We describe factors determining retention and survival among HIV-infected children and adolescents engaged in two health care delivery models in Kampala, Uganda: one is a community home-based care (CHBC) and the other is a facility-based family-centred approach (FBFCA). This retrospective cohort study reviewed records from children aged from 0 to 18 years engaged in the two models from 2003 to 2010 focussing on retention/loss to follow-up, mortality, use of antiretroviral therapy (ART), and clinical characteristics. Kaplan Meier survival curves with log rank tests were used to describe and compare retention and survival. Overall, 1,623 children were included, 90.0% (1460/1623) from the CHBC. Children completed an average of 4.2 years of follow-up (maximum 7.7 years). Median age was 53 (IQR: 11–109) months at enrolment. In the CHBC, retention differed significantly between patients on ART and those not (log-rank test, adjusted,
Sub-Saharan Africa (SSA) is home to the vast majority of infants, children, and adolescents living with HIV and morbidity and mortality remain high [
Significant child mortality can be averted if antiretroviral therapy (ART) is started early [
Retention in care while awaiting ART eligibility can also be a challenge. As an illustration, retention varied from 71% to 95% and 62% to 93% at 12 and 24 months, respectively, among children and adolescents in ART programmes in several countries of SSA [
The present study focuses on retention and survival in two different ART delivery models for HIV-infected children and adolescents in Kampala, Uganda. One is a facility-based, family-centred approach (FBFCA) adopted by the mother to child transmission (MTCT)-Plus programme of the Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration. The other is a community home-based care (CHBC) implemented by the children’s HIV programme of the Home Care Department of Nsambya Hospital. The American Academy of Paediatrics defined family-centred care as based on the understanding that the family is the child’s primary source of strength and support [
Factors that determine retention and survival of HIV-infected children and adolescents in these health care models are not well understood. The present study therefore aims at identifying factors that determine these outcomes for the CHBC of Nsambya Hospital and the FBFCA of MU-JHU. We also examine pre-ART deaths among children and adolescents in the CHBC to compare mortality rates prior to and after ART initiation and to ascertain whether children experiencing mortality prior to initiating ART had met the 2010 WHO [
This retrospective cohort study covered eight years of records review (2003 to 2010) from two facilities implementing HIV paediatric programmes in Kampala, Uganda. They included the children’s HIV programme of the Home Care Department of Nsambya Hospital, which uses community home-based care (CHBC) and the MTCT-plus programme of MU-JHU Research Collaboration, which adopts a facility-based family-centred approach (FBFCA). Prior to the study, all children in the FBFCA had been initiated on ART; thus, the record review at the FBFCA involved only children on ART. The facilities are both private-not-for-profit but differ in service delivery approaches, including catchment areas and enrolment practices. The study population included all HIV positive infants, children, and adolescents aged 0–18 years, enrolled in both programmes over the study period. Services are generally free of charge under both models.
The FBFCA of MU-JHU Collaboration was established in 2003 with funding from Columbia University. Its catchment area includes Kampala and Wakiso districts and covers approximately 20 km radius from Mulago hospital in Kampala. Enrolment into the FBFCA occurred between 2003 and 2005 and targeted all HIV-infected family members as a unit. However, HIV-infected pregnant women in PMTCT served as the starting point for identifying other infected family members such as infants, children, and spouses or partners to be enrolled into care. Eligibility of the women included being pregnant, testing HIV positive, attendance of PMTCT clinic, disclosure of HIV status to spouse or partner, willingness to be home visited, and living within 20 km radius from Mulago Hospital. The FBFCA offered comprehensive HIV care, including early infant diagnosis (EID), treatment and psychosocial support services, other medical services, and routine follow-up to eligible women and their families. All children enrolled in the study had been initiated on ART prior to the study start date, in contrast to the CHBC. The programme has a uniform design that has been implemented in many countries. Although funding ended in December 2011, the families continue to be followed in a family care approach with funding from the US President’s Emergency Plan for AIDS Relief (PEPFAR).
The CHBC also started in 2003 and it integrates facility-based care with home-based care using community involvements as important linkages to decentralize HIV services. It has a catchment area covering four districts: Kampala, Wakiso, Mukono, and Mpigi within 21 km radius from Nsambya hospital. In contrast to the FBFCA, children and adolescents in the CHBC were identified directly for participation. The components of the CHBC, details of enrolment practice, pre-ART care, and ART care packages, as well as patient tracking system, have been described in an earlier work [
Both health care models share some common elements such as providing additional support including nutritional supplements, patient education, and counselling of patients and their caregivers. Additionally, peer support groups for both adults and children have been developed to promote emotional support. Other components of psychosocial support include financial assistance for income generating activities, a music, dance, and drama group, and home visiting to track defaulting patients. Furthermore, the FBFCA trains peer-educators to provide support and help in the clinics.
