Outcomes Of HIV-infected Children Research Articles

Treatment Outcomes of HIV Infected Children After Initiation of Antiretroviral Therapy in Southwest China: An Observational Cohort Study.

BackgroundThe number of HIV infected children receiving antiviral treatment in Guangxi is increasing. Understanding factors and trends of mortality and attrition in HIV-infected children under antiretroviral therapy (ART) was an urgent need to improve treatment outcomes. This study aimed to estimate mortality and attrition rates and identify factors that were associated with mortality and attrition after ART initiation among children with HIV in Guangxi, China between 2004 and 2018.MethodsCohort study data were extracted from the National Free Antiretroviral Treatment Program (NFATP) database, which has standard guidelines for core treatment indicators and other data at all HIV/AIDS treatment facilities in Guangxi. A total of 901 HIV-infected children who have started ART were included in the study. The study collected the following data: age, gender, WHO clinic stages before ART, CD4 cell count before ART, Cotrimoxazole prophylaxis (CTX) use before ART, initial ART regimen, malnutrition before ART, abnormal liver function before ART, abnormal kidney function before ART, severe anemia before ART, and the time lag between an HIV diagnosis and ART initiation.ResultsHIV-infected children under ART had a mortality rate of 0.87 per 100 person-years [95% Confidence Interval (CI) 0.63–1.11], and an attrition rate of 3.02 per 100 person-years (95% CI 2.57–3.47). Mortality was lower among children with a CD4 count between 200 and 500 copies/ml [Adjusted Hazard Ratio (AHR) 0.22, 95% CI 0.09–0.55], and CD4 count ≥500 copies/ml (AHR 0.10, 95% CI 0.03–0.29); but higher among children with late ART initiation at 1–3 months (AHR 2.30, 95% CI 1.07–4.94), and at ≥3 months (AHR 2.22, 95% CI 1.04–4.74). Attrition was lower among children with a CD4 count ≥500 copies/ml (AHR 0.62, 95% CI 0.41–0.95), but higher among children with late ART initiation at 1–3 months (AHR 1.55, 95% CI 1.05–2.30).ConclusionSupportive programs are needed to educate children's families and parents on early ART, link HIV-infected children to care and retain them in care among other programs that treat and manage the medical conditions of HIV-infected children before ART initiation.

Prevalence and outcome of HIV infected children admitted in a tertiary hospital in Northern Tanzania

BackgroundProvider Initiated Testing and Counseling (PITC) among hospitalized children have shown to increase the probability of identifying HIV-infected children and hence be able to link them to HIV care. We aimed at determining the prevalence, clinical characteristics and outcome of HIV-infected children admitted at Bugando Medical Centre (BMC) after active provision of PITC services.MethodsA cross-sectional study with follow up at three months post enrollment was done. Children with unknown HIV status were tested for HIV infection as per 2012 Tanzanian algorithm. Questionnaires were used to collect demographic, clinical and follow up information. Data was statistically analyzed in STATA v13.ResultsA total of 525 children were enrolled in the study. Median [IQR] age was 28 [15–54] months. Males consisted of 60.2% of all the participants. HIV prevalence was 9.3% (49/525). Thirty-three (67.3%) of HIV-infected children were newly diagnosed at enrolment. Thirty-nine (79.6%) of all HIV-infected patients had WHO HIV/AIDS clinical stage four disease, 10 (20.4%) had WHO clinical stage three and none qualified in stage one or two. About 84% (41/49) of HIV infected children had severe immunodeficiency at the time of the study. Factors that were independently associated with HIV infection were, cough (OR 2.40 [1.08–5.31], p = 0.031), oral thrush (OR 20.06[8.29–48.52], p < 0.001), generalized lymphadenopathy (OR 5.61 [1.06–29.56], p = 0.042), severe acute malnutrition (OR 6.78 [2.28–20.12], p = 0.001), severe stunting (OR 9.09[2.80–29.53], p = 0.034) and death of one or both parents (OR 3.62 [1.10–11.87], p = 0.034). The overall mortality (in-hospital and post-hospital) was 38.8% among HIV-infected children compared with 14.0% in HIV-uninfected children. Within three months period after discharge from the hospital, 71.4% (25/35) of discharged HIV-infected children reported to have attended HIV clinic at least once and 60.0% (21/35) were on antiretroviral medications.ConclusionPITC to all admitted children identified significant number of HIV-infected children. Mortality among HIV-infected children is high compared to HIV-uninfected. At the time of follow up about 30% of discharged HIV-infected children did not attend to any HIV care and treatment clinics. Therefore effective efforts are needed to guarantee early diagnosis and linkage to HIV care so as to reduce morbidity and mortality among these children.

