Abstract
Background
There are limited data on opportunistic infections (OI) and factors associated with their occurrence after highly active antiretroviral therapy (HAART) in Asian children. The use of HAART in Asia started much later than in developed countries and therefore reported findings may not be fully applicable to the pediatric HIV epidemic in Asia.
Methods
Retrospective and prospectively collected data from the TREAT Asia Pediatric HIV Observational Database cohort study from March 1993 to March 2009 were analyzed. OIs were defined according to WHO clinical staging criteria, and incidence rates calculated. Factors associated with the incidence of severe OIs were analyzed using random effects Poisson regression modeling.
Results
Of 2280 children in the cohort, 1752 were ever reported to have received ART, of whom 1480 (84%) started on HAART. Before commencing any ART, OIs occurred at a rate of 89.5 per 100 person-years. The incidence rate was 28.8 infections per 100 person-years during mono- or dual-therapy, and 10.5 infections per 100 person-years during HAART. The most common OIs both before and after ART initiation were recurrent upper respiratory tract infections, persistent oral candidiasis, and pulmonary tuberculosis. The incidence rates of WHO clinical stage 3 or 4 OIs after HAART were highest among children <18 months of age and those with low weight-for-age z scores, CD4 cell percentage <15%, and WHO stage 3 at HAART initiation.
Conclusions
Despite dramatic declines in their incidence, OIs remained important causes of morbidity after HAART initiation in this regional cohort of HIV-infected children in Asia.
Keywords: Asia, pediatric HIV, HAART, opportunistic infection
INTRODUCTION
In the past decade, dramatic declines in the incidence of and mortality related to opportunistic infections (OI) in HIV-infected adults1, 2 and children3-6 have been observed. These reductions have resulted from the advent of highly active antiretroviral therapy (HAART) in the mid-1990s and routine use of antimicrobial prophylaxis. In Switzerland, Ledergerber, et al examined a population-based prospective cohort of 2410 adults starting therapy between 1995 and 1997 and found that the incidence of any OI decreased from 15.1 per 100 person-years in the six months before therapy to 7.7 in the first three months after starting treatment and to 2.6 in the following six months.1 The US Perinatal AIDS Collaborative Transmission study, in an analysis of 364 HIV-infected children 17 years or younger, reported that incidence rates for all documented OIs had decreased from 14.4 per 100 person-years during the pre-HAART era to 1.1 after HAART.4 In Brazil, the incidence of OIs among children and adolescents was 18.3 per 100 person-years in the pre- and 2.6 in the post-HAART periods.5
In Asia, regional HAART scale-up in HIV-infected children began according to the current World Health Organization (WHO) and United States Department of Health and Human Services (US DHHS) recommendations in early 2000s. A number of studies have reported a decline in mortality and hospitalizations after receiving HAART in Asian children within individual site cohorts.7, 8 Specific data regarding regional trends in OIs and the factors associated with their occurrence after HAART are limited. In this study we examined the incidence rates and patterns of OI occurrence, and risk factors for developing OIs in HIV-infected children followed in the Therapeutic Research, Education and AIDS Training (TREAT) Asia Pediatric HIV Observational Database (TApHOD).
MATERIALS AND METHODS
TApHOD is an ongoing collaborative observational cohort study of infants and children with HIV in the Asia-Pacific region which has been described elsewhere.9 This analysis included patient data from 14 participating clinics in Cambodia (n=3), India (n=1), Indonesia (n=1), Malaysia (n=4), and Thailand (n=5). Patients were eligible for inclusion in TApHOD if age ≤18 years and conclusively diagnosed with HIV, using age-appropriate testing or through a presumptive clinical diagnosis of HIV infection defined as meeting WHO criteria for initiating antiretroviral therapy (ART) 10. Prospective data collection for TApHOD commenced in 2008, with retrospective data provided where available. Data collection included information on demographic characteristics, anthropometric parameters, CD4 T cell and HIV viral load levels, other laboratory tests, ART histories, OIs, and causes of death. Data were anonymized and transferred to the Kirby Institute, Sydney, Australia, every six months for quality control and assurance procedures to verify the consistency and reliability of data. Ethical approval was obtained from all related institutional review boards (IRB) for the participating sites; and the data management (Kirby Institute) and the coordinating centers (TREATAsia/amfAR). Because data were observational and anonymously collected, informed consent was waived unless locally required. The study population for this analysis included all patients enrolled in TApHOD between March 1993 and March 2009.