Patients were followed up routinely using similar appointment systems, standard guidelines, and procedures. Generally, children on ART had monthly clinic visits under both models, while visits for pre-ART patients depended on their clinical conditions and varied between one month under the CHBC and 3–6 months under the FBFCA. Initiation of ART was based on the Ugandan National ART guidelines that are adopted from the WHO guidelines [
The main study outcomes were (a) retention in care, (b) deaths among patients on ART, and (c) pre-ART deaths (deaths before ART initiation) among patients in the CHBC programme. Death was ascertained through medical records and verbal autopsies carried out by trained community volunteers and counsellors. Retention was defined as the proportion of patients known to be alive (either by patient record review or by telephone calls or home visits) and in care at the end of the follow-up period. We defined loss to follow-up (LTFU) as 90 days or more (if on ART) and 180 days or more (if not on ART) without contact since the last clinic appointment. Attrition included deaths and LTFU. Known transfers to continue ART or care at other facilities were not considered as attrition.
We analysed factors that determined retention and mortality among children and adolescents enrolled in the two HIV service delivery models described above. We used frequency distributions, medians, and interquartile range (IQR) to describe baseline characteristics and compared these using Chi-square and Wilcoxon Rank-Sum tests, respectively. The baseline characteristics included age groups (at enrolment), gender, CD4 cell counts, CD4 percent, growth responses (weight-for-age and height-for-age
Ethical clearance was approved by the MildMay Institutional Review Board and Ethics Committee, and the study was registered by the Uganda National Council for Science and Technology (UNCST, ref. no. HS 1021). The relevant committees waived informed consent. The study was funded by the University of Padua and supported by Casa Accoglienza alla vita padre Angelo and PENTA Foundation.
Overall, 1,623 infants, children, and adolescents were included in the analyses, 90.0% (1460/1623) were in the CHBC (Table
Baseline characteristics of HIV-infected children and adolescents in a community home-based care model and a facility-based family-centred approach, Kampala, Uganda, 2003–2010.
Characteristics | Community home-based care approach |
Facility-based family-centred approach |
Total |
|
---|---|---|---|---|
|
|
|
||
Age (months) | ||||
<12 | 371 (25.4) | 54 (33.1) | 425 (26.2) | 0.097 |
12–35 | 228 (15.6) | 21 (12.9) | 249 (15.3) | |
36–59 | 173 (11.9) | 23 (14.1) | 196 (12.1) | |
60+ | 688 (47.1) | 65 (38.9) | 753 (46.4) | |
Gender | ||||
Female | 746 (51.1) | 87 (53.4) | 833 (51.3) | 0.581 |
Male | 714 (48.9) | 77 (46.6) | 790 (48.7) | |
Cd4 count and percent | ||||
Median CD4 (IQR) | 393 (51–762) | 727 (442–1348) | 438 (78–824) | <0.001 |
Median CD4% (IQR) | 5.8 (0.1–16.9) | 17.0 (10.0–25.0) | 8.1 (0.2–18.1) | <0.001 |
Level of immunosuppression by CD4 | ||||
Not significant | 273 (24.4) | 39 (25.0) | 312 (24.4) | 0.424 |
Mild | 122 (10.8) | 21 (13.5) | 143 (11.1) | |
Advanced | 131 (11.6) | 12 (7.7) | 143 (11.1) | |
Severe | 605 (53.5) | 84 (53.8) | 689 (53.5) | |
On ART | ||||
Yes | 441 (30.2) | 163 (100) | 604 (37.2) | <0.001 |
No | 1019 (69.8) | 0 (0.0) | 1019 (62.8) | |
Age at ART initiation (months) | ||||
Median (IQR) | 91.0 (48.9–135.5) | 45.9 (6.5–85.0) | 78.6 (34.0–124.6) | <0.001 |
WHO clinical staging | ||||
I-II | 1258 (86.4) | 157 (96.9) | 1415 (87.5) | <0.001 |
III-IV | 198 (13.6) | 5 (3.1) | 203 (12.5) | |
Growth response weight-for-age | ||||
≤−2SD | 430 (37.4) | 24 (16.9) | 454 (35.2) | <0.001 |
>−2SD | 719 (62.6) | 118 (83.1) | 837 (64.8) | |
Height-for-age | ||||
≤−2SD | 508 (44.3) | 43 (30.3) | 551 (42.8) | 0.001 |
>−2SD | 639 (55.7) | 99 (69.7) | 738 (57.2) |
An overall average of 4.2 years of follow-up was observed (maximum 7.7 years). Retention in care was substantially and significantly higher among children on ART compared to those not on ART within the CHBC model (
Retention in care, HIV-infected children and adolescents in a facility-based family centred approach (FBFCA) and a community home-based care (CHBC) model, on and not on ART, Kampala, Uganda, 2003–2010. It compares retention among patients on ART in the two models, and it was higher in the CHBC.