Effect of antiretroviral therapy care interruptions on mortality in children living with HIV.

To evaluate the characteristics and outcomes of HIV-infected children that have care interruptions, during which the child's health status and use of medication is unknown. We included data on children initiating ART between 2004 and 2016 at less than 16 years old at 16 International Epidemiologic Databases to Evaluate AIDS Southern Africa cohorts. Children were classified as loss to follow up (LTFU) if they had not attended clinic for more than 180 days. Children had a care interruption if they were classified as LTFU, and subsequently returned to care. Children who died within 180 days of ART start were excluded. The main outcome was all cause mortality. Two exposed groups were considered: those with a first care interruption within the first 6 months on ART, and those with a first care interruption after 6 months on ART. Adjusted hazard ratios were determined using a Cox regression model. Among 53 674 children included, 23 437 (44%) had a care interruption, of which 10 629 (20%) had a first care interruption within 6 months on ART and 12 808 (24%) had a first care interruption after 6 months on ART. Increased mortality was associated with a care interruption within 6 months on ART [adjusted hazard ratio (AHR) = 1.52, 95% CI 1.12-2.04] but not with a care interruption after 6 months on ART (AHR = 1.05, 95% CI 0.77-1.44). The findings suggest that strengthening retention of children in care in the early period after ART initiation is critical to improving paediatric ART outcomes.

Immunological factors associated with discordant virological response postcombination antiretroviral therapy in pediatric human immunodeficiency virus infection.

Evaluation of immunological factors responsible for discordant virological responses postcombination antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-positive children aged &lt;5 years. Immunological profiling of enrolled 30 HIV-positive children was done at enrollment, 6 and 12 months. Flow cytometric analysis was performed for enumeration of counts and percentage of CD4⁺, CD8⁺, and CD19⁺ cells; expression of CD19, CD86, PD-1, CD3, CD8 and CD28 on lymphocytes was evaluated using whole blood staining technique with monoclonal antibodies. HIV-1 viral load was quantified using a real-time polymerase chain reaction. Serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin (IgM), and interleukin (IL)-7 were quantitated using quantitative enzyme-linked immunosorbent assay kits. The HIV-infected children were categorized into virological responders (VRs; HIV-1 plasma viral load &lt;47 copies/mL) and virological nonresponders (VNRs; HIV-1 plasma viral load &gt;1000 copies/mL) following 1-year cART. The frequency of CD28⁺ CTLs cells was higher (P &lt; 0.0001), and the frequency of CD28-CTLs cells was lower (P &lt; 0.0001) in VRs than VNRs. CD28⁺ and CD28-CTLs cells correlated with HIV-1 plasma viremia (r = -0.4695, P = 0.01; r = 0.40, P = 0.03, respectively). VRs had higher CD19 percentage (P = 0.04) and count (P = 0.01) than VNRs. CD19⁺ B cells in the VRs had lower expression of CD86 (P = 0.03) and PD-1 (P = 0.002) than VNRs. VR had lower levels of serum IgG (P = 0.03), IgM (P = 0.04), and IL-7 (P = 0.01) than VNRs. High baseline B-cell counts, lower serum IgG, IgM, IL-7 levels, lower activation and exhaustion of B cells, and higher frequency of CD28⁺ CTLs are associated with positive virological response, whereas elevated CD28-CTLs are associated with the poor virological outcomes in HIV-infected children.

