METHODS: A prospective cohort study among ALHIV and matched HIV-uninfected controls aged 12-18 years was conducted at 9 sites in Malaysia, Thailand, and Vietnam from July 2013 to March 2017. Participants completed an audio computer-assisted self-interview at weeks 0, 48, 96, and 144. Virologic failure (VF) was defined as ≥1 viral load (VL) measurement >1000 copies/mL. Generalized estimating equations were used to identify predictors for VF.
RESULTS: Of 250 ALHIV and 59 HIV-uninfected controls, 58% were Thai and 51% females. The median age was 14 years at enrollment; 93% of ALHIV were perinatally infected. At week 144, 66% of ALHIV were orphans vs. 28% of controls (P < 0.01); similar proportions of ALHIV and controls drank alcohol (58% vs. 65%), used inhalants (1% vs. 2%), had been sexually active (31% vs. 21%), and consistently used condoms (42% vs. 44%). Of the 73% of ALHIV with week 144 VL testing, median log VL was 1.60 (interquartile range 1.30-1.70) and 19% had VF. Over 70% of ALHIV had not disclosed their HIV status. Self-reported adherence ≥95% was 60% at week 144. Smoking cigarettes, >1 sexual partner, and living with nonparent relatives, a partner or alone, were associated with VF at any time.
CONCLUSIONS: The subset of ALHIV with poorer adherence and VF require comprehensive interventions that address sexual risk, substance use, and HIV-status disclosure.
OBJECTIVES: To assess the effectiveness of antenatal breastfeeding (BF) education for increasing BF initiation and duration.
SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register on 1 March 2016, CENTRAL (The Cochrane Library, 2016, Issue 3), MEDLINE (1966 to 1 March 2016) and Scopus (January 1985 to 1 March 2016). We contacted experts and searched reference lists of retrieved articles.
SELECTION CRITERIA: All identified published, unpublished and ongoing randomised controlled trials (RCTs) assessing the effect of formal antenatal BF education or comparing two different methods of formal antenatal BF education, on the duration of BF. We included RCTs that only included antenatal interventions and excluded those that combined antenatal and intrapartum or postpartum BF education components. Cluster-randomised trials were included in this review. Quasi-randomised trials were not eligible for inclusion.
DATA COLLECTION AND ANALYSIS: We assessed all potential studies identified as a result of the search strategy. Two review authors extracted data from each included study using the agreed form and assessed risk of bias. We resolved discrepancies through discussion. We assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS: This review update includes 24 studies (10,056 women). Twenty studies (9789 women) contribute data to analyses. Most studies took place in high-income countries such as the USA, UK, Canada and Australia. In the first five comparisons, we display the included trials according to type of intervention without pooling data. For the 'Summary of findings' we pooled data for a summary effect.Five included studies were cluster-randomised trials: all of these adjusted data and reported adjustments as odds ratios (OR). We have analysed the data using the generic inverse variance method and presented results as odds ratios, because we were unable to derive a cluster-adjusted risk ratio from the published cluster-trial. We acknowledge that the use of odds ratio prevents the pooling of these cluster trials in our main analyses. One method of BF education with standard (routine) careThere were no group differences for duration of any BF in days or weeks. There was no evidence that interventions improved the proportion of women with any BF or exclusive BF at three or six months. Single trials of different interventions were unable to show that education improved initiation of BF, apart from one small trial at high risk of attrition bias. Many trial results marginally favoured the intervention but had wide confidence intervals crossing the line of no effect. BF complications such as mastitis and other BF problems were similar in treatment arms in single trials reporting these outcomes. Multiple methods of BF education versus standard careFor all trials included in this comparison we have presented the cluster-adjusted odds ratios as reported in trial publications. One three-arm study found the intervention of BF booklet plus video plus Lactation Consultant versus standard care improved the proportion of women exclusively BF at three months (OR 2.60, 95% CI 1.25 to 5.40; women = 159) and marginally at six months (OR 2.40, 95% CI 1.00 to 5.76; women = 175). For the same trial, an intervention arm without a lactation consultant but with the BF booklet and video did not have the same effect on proportion of women exclusively BF at three months (OR 1.80, 95% CI 0.80 to 4.05; women = 159) or six months (OR 0.90, 95% CI 0.30 to 2.70; women = 