunological suppression at ART initiation in this cohort were likely due to late diagnosis and referral for ART initiation; the national program for early infant diagnosis started in 2007, and full access to the national ART program started in 2003 to 2004 [10
]. Therefore, 92% of children in this cohort initiated ART in or after 2003. The finding that children at CHs had significantly lower baseline WAZ and more advanced stage HIV infection is likely due to the abovementioned reasons and the lower in socio-economic status of families living in more rural areas.
In this study, adherence level remained high among children in follow-up at both CRH and CHs, and much of the success of the paediatric care network may be attributed to good adherence. Adherence requires special attention to children because of the need for caregiver support, paediatric formulations and palatable medications with easy dosing schedules. Paediatric treatment is made more challenging as a result of the high level of adherence required to prevent sub-optimal viral suppression, a risk factor for development of HIV drug resistance [18
] and mortality [20
]. Although comparison across studies should be done with caution, this study reported better adherence than most paediatric treatment programs, with several studies reporting 50 to 80% adherence [21
]. The intensity and support given to patients and caregivers in this program may explain the high level of adherence and suggest that multiple approaches combining educational and behavioural components are useful in achieving desirable adherence levels [24
Weight gain, VL and CD4% responses to ART in this cohort compare favourably to other studies. A prospective cohort study of 107 children in the neighbouring Chiang Mai province reported similar responses [25
]. In the Paediatric AIDS Clinical Trials Group (PACTG) 219 study, 33% of children who initiated treatment with CD4<5% reached normal levels after three years of treatment, compared to 45% after four years in our study [26
]. Both the Chiang Mai and PACTG studies were conducted in settings where clinical care was provided by paediatricians; obtaining similar results in a community-based program with non-paediatric and non-physician staff is quite encouraging.
The mortality rate of 4.1/100 child-years of follow-up with most deaths occurring within the first three months of treatment was comparable to other paediatric cohorts in resource-limited countries [8
], as was the association between advanced HIV-related disease and mortality [9
]. These findings underscore the importance of early identification of HIV-infected children and timely initiation of ART. However, the finding that most children who stayed in follow-up had viral suppression and remained on first-line ART through 48 months confirms the reported high level of ART adherence and the importance of intensive adherence support in this program [25
]. The absence of deaths among children followed up at CHs is not surprising given that patients were referred when clinically stable, typically at least six months after ART initiation.
Although not a direct comparison of tertiary and CH treatment outcomes, study results are of interest, especially given the strategy of WHO [31
] to shift tasks to less specialized healthcare workers and thereby increase access to care. The success of this model highlights its potential for other settings with high HIV burdens and limited resources, such a sub-Saharan Africa. Similar findings on improvement of clinical and virological outcomes for decentralized care for both adults and children have been reported in several African countries [32
]. Of note, the provision of adherence support by non-clinical staff, mainly PLHIV, could off-set the limited number of trained healthcare workers. The level of adherence support in this program, however, is intensive, and replicating it in less developed countries with higher HIV burdens may prove challenging.
Although these results compare favourably with other published literature, there were several limitations. Missing data was probably due to a retrospective study designed and utilized routine program data. However, in the multiple imputative analyses, results and overall interpretations were not changed. Some data, such as VL, were limited because of programmatic reasons, and findings may not be generalizable to the entire cohort. Although the rates and causes of mortality are consistent with other studies, the incompleteness of data limits the conclusions about cause-specific mortality. Additionally, although efforts were made to objectively compare treatment outcomes between children in follow-up at CRH and CHs, the unmatched design, differences in baseline WAZ, referral of patients based on the clinician's judgment and the willingness of the caregiver to have the child receive ART in the CH, all may have limited the ability to compare the two groups. Nevertheless, baseline age, gender and clinical characteristics, with the exception of WAZ, were similar between the groups. Finally, few young children and infants in the entire cohort and only ART-naïve children were included in the sub-group analysis; thus, findings may not be generalizable to younger and ART-experienced children. The median age of this cohort and the absence of young infants reflect the increased uptake of PMTCT interventions [36
] with only 41 children (10%) in this cohort born with HIV-infection after 2000.
In summary, this study demonstrates improvements in clinical immunological and virological outcomes in children followed up in a tertiary and community-based ART network, over a long follow-up period. This study also suggests that paediatric HIV care can be shifted from tertiary to community-based settings when tertiary care staff initiate ART, train community teams and consistently monitor and support community staff work. This may help increase patient's access to treatment, while at the same time reducing workload at overburdened tertiary hospitals.