A Comparative Study on Effect of Caregivers Training on Health Outcomes of HIV Infected Children on Antiretroviral Therapy in Kenya

The purpose of this cohort study was to assess the effect of caregiver training on health outcomes of HIV-infected children aged 1-14 years on antiretroviral therapy in South Rift Valley, Kenya. Three hundred and twenty children of trained caregivers and 778 children of non-trained caregivers were targeted from four hospitals. Population proportionate to size sampling technique was used to calculate number of children enrolled. Children medical chart for trained and non-trained caregivers were stratified as per year of training, 2014, 2015, 2016 and randomly selected numbers matched with corresponding medical record. Data was collected through review of medical records, questionnaires and caregivers interview. There was significant association between caregiver training and adherence (Fisher's Exact Test X 2 =22.740, p = .001). Children of trained caregivers had significant reductions in viral load (Kruskal Wallis X 2 =7.124, p = .028); significant difference in viral loads was also observed between trained and non-trained caregivers (Mann-Whitney U=19846, p =.012), significant association in episodes of opportunistic infections before, after and among non-trained caregivers (Fisher's Exact Test X 2 =76.768, p = .001). Nutritional status of children was not associated with caregivers training (Pearson Chi-square X 2 = 11.616, p =.072). Most caregivers perceived training to be useful. The study found that, training enables caregivers to improve adherence levels of HIV infected children on antiretroviral therapy. Even though there are HIV information in public domain, the study found, if this information is provided in a structured manner, enables suppression of viral loads of HIV infected children. Training caregivers significantly reduces frequency of opportunistic infections among HIV infected children on antiretroviral therapy. Providing information on nutrition to caregivers does not affect nutritional status of HIV infected children. Training caregivers on HIV information improves health outcomes of HIV infected children thus study provide evidence–based decision making in rolling out caregivers training nationally. Keywords: HIV, Caregivers, Training, Children, Adherence, DOI: 10.7176/JHMN/76-05 Publication date: June 30th 2020

Long-term survival outcomes of HIV infected children receiving antiretroviral therapy: an observational study from Zambia (2003\u20132015)

BackgroundIn 2017, 64% of children living with HIV in Zambia accessed Antiretroviral Therapy (ART). Despite expanded ART coverage, there is paucity of information on effectiveness of pediatric ART in reducing mortality. The aim of this research is to describe treatment outcomes, measure mortality rates and assess predictors of mortality among children receiving ART.MethodsUsing a retrospective cohort study design, we abstracted routinely collected clinical data from medical records of children from birth to 15 years old, who had received ART for at least 6 months at Livingstone Central Hospital in Southern Province Zambia, between January 2003 and June 2015. The primary outcome was death. Cause of death was ascertained from medical records and death certificates. Distribution of survival times according to baseline covariates were estimated using Kaplan Meier and Cox Proportional Hazards methods.ResultsOverall, 1039 children were commenced on ART during the study period. The median age at treatment initiation was 3.6 years (IQR: 1.3–8.6) and 520 (50%) children were female. Of these, 71 (7%) died, 164 (16%) were lost to follow-up, 210 (20%) transferred and 594 (56%) were actively on treatment. After 4450 person years, mortality rate was 1.6/100 (95% CI: 1.4–1.8). Mortality was highest during the first 3 months of treatment (11.7/100 (95% CI: 7.6–16.3). In multivariable proportional hazards regression, the adjusted hazards of death were highest among children aged < 1 year (aHR = 3.1 (95% CI: 1.3–6.4), compared to those aged 6–15 years, WHO stage 4 (aHR =4.8 (95% CI: 2.3–10), compared to WHO stage 1 and 2. In the sensitivity analysis to address bias due to loss to follow-up, mortality increased 5 times when we assumed that all the children who were lost to follow up died within 90 days of their last visit.ConclusionWe observed low attrition due to mortality among children on ART. Loss to follow-up was high (16%). Mortality was highest during the first 3 months of treatment. Children aged less than one year and those with advanced WHO disease stage had higher mortality. We recommend effective interventions to improve retention in care and early diagnosis of HIV in children.

Resistance profile and treatment outcomes in HIV-infected children at virological failure in Benin, West Africa.