184). One study compared monthly BF sessions and weekly cell phone message versus standard care and reported improvements in the proportion of women exclusively BF at both three and six months (three months OR 1.80, 95% CI 1.10 to 2.95; women = 390; six months OR 2.40, 95% CI 1.40 to 4.11; women = 390). One study found monthly BF sessions and weekly cell phone messages improved initiation of BF over standard care (OR 2.61, 95% CI 1.61 to 4.24; women = 380). BF education session versus standard care, pooled analyses for 'Summary of findings' (SoF)This comparison does not include cluster-randomised trials reporting adjusted odds ratios. We did not downgrade any evidence for trials' lack of blinding; no trial had adequate blinding of staff and participants. The SoF table presents risk ratios for all outcomes analysed. For proportion of women exclusively BF there is no evidence that antenatal BF education improved BF at three months (RR 1.06, 95% CI 0.90 to 1.25; women = 822; studies = 3; moderate quality evidence) or at six months (RR 1.07, 95% CI 0.87 to 1.30; women = 2161; studies = 4; moderate quality evidence). For proportion of women with any BF there were no group differences in BF at three (average RR 0.98, 95% CI 0.82 to 1.18; women = 654; studies = 2; I² = 60%; low-quality evidence) or six months (average RR 1.05, 95% CI 0.90 to 1.23; women = 1636; studies = 4; I² = 61%; high-quality evidence). There was no evidence that antenatal BF education could improve initiation of BF (average RR 1.01, 95% CI 0.94 to 1.09; women = 3505; studies = 8; I² = 69%; high-quality evidence). Where we downgraded evidence this was due to small sample size or wide confidence intervals crossing the line of no effect, or both.There was insufficient data for subgroup analysis of mother's occupation or education.
AUTHORS' CONCLUSIONS: There was no conclusive evidence supporting any antenatal BF education for improving initiation of BF, proportion of women giving any BF or exclusively BF at three or six months or the duration of BF. There is an urgent need to conduct a high-quality, randomised controlled study to evaluate the effectiveness and adverse effects of antenatal BF education, especially in low- and middle-income countries. Evidence in this review is primarily relevant to high-income settings.
METHODS: Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index-for-age Z score less than -3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age Z score less than -3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification.
RESULTS: Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from -5.6 at ART initiation to -2.3 after 36 months. Not using trimethoprim-sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66-3.74; P < 0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.08-2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.24-5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years, and rates did not differ by malnutrition severity.
CONCLUSION: Trimethoprim-sulfamethoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for-age Z score, which may contribute to their high rate of mortality.
DESIGN: Ongoing observational database collating clinical data on HIV-infected children and adolescents in Asia.
METHODS: Data from 2001 to 2016 relating to adolescents (10-19 years) with perinatal HIV infection were analysed to describe characteristics at adolescent entry and transition and combination antiretroviral therapy (cART) regimens across adolescence. A competing risk regression analysis was used to determine characteristics at adolescent entry associated with mortality. Outcomes at transition were compared on the basis of age at cART initiation.
RESULTS: Of 3448 PHIVA, 644 had reached transition. Median age at HIV diagnosis was 5.5 years, cART initiation 7.2 years and transition 17.9 years. At adolescent entry, 35.0% had CD4+ cell count less than 500 cells/μl and 51.1% had experienced a WHO stage III/IV clinical event. At transition, 38.9% had CD4+ cell count less than 500 copies/ml, and 53.4% had experienced a WHO stage III/IV clinical event. Mortality rate was 0.71 per 100 person-years, with HIV RNA ≥1000 copies/ml, CD4+ cell count less than 500 cells/μl, height-for-age or weight-for-age z-score less than -2, history of a WHO stage III/IV clinical event or hospitalization and at least second cART associated with mortality. For transitioning PHIVA, those who commenced cART age less than 5 years had better virologic and immunologic outcomes, though were more likely to be on at least second cART.
CONCLUSION: Delayed HIV diagnosis and cART initiation resulted in considerable morbidity and poor immune status by adolescent entry. Durable first-line cART regimens to optimize disease control are key to minimizing mortality. Early cART initiation provides the best virologic and immunologic outcomes at transition.