ART regimens were classified as mono- or dual-nucleoside reverse transcriptase inhibitor (NRTI) therapy, and HAART as triple-NRTI therapy, or two NRTIs plus a non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). OIs were those used to define WHO clinical stages 2, 3 and 4.11 Severe anemia was defined according to US DHHS guidelines as a hemoglobin level <7.5 g/dL.12 For height-for-age z score (HAZ), the WHO 2006/2007 Child Growth Standards13 were used. WHO 1977 Standards were used for weight-for-age z scores (WAZ), to allow for scoring children >10 years of age.14 Baseline values were taken as the values most closely preceding the HAART initiation date within the prior three months. For reporting CD4 percent at the time of a specific OI, the closest value within three months before and one month after the occurrence of that OI was used.
Statistical Methods
Baseline values at the time of ART initiation were reported as means (standard deviation, SD) and frequencies (%), and the differences between groups (started on HAART vs. mono- or dual-therapy) were tested using Chi-squared tests (Fisher's exact or Cochran-Armitage test for trend) and Kruskal Wallis testing as appropriate. The incidence of OI was calculated by dividing the total number of events observed by the total person-years of observation forming the risk period. Children were considered at risk for developing OIs from the date of starting their first ART regimen or their first clinic visit for those who never received ART, until their death or their last reported clinic visit. The OI incidence rate (IR) was calculated: (1) during the period of not receiving any ART (2) during HAART use for children who started their treatment with these regimens and (3) during mono- or dual-therapy for children who started their treatment with these regimens. For children who started on mono- or dual-therapy and later switched to HAART, the date of switch was considered the end of study follow-up. We calculated the probability of developing stage 3 and 4 OIs during the HAART period using the Kaplan-Meier method. These estimates were plotted by baseline CD4 percentage strata.
We assessed factors associated with increased incidence of severe OI infections (WHO stage 3 and 4) by using random effects Poisson regression modeling in order to allow for the repeated-event nature of the data for children with multiple OI events. Covariates assessed for inclusion in the multivariate model were sex, age, HAART regimen, CD4 percentage and cell count, WHO clinical staging, WAZ, HAZ, and anemia. CD4 percentage was considered a time-dependent variable and the remaining variables were fixed factors assessed at baseline. Only patients who initiated their first treatment with HAART were included in the risk factor analysis. Covariates were entered into the model if they had a P value of <0.10 in the univariate analysis. The forward step-wise method was used to assess the contribution to the model. Independent variables were considered significant at the P value <0.05 level. Stata version 9 (StataCorp LP, College Station) was used for all statistical analyses.
RESULTS
Demographic information
Between March 1993 and March 2009, 2280 children were enrolled in TApHOD, of whom 1752 (77%) had ever received ART. Of these, 1480 (84%) initiated treatment with HAART and 272 (16%) started with mono- or dual-NRTI therapy (Table 1). Eighty-nine percent of children on mono- or dual-therapy started their first treatment between 1995 and 2004, while most of patients who started with HAART (1444; 97.5%) received their first regimen after 2002. Those who started with HAART were significantly older than those on mono- or dual-therapy (median age: 7.0 vs 3.3 years; P <0.0001); a higher proportion had pre-ART CD4 counts of <50 cells/mm3 (26.2% vs 7.7%; P <0.0001), pre-ART CD4 <15% (59.4% vs 5.4%; P <0.0001), experienced WHO clinical stage 4 (27.3% vs 14%; P <0.0001), and had lower WAZ and HAZ (P <0.002 and P <0.03, respectively). At the closure of the dataset for analysis, 26% of the children who started with mono- or dual-therapy had remained on mono- or dual-therapy.
Table 1.
