Beyond early infant diagnosis: case finding strategies for identification of HIV-infected infants and children.
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ABSTRACT:
SUBMITTER: Ahmed S
PROVIDER: S-EPMC4122794 | biostudies-other | 2013 Nov
REPOSITORIES: biostudies-other
Publications
Beyond early infant diagnosis: case finding strategies for identification of HIV-infected infants and children.
Ahmed Saeed S Kim Maria H MH Sugandhi Nandita N Phelps B Ryan BR Sabelli Rachael R Diallo Mamadou O MO Young Paul P Duncan Dana D Kellerman Scott E SE
AIDS (London, England) 20131101
There are 3.4 million children infected with HIV worldwide, with up to 2.6 million eligible for treatment under current guidelines. However, roughly 70% of infected children are not receiving live-saving HIV care and treatment. Strengthening case finding through improved diagnosis strategies, and actively linking identified HIV-infected children to care and treatment is essential to ensuring that these children benefit from the care and treatment available to them. Without attention or advocacy, ...[more]
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Project description:BackgroundHIV-infected infants have high risk of death in the first two years of life if untreated. WHO guidelines recommend early infant HIV diagnosis (EID) of all HIV-exposed infants and immediate antiretroviral therapy (ART) in HIV-infected children under 24-months. We assessed the cost-effectiveness of this strategy in HIV-exposed non-breastfed children in Thailand.MethodsA decision analytic model of HIV diagnosis and disease progression compared: EID using DNA PCR with immediate ART (Early-Early); or EID with deferred ART based on immune/clinical criteria (Early-Late); vs. clinical/serology based diagnosis and deferred ART (Reference). The model was populated with survival and cost data from a Thai observational cohort and the literature. Incremental cost-effectiveness ratio per life-year gained (LYG) was compared against the Reference strategy. Costs and outcomes were discounted at 3%.ResultsMean discounted life expectancy of HIV-infected children increased from 13.3 years in the Reference strategy to 14.3 in the Early-Late and 17.8 years in Early-Early strategies. The mean discounted lifetime cost was $17,335, $22,583 and $29,108, respectively. The cost-effectiveness ratio of Early-Late and Early-Early strategies was $5,149 and $2,615 per LYG, respectively as compared to the Reference strategy. The Early-Early strategy was most cost-effective at approximately half the domestic product per capita per LYG ($4,420 in Thailand 2011). The results were robust in deterministic and probabilistic sensitivity analyses including varying perinatal transmission rates.ConclusionIn Thailand, EID and immediate ART would lead to major survival benefits and is cost- effective. These findings strongly support the adoption of WHO recommendations as routine care.
| S-EPMC3954590 | biostudies-literature
Project description:Setting: Mzuzu Central Hospital (MZCH), Mzuzu, and Chitipa District Hospital (CDH), Chitipa, Malawi. Objective: To compare management and outcomes of human immunodeficiency virus (HIV) exposed infants in early infant diagnosis (EID) programmes at MZCH, where DNA polymerase chain reaction (PCR) testing is performed on site, and CDH, where samples are sent to MZCH, between 2013 and 2014. Design: Retrospective cohort study. Results: Of infants enrolled at MZCH (n = 409) and CDH (n = 176), DNA PCR results were communicated to the children's guardians in respectively 56% and 51% of cases. The median time from sample collection to guardians receiving results was 34 days for MZCH and 56 days for CDH. In both hospitals, only half of the dried blood spot (DBS) samples were collected between 6 and 8 weeks. More guardians from MZCH than CDH received test results within 1 month of sample collection (25% vs. 10%). Among the HIV-positive infants, a higher proportion at MZCH (92%) started antiretroviral therapy than at CDH (46%). The relative risk (RR) of death was higher among infants with late DBS collection (RR 1.3, 95%CI 1.0-1.7) or no collection (RR 5.8, 95%CI 4.6-7.2), and when guardians did not receive test results (RR 8.3, 95%CI 5.7-11.9). Conclusion: EID programmes performed equally poorly at both hospitals, and might be helped by point-of-care DNA PCR testing. Better programme implementation and active follow-up might improve infant outcome and retention in care.