DESIGN: Death-related data were retrospectively and prospectively assessed in a longitudinal regional cohort study.
METHODS: Children under routine HIV care at sites in Cambodia, India, Indonesia, Malaysia, Thailand, and Vietnam between 2008 and 2017 were followed. Causes of death were reported and then independently and centrally reviewed. Predictors were compared using competing risks survival regression analyses.
RESULTS: Among 5918 children, 5523 (93%; 52% male) had ever been on combination antiretroviral therapy. Of 371 (6.3%) deaths, 312 (84%) occurred in those with a history of combination antiretroviral therapy (crude all-cause mortality 9.6 per 1000 person-years; total follow-up time 32 361 person-years). In this group, median age at death was 7.0 (2.9-13) years; median CD4 cell count was 73 (16-325) cells/μl. The most common underlying causes of death were pneumonia due to unspecified pathogens (17%), tuberculosis (16%), sepsis (8.0%), and AIDS (6.7%); 12% of causes were unknown. These clinical diagnoses were further grouped into AIDS-related infections (22%) and noninfections (5.8%), and non-AIDS-related infections (47%) and noninfections (11%); with 12% unknown, 2.2% not reviewed. Higher CD4 cell count and better weight-for-age z-score were protective against death.
CONCLUSION: Our standardized cause of death assessment provides robust data to inform regional resource allocation for pediatric diagnostic evaluations and prioritization of clinical interventions, and highlight the continued importance of opportunistic and nonopportunistic infections as causes of death in our cohort.
METHODS: Data collected 2001 to 2016 from PHIVA 10-19 years of age within a regional Asian cohort were analyzed using competing risk time-to-event and Poisson regression analyses to describe the nature and incidence of morbidity events and hospitalizations and identify factors associated with disease-related, treatment-related and overall morbidity. Morbidity was defined according to World Health Organization clinical staging criteria and U.S. National Institutes of Health Division of AIDS criteria.
RESULTS: A total 3,448 PHIVA contributed 17,778 person-years. Median age at HIV diagnosis was 5.5 years, and ART initiation was 6.9 years. There were 2,562 morbidity events and 307 hospitalizations. Cumulative incidence for any morbidity was 51.7%, and hospitalization was 10.0%. Early adolescence was dominated by disease-related infectious morbidity, with a trend toward noninfectious and treatment-related morbidity in later adolescence. Higher overall morbidity rates were associated with a CD4 count <350 cells/µL, HIV viral load ≥10,000 copies/mL and experiencing prior morbidity at age <10 years. Lower overall morbidity rates were found for those 15-19 years of age compared with 10-14 years and those who initiated ART at age 5-9 years compared with <5 or ≥10 years.
CONCLUSIONS: Half of our PHIVA cohort experienced a morbidity event, with a trend from disease-related infectious events to treatment-related and noninfectious events as PHIVA age. ART initiation to prevent immune system damage, optimize virologic control and minimize childhood morbidity are key to limiting adolescent morbidity.
SETTING: Asian regional cohort incorporating 16 pediatric HIV services across 6 countries.
METHODS: Data from PHIVA (aged 10-19 years) who received combination antiretroviral therapy 2007-2016 were used to analyze LTFU through (1) an International epidemiology Databases to Evaluate AIDS (IeDEA) method that determined LTFU as >90 days late for an estimated next scheduled appointment without returning to care and (2) the absence of patient-level data for >365 days before the last data transfer from clinic sites. Descriptive analyses and competing-risk survival and regression analyses were used to evaluate LTFU epidemiology and associated factors when analyzed using each method.
RESULTS: Of 3509 included PHIVA, 275 (7.8%) met IeDEA and 149 (4.3%) met 365-day absence LTFU criteria. Cumulative incidence of LTFU was 19.9% and 11.8% using IeDEA and 365-day absence criteria, respectively. Risk factors for LTFU across both criteria included the following: age at combination antiretroviral therapy initiation <5 years compared with age ≥5 years, rural clinic settings compared with urban clinic settings, and high viral loads compared with undetectable viral loads. Age 10-14 years compared with age 15-19 years was another risk factor identified using 365-day absence criteria but not IeDEA LTFU criteria.
