Nia Kurniati

Survival of HIV-Infected Children: A Cohort Study From the Asia-Pacific Region

Background:Combination antiretroviral therapy (ART) has been used for HIV-infected children in many Asian countries since 2002. This study describes survival outcomes among HIV-infected children in a multicenter regional cohort in Asia. Patients and Methods:Retrospective and prospective data collected through March 2009 from children in 5 countries enrolled in TREAT Asias Pediatric HIV Observational Database were analysed. Multivariate Cox proportional hazard models were used to assess factors associated with mortality in children who received ART. Results:Among 2280 children, 1752 (77%) had received ART. During a median follow-up of 3.1 years after ART, 115 (6.6%) deaths occurred, giving a crude mortality rate of 1.9 per 100 child-years [95% confidence interval (CI): 1.6 to 2.4]. The mortality rate was highest in the first 3 months of ART (10.2 per 100 child-years; 95% CI: 7.5 to 13.7) and declined after 12 months (0.9 per 100 child-years; 95% CI: 0.7 to 1.3). Those with a low recent CD4 percentage, who started ART with lower baseline weight-for-age Z score, or with WHO clinical stage 4 had an increased risk of death. Of 528 (23%) children who never received ART, 36 (6.8%) died after presenting to care, giving a crude mortality rate of 4.1 per 100 child-years (95% CI: 3.0 to 5.7), with a lost-to-program rate of 31.5 per 100 child-years (95% CI: 28.0 to 35.5). Conclusions:The high mortality during the first 3 months of ART and in those with low CD4 percentage support the implementation of early diagnosis and ART initiation.

Cohort profile: the TREAT Asia pediatric HIV observational database.

This cohort profile focuses on the Therapeutic Research Education and AIDS Training (TREAT) Asia Pediatric HIV Observational Database (TApHOD) a collaborative cohort of HIV-infected children in the Asia-Pacific region. It describes many aspects of this cohort including: how it was established the objectives the sample characteristics of participating sites patient characteristics measurements findings attrition strengths and weaknesses and funding information.

Antiretroviral therapy outcomes of HIV-infected children in the TREAT Asia pediatric HIV observational database.

Introduction:We report responses to combination antiretroviral therapy (cART) in the Therapeutics Research, Education, and AIDS Training in Asia Pediatric HIV Observational Database. Methods:Children included were those who had received cART (ie, ≥3 antiretrovirals) at <18 years. The analysis was intention-to-treat by the first cART regimen. Median values are provided with interquartile ranges; hazard ratios (HRs) with 95% confidence intervals. Results:Of the 1655 children included, 50.4% were male, with a median age at cART of 7.0 (3.9-9.8) years and CD4 of 8% (2.0%-15%); 92.5% were started on an NNRTI; median duration of follow-up was 2.9 (1.4-4.6) years. Loss-to-follow-up and death rates were 4.2 (3.7-4.8) and 2.1 (1.7-2.5) per 100 person-years, respectively. At 36 months, median CD4 was 26% (21%-31%); 81% of those with viral load (n = 302) were <400 copies per milliliter. Children who reached CD4 ≥25% within 5 years were more likely to be females (HR: 1.4; 1.2-1.7), start before 18 months old (HR: 3.8; 2.4-6.2), lack a history of monotherapy/dual therapy (HR: 1.7; 1.4-2.5), and have a higher baseline CD4 (per 10% increase: HR: 2; 1.9-2.2). Conclusions:These data underscore the need for early diagnosis and cART initiation to preserve immune function.

A biregional survey and review of first-line treatment failure and second-line paediatric antiretroviral access and use in Asia and southern Africa.

To better understand the need for paediatric second‐line antiretroviral therapy (ART), an ART management survey and a cross‐sectional analysis of second‐line ART use were conducted in the TREAT Asia Paediatric HIV Observational Database and the IeDEA Southern Africa (International Epidemiologic Databases to Evaluate AIDS) regional cohorts.

Characterizing HIV manifestations and treatment outcomes of perinatally infected adolescents in Asia.

