Antiretroviral Therapy Initiation In Children Research Articles

Predicting mortality within 1 year of ART initiation in children and adolescents living with HIV in sub-Saharan Africa: a retrospective observational cohort study

Differentiated service delivery (DSD) for children and adolescents living with HIV can improve targeted resource use. We derived a mortality prediction score to guide clinical decision making for children and adolescents living with HIV. Data for this retrospective observational cohort study were evaluated for all children and adolescents living with HIV and initiating antiretroviral therapy (ART); aged 0-19 years; and enrolled at Baylor clinics in Eswatini, Malawi, Lesotho, Tanzania, and Uganda between 2005 and 2020. Data for clinical prediction, including anthropometric values, physical examination, ART, WHO stage, and laboratory tests were captured at ART initiation. Backward stepwise variable selection and logistic regression were performed to develop predictive models for mortality within 1 year of ART initiation. Probabilities of mortality were generated, compared with true outcomes, internally validated, and evaluated against WHO advanced HIV criteria. The study population included 16 958 children and adolescents living with HIV and initiated on ART between May 18, 2005, and Dec 18, 2020. Predictive variables for the most accurate model included: age, CD4 percentage, white blood cell count, haemoglobin concentration, platelet count, and BMI Z score as continuous variables, and WHO clinical stage and oedema, abnormal muscle tone and respiratory distress on examination as categorical variables. The area under the curve (AUC) of the predictive model was 0·851 (95% CI 0·839-0·863) in the training set and 0·822 (0·800-0·845) in the test set, compared with 0·606 (0·595-0·617) for the WHO advanced HIV criteria (p<0·0001). This study evaluated a large, multinational population to derive a mortality prediction tool for children and adolescents living with HIV. The model more accurately predicted clinical outcomes than the WHO advanced HIV criteria and has the potential to improve DSD for children and adolescents living with HIV in high-burden settings. National Institute of Health Fogarty International Center.

Optimal Timing of Antiretroviral Therapy Initiation in Children and Adolescents With Human Immunodeficiency Virus-Associated Pulmonary Tuberculosis.

There is insufficient evidence in children and adolescents with human immunodeficiency virus (CAHIV) to guide the timing of antiretroviral treatment (ART) initiation after starting treatment for pulmonary tuberculosis (pTB). To address this knowledge gap, we evaluated the risk of mortality associated with timing of ART initiation in ART-naive CAHIV treated for pTB. Data were extracted from electronic medical records of ART-naive patients, aged 0-19 years, who were treated for HIV-associated pTB at Baylor Centers of Excellence in Botswana, Eswatini, Malawi, Lesotho, Tanzania, or Uganda between 2013 and 2020. Data were analyzed against a primary outcome of all-cause mortality with unadjusted Kaplan-Meier curves and Cox proportional hazard models. The study population included 774 CAHIV with variable intervals to ART initiation after starting TB treatment: <2 weeks (n = 266), 2 weeks to 2 months (n = 398), >2 months (n = 66), and no ART initiated (n = 44). Adjusted Cox proportional hazards models demonstrated increased mortality 1 year from TB treatment initiation in children never starting ART (adjusted HR [aHR]: 2.67; 95% CI: 1.03, 6.94) versus children initiating ART between 2 weeks and 2 months from TB treatment initiation. Mortality risk did not differ for the <2-weeks group (aHR: 1.02; 95% CI: .55, 1.89) versus the group initiating ART between 2 weeks and 2 months. This retrospective study demonstrated no increase in mortality among CAHIV initiating ART <2 weeks from TB treatment initiation. Given the broad health benefits of ART, this evidence supports the recent WHO recommendation for CAHIV to initiate ART within 2 weeks of initiating TB treatment.