In Africa a high percentage of HIV-infected children continue to experience HIV treatment failure despite enormous progress. In Benin (West Africa), there are currently no data on HIV drug resistance at failure in paediatric populations. To assess the frequency and patterns of HIV drug resistance among children with virological ART failures. Dried blood spots from 62 HIV-infected children with virological failure were collected at the paediatric clinic of the National Hospital Center in Cotonou for genotyping and plasma drug concentration determination. Characteristics of the population show a median age of 10 years (IQR 6-13) and a median duration on ART of 5 years (IQR 3-7). Viruses from 53 children were successfully amplified. Of these, 76% of patients were on an NNRTI-based regimen and 24% on a boosted PI-based regimen. NRTI, NNRTI and dual-class resistance was present in 71%, 84% and 65% of cases, respectively. Only 4% of the children had major resistance mutations to PIs and none had major resistance mutations to integrase inhibitors. Among the participants, 25% had undetectable antiretroviral concentrations. Our results showed that the development of drug resistance could be one of the main consequences of high and continuous viral replication in HIV-infected children in Benin. Thus, inadequate attention to monitoring lifelong ART in children may prevent achievement of the goal of the United Nations Program on HIV and AIDS (UNAIDS) of 90% viral suppression among patients receiving ART.

Despite Access to Antiretrovirals for Prevention and Treatment, High Rates of Mortality Persist Among HIV-infected Infants and Young Children

Outcomes of HIV-infected children before widespread use of antiretroviral therapy (ART) for treatment and prevention of mother-to-child transmission (PMTCT) have been well characterized but less is known about children who acquire HIV infection in the context of good ART access. We enrolled newly diagnosed HIV-infected children ≤24 months of age at 3 hospitals and 2 clinics in Johannesburg, South Africa. We report ART initiation and mortality rates during 6 months from enrollment and factors associated with mortality. Of 272 children enrolled, median age 6.1 months, 69.5% were diagnosed during hospitalization. By 6 months postenrollment, 53 (19.5%) died and 73 (26.8%) were lost-to-follow-up. Using Kaplan-Meier analysis, the probability of death by 6 months after enrollment was 23.5%. The median age of death was 9.1 months [95% confidence interval (CI): 8.6-12.0]. Overall, 226 (83%) children initiated ART which was associated with a 71% reduction in risk of death [hazard ratio (HR) = 0.29 (95% CI: 0.15-0.58)]. In multivariable analysis of infant factors, weight-for-age Z score < -2 standard deviation (SD) [HR = 2.43 (95% CI: 1.03-5.73)], CD4 <20% [HR = 3.29 (95% CI: 1.60-6.76)] and identification during hospitalization [HR = 2.89 (95% CI: 1.16-7.25)] were independently associated with mortality. In multivariable analysis of maternal factors, CD4 ≤350/no maternal ART was associated with increased mortality risk [HR = 2.57 (95% CI: 1.19-5.59)] versus CD4 >350/no maternal ART; exposure to maternal/infant antiretrovirals for PMTCT was associated with reduced mortality risk [HR = 0.53 (95% CI: 0.28-0.99)] versus no PMTCT. ART initiation is highly protective against death in young children. However, despite improved access to ART, young children remain at risk for early death; innovative approaches to rapidly diagnose and initiate treatment as early in life as possible are needed.

Outcomes of Paediatrics HIV care at the University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu after ten years of service

Background: Antiretroviral therapy is associated with improved survival among HIV-infected children. In Nigeria, HIV treatment scale up was extended to children over a decade ago. This poses new challenges of sustained quality care.Aim: To determine the outcomes for HIV infected children and factors that influenced retention in care at the University of Nigeria Teaching Hospital, Ituku/Ozalla, Enugu.Methods: This was a study of HIV-infected children seen between September 2004 and October 2015 and at the Paediatric HIV clinic of the University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu. Data collected include socio-demographics, HAART regimen and outcomes. Data analysis were done with Statistical Package for Social Sciences (SPSS) version 19 (Chicago IL).Results: Five hundred and nineteen of 555 enrolled children with complete data were included in the data analysis. Two hundred and sixty-seven (51.4%) were females. Three hundred and thirty-nine participants (65.3%) were still in care, 12345 (23.7%) had been lost to follow up, or 22 (4.2%) dead while 35 (6.87%) were transferred out to other health facilities or into the adult ART clinic. Factors associated with retention in care were both parents being HIV positive (p&lt;0.0001), commencement of HAART (p&lt;0.0001) and HIV disclosure status of the child (Fisher’s exact Test =0.003).Conclusions: About a quarter of our HIV-infected children were lost to follow up. Prompt initiation of HAART and HIV disclosure will positively influence retention in care.Keywords: Paediatric HIV, children, outcomes, Enugu

Pediatric HIV Disclosure Intervention Improves Knowledge and Clinical Outcomes in HIV-Infected Children in Namibia.