CONCLUSIONS: Between 12% and 20% of PHIVA were determined LTFU with treatment fatigue and rural treatment settings consistent risk factors. Better tracking of adolescents is required to provide a definitive understanding of LTFU and optimize evidence-based models of care.
METHODS: Individuals enrolled in the Therapeutics Research, Education, and AIDS Training in Asia Pediatric HIV Observational Database were included if they started ART at ages 1 month-14 years and had both height and weight measurements available at ART initiation (baseline). Generalized estimating equations were used to identify factors associated with change in height-for-age z-score (HAZ), follow-up HAZ ≥ -2, change in weight-for-age z-score (WAZ), and follow-up WAZ ≥ -2.
RESULTS: A total of 3217 children were eligible for analysis. The adjusted mean change in HAZ among cotrimoxazole and non-cotrimoxazole users did not differ significantly over the first 24 months of ART. In children who were stunted (HAZ < -2) at baseline, cotrimoxazole use was not associated with a follow-up HAZ ≥ -2. The adjusted mean change in WAZ among children with a baseline CD4 percentage (CD4%) >25% became significantly different between cotrimoxazole and non-cotrimoxazole users after 6 months of ART and remained significant after 24 months (overall P < .01). Similar changes in WAZ were observed in those with a baseline CD4% between 10% and 24% (overall P < .01). Cotrimoxazole use was not associated with a significant difference in follow-up WAZ in children with a baseline CD4% <10%. In those underweight (WAZ < -2) at baseline, cotrimoxazole use was associated with a follow-up WAZ ≥ -2 (adjusted odds ratio, 1.70 vs not using cotrimoxazole [95% confidence interval, 1.28-2.25], P < .01). This association was driven by children with a baseline CD4% ≥10%.
CONCLUSIONS: Cotrimoxazole use is associated with benefits to WAZ but not HAZ during early ART in Asian children.
SETTING: An Asian cohort in 16 pediatric HIV services across 6 countries.
METHODS: From 2005 to 2014, patients younger than 20 years who achieved virologic suppression and had subsequent viral load testing were included. Early virologic failure was defined as a HIV RNA ≥1000 copies per milliliter within 12 months of virologic suppression, and late virologic as a HIV RNA ≥1000 copies per milliliter after 12 months following virologic suppression. Characteristics at combination antiretroviral therapy initiation and virologic suppression were described, and a competing risk time-to-event analysis was used to determine cumulative incidence of virologic failure and factors at virologic suppression associated with early and late virologic failure.
RESULTS: Of 1105 included in the analysis, 182 (17.9%) experienced virologic failure. The median age at virologic suppression was 6.9 years, and the median time to virologic failure was 24.6 months after virologic suppression. The incidence rate for a first virologic failure event was 3.3 per 100 person-years. Factors at virologic suppression associated with late virologic failure included older age, mostly rural clinic setting, tuberculosis, protease inhibitor-based regimens, and early virologic failure. No risk factors were identified for early virologic failure.
CONCLUSIONS: Around 1 in 5 experienced virologic failure in our cohort after achieving virologic suppression. Targeted interventions to manage complex treatment scenarios, including adolescents, tuberculosis coinfection, and those with poor virologic control are required.
METHODS: A cross-sectional standardised survey was completed in 2014-2015 by sites providing paediatric HIV care across regions of the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We developed a comprehensiveness score based on the WHO's nine categories of essential services to categorise sites as 'low' (0-5), 'medium', (6-7) or 'high' (8-9). When available, comprehensiveness scores were compared with scores from a 2009 survey. We used patient-level data with site services to investigate the relationship between the comprehensiveness of services and retention.