Characteristics of HIV-infected children at antiretroviral therapy initiation in TApHOD
| Characteristics | HAART (n=1480) | mono/dual NRTI (n=272) | P-value |
|---|---|---|---|
| Sex: Male | 748 (50.5) | 141 (51.8) | 0.7 |
| Age | <0.0001 | ||
| <18 months | 159 (10.7) | 117 (43.0) | |
| 18-59 months | 313 (21.2) | 84 (30.9) | |
| 60-155 months | 930 (62.8) | 64 (23.5) | |
| ≥156 months | 78 (5.3) | 7 (2.6) | |
| Mean age, years | 7.0 (3.8) | 3.3 (3.3) | |
| Ethnicity | <0.0001 | ||
| Thai | 1061 (71.7) | 205 (75.4) | |
| Indonesian | 113 (7.6) | 21 (7.7) | |
| Indian | 86 (5.8) | 37 (13.6) | |
| Malay | 85 (5.7) | 4 (1.5) | |
| Khmer | 68 (4.6) | 1 (0.4) | |
| Others | 45 (4.5) | 4 (1.5) | |
| CD4 cell count (cells/mm3) | <0.0001 | ||
| 0-49 | 387 (26.2) | 21 (7.7) | |
| 50-199 | 284 (19.2) | 20 (7.4) | |
| ≥200 | 521 (35.2) | 138 (50.7) | |
| Unknown | 288 (19.5) | 93 (34.2) | |
| Mean CD4 count (cell/mm3) | 326.4 (488.2) | 932.1 (957.2) | |
| CD4 cell percentage | <0.0001 | ||
| <15% | 879 (59.4) | 69 (5.4) | |
| 15-24% | 191 (12.9) | 64 (23.5) | |
| ≥25% | 68 (4.6) | 35 (12.9) | |
| Unknown | 342 (23.1) | 104 (38.2) | |
| Mean (SD) | 9.1 (8.4) | 16.9 (10.2) | |
| WHO clinical staging | |||
| Stage 1/2 | 406 (27.4) | 50 (18.4) | <0.0001 |
| Stage 3 | 411 (27.8) | 85 (31.3) | |
| Stage 4 | 404 (27.3) | 38 (14.0) | |
| Unknown | 259 (17.5) | 99 (36.4) | |
| Weight for age Z score (n=1121) | −2.9 (2.0) | −2.5 (2.1) | 0.002 |
| Height for age Z score (n=1026) | −2.4 (1.7) | −2.1 (1.6) | 0.03 |
| First ART regimen | |||
| HAART-NNRTI | 1382 (93.4) | 0 | |
| HAART-PI | 87 (5.9) | 0 | |
| HAART-others | 11 (0.8) | 0 | |
| Mono- NRTI therapy | 0 | 47 (2.7) | |
| Dual-NRTI therapy | 0 | 225 (12.8) |
Note: Data shown in number (%) or mean (SD, standard deviation), Statistical test performed on non-missing values
ART: antiretroviral therapy; HAART: highly active antiretroviral therapy; NRTI: nucleoside reverse transcriptase inhibitors; NNRTI: non-nucleoside reverse transcriptase inhibitors; PI: protease inhibitors.
Incidence of OIs
There were 1637 OI events in 866/2280 children (median event 1, IQR 0-1; IR 89.5 per 100 person-years) during a median pre-ART follow-up time of 2.4 months; 226 events among 114/272 children (median 0, IQR 0-1; IR 28.8 per 100 person-years) during mono-dual treatment with a median follow-up time of 2.4 years, and 462 events in 279/1480 children (median event 0, IQR 0-0; IR 10.5 per 100 person-years) during a median follow-up time on HAART (Table 2). The most common OIs were recurrent upper respiratory tract infection, oral candidiasis, and pulmonary tuberculosis. The IR of all OIs combined in the first six months after starting treatment compared to the subsequent time period after the first six months went from 25.4 per 100 person-years to 7.7 for children started with HAART, and 66.2 per 100 person-years to 21.8 during the mono-dual- period for those who started with these regimens (Table 3).
Table 2.