Background: More perinatally HIV-infected children in Asia are reaching adolescence. Methods: We analyzed data from July 1991 to March 2011 reported by 18 clinics in 6 countries of children age >12 years. Results: Of 1254 adolescents, 33 (2.6%) died, and 52 (4.1%) were lost to follow-up within 2.4-year (3566 person-years) median follow-up period. Of 1061 adolescents under active follow-up, 485 (46%) were male, median (interquartile range) age was 14.7 (13.3–16.4) years, 73% had lost a parent(s), 93% attended school and 62% were aware of their HIV status. At the most recent evaluation, 93% were receiving highly active antiretroviral therapy, 71% (N = 737/1035) had CD4 ≥500 cells/mm3 and 87% (N = 718/830) had viral load (VL) <400 copies/mL. Current CD4 ≥200 cells/mm3, no previous World Health Organization stage 3 or 4 and being on a first-line regimen were independently associated with recent VL <400 copies/mL. Current age <15 years, VL <400 copies/mL, CD4 15–24% (vs. <10%) at antiretroviral therapy initiation, no previous World Health Organization stage 3 or 4 and antiretroviral therapy duration of ≥1 year were associated with recent CD4 ≥500 cells/mm3. Primary causes of death after age 12 were opportunistic infections (N = 15/33) and other AIDS- or treatment-related conditions (N = 9/33). Those at age 12 with CD4 <200 versus ≥500 cells/mm3 and those with VL ≥10,000 versus <10,000 copies/mL were 17.4 and 4.76 times more likely to die in adolescence, respectively. Conclusion: Adolescents in this cohort have been successfully maintained in HIV care. Initiating treatment at earlier stages of disease was associated with immune recovery and virologic suppression during adolescence.

Serotype Distribution and Antibiotic Susceptibility of Streptococcus pneumoniae Strains Carried by Children Infected with Human Immunodeficiency Virus

Abstract Background We studied the serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae isolates carried by children infected with HIV in Jakarta, Indonesia. Methods Nasopharyngeal swabs were collected from 90 HIV infected children aged 4 to 144 months. S. pneumoniae was identified by conventional and molecular methods. Serotyping was performed with sequential multiplex PCR and antibiotic susceptibility with the disk diffusion method. Results We identified S. pneumoniae carriage in 41 children (46%). Serotype 19F was most common among 42 cultured strains (19%) followed by 19A and 6A/B (10% each), and 23F (7%). Most isolates were susceptible to chloramphenicol (86%), followed by clindamycin (79%), erythromycin (76%), tetracycline (43%), and sulphamethoxazole/trimethoprim (41%). Resistance to penicillin was most common with only 33% of strains being susceptible. Strains of serotypes targeted by the 13-valent pneumococcal conjugate polysaccharide vaccine (PCV13) were more likely to be multidrug resistant (13 of 25 or 52%) compared to non-PCV13 serotype isolates (3 of 17 or 18%; Fisher exact test p = 0.05). Conclusion Our study provides insight into the epidemiology of pneumococcal carriage in young HIV patients in Indonesia. These findings may facilitate potential preventive strategies that target invasive pneumococcal disease in Indonesia.

Cardiovascular manifestations of HIV infection in children

Background HIV infection in children is now considered as a chronic condition, in which various non-infectious complications may occur, including those affecting the developing cardiovascular system. As children are expected to survive well into adulthood, understanding childhood as well as potential future cardiovascular complications is of major importance. Methods and results We reviewed published literature on childhood cardiac manifestations and longer term effects of pediatric HIV infection on the cardiovascular system. Evidence gaps that should be prioritized in research are highlighted. Through poorly understood mechanisms, HIV infection may cause various cardiac complications already manifesting in childhood, such as structural and functional myocardial derangements, pulmonary hypertension, pericardial effusion and possibly endocarditis. Evidence indicates that HIV infection in children also has unfavorable effects on the vasculature and cardiovascular biomarkers, such as increased intima-media thickness and decreased flow-mediated dilation, a marker of endothelial function. However, studies are small and predominantly include antiretroviral therapy-treated children, so that it is difficult to differentiate between effects of HIV infection per se and antiretroviral therapy treatment, reported in adults to have cardiovascular side effects. Conclusions HIV infection in children may greatly impact the cardiovascular system, including effects on the heart, which tend to manifest early in childhood, and on the vasculature. The underlying mechanisms, essential for targeted prevention, are poorly understood. Current evidence largely stems from research in adults. However, as modes of infection, immune maturity, growth and development, and treatment are markedly different in children, specific pediatric research, accounting for the complex interplay of normal growth and development, HIV infection and treatment, is clearly warranted.