| S-EPMC5493108 | biostudies-other
Project description:Early infant diagnosis (EID) involves age-specific tracking and testing of HIV-exposed infants during the first 18 months of life and rapid initiation of life-saving treatment for those infected. In Kenya, pre-2013 data estimate EID lost to follow-up (LTFU) at 39-65%, yet no study has documented LTFU rates and predictors throughout the EID cascade since Option B+ fundamentally changed services by placing all HIV-positive expectant mothers on lifelong treatment. Using an explanatory mixed-method design, we assessed LTFU rates and predictors among 870 mother-infant dyads enrolled in EID in six urban/peri-urban Kenyan government hospitals. Mothers completed baseline surveys, and dyads were tracked through EID. We selected 12 baseline variables and modeled odds of LTFU at 9 and 18 months using mixed logistic regression. Qualitative interviews were conducted with 61 mothers to assess barriers and facilitators to completing EID. Thematically coded transcripts were used to interpret quantitative predictors of LTFU. By the 18-month test, 145 dyads (22%) were LTFU, with three-quarters of LTFU occurring between 9- and 18-month tests. Odds of LTFU at 18 months decreased by 10% for each additional year of maternal age and by 66% with HIV status disclosure. Qualitative data revealed how disclosure facilitated essential social support for EID completion and how older mothers attributed maturity and life experience to successful engagement in care. Findings suggest LTFU rates in Kenya have declined, but gaps remain in ensuring universal coverage. Efforts to improve retention should focus on increasing support for younger mothers and those who have not disclosed their HIV status.
| S-EPMC6661912 | biostudies-literature
Project description:In countries with a high seroprevalence of human immunodeficiency virus type 1 (HIV-1), HIV infection contributes significantly to infant mortality. We investigated antiretroviral-treatment strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial.HIV-infected infants 6 to 12 weeks of age with a CD4 lymphocyte percentage (the CD4 percentage) of 25% or more were randomly assigned to receive antiretroviral therapy (lopinavir-ritonavir, zidovudine, and lamivudine) when the CD4 percentage decreased to less than 20% (or 25% if the child was younger than 1 year) or clinical criteria were met (the deferred antiretroviral-therapy group) or to immediate initiation of limited antiretroviral therapy until 1 year of age or 2 years of age (the early antiretroviral-therapy groups). We report the early outcomes for infants who received deferred antiretroviral therapy as compared with early antiretroviral therapy.At a median age of 7.4 weeks (interquartile range, 6.6 to 8.9) and a CD4 percentage of 35.2% (interquartile range, 29.1 to 41.2), 125 infants were randomly assigned to receive deferred therapy, and 252 infants were randomly assigned to receive early therapy. After a median follow-up of 40 weeks (interquartile range, 24 to 58), antiretroviral therapy was initiated in 66% of infants in the deferred-therapy group. Twenty infants in the deferred-therapy group (16%) died versus 10 infants in the early-therapy groups (4%) (hazard ratio for death, 0.24; 95% confidence interval [CI], 0.11 to 0.51; P<0.001). In 32 infants in the deferred-therapy group (26%) versus 16 infants in the early-therapy groups (6%), disease progressed to Centers for Disease Control and Prevention stage C or severe stage B (hazard ratio for disease progression, 0.25; 95% CI, 0.15 to 0.41; P<0.001). Stavudine was substituted for zidovudine in four infants in the early-therapy groups because of neutropenia in three infants and anemia in one infant; no drugs were permanently discontinued. After a review by the data and safety monitoring board, the deferred-therapy group was modified, and infants in this group were all reassessed for initiation of antiretroviral therapy.Early HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76% and HIV progression by 75%. (ClinicalTrials.gov number, NCT00102960.)
| S-EPMC2950021 | biostudies-literature
Project description:Interventions to prevent mother-to-child HIV transmission have been extremely successful, but new HIV infections continue to occur in infants. Strong evidence indicates that combination antiretroviral therapy (ART) for treatment should be started in HIV-infected infants to prevent early morbidity and mortality. In 2013, the report of the Mississippi baby, who was started on ART within 30 h of life and maintained off-treatment remission for 27 months before HIV was once again detectable, generated renewed interest in very early ART initiation. The case stimulated interest in the possibility of HIV remission, which we define as maintenance of plasma viraemia below the threshold of detection in the absence of ART, after early treatment initiation. The possibility of HIV remission elicits much hope, given that children with HIV infection currently face a lifetime of treatment. The potential for early ART to lead to HIV remission in infants can be thought of in terms of six factors: rapidity of viral suppression with very early ART; initial viral suppression rate with early ART; later virological control after early treatment; the effect of early treatment on the viral reservoir size; outcomes of randomised trials of structured treatment interruption; and the likelihood of viral rebound in neonates after ART cessation. Review of existing data suggests that achieving long-term remission off treatment remains elusive, and concentrated attention and commitment of the scientific community is needed to investigate the factors that might help to reach this goal.