In univariate analysis, attrition was significantly associated with model of care (HR: 0.40, 95%CI: 0.23–0.70,
At multivariate modelling, the risk of attrition was significantly associated with model of care (HR: 0.29, 95% CI: 0.12–0.70,
Factors associated with
Characteristics | Unadjusted (univariate analysis) | Adjusted* (multivariate analysis) | ||
---|---|---|---|---|
HR‡ (95% CI) |
|
HR‡ (95% CI) |
| |
Model of care | ||||
FBFCA | 1 | 0.002 | 1 | 0.006 |
CHBC | 0.40 (0.23–0.70) | 0.29 (0.12–0.70) | ||
Age (months) | ||||
<12 | 1 | 1 | ||
12–35 | 0.73 (0.31–0.70) | 0.465 | 1.95 (0.39–9.89) | 0.419 |
36–59 | 0.29 (0.09–0.87) | 0.028 | 1.63 (0.18–15.17) | 0.664 |
60+ | 0.43 (0.22–0.85) | 0.015 | 3.19 (0.27–37.03) | 0.354 |
Gender | ||||
Female | 1 | 0.675 | ||
Male | 1.13 (0.64–1.99) | |||
Cd4 count and percent | ||||
CD4† | 0.86 (0.69–1.06) | 0.162 | ||
CD4%† | 1.00 (0.57–1.77) | 0.992 | ||
Level of immunosuppression by CD4 | ||||
Not significant | 1 | 1 | ||
Mild | 4.17 (1.31–13.31) | 0.016 | 4.66 (1.21–17.98) | 0.026 |
Advanced | 0.87 (0.16–4.73) | 0.868 | 0.89 (0.09–9.12) | 0.921 |
Severe | 3.14 (1.10–8.94) | 0.032 | 3.16 (0.81–12.39) | 0.099 |
Age at ART initiation | ||||
Months† | 0.74 (0.61–0.90) | 0.003 | 0.67 (0.31–1.44) | 0.309 |
WHO clinical staging | ||||
I-II | 1 | 0.309 | ||
III-IV | 1.52 (0.68–3.38) | |||
Growth response |
||||
≤−2SD | 1 | 0.006 | 1 | 0.002 |
>−2SD | 0.40 (0.21–0.77) | 0.31 (0.15–0.65) | ||
Height-for-age | ||||
≤−2SD | 1 | 0.060 | ||
>−2SD | 0.54 (0.28–1.03) |
*only factors significant at univariate or borderline were considered into multivariate.