RESULTS: Survey data from 174 IeDEA sites in 32 countries were analysed. Of the WHO essential services, sites were most likely to offer antiretroviral therapy (ART) provision and counselling (n=173; 99%), co-trimoxazole prophylaxis (168; 97%), prevention of perinatal transmission services (167; 96%), outreach for patient engagement and follow-up (166; 95%), CD4 cell count testing (126; 88%), tuberculosis screening (151; 87%) and select immunisation services (126; 72%). Sites were less likely to offer nutrition/food support (97; 56%), viral load testing (99; 69%) and HIV counselling and testing (69; 40%). 10% of sites rated 'low', 59% 'medium' and 31% 'high' in the comprehensiveness score. The mean comprehensiveness of services score increased significantly from 5.6 in 2009 to 7.3 in 2014 (p<0.001; n=30). Patient-level analysis of lost to follow-up after ART initiation estimated the hazard was highest in sites rated 'low' and lowest in sites rated 'high'.
CONCLUSION: This global assessment suggests the potential care impact of scaling-up and sustaining comprehensive paediatric HIV services. Meeting recommendations for comprehensive HIV services should remain a global priority.
OBJECTIVES: To study the initial ART regimens and the rate of switch of ART regimens used during the first 36 months in HIV-infected children with severe anemia and to evaluate their clinical and laboratory outcomes.
METHODS: We analyzed regional cohort data of 130 Asian children aged <18 years with baseline severe anemia (hemoglobin <7.5 g/dl) who started antiretroviral therapy (ART) between January 2003 and September 2013.
RESULTS: At ART initiation, median age was 3.5 years old (interquartile range (IQR) 1.7 to 6.3) and median hemoglobin was 6.7 g/dL (IQR 5.9-7.1, range 3.0-7.4). Initial ART regimens included stavudine (85.4%), zidovudine (13.8%), and abacavir (0.8%). In 81 children with available hemoglobin data after 6 months of ART, 90% recovered from severe anemia with a median hemoglobin of 10.7 g/dL (IQR 9.6-11.7, range 4.4-13.5). Those starting AZT-based ART had a mortality rate of 10.8 (95% confidence interval (CI) 4.8-23.9) per 100 patient-years compared to 2.7 (95% CI 1.6-4.6) per 100 patient-years among those who started d4T-based ART.
CONCLUSIONS: With the phase-out of stavudine, age-appropriate non-zidovudine options are needed for younger Asian children with severe anemia.
METHODS: Data (2014-2018) from a regional cohort of Asian PHIVA who received at least 6 months of continuous cART were analyzed. Treatment failure was defined according to World Health Organization criteria. Descriptive analyses were used to report treatment failure and subsequent management and evaluate postfailure CD4 count and viral load trends. Kaplan-Meier survival analyses were used to compare the cumulative incidence of death and loss to follow-up (LTFU) by treatment failure status.
RESULTS: A total 3196 PHIVA were included in the analysis with a median follow-up period of 3.0 years, of whom 230 (7.2%) had experienced 292 treatment failure events (161 virologic, 128 immunologic, 11 clinical) at a rate of 3.78 per 100 person-years. Of the 292 treatment failure events, 31 (10.6%) had a subsequent cART switch within 6 months, which resulted in better immunologic and virologic outcomes compared to those who did not switch cART. The 5-year cumulative incidence of death and LTFU following treatment failure was 18.5% compared to 10.1% without treatment failure.
CONCLUSIONS: Improved implementation of virologic monitoring is required to realize the benefits of virologic determination of cART failure. There is a need to address issues related to accessibility to subsequent cART regimens, poor adherence limiting scope to switch regimens, and the role of antiretroviral resistance testing.
METHODS: Nine hospitals in Indonesia, Malaysia, the Philippines and Thailand participated in SEA-ORCHID. These hospitals were supported by researchers from three Australian centres. Health care practices and outcomes were assessed for 1000 women at each hospital both before and after the intervention. The capacity development intervention was tailored to the needs and context of each hospital and delivered over an 18 month period. Main outcomes included adherence to forms of care likely to be beneficial and avoidance of forms of care likely to be ineffective or harmful.
RESULTS: We observed substantial variation in clinical practice change between sites. The capacity development intervention had a positive impact on some care practices across all countries, including increased family support during labour and decreased perineal shaving before birth, but in some areas there was no significant change in practice and a few beneficial practices were followed less often.
CONCLUSION: The results of SEA-ORCHID demonstrate that investing in developing capacity for research use, synthesis and generation can lead to improvements in maternal and neonatal health practice and highlight the difficulty of implementing evidence-based practice change.