Growth improvement following antiretroviral therapy initiation in children with perinatally-acquired HIV diagnosed in older childhood in Zimbabwe: a prospective cohort study

BackgroundChildren who initiate antiretroviral therapy (ART) before age 5 years can recover height and weight compared to uninfected peers, but growth outcomes are unknown for children initiating ART at older ages. We investigated factors associated with growth failure at ART initiation and modelled growth by age on ART.MethodsWe conducted secondary analysis of cohort of children aged 6–15 years late-diagnosed with HIV in Harare, Zimbabwe, with entry at ART initiation in 2013–2015.Factors associated with height-for-age (HAZ), weight-for-age (WAZ) and BMI-for-age (BAZ) z-scores <− 2 (stunting, underweight and wasting respectively) at ART initiation were assessed using multivariable logistic regression. These outcomes were compared at ART initiation and 12 month follow-up using paired t-tests. HAZ and BAZ were modelled using restricted cubic splines.ResultsParticipants (N = 302; 51.6% female; median age 11 years) were followed for a median of 16.6 months (IQR 11.0–19.8). At ART initiation 34.8% were stunted, 34.5% underweight and 15.1% wasted. Stunting was associated with age ≥ 12 years, CD4 count < 200 cells/μl, tuberculosis (TB) history and history of hospitalisation. Underweight was associated with older age, male sex and TB history, and wasting was associated with older age, TB history and hospitalisation. One year post-initiation, t-tests showed increased WAZ (p = 0.007) and BAZ (p = 0.004), but no evidence of changed HAZ (p = 0.85). Modelling showed that HAZ and BAZ decreased in early adolescence for boys on ART, but not girls.ConclusionStunting and underweight were prevalent at ART initiation among late-diagnosed children, and HAZ did not improve after 1 year. Adolescent boys with perinatally acquired HIV and late diagnosis are particularly at risk of growth failure in puberty.

Impact of WHO guidelines on trends in HIV testing and ART initiation among children living with HIV in Zambia

BackgroundAbout 13 years since the introduction of antiretroviral therapy (ART) for children living with HIV (CLHIV) in Zambia, HIV/AIDS testing and treatment guidelines for children have evolved over the years with limited documentation of long-term trends in the numbers testing HIV positive and initiating ART. We examined trends in HIV testing and ART initiation in Zambia.MethodsWe conducted a retrospective cohort study using routinely collected patient level data from 496 health facilities across Zambia. We used Poisson regression to derive incident rate ratios and 95% confidence intervals (95% CI) for background characteristics and used a Cuzick non-parametric test for trends to test the 13-year trends. Median time from testing to ART initiation in days and incidence rates were derived using life tables in survival analysis. We used multi-level random effects Poisson regression model to determine variations in time from HIV testing to ART initiation by facility.ResultsOverall, the cumulative proportion of the children who tested positive and initiated antiretroviral therapy (ART for HIV) from 2004 to 2017 was 69% (n = 99 592). During the period under review proportions of ART initiation increased from 52% in 2004–2006 to 97% in 2016–2017 (P < 0.001) and time from testing to ART initiation reduced from a median of 17 days IQR (1–161) in 2004 to one day IQR (1–14), P < 0.001 in 2016–2017. CLHIV were 15 times more likely to be initiated on ART in 2016-17 compared to period 2004-6 (IRR = 15.2, 95% CI 14.7–15.7). Time to ART initiation increased with age and was higher in rural health facilities compared to urban facilities. About 11% of the variability in time to ART initiation in children could be attributed to differences between facilities.ConclusionsThe substantial increase in ART initiation and reduction in time to ART initiation among CLHIV identified in this study, reflects improvements in the paediatric HIV programme in Zambia in relation to health care delivery and adherence to national testing and treatment guidelines that were adapted from WHO guidelines. However, age-related differentials in rates of ART initiation suggests that urgent interventions are needed to sustain and further improve programme performance.

Caregiver-reported antiretroviral therapy non-adherence during the first week and after a month of treatment initiation among children diagnosed with HIV in Ethiopia

ABSTRACTTo achieve optimal virologic suppression for children undergoing antiretroviral therapy (ART), adherence must be excellent. This is defined as taking more than 95% of their prescribed doses. To our knowledge, no study in Ethiopia has evaluated the level of treatment adherence at the beginning of the child’s treatment. Our aim was therefore to evaluate caregiver-reported ART non-adherence among children and any predictors for this during the early course of treatment. We conducted a prospective cohort study of 306 children with HIV in eight health facilities in Ethiopia who were registered at ART clinics between 20 December 2014 and 20 April 2015. The adherence rate reported by caregivers during the first week and after a month of treatment initiation was 92.8% and 93.8%, respectively. Our findings highlight important predictors of non-adherence. Children whose caregivers were not undergoing HIV treatment and care themselves were less likely to be non-adherent during the first week of treatment (aOR = 0.17, 95% CI: 0.04, 0.71) and the children whose caregivers did not use a medication reminder after one month of treatment initiation (aOR = 5.21, 95% CI: 2.23, 12.16) were more likely to miss the prescribed dose. Moreover, after one month of the treatment initiation, those receiving protease inhibitor (LPV/r) or ABC-based treatment regimens were more likely to be non-adherent (aOR = 12.32, 95% CI: 3.25, 46.67). To promote treatment adherence during ART initiation in children, particular emphasis needs to be placed on a baseline treatment regimen and ways to issue reminders about the child’s medication to both the health care system and caregivers. Further, large scale studies using a combination of adherence measuring methods upon treatment initiation are needed to better define the magnitude and predictors of ART non-adherence in resource-limited settings.