Objectives:Using routinely collected data, we evaluated a nationally implemented intervention to assist health care workers and caregivers with HIV disclosure to children. We assessed the impact of the intervention on child's knowledge and health outcomes.Methods:Data were abstracted from national databases and patient charts for HIV-infected children aged 7–15 years attending 4 high-volume HIV clinics in Namibia. Disclosure rates, time to disclosure, and HIV knowledge in 314 children participating in the intervention were analyzed. Logistic regression was used to identify correlates of partial vs. full disclosure. Paired t-tests and McNemar tests were used to compare adherence and viral load (VL) before versus after intervention enrollment.Results:Among children who participated in the disclosure intervention, 11% knew their HIV status at enrollment and an additional 38% reached full disclosure after enrollment. The average time to full disclosure was 2.5 years (interquartile range: 1.2–3 years). Children who achieved full disclosure were more likely to be older, have lower VLs, and have been enrolled in the intervention longer. Among children who reported incorrect knowledge regarding why they take their medicine, 83% showed improved knowledge after the intervention, defined as knowledge of HIV status or adopting intervention-specific language. On comparing 0–12 months before vs. 12–24 months after enrollment in the intervention, VL decreased by 0.5 log10 copies per milliliter (N = 42, P = 0.004), whereas mean adherence scores increased by 10% (N = 88, P value < 0.001).Conclusions:This HIV disclosure intervention demonstrated improved viral suppression, adherence, and HIV knowledge and should be considered for translation to other settings.

High Viremia and Wasting Before Antiretroviral Therapy Are Associated With Pneumonia in Early-Treated HIV-Infected Kenyan Infants.

Human immunodeficiency virus (HIV)-infected children are particularly susceptible to acute respiratory infections (ARIs). We determined incidence and cofactors for ARIs in HIV-infected infants receiving antiretroviral therapy (ART). Human immunodeficiency virus-infected infants initiated ART at ≤12 months of age and were observed monthly for 2 years in Nairobi. Acute respiratory infection rates and cofactors were determined using Andersen-Gill models, allowing for multiple events per infant. Among 111 HIV-infected infants, median age at ART initiation was 4.5 months. Pre-ART median CD4% was 19%, and 29% had wasting. During 24-months follow-up while on ART, upper respiratory infection (URI) and pneumonia rates were 122.6 and 34.7 per 100 person-years (py), respectively. Infants with higher pre-ART viral load (VL) (plasma HIV ribonucleic acid [RNA] ≥7 log10 copies/mL) had 4.12-fold increased risk of pneumonia (95% confidence interval [CI], 2.17-7.80), and infants with wasting (weight-for-height z-score < -2) had 2.87-fold increased risk (95% CI, 1.56-5.28). Infants with both high pre-ART VL and wasting had a higher pneumonia rate (166.8 per 100 py) than those with only 1 of these risk factors (44.4 per 100 py) or neither (17.0 per 100 py). Infants with exposure to wood fuel had significantly higher risk of URI (hazard ratio [HR] = 1.82; 95% CI, 1.44-2.28) and pneumonia (HR = 3.31; 95% CI, 1.76-6.21). In early ART-treated HIV-infected infants, higher HIV RNA and wasting before ART were independent risk factors for pneumonia. Wood fuel use was associated with URI and pneumonia. Additional data on air pollution and respiratory outcomes in HIV-infected children may help optimize interventions to improve their lung health.

CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States.