Incidence rate (IR per 100 person-years) of opportunistic infection-related events among HIV-infected children in TApHOD
| Opportunistic infections | Before ART N=2129 * | After HAART N=1480 | After mono-or dual-therapy N=272 | |||
|---|---|---|---|---|---|---|
| N | IR (95% CI) | N | IR (95% CI) | N | IR (95% CI) | |
| WHO stage 2 | 440 | 24.05 (21.90-26.41) | 198 | 4.50 (3.92-5.17) | 79 | 10.05 (8.06-12.53) |
| recurrent upper respiratory tract infections | 402 | 22.0 (19.9-24.2) | 188 | 4.27 (3.71-4.93) | 76 | 9. 67(7.72-12.11) |
| fungal nail infections | 23 | 1.26(0.84-1.89) | 5 | 0.11(0.05-0.27) | 1 | 0.13(0.02-0.90) |
| extensive Molluscum contagiosum | 10 | 0.55(0.29-1.02) | 3 | 0.07 (0.02-0.21) | 1 | 0.13(0.02-0.90) |
| extensive wart virus infection | 5 | 0.27(0.11-0.66) | 2 | 0.05 (0.01-0.18) | 1 | 0.13(0.02-0.90) |
| WHO stage 3 | 1017 | 55.59 (52.27-59.11) | 197 | 4.48 (3.90-5.15) | 135 | 17.18 (14.51-20.33) |
| oral candidiasis | 376 | 20.55(18.58-22.74) | 47 | 1.07(0.80-1.42) | 50 | 6.36(4.82-8.39) |
| pulmonary tuberculosis | 336 | 18.37(16.50-20.44) | 71 | 1.61(1.28-2.04) | 25 | 3.18(2.15-4.71) |
| diarrhea | 154 | 8.42(7.19-9.86) | 23 | 0.52(0.35-0.79) | 20 | 2.55(1.64-3.94) |
| severe recurrent bacterial pneumonia | 90 | 4.92(4.00-6.05) | 44 | 1.00(0.75-1.34) | 26 | 3.31(2.25-4.86) |
| lymph node tuberculosis | 33 | 1.80(1.28-2.54) | 5 | 0.11(0.05-0.27) | 10 | 1.27(0.69-2.37) |
| lymphoid interstitial pneumonitis | 25 | 1.37(0.92-2.02) | 7 | 0.16(0.08-0.33) | 3 | 0.38(0.12-1.18) |
| Acute necrotizing ulcerative gingivitis/periodontitis | 3 | 0.16 (0.05-0.51) | 0 | - | 1 | 0.13(0.02-0.90) |
| WHO stage 4 | 180 | 9.84 (8.50-11.39) | 67 | 1.52 (1.20-1.94) | 12 | 1.53 (0.87-2.69) |
| Pneumocystis pneumonia | 60 | 3.28(2.55-4.22) | 8 | 0.18(0.09-0.36) | 1 | 0.13(0.02-0.90) |
| extrapulmonary or disseminated tuberculosis | 23 | 1.26(0.84-1.89) | 9 | 0.21(0.11-0.39) | 1 | 0.13(0.02-0.90) |
| cytomegalovirus retinitis or cytomegalovirus infection | 18 | 0.98(0.62-1.56) | 8 | 0.18(0.09-0.36) | 3 | 0.38(0.12-1.18) |
| disseminated mycosis | 16 | 0.88(0.54-1.43) | 10 | 0.23(0.12-0.42) | 0 | - |
| extrapulmonary cryptococcosis | 15 | 0.82(0.49-1.36) | 6 | 0.14(0.06-0.30) | 0 | - |
| chronic herpes simplex infection | 15 | 0.82(0.49-1.36) | 3 | 0.07(0.02-0.21) | 1 | 0.13(0.02-0.90) |
| recurrent severe bacterial infection | 12 | 0.66(0.37-1.16) | 10 | 0.23(0.12-0.42) | 2 | 0.25(0.06-1.02) |
| esophageal candidiasis | 7 | 0.38(0.18-0.80) | 2 | 0.05 (0.01-0.18) | 1 | 0.13(0.02-0.90) |
| disseminated mycobacteriosis | 6 | 0.33(0.15-0.73) | 7 | 0.16(0.08-0.33) | 2 | 0.25(0.06-1.02) |
| central nervous system toxoplasmosis | 5 | 0.27(0.11-0.66) | 2 | 0.05 (0.01-0.18) | 0 | - |
| chronic cryptosporidiosis | 2 | 0.11(0.03-0.44) | 2 | 0.05 (0.01-0.18) | 1 | 0.13(0.02-0.90) |
| Kaposi's sarcoma | 1 | 0.06(0.01-0.39) | 0 | - | 0 | - |
151 children were not included as they started their antiretroviral therapy before their first clinic visit.