Incidence and Prevalence of Opportunistic and Other Infections and the Impact of Antiretroviral Therapy Among HIV-infected Children in Low- and Middle-income Countries: A Systematic Review and Meta-analysis.

We conducted a systematic review and meta-analysis to evaluate the incidence and prevalence of 14 opportunistic infections (OIs) and other infections as well as the impact of antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected children (aged <18 years) in low- and middle-income countries (LMICs), to understand regional burden of disease, and inform delivery of HIV services. Eligible studies described the incidence of OIs and other infections in ART-naive and -exposed children from January 1990 to November 2013, using Medline, Global Health, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Knowledge, and Literatura Latino Americana em Ciências da Saúde databases. Summary incident risk (IR) and prevalent risk for each OI in ART-naive and ART-exposed children were calculated, and unadjusted odds ratios calculated for impact of ART. The number of OI cases and associated costs averted were estimated using the AIDS impact model. We identified 4542 citations, and 88 studies were included, comprising 55 679 HIV-infected children. Bacterial pneumonia and tuberculosis were the most common incident and prevalent infections in both ART-naive and ART-exposed children. There was a significant reduction in IR with ART for the majority of OIs. There was a smaller impact on bacterial sepsis and pneumonia, and an increase observed for varicella zoster. ART initiation based on 2010 World Health Organization guidelines criteria for ART initiation in children was estimated to potentially avert >161 000 OIs (2013 UNAIDS data) with estimated cost savings of at least US$17 million per year. There is a decrease in the risk of most OIs with ART use in HIV-infected children in LMICs, and estimated large potential cost savings in OIs averted with ART use, although there are greater uncertainties in pediatric data compared with that of adults.

Age-specific and sex-specific weight gain norms to monitor antiretroviral therapy in children in low-income and middle-income countries.

Viral load and CD4% are often not available in resource-limited settings for monitoring children's responses to antiretroviral therapy (ART). We aimed to construct normative curves for weight gain at 6, 12, 18, and 24 months following initiation of ART in children, and to assess the association between poor weight gain and subsequent responses to ART. Analysis of data from HIV-infected children younger than 10 years old from African and Asian clinics participating in the International epidemiologic Databases to Evaluate AIDS. The generalized additive model for location, scale, and shape was used to construct normative percentile curves for weight gain at 6, 12, 18, and 24 months following ART initiation. Cox proportional models were used to assess the association between lower percentiles (< 50th) of weight gain distribution at the different time points and subsequent death, virological suppression, and virological failure. Among 7173 children from five regions of the world, 45% were underweight at baseline. Weight gain below the 50th percentile at 6, 12, 18, and 24 months of ART was associated with increased risk of death, independent of baseline characteristics. Poor weight gain was not associated with increased hazards of virological suppression or virological failure. Monitoring weight gain on ART using age-specific and sex-specific normative curves specifically developed for HIV-infected children on ART is a simple, rapid, sustainable tool that can aid in the identification of children who are at increased risk of death in the first year of ART.

Randomized clinical trial of immediate versus deferred antiretroviral therapy initiation in children older than one year with moderate immunodeficiency: The PREDICT study

Randomized clinical trial of immediate versus deferred antiretroviral therapy initiation in children older than one year with moderate immunodeficiency: The PREDICT study

When to start antiretroviral therapy in children with TB?