Objective:This study compared 12-month CD4+ and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies.Design:This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C.Methods:Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4+% and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models.Results:Virologic failure occurred in 939 out of 2373 (40%) children. At 12 months, children switching to new cART (16%) had a nonsignificant increase in CD4+% from baseline, 0.59 percentage points [95% confidence interval (95% CI) −1.01 to 2.19], not different than those who continued failing cART (71%) (−0.64 percentage points, P = 0.15) or switched to a drug-sparing regimen (5%) (1.40 percentage points, P = 0.64). Children discontinuing all ART (7%) experienced significant CD4+% decline −3.18 percentage points (95% CI −5.25 to −1.11) compared with those initiating new cART (P = 0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log10VL by 12 months, the new cART group having the largest drop (−1.15 log10VL).Conclusion:In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring.

Early diagnosis is critical to ensure good outcomes in HIV-infected children: outlining barriers to care

HIV-infected children require early initiation of antiretroviral therapy (ART) to ensure good outcomes. The aim was to investigate missed opportunities in childhood HIV diagnosis leading to delayed ART initiation. Baseline data were reviewed of all children aged <15 years referred over a 1-year period for ART initiation to the Kalafong Hospital HIV services in Gauteng, South Africa. Of the 250 children, one-quarter (24.5%) was of school-going age, 34.5% in the preschool group, 18% between 6 and 12 months old and 23% below 6 months of age (median age = 1.5 years [interquartile range 0.5–4.8]). Most children (82%) presented with advanced/severe HIV disease, particularly those aged 6–12 months (95%). Malnutrition was prominent and referrals were mostly from hospital inpatient services (61%). A structured caregiver interview was conducted in a subgroup, with detailed review of medical records and HIV results. The majority (≥89%) of the 65 interviewed caregivers reported good access to routine healthcare, except for postnatal care (26%). Maternal HIV-testing was mostly done during the second and third pregnancy trimesters (69%). Maternal non-disclosure of HIV status was common (63%) and 83% of mothers reported a lack of psychosocial support. Routine infant HIV-testing was not done in 66%, and inadequate reporting on patient-held records (Road-to-Health Cards/Booklets) occurred frequently (74%). Children with symptomatic HIV disease were not investigated at primary healthcare in 53%, and in 68% of families the siblings were not tested. One-third of children (35%) had a previous HIV diagnosis, with 77% of caregivers aware of these prior results, while 50% acknowledged failing to attend ART services despite referral. In conclusion, a clear strategy on paediatric HIV case finding, especially at primary healthcare, is vital. Multiple barriers need to be overcome in the HIV care pathway to reach high uptake of services, of which especially maternal reasons for not attending paediatric ART services need further exploration.

Early viral suppression improves neurocognitive outcomes in HIV-infected children

To estimate the association of age of viral suppression and central nervous system penetration effectiveness (CPE) score with neurocognitive functioning among school-age children with perinatally acquired HIV infection (PHIV+). We analyzed data from two US-based multisite prospective cohort studies. Multivariable general linear regression models were used to evaluate associations of age at viral suppression and CPE scores (of initial antiretroviral therapy regimen and weighted average) with the Wechsler Intelligence Scale for Children, Third or Fourth Edition neurocognitive assessments [Full-Scale Intelligence Quotient (FSIQ); Performance IQ/Perceptual Reasoning Index (PIQ/PRI); and Verbal IQ/Verbal Comprehension Index (VIQ/VCI)], adjusted for demographic and clinical covariates. Sensitivity analyses were stratified by birth cohort (before versus after 1996). A total of 396 PHIV+ children were included. Estimated differences in mean FSIQ (comparing virally suppressed versus unsuppressed children) by each age cutoff were 3.7, 2.2, 3.2, 4.4, and 3.9 points at ages 1, 2, 3, 4, and 5, respectively. For PIQ/PRI, estimated mean differences were 3.7, 2.4, 2.2, 4.6, and 4.5 at ages 1 through 5, respectively. In both cases, these differences were significant only at the age 4 and 5 thresholds. After stratifying by birth cohort, the association between age at suppression and cognitive function persisted only among those born after 1996. Age at viral suppression was not associated with VIQ/VCI; CPE score was not associated with FSIQ, verbal comprehension, or perceptual reasoning indices. Virologic suppression during infancy or early childhood is associated with improved neurocognitive outcomes in school-aged PHIV+ children. In contrast, CPE scores showed no association with neurocognitive outcomes.