ART: antiretroviral therapy; HAART: highly active antiretroviral therapy; IR: incidence rates; CI: confidence interval
Table 3.
Incidence rates (IR per 100 person-years) of opportunistic infection-related events and mortality during and after the first six months of starting antiretroviral therapy
| Before ART | Mono- or dual-therapy | HAART | |||
|---|---|---|---|---|---|
| During the first 6 months | After the first 6 months | During the first 6 months | After the first 6 months | ||
| Follow-up | 1830 | 121 | 665 | 693 | 3702 |
| All OIs | 89.5 (85.2-93.9) | 66.2 (53.2-82.5) | 21.8 (18.5-25.7) | 25.4 (21.9-29.5) | 7.7 (6.9-8.7) |
| WHO stage 2 | 24.1 (21.9-26.4) | 17.4 (11.3-26.7) | 8.7 (6.7-11.3) | 7.5 (5.7-9.9) | 3.9 (3.4-4.6) |
| WHO stage 3 | 55.6 (52.3-59.1) | 45.5 (35.0-59.3) | 11.9 (9.5-14.8) | 12.3 (99-15.2)) | 3.0 (2.5-3.6) |
| WHO stage 4 | 9.8 (8.5-11.4) | 3.3 (1.2-8.8) | 1.2 (0.6-2.4) | 5.6 (4.1-7.7) | 0.8 (0.5-1.1) |
| OI-related death | 0.9 (0.6-1.5) | 1.7 (0.4-6.6) | 0.3 (0.1-1.2) | 6.6 (5.0-8.9) | 0.6 (0.4-0.9) |
| All causes of death | 2. 0 (1.4-2.7) | 1.7 (0.4-6.6) | 1.1 (0.5-2.2) | 8.2 (6.3-10.7) | 1.1 (0.8-1.5) |
ART: antiretroviral therapy; HAART: highly active antiretroviral therapy; OI: opportunistic infection
There were 99 deaths after HAART, and 36 during the period prior to any ART. Overall, the reported cause of death was OI (63% of the cases) and other infections, or unknown (37%); 80% of all deaths occurring in the first six months of ART were OI-related. The IRs of all deaths decreased from 8.2 per 100 person-years to 1.1 after six months of HAART, and 1.7 per 100 person-years to 1.1 after six months of mono- or dual-therapy (Table 3).
Risk factors for OIs
Of 462 OIs documented in 1480 children initiating treatment with HAART, 264 OI events (57%) were WHO stage 3 or 4 defining. In multivariate Poisson regression analyses, time-dependent lower CD4 percentage, younger age, WHO clinical stage 3, and lower WAZ at baseline were associated with development of OIs after HAART. Compared with children with CD4 >25%, the relative risk for developing OIs was 21.0 (95% CI: 11.8-37.1) for CD4 <15%, and 2.7 (95% CI: 1.4-5.1) for CD4 15-24%. The median CD4 cell counts at OI diagnosis were 91 (IQR 16-208) cells/mm3 for oral candidiasis, 191 (IQR 68-621) cells/mm3 for pulmonary tuberculosis (TB), and 102 (IQR 27-500) cells/mm3 for severe recurrent bacterial pneumonia. Children <18 months of age at initiation of HAART had the highest risk of having severe OIs of any age group. Those with a baseline WHO clinical stage 3 were 3.7 times more likely to develop severe OIs after HAART than those with baseline clinical stage 1 and 2. The risk of OI decreased with increasing baseline WAZ (RR: 0.8; 95% CI: 0.7-0.9). The risks of OIs in those who started with a PI-based regimen were not different to that for children who started with an NNRTI-based regimen (Supplemental Digital Content 1).
Kaplan-Meier analyses showed that children who started their therapy at a baseline CD4 <15% had a higher frequency of OIs, especially during the first year of HAART, as compared with those with a baseline CD4 15-24% (Figure 1). Of 68 children with a baseline CD4 >25%, 13 (19%) experienced 15 events of severe OI infections after HAART; 14 happened in the first year of treatment. Of these 13 children, eight were <18 months at HAART initiation.
Figure 1.