| S-EPMC7487171 | biostudies-literature
Project description:Introduction. Early infant diagnosis (EID) of human immunodeficiency virus (HIV) ensures prompt treatment and infant survival. In Kaabong Hospital, 20% of HIV exposed infants (HEIs) had access to HIV diagnosis by eight weeks. We aimed to improve EID of HIV by deoxyribonucleic acid-polymerase chain reaction (DNA-PCR) testing by eight weeks from 20 to 100% between June 2014 and November 2015. Method. In this quality improvement (QI) project, EID data was reviewed, gaps prioritized using theme matrix selection, root causes analyzed using fishbone tool, and improvement changes were selected using counter measures matrix but implemented using Plan-Do-Study-Act cycle. Root causes of low first DNA-PCR testing included maternal EID ignorance, absent lost mother-baby pairs (LMBP) tracking system, and no EID performance reviews. Health education, Continuous Medical Education (CMEs), and integration of laboratory and EID services were initial improvement changes used. Results. DNA-PCR testing increased from 20 to 100% between June 2014 and July 2015 and was sustained at 100% until February 2016. Two declines, 67% in September 2014 and 75% in June 2015, due to LMBP were addressed using expert clients and peer mothers, respectively. Conclusion. Formation of WIT, laboratory service integration at MBCP, and task shifting along EID cascade improved EID outcomes at 6 weeks.
| S-EPMC5220451 | biostudies-literature
Project description:IntroductionViral load testing is essential to manage HIV disease, especially in infants and children. Early infant diagnosis is performed using nucleic-acid testing in children under 18 months. Resource-limited health systems face severe challenges to scale-up both viral load and early infant diagnosis to unprecedented levels. Streamlining laboratory systems would be beneficial to improve access to quality testing and to increase efficiency of antiretroviral treatment programmes. We evaluated the performance of viral load testing to serve as an early infant diagnosis assay in children younger than 18 months.MethodsThis study was an observational, prospective study, including children between one and 18 months of age who were born to HIV-positive mothers in 134 health facilities in Maputo City and Maputo Province, Mozambique. Dried blood spot specimens from heel or toe pricks were collected between January and April 2018, processed using SPEX buffer for both assays, and tested for routine EID and VL testing using the Roche CAP/CTM HIV-1 Qualitative v2 and Roche CAP/CTM HIV-1 Quantitative v2 assays respectively. The sensitivity, specificity and positive and negative predictive values were estimated using the EID results as the reference standard.ResultsA total of 1021 infants were included in the study, of which 47% were female. Over 95% of mothers and children were on antiretroviral treatment or received antiretroviral prophylaxis respectively. The sensitivity and specificity of using the viral load assay to detect infection were 100% (95% CI: 96.2 to 100%) and 99.9% (95% CI: 99.4 to 100%). The positive and negative predictive values were 99.0% (95% CI: 94.3 to 100%) and 100% (95% CI: 99.6 to 100%). The McNemar's test was 1.000 and Cohen's kappa was 0.994.ConclusionsThe comparable performance suggests that viral load assays can be used as an infant diagnostic assay. Infants with either low levels of viraemia or high cycle threshold values should be repeat tested to ensure the result is truly positive prior to treatment initiation, regardless of assay used. Viral load assays could replace traditional early infant diagnosis testing, substantially streamlining molecular laboratory services for children and lowering costs, with the additional advantage of providing baseline viral load results for antiretroviral treatment management.
| S-EPMC6948022 | biostudies-literature
Project description:Eliciting protective neutralizing antibodies (NAbs) against HIV-1 is daunting because of the extensive genetic and antigenic diversity of HIV-1. Moreover, broad and potent responses are uncommon even during persistent infection, with only a subset of adults developing broadly neutralizing antibodies (bNAbs) that recognize viral variants from different HIV-1 clades. It is not known whether bNAbs can also arise in HIV-1-infected infants, who typically progress to disease faster than adults, presumably in part due to an immature immune system. Here, we show that bNAbs develop at least as commonly in infants as in adults. Cross-clade NAb responses were detected in 20/28 infected infants, in some cases within 1 year of infection. Among infants with breadth of responses within the top quartile, neutralization of tier 2 or 3 variants from multiple clades was detected at 20 months after infection. These findings suggest that, even in early life, there is sufficient B cell functionality to mount bNAbs against HIV-1. Additionally, the relatively early appearance of bNAbs in infants may provide a unique setting for understanding the pathways of B cell maturation leading to bNAbs.