Poor clinical outcomes for HIV infected children on antiretroviral therapy in rural Mozambique: need for program quality improvement and community engagement.

IntroductionResidents of Zambézia Province, Mozambique live from rural subsistence farming and fishing. The 2009 provincial HIV prevalence for adults 15–49 years was 12.6%, higher among women (15.3%) than men (8.9%). We reviewed clinical data to assess outcomes for HIV-infected children on combination antiretroviral therapy (cART) in a highly resource-limited setting.MethodsWe studied rates of 2-year mortality and loss to follow-up (LTFU) for children <15 years of age initiating cART between June 2006–July 2011 in 10 rural districts. National guidelines define LTFU as >60 days following last-scheduled medication pickup. Kaplan-Meier estimates to compute mortality assumed non-informative censoring. Cumulative LTFU incidence calculations treated death as a competing risk.ResultsOf 753 children, 29.0% (95% CI: 24.5, 33.2) were confirmed dead by 2 years and 39.0% (95% CI: 34.8, 42.9) were LTFU with unknown clinical outcomes. The cohort mortality rate was 8.4% (95% CI: 6.3, 10.4) after 90 days on cART and 19.2% (95% CI: 16.0, 22.3) after 365 days. Higher hemoglobin at cART initiation was associated with being alive and on cART at 2 years (alive: 9.3 g/dL vs. dead or LTFU: 8.3–8.4 g/dL, p<0.01). Cotrimoxazole use within 90 days of ART initiation was associated with improved 2-year outcomes Treatment was initiated late (WHO stage III/IV) among 48% of the children with WHO stage recorded in their records. Marked heterogeneity in outcomes by district was noted (p<0.001).ConclusionsWe found poor clinical and programmatic outcomes among children taking cART in rural Mozambique. Expanded testing, early infant diagnosis, counseling/support services, case finding, and outreach are insufficiently implemented. Our quality improvement efforts seek to better link pregnancy and HIV services, expand coverage and timeliness of infant diagnosis and treatment, and increase follow-up and adherence.

A model‐based approach for the evaluation of once daily dosing of lamivudine in HIV‐infected children

Little attention has been paid to the effects of compliance and prescription practice on treatment outcome in HIV-infected children. In this context, an evaluation of the role of covariates on pharmacokinetics is required to establish the impact of differences in dosing regimens. Here we investigate whether a once daily dosing regimen of lamivudine provides comparable exposure to the currently approved paediatric regimen. A hypothetical group of 180 patients between 3 months and 12 years old was used to evaluate the impact of body weight on systemic exposure to lamivudine. Simulation scenarios were evaluated using AUC and Cmax as parameters of interest. The analysis was performed using a population pharmacokinetic model previously implemented in nonmem v.6.2. The simulations show that once daily dosing of lamivudine yields comparable exposure to historical values observed in children and adults, both for liquid and solid dosage forms. Simulated steady-state AUC(0-24 h) and Cmax values after once daily doses ranged respectively from 9.9 mg l⁻¹ h and 1.9 mg l⁻¹ for children lighter than 14 kg to 13.75 mg l⁻¹ h and 3.0 mg l⁻¹ for children heavier than 30 kg. These values are comparable or higher than historical values observed after once daily dosing in children and adults. Our findings illustrate how dosing regimens can be evaluated taking into account the effects of developmental growth on drug disposition. Most importantly, they suggest that the reduction in dosing frequency to once daily leads to comparable lamivudine exposure, as observed after administration of a twice daily dosing regimen.

Baseline clinical and immunological characteristics of pediatric antiretroviral (ART) patients in Vietnam, 2006-2010

Purpose of the study: The PMTCT and pediatric ART programs in Vietnam started in 2005 and pediatric ART has expanded to 42/63 (67%) provinces with over 3,300 children currently receiving ART. National care and treatment guidelines were revised in August 2009 and again in January 2011 to recommend immediate ART for children Method: A retrospective cohort study was conducted between May - July 2011 at 20 pediatric HIV clinics. Data were abstracted from medical records of children initiating ART during January 2006 - December 2010. Summary of results: Mean age at ART initiation among 2,362 children was 4.4 years, and 52% of children were male. The mean proportion with baseline WHO clinical stage 3-4 was 43%, with no reduction over time (p>0.05, Chi square for trend). Mean weight for height z-score was -0.9. Mean CD4% was 11.9%, and this increased from 10.3% in 2006 to 13.4% in 2010 (p Conclusion: Baseline CD4% at ART initiation increased with program expansion. Among children aged <1, there was no significant increase in ART initiation and no change in baseline CD4% or clinical stage. Earlier identification of infected children, linkages to care, and earlier ART initiation are critical to improving outcomes for HIV-infected children in Vietnam.