Second-line protease inhibitor-based highly active antiretroviral therapy after failing non-nucleoside reverse transcriptase inhibitors-based regimens in Asian HIV-infected children

BACKGROUND The World Health Organization (WHO) recommends boosted protease inhibitor (bPI)-based HAART after failing non-nucleoside reverse transcriptase inhibitor (NNRTI) treatment. We examined outcomes of this regimen in Asian HIV-infected children. METHODS Children from five Asian countries in the TREAT Asia Pediatric HIV Observational Database (TApHOD) with ≥ 24 weeks of NNRTI-based HAART followed by ≥ 24 weeks of bPI-based HAART were eligible. Primary outcomes were the proportions with virological suppression (HIV RNA < 400 copies/ml) and immune recovery (CD4+ T-cell percentage [CD4%]≥ 25% if age < 5 years and CD4+ T-cell count ≥ 500 cells/mm3 if age ≥ 5 years) at 48 and 96 weeks. RESULTS Of 3,422 children, 153 were eligible; 52% were female. At switch, median age was 10 years, 26% were in WHO stage 4. Median weight-for-age z-score (WAZ) was -1.9 (n = 121), CD4% was 12.5% (n = 106), CD4+ T-cell count was 237 cells/mm3 (n = 112), and HIV RNA was 4.6 log10 copies/ml (n = 61). The most common bPI was lopinavir/ritonavir (83%). At 48 weeks, 61% (79/129) had immune recovery, 60% (26/43) had undetectable HIV RNA and 73% (58/79) had fasting triglycerides ≥ 130 mg/dl. By 96 weeks, 70% (57/82) achieved immune recovery, 65% (17/26) had virological suppression, and hypertriglyceridaemia occurred in 66% (33/50). Predictors for virological suppression at week 48 were longer duration of NNRTI-based HAART (P = 0.006), younger age (P = 0.007), higher WAZ (P = 0.020) and HIV RNA at switch < 10,000 copies/ml (P = 0.049). CONCLUSIONS In this regional cohort of Asian children on bPI-based second-line HAART, 60% of children tested had immune recovery by 1 year, and two-thirds had hyperlipidaemia, highlighting difficulties in optimizing second-line HAART with limited drug options.

Weight as predictors of clinical progression and treatment failure: results from the TREAT Asia Pediatric HIV Observational Database.

Objective:To evaluate the value of time-updated weight and height in predicting clinical progression, and immunological and virological failure in children receiving combination antiretroviral therapy (cART). Methods:We used Cox regression to analyze data of a cohort of Asian children. Results:A total of 2608 children were included; median age at cART was 5.7 years. Time-updated weight for age z score < −3 was associated with mortality (P < 0.001) independent of CD4% and < −2 was associated with immunological failure (P ⩽ 0.03) independent of age at cART. Conclusions:Weight monitoring provides useful data to inform clinical management of children on cART in resource-limited settings.

Incidence and predictors of severe anemia in Asian HIV-infected children using first-line antiretroviral therapy

BACKGROUND There are limited data on treatment-related anemia in Asian HIV-infected children. METHODS Data from Asian HIV-infected children aged <18 years on first-line highly active antiretroviral therapy (HAART) were used. Children who had pre-existing severe anemia at baseline were excluded. Anemia was graded using the United States Division of AIDS (DAIDS) 2004 table. Potential risk factors for severe anemia were assessed by logistic regression. RESULTS Data from 1648 children (51.9% female, 62.8% World Health Organization (WHO) stage 3/4) were analyzed. Median (interquartile range) age was 6.8 (3.7-9.6) years, CD4% was 9 (3-16)%, and plasma HIV-RNA was 5.2 (4.7-5.6) log10 copies/ml at HAART initiation in those with available testing. The most common regimens were stavudine/lamivudine/nevirapine (42%) and zidovudine/lamivudine/nevirapine (25%). Severe anemia was identified in 47 (2.9%) children after a median time of 6 months after HAART initiation, with an incidence rate of 5.4 per 100 child-years. Mild anemia or moderate anemia at baseline (p = 0.024 and p = 0.005, respectively), previous or current use of zidovudine (p < 0.0001 and p = 0.013, respectively), and male sex (p = 0.008) were associated with severe anemia. Higher weight-for-age z-score (p = 0.004) was protective. CONCLUSIONS The incidence of severe anemia in Asian HIV-infected children after HAART initiation was low and mainly occurred during the first few months after HAART initiation. Mild to moderate anemia at baseline and using zidovudine were independent risk factors for the development of severe anemia.