Evaluation of: Yotebieng M, Van Rie A, Moultrie H et al. Effect on mortality and virological response of delaying antiretroviral therapy initiation in children receiving tuberculosis treatment. AIDS 24, 1341–1349 (2010).The initiation of antiretroviral therapy (ART) after starting TB treatment is complex, involving many variables including treatment tolerance, drug co-toxicities, pharmacokinetic drug interactions and polypharmacy impacts on adherence. Delayed ART potentially allows better determination of a specific cause for a drug side effect, decreasing the severity of paradoxical reactions and adherence difficulties. However, of overriding importance is mortality associated with delayed ART initiation versus mortality associated with immune restoration disease with early ART. While results of adult randomized trials addressing this question are becoming available, there are little data to inform the ‘when to start’ question for children.

The clinical pattern, prevalence, and factors associated with immune reconstitution inflammatory syndrome in Ugandan children

To determine clinical pattern, prevalence, and factors associated with pediatric immune reconstitution inflammatory syndrome (IRIS) in Uganda. A prospective, multicenter cross-sectional study. We enrolled HIV-infected children receiving antiretroviral therapy (ART) between 0.5 and 6 months duration from December 2006 to October 2007 at three pediatric clinics in Uganda. Children were evaluated for IRIS at a one-time study visit by a standardized pediatric case definition. The IRIS prevalence was 38% [95% confidence interval (CI) 31-46] among 162 children (57% female) with a median age of 6 years (interquartile range 2.5-11 years). Of the IRIS events, 77% were unmasking of a new opportunistic infection and 23% were probable paradoxical IRIS events toward prior opportunistic infections. The majority of IRIS events (55%) occurred in the first month of ART. The clinical events were diverse, with tuberculosis-IRIS (29%) being the most frequent presentation. Independent risk factors for IRIS were pre-ART CD4(+) cell percentage below 15% (odds ratio = 3.1, 95% CI 1.2-8.4, P = 0.027), current CD8(+) cell absolute count below 1000 cells/microl (odds ratio = 4.3, 95% CI 1.8-10.4, P = 0.001), male sex (odds ratio = 2.6, 95% CI 1.06-8.4, P = 0.01), and a cough of more than 1 week duration at the current clinic visit (odds ratio = 4.3, 95% CI 1.7-10.7, P = 0.002). A more than 25 CD4(+) T-cells increase at current study visit from the pre-ART baseline was associated with IRIS by univariate (P = 0.005) but not multivariate analysis. IRIS events commonly occur early after ART initiation in children with advanced immunosuppression, as commonly seen in resource-limited areas. Both healthcare providers and caregivers of the children need awareness of IRIS to minimize ART nonadherence.

Effect on mortality and virological response of delaying antiretroviral therapy initiation in children receiving tuberculosis treatment.

To estimate the effect of delaying antiretroviral treatment (ART) for 15, 30, or 60 days after tuberculosis (TB) treatment initiation on mortality and virological suppression. Cohort of 573 ART-naive HIV-infected children initiated on TB treatment at an outpatient clinic in South Africa between April 2004 and March 2008. Hazard ratios for mortality and viral suppression were estimated using marginal structural models and multivariate Cox models, respectively. During follow-up (median 9.64 months), 37 HIV-infected children died after a median of 62 days of TB treatment. ART was initiated in 461 children at a median of 17 days after TB treatment initiation, 415 (90%) achieved viral suppression. The hazard ratios of death for initiating ART more than 15, more than 30, or more than 60 days of TB treatment compared with initiating within 15, 30 and 60 days, respectively, were 0.82 (95% CI: 0.48, 1.41), 0.86 (95% CI: 0.46, 1.60), and 1.32 (95% CI: 0.55, 3.16). Hazard ratios for analysis restricted to severely immunosuppressed children were: 0.92 (95% CI: 0.51, 1.63), 1.08 (95% CI: 0.56, 2.08), and 2.23 (95% CI: 0.85, 5.80), respectively. Hazard ratios for viral suppression were 0.98 (95% CI: 0.76, 1.26), 0.95, (95% CI: 0.73, 1.23), 0.84 (95% CI: 0.61, 1.15), respectively and did not change with restriction to children severely immunosuppressed. In this observational study, we found that delaying ART for 2 months or more in children diagnosed with TB may be associated with poorer virological response and increased mortality, particularly in children with severe immunosuppression. These findings should be confirmed in a randomized controlled trial.

Effect on mortality and virological response of delaying antiretroviral therapy initiation in children receiving tuberculosis treatment

Effect on mortality and virological response of delaying antiretroviral therapy initiation in children receiving tuberculosis treatment

When to start antiretroviral therapy in HIV-infected children

No abstract available.