At univariate analysis, the risk of attrition in the CHBC was significantly associated with age group 36–59 months (HR: 0.46, 95% CI: 0.33–0.64,
At multivariate analysis, the risk of attrition was significantly associated with CD4 cell count (HR: 0.84, 95% CI: 0.74–0.95,
Factors associated with
Characteristics | Unadjusted (univariate analysis) | Adjusted* (multivariate analysis) | ||
---|---|---|---|---|
HR‡ (95% CI) |
|
HR‡ (95% CI) |
| |
ART | ||||
No | 1 | <0.001 | 1 | <0.001 |
Yes | 0.06 (0.04–0.09) | 0.04 (0.02–0.08) | ||
Age (months) | ||||
<12 | 1 | 1 | ||
12–35 | 0.85 (0.65–1.10) | 0.218 | 2.18 (0.97–4.92) | 0.060 |
36–59 | 0.46 (0.33–0.64) | <0.001 | 1.65 (0.74–3.69) | 0.225 |
60+ | 0.44 (0.35–0.56) | <0.001 | 1.38 (0.63–3.01) | 0.418 |
Gender | ||||
Female | 1 | 0.243 | ||
Male | 1.11 (0.93–1.33) | |||
Cd4 count and percent | ||||
CD4† | 0.85 (0.78–0.93) | <0.001 | 0.84 (0.74–0.95) | 0.006 |
CD4%† | 0.80 (0.66–0.96) | 0.016 | ||
Level of immunosuppression by CD4 | ||||
Not significant | 1 | |||
Mild | 0.99 (0.66–1.49) | 0.968 | ||
Advanced | 0.89 (0.59–1.34) | 0.590 | ||
Severe | 1.87 (1.44–2.43) | <0.001 | ||
Age at ART initiation | ||||
Months† | 0.85 (0.66–1.10) | 0.209 | ||
WHO clinical staging | ||||
I-II | 1 | <0.001 | 1.94 (1.34–2.80) | <0.001 |
III-IV | 1.84 (1.47–2.29) | |||
Growth response weight-for-age | ||||
≤−2SD | 1 | 0.007 | ||
>−2SD | 0.76 (0.62–0.93) | |||
Height-for-age | ||||
≤−2SD | 1 | <0.001 | 0.81 (0.60–1.09) | 0.162 |
>−2SD | 0.69 (0.56–0.84) |
*only factors significant at univariate or borderline were considered into multivariate.
When retention was stratified by age groups among children and adolescents in the two models, the difference was only significant in the age group 12–35 months (
Retention stratified by age group among HIV-infected children and adolescents in a CHBC and a FBFCA in Kampala, Uganda (2003–2010). It stratifies retention by age groups in the two models. Age groups 12–35 months and 36–59 months appear to be confounders for retention.
There was no significant difference in survival of children and adolescents receiving ART between the two models (Figure
Survival on antiretroviral therapy (ART) among HIV-infected children and adolescents in a facility-based family-centred approach (FBFCA) and a community home-based care (CHBC) model, Kampala, Uganda, 2003–2010. (a) compares survival trends among children and adolescents on ART in both models and shows that they were not significantly different. On the other hand, (b) shows that survival trends differed significantly between patients on ART in the CHBC and those not receiving ART (pre-ART).
When survival was stratified by age groups in the two models, there was no significant difference, except a borderline effect for age group 36–59 months (log rank test:
Survival stratified by age group among HIV-infected children and adolescents in a CHBC and a FBFCA in Kampala, Uganda (2003–2010). It stratifies survival by age groups in the two models. Apart from a borderline effect for age group 36–59 months (
Sixty deaths were recorded among children in the CHBC who were not on ART (Table
Deaths among children and adolescents in community home-based care who were not on ART classified according to whether the US 2011 or WHO 2010 initiation guidelines were met or not, Kampala, Uganda, 2003–2010.
Age group for US (months) |
|
US CDC guidelines1 for ART met | Age group for WHO (months) |
|
WHO guidelines2 for ART met |
---|---|---|---|---|---|
<12 | 11 | 11 (100%) | <12 | 11 | 11 (100%) |
12–35 | 13 | 10 (76.9%) | 12–24 | 9 | 9 (100%) |
36–59 | 4 | 3 (75.0%) | 24–59 | 8 | 5 (62.5%) |
60+ | 32 | 25 (78.1%) | >60 | 32 | 23 (71.9%) |
|
|||||
Overall | 60 | 49 (81.7%) | Overall | 60 | 48 (80.0%) |
Source: WHO and US treatment guidelines.
1US CDC 2011 criteria for ART initiation: <12 months all should be on ART; 12–35 months if CD4 < 1000 or <25%; 36–59 months if CD4 < 750 or <25%; 60+ months if CD4 < 500.
2WHO 2010 criteria for ART initiation: <12 months all should be on ART; 12–24 months all should be ART; 24–59 months if CD4 < 750 or <25%; 60+ months if CD4 < 350.