Cumulative proportion of opportunistic infection WHO stage 3 and 4-free children stratified by CD4 level at the time of HAART initiation
DISCUSSION
In this regional cohort, we found a substantial reduction in the incidence rates of OIs from 89.5 per 100 person-years during the pre-treatment period to 66.2 per 100 person-years in the first six months after mono- or dual-therapy, and 25.4 per 100 person-years after six months of HAART. The incidence rates further declined to 21.8 (18.5-25.7) and 7.7 (6.9-8.7) per 100 person-years beyond six months of mono- or dual-therapy and HAART. Although these results were in agreement with previous studies in adults and children from other settings and within our region,1, 3-5, 15 our OI incidence after HAART was of higher magnitude. This may have been caused by cross-cohort differences, including levels of immunosuppression and differences in intensity of reporting and analytical method. In this study we did not censor data after the first OI event in a given patient, but continued follow-up, allowing for a more complete assessment of the longer-term impact of ART on OI incidence.
It is also noteworthy that the spectrum of infection and the relative frequencies of OIs have not changed after starting ART. Recurrent upper respiratory tract infections, persistent oral candidiasis, and pulmonary TB continued to be the most common OIs. CDC stage 2 or 3 bacterial infections and non-TB infections accounted for the most of OIs among a US and European children cohort in both the pre- and post-HAART periods.3, 4, 16-19 However, the rates of TB infection in our study and in the region were much higher than in the US and Europe. This information is similar to previous reports in Asia which have shown that TB has been the most common co-infection in HIV-infected patients. 20-23 This likely reflects the higher burden of TB in Asia. Although ART had a significant impact on lowering TB incidence in our cohort, the more rapid TB disease progression seen in HIV-infected children makes it essential that HIV programs prioritize prophylaxis and screening of TB in children.24-26 Additionally, although the rates of recurrent bacterial infections have markedly decreased after HAART, they remained persistent which is similar to findings from the US and Europe cohorts. 4, 19, 27
Our study showed low incidences of preventable OIs, such as Pneumocystis jirovecii pneumonia (PCP) and Mycobacterium avium complex (MAC) infection. Although this could be attributable to primary and secondary chemoprophylaxis, our study was not able to examine the relationship between chemoprophylaxis and OIs and the lower incidence of MAC could be due to surveillance bias, as there was limited access to sensitive mycobacterial culture systems in the region during the pre-HAART era. Another study in an adult regional cohort showed that cotrimoxazole prophylaxis is still not consistently provided in all regional programs.28
The overall rate of OIs after HAART was found to be lower than after mono- or dual-therapy (10.5 vs. 28.8 per 100 person-years), as OI incidence fell with time after initiating ART and children who were receiving HAART had a longer period of follow-up than those who received mono- or dual-therapy. Most of the children who received mono- or dual-therapy were switched to HAART and were then censored from the analysis.
The OI-related death rate among children who started with HAART was higher than among children who started with mono- or dual-therapy (7.2 vs. 2.0 per 100 person years), and higher than in the period prior to ART. Reasons for this could be that children started with HAART were in a more advanced stage of HIV with lower CD4 levels than those who started with mono/dual therapy, and were consequently at higher risk of immune reconstitution syndrome (IRIS). An earlier study in Thai children reported an incidence of IRIS of 19%.29
Poor immunological status, younger age, and lower weight for age z score at the start of ART were significant risk factors for developing OIs after initiation of HAART. Similar to findings from The Children with HIV Early Antiretroviral Therapy (CHER) trial in South Africa on early infant diagnosis and treatment30, our results also emphasize the importance of earlier identification of children with HIV and initiation of ART before advanced disease progression and concomitant higher risk of OIs. Although national programs in Asia are currently moving towards treating all infants under 12 months of age, implementation of this policy will require stronger linkages between obstetric and pediatric services in order to achieve this goal.