Assessment of Five Years’Comprehensive Management of HIV-Infected Children in Parakou

Introduction: The Pediatric Unit of the Borgou Regional Hospital (CHD-Borgou) in Parakou has initiated treating HIV-infected children with Anti-Retroviral (ARV) drugs since 2005. This study aimed to describe the profile and the future of the HIV-infected children who were provided medical care at the Pediatric Unit of the CHD-Borgou from 2005 to 2009. Patients and methods: It is a retrospective study with descriptive and analytical objective, carried out from January 2005 to December 2009 on 105 HIV-infected children from both sexes cared in that Unit. Results: HIV infection represented 0.43% of the children brought for medical examination during the study period. Among these children, 82.9% were at clinical stages 3 or 4 on inclusion into patient panel and 76.2% had severe immunodeficiciency. The proportion of children on Anti-Retroviral Therapy (ART) was 69.1%. The main opportunistic infections found were digestive (30.3%), pulmonary (28.5%), dermatological (24.1%) and ENT (10.5%) ones. The problems identified included lack of early diagnostic tools, frequent shortage of antiretroviral drugs, treatment or therapeutic failures, causes related to poor compliance and follow up. The lost of follow up rate was 39%. Death rate was 33.3%. Death was significantly associated with the advanced clinical stage of disease on admission (p=0.002), with age at the time of screening (p=0.017) and with follow up duration (p=0.000). Conclusion: Despite the difficulties noted, this study showed that, in limited resources settings like ours, it is possible to improve the clinical outcome of HIV infected children. The high mortality rate noted related to the delayed HIV diagnosis can be reduced by strengthening the Prevention of Mother to Child Transmission (PMTCT) program.

Mortality and Clinical Outcomes in HIV-Infected Children on Antiretroviral Therapy in Malawi, Lesotho, and Swaziland

To determine mortality and immune status improvement in HIV-infected pediatric patients on antiretroviral treatment (ART) in Malawi, Lesotho, and Swaziland. We conducted a retrospective cohort study of patients aged <12 years at ART initiation at 3 sites in sub-Saharan Africa between 2004 and 2009. Twelve-month and overall mortality were estimated, and factors associated with mortality and immune status improvement were evaluated. Included in the study were 2306 patients with an average follow-up time on ART of 2.3 years (interquartile range 1.5-3.1 years). One hundred four patients (4.5%) died, 9.0% were lost to follow-up, and 1.3% discontinued ART. Of the 104 deaths, 77.9% occurred in the first year of treatment with a 12-month mortality rate of 3.5%. The overall mortality rate was 2.25 deaths/100 person-years (95% confidence interval [CI] 1.84-2.71). Increased 12-month mortality was associated with younger age; <6 months (hazard ratio [HR] = 8.11, CI 4.51-14.58), 6 to <12 months (HR = 3.43, CI 1.96-6.02), and 12 to <36 months (HR = 1.92, CI 1.16-3.19), and World Health Organization stage IV (HR = 4.35, CI 2.19-8.67). Immune status improvement at 12 months was less likely in patients with advanced disease and age <12 months. Despite challenges associated with pediatric ART in developing countries, low mortality and good treatment outcomes can be achieved. However, outcomes are worse in younger patients and those with advanced disease at the time of ART initiation, highlighting the importance of early diagnosis and treatment.

Mortality and Clinical Outcomes in HIV-Infected Children on Antiretroviral Therapy in Malawi, Lesotho, and Swaziland

Mortality and Clinical Outcomes in HIV-Infected Children on Antiretroviral Therapy in Malawi, Lesotho, and Swaziland