We found that by far the most significant factor determining retention in care among infants, children, and adolescents with HIV was being on ART. Once on ART, there was no difference in survival between the CHBC and FBFCA. In addition to ART initiation directly promoting survival [
We also observed that the majority of the pre-ART deaths occurred in children and adolescents who had met the 2011 US and the 2010 WHO treatment guidelines but did not initiate therapy for various reasons. This finding illustrates the failure of timely initiation of ART, which in turn may be linked to programmes that are not tailored to meet the needs of the infected child and family. For instance, at the time of this study, there were no PMTCT/EID services within the CHBC. That scenario, coupled with delayed HIV diagnosis, drug stock-outs, logistic challenges, and fragile linkages to ART initiation and psychosocial support services may have resulted in considerable LTFU and deaths (Figures
We also saw that nearly one out of every five deaths occurred in children and adolescents who had not yet met eligibility for initiation according to local guidelines. As shown by the literature, significant clinical events do occur in HIV-infected children and adolescents even before meeting the previous guidelines [
Among patients on ART in both models, retention was higher in the CHBC. Factors that may explain this observation include decentralized voluntary counselling and testing and ART refills involving outreach clinics within the communities. In addition, ART patients in the CHBC have a “priority” tracking system within the clinics compared to patients not receiving ART, due to scanty resources [
We also noted that age was a confounder for retention but not survival (Figures
Additionally, we found that among patients receiving ART, attrition was significantly associated with model of care, mild immunosuppression, and being more underweight (Table
In terms of growth responses, we saw that children in the CHBC were significantly more underweight, whereas those in the FBFCA were significantly more stunted with some overlap. Although it is well recognized that HIV infection in children compromises growth responses, in Uganda, 39% and 16% of all children less than 5 years are stunted and underweight, respectively, demonstrating that important non-HIV contributors to stunting and wasting exist in particular high background rates of TB and other coinfections, food insecurity, and malnutrition [
We note potential limitations to our data and conclusions. First, the data were observational and based on programmatic information. Second, the two programmes should be interpreted in the context of reaching different populations of children and the direct comparisons are cautious. Patients were not randomized for one or the other model, but rather circumstances (such as distance to facilities) dictated what options were available. Third, some aspects of the interventions were shared by both models, such as guidelines for initiating ART and nutritional support and could be potentially confounding. Fourth, the high level of loss to follow-up among patients not on ART in the CHBC leaves much doubt on the final disposition of the children in that programme. We expect that many of the children lost to care may have died; however, the characteristics of those who died and those who may have accessed care elsewhere are not known [
We also acknowledge that our findings reflect data from programmes in one urban setting in East Africa and therefore may not be generalizable to family-centred approach and community home-based care models in other settings. Despite the limitations, we firmly believe that our findings remain valid and relevant.
We conclude that, irrespective of model of care, children receiving ART had better retention in care and therefore long-term survival. Encouragingly, if children were on ART, then their survival was as good, if not slightly better, in the CHBC compared to the FBFCA. Based on our observations, substantial improvement in child survival can be achieved in either a community-based or a family-care model as long as HIV-infected children are identified early and begun on ART. To ensure this occurs, early identification of HIV-infected children requires strong linkages of pregnant HIV-infected women to PMTCT services and active tracking to ensure all HIV exposed infants receive Polymerase Chain Reaction-based early infant diagnosis. Additionally, rapid early initiation of ART among HIV-infected infants and children is essential. We anticipate the move to early initiation of ART in all HIV-infected children and adolescents in resource-limited settings, irrespective of their CD4 cell counts, will improve survival.
Among ART patients in both models, attrition was significantly associated with model of care, mild immunosuppression, and being underweight. In the CHBC, attrition was significantly associated with CD4 cell count, WHO clinical stages III-IV, and absence of ART.
The authors declare that they have no conflict of interests.
W. Massavon conceived the study and participated in the drafting and editing of the paper, data analysis, and interpretation of the findings. L. Barlow-Mosha, L. Mugenyi, W. McFarland, and G. Gray participated in the data analysis, editing of the paper, and interpretation of findings. R. Lundin, P. Costenaro, M. M. Nannyonga, P. C. Namisi, and D. Wabwire participated in the drafting and editing of the paper. D. Bagenda and M. Mubiru participated in the data analysis. A. Mazza, S. Kironde, and D. Bilardi participated in editing the paper. M. Penazzato, P. Musoke, M. G. Fowler, and C. Giaquinto participated in editing of the paper and interpretation of findings. All authors read and approved the final paper.
This paper was developed through a Manuscript Writing Workshop organized by the NIH Office of AIDS Research-funded OCTAVE Project, NIMH-funded UCSF ITAPS Programme (R25MH064712-08), and the Fogarty International Centre AITRP Programme (D43TW00003). The authors are grateful to all the children and families enrolled in both programmes. The authors appreciate the support offered by the management of both institutions. The authors thank Peter Mudiope and Tobias Chirwa for assisting with data analysis. The authors thank the