| S-EPMC4060046 | biostudies-literature
Project description:IntroductionIdentification and retention of HIV-exposed infants in early infant diagnosis (EID) services helps to ensure optimal health outcomes. This systematic review and meta-analysis examines the magnitude of attrition from EID services in low- and middle-income countries (LMICs).MethodsWe performed a comprehensive database search through April 2016. We included original studies reporting retention/attrition data for HIV-exposed infants in LMICs. Outcomes included loss to follow-up (LTFU), death and overall attrition (LTFU + death) at time points along the continuum of EID services. At least two authors determined study eligibility, performed data extraction and made quality assessments. We used random-effects meta-analytic methods to aggregate effect sizes and perform meta-regression analyses. This study adhered to PRISMA reporting guidelines.ResultsWe identified 3040 unique studies, of which 92 met eligibility criteria and were included in the quantitative synthesis. The included studies represent data from 110,805 HIV-exposed infants, the majority of whom were from Africa (77%). LTFU definitions varied widely, and there was significant variability in outcomes across studies. The bulk of attrition occurred in the first six months of follow-up, with additional losses over time. Overall, 39% of HIV-exposed infants were no longer in care at 18 months. When restricted to non-intervention studies, 43% were not retained at 18 months.ConclusionsThese findings underscore the high attrition of HIV-exposed infants from EID services in LMICs and the urgent need for implementation research and resources to improve retention among this vulnerable population.
| S-EPMC6287094 | biostudies-literature
Project description:BACKGROUND:Interim results from the children with HIV early antiretroviral (CHER) trial showed that early antiretroviral therapy (ART) was life-saving for infants infected with HIV. In view of the few treatment options and the potential toxicity associated with lifelong ART, in the CHER trial we compared early time-limited ART with deferred ART. METHODS:CHER was an open-label randomised controlled trial of HIV-infected asymptomatic infants younger than 12 weeks in two South African trial sites with a percentage of CD4-positive T lymphocytes (CD4%) of 25% or higher. 377 infants were randomly allocated to one of three groups: deferred ART (ART-Def), immediate ART for 40 weeks (ART-40W), or immediate ART for 96 weeks (ART-96W), with subsequent treatment interruption. The randomisation schedule was stratified by clinical site with permuted blocks of random sizes to balance the numbers of infants allocated to each group. Criteria for ART initiation in the ART-Def group and re-initiation after interruption in the other groups were CD4% less than 25% in infancy; otherwise, the criteria were CD4% less than 20% or Centers for Disease Control and Prevention severe stage B or stage C disease. Combination therapy of lopinavir-ritonavir, zidovudine, and lamivudine was the first-line treatment regimen at ART initiation and re-initiation. The primary endpoint was time to failure of first-line ART (immunological, clinical, or virological) or death. Comparisons were done by intention-to-treat analysis, with use of time-to-event methods. This trial is registered with ClinicalTrials.gov, number NCT00102960. FINDINGS:377 infants were enrolled, with a median age of 7·4 weeks, CD4% of 35%, and HIV RNA log 5·7 copies per mL. Median follow-up was 4·8 years; 34 infants (9%) were lost to follow-up. Median time to ART initiation in the ART-Def group was 20 weeks (IQR 16-25). Time to restarting of ART after interruption was 33 weeks (26-45) in ART-40W and 70 weeks (35-109) in ART-96W; at the end of the trial, 19% of patients in ART-40W and 32% of patients in ART-96W remained off ART. Proportions of follow-up time spent on ART were 81% in the ART-Def group, 70% in the ART-40W group, and 69% in the ART-96W group. 48 (38%) of 125 children in the ART-Def group, 32 (25%) of 126 in the ART-40W group, and 26 (21%) of 126 in the ART-96W group reached the primary endpoint. The hazard ratio, relative to ART-Def, was 0·59 (95% CI 0·38-0·93, p=0·02) for ART-40W and 0·47 (0·27-0·76, p=0·002) for ART-96W. Three children in ART-Def, three in ART-40W, and one in ART-96W switched to second-line ART. INTERPRETATION:Early time-limited ART had better clinical and immunological outcomes than deferred ART, with no evidence of excess disease progression during subsequent treatment interruption and less overall ART exposure than deferred ART. Longer time on primary ART permits longer subsequent interruption, with marginally better outcomes. FUNDING:US National Institutes of Health.
| S-EPMC4104982 | biostudies-literature