This study provides useful insights into the evolution of the pediatric HIV epidemic and treatment scale-up in Asia. Local production of fixed-dose combination (FDC) since the early 2000s led to greater access to lower-cost antiretrovirals in the Asia-Pacific region.31 In this study, only 6% of children were initiated with PI-based HAART. However, we did not find a difference in the rate of OIs by initial HAART regimen. Although the P1060 and CHER trials in Africa have shown a mortality benefit to PI-based HAART in young children in largely resource-limited settings30, 32, the PENPACT-1 study of children across Europe and America reported no difference in clinical, immunological and virological outcomes between children starting with PI-based vs. NNRTI-based regimens.33
The primary limitation of this study is that data are observational and collected through the course of routine care. Our analysis is further limited by inclusion of children primarily receiving care at university-based clinics and/or referral centers, which usually have greater availability of human and treatment-related resources and accessibility to ART. Therefore, children in this study may not be fully representative of HIV-infected children in primary care centers or in rural areas.
Supplementary Material
Acknowledgements
The TREAT Asia Pediatric HIV Observational Database is an initiative of TREAT Asia, a program of amfAR, The Foundation for AIDS Research, with support from the U.S. National Institutes of Health's National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Cancer Institute as part of the International Epidemiologic Databases to Evaluate AIDS (IeDEA; U01AI069907), and the Austrian AIDS Life Association. The Kirby Institute is funded by the Australian Government Department of Health and Ageing, and is affiliated with the Faculty of Medicine, The University of New South Wales. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of any of the institutions mentioned above.
APPENDIX
The TREAT Asia Pediatric HIV Network
CV Mean, V Saphonn* and S Saramony, National Centre for HIV/AIDS Dermatology and STDs, Phnom Penh, Cambodia;
U Vibol*‡, P Moroun, K Yuvatha and C Bunnthy, National Pediatric Hospital, Phnom Penh, Cambodia;
J Tucker, New Hope for Cambodian Children, Phnom Penh, Cambodia;
FJ Zhang, Beijing Ditan Hospital, Capital Medical University, Beijing, China;
N Kumarasamy* and S Saghayam, YR Gaitonde Centre for AIDS Research and Education, Chennai, India;
DK Wati*, LPP Atmikasari and IY Malino, Sanglah Hospital, Udayana University, Bali, Indonesia;
N Kurniati* and D Muktiarti, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia;
SM Fong* and M Thien, Hospital Likas, Kota Kinabalu, Malaysia;
NK Nik Yusoff*, LC Hai, and P Mohamad, Hospital Raja Perempuan Zainab II, Kelantan, Malaysia;
KA Razali *, TJ Mohamed, and NF Abdul Rahman, Pediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia;
R Nallusamy*† and KC Chan, Penang Hospital, Penang, Malaysia;
V Sirisanthana*, P Oberdorfer, L Aurpibul, and T. Sudjaritruk, Research Institute for Health Sciences and Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand;
R Hansudewechakul*, S Denjunta and P Taeprasert, Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand;
P Lumbiganon*, P Kosalaraksa, P Tharnprisan and T Udomphanit, Khon Kaen University, Khon Kaen, Thailand;
G Jourdain, PHPT (IRD UMI 174 and Chiang Mai University), Chiang Mai, Thailand;
J Ananworanich*, S Phonphithak, and T Puthanakit, HIV-NAT/Thai Red Cross AIDS Research Centre, Bangkok, Thailand;
K Chokephaibulkit*, K Lapphra, W Phongsamart and O Wittawatmongkol, Siriraj Hospital, Mahidol University, Bangkok, Thailand;
HK Truong*, TQ Du and NH Chau, Children's Hospital 1, Ho Chi Minh City, Vietnam;
CV Do* and MT Ha, Children's Hospital 2, Ho Chi Minh City, Vietnam;
KTK Dung, NV Lam*, PN An and NT Loan, National Hospital of Pediatrics, Hanoi, Vietnam;
NO Le, Worldwide Orphans Foundation, Ho Chi Minh City, Vietnam;
AH Sohn*, N Durier, and P Nipathakosol, TREAT Asia, amfAR -- The Foundation for AIDS Research, Bangkok, Thailand;
DA Cooper, MG Law*, and A Kariminia, The Kirby Institute, University of New South Wales, Sydney, Australia;
Footnotes
Note of interest: These data were presented in part at the 1st International Workshop on HIV Pediatrics, July 17-18, 2009, Cape Town, South Africa.
Conflicts of Interest: All authors declare no conflict of interest.
TApHOD Steering Committee member
Current Steering Committee Chair;
co-Chair
References
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