Misclassification of Antiretroviral Treatment Failure Using WHO 2006 and 2010/2013 Immunologic Criteria in HIV-Infected Children and Adolescents in Western Kenya.
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ABSTRACT:
SUBMITTER: Dufort EM
PROVIDER: S-EPMC5907858 | biostudies-other | 2017 Sep
REPOSITORIES: biostudies-other
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Misclassification of Antiretroviral Treatment Failure Using WHO 2006 and 2010/2013 Immunologic Criteria in HIV-Infected Children and Adolescents in Western Kenya.
Dufort Elizabeth M EM DeLong Allison K AK Mann Marita M Nyandiko Winstone M WM Ayaya Samuel O SO Hogan Joseph W JW Kantor Rami R
Journal of the Pediatric Infectious Diseases Society 20170901 3
We evaluated treatment failure misclassification in human immunodeficiency virus-infected Kenyan children whose targeted viral loads were determined after suspected immunologic/clinical failure according to 2006 and 2010/2013 World Health Organization guidelines. The misclassification rate was 21% for the 2006 guidelines and 46% for the 2010/2013 guidelines, which supports current recommendations for routine viral load monitoring but not necessarily the proposed CD4 thresholds. ...[more]
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Project description:IntroductionHigh levels of adherence to antiretroviral therapy (ART) are central to HIV management. The objective of this study was to compare multiple measures of adherence and investigate factors associated with adherence among HIV-infected children in western Kenya.MethodsWe evaluated ART adherence prospectively for six months among HIV-infected children aged ≤14 years attending a large outpatient HIV clinic in Kenya. Adherence was reported using caregiver report, plasma drug concentrations and Medication Event Monitoring Systems (MEMS®). Kappa statistics were used to compare adherence estimates with MEMS®. Logistic regression analyses were performed to assess the association between child, caregiver and household characteristics with dichotomized adherence (MEMS® adherence ≥90% vs. <90%) and MEMS® treatment interruptions of ≥48 hours. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsAmong 191 children, mean age at baseline was 8.2 years and 55% were female. Median adherence by MEMS® was 96.3% and improved over the course of follow-up (p<0.01), although 49.5% of children had at least one MEMS® treatment interruption of ≥48 hours. Adherence estimates were highest by caregiver report, and there was poor agreement between MEMS® and other adherence measures (Kappa statistics 0.04-0.37). In multivariable logistic regression, only caregiver-reported missed doses in the past 30 days (OR 1.25, 95% CI 1.14-1.39), late doses in the past seven days (OR 1.14, 95% CI 1.05-1.22) and caregiver-reported problems with getting the child to take ART (OR 1.10, 95% CI 1.01-1.20) were significantly associated with dichotomized MEMS® adherence. The caregivers reporting that ART made the child sick (OR 1.12, 95% CI 1.01-1.25) and reporting difficulties in the community that made giving ART more difficult (e.g. stigma) (OR 1.14, 95% CI 1.02-1.27) were significantly associated with MEMS® treatment interruptions in multivariable logistic regression.ConclusionsNon-adherence in the form of missed and late doses, treatment interruptions of more than 48 hours and sub-therapeutic drug levels were common in this cohort. Adherence varied significantly by adherence measure, suggesting that additional validation of adherence measures is needed. Few factors were consistently associated with non-adherence or treatment interruptions.
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Project description:Emphasis on adolescent HIV has increased worldwide as antiretroviral treatment has greatly extended life expectancies of HIV-positive children. Few evidence-based guidelines exist on the optimal time to disclose to an adolescent living with HIV (ALHIV); little is known about the medical effects of disclosure. This study looked to determine whether disclosure is associated with improved medical outcomes in ALHIV. Prior work has tended to be qualitative, cross-sectional, and with an emphasis on psychosocial outcomes. This paper addresses the adolescent cohort retrospectively (longitudinally), building upon what is already known about disclosure.Retrospective, longitudinal clinical record reviews of ALHIV seen at Kericho District Hospital between April 2004 and November 2012 were performed. Patient demographics and clinical outcomes were systematically extracted. The student's t-test was used to calculate changes in mean CD4 count, antiretroviral therapy (ART), and cotrimoxazole adherence pre- vs. post-disclosure. Linear regression modelling assessed for trends in those clinical outcomes associated with age of disclosure.Ninety-six ALHIV (54 female, 42 male) were included; most (73%) entered care through the outpatient department. Nearly half were cared for by parents, and 20% experienced a change in their primary caregiver. The mean time in the study was 2.47 years; mean number of visits 10.97 per patient over the mean time in the study. Mean disclosure age was 12.34 years. An increase in mean ART adherence percentage was found with disclosure (0.802 vs. 0.917; p = 0.0015). Younger disclosure age was associated with significantly higher mean CD4 counts over the course of the study (p = 0.001), and a nonsignificant trend toward a higher mean ART adherence percentage (p = 0.055).ART adherence and improved immunologic status are both associated with disclosure of HIV infection to adolescent patients. Disclosure of an HIV diagnosis to an adolescent is an important means to improve HIV care.
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Project description:Routine HIV viral load (VL) monitoring is the standard of care for persons receiving antiretroviral therapy (ART) in developed countries. Although the World Health Organization recommends annual VL monitoring of patients on ART, recognizing difficulties in conducting routine VL testing, the WHO continues to recommend targeted VL testing to confirm treatment failure for persons who meet selected immunologic and clinical criteria. Studies have measured positive predictive value (PPV), negative predictive value, sensitivity and specificity of these criteria among patients receiving first-line ART but not specifically among those on second-line or subsequent regimens. Between 2008 and 2011, adult ART patients in Nyanza, Kenya who met national clinical or immunologic criteria for treatment failure received targeted VL testing. We calculated PPV and 95% confidence intervals (CI) of these criteria to detect virologic treatment failure among patients receiving a) first-line ART, b) second/subsequent ART, and c) any regimen. Of 12,134 patient specimens tested, 2,874 (23.7%) were virologically confirmed as treatment failures. The PPV for 2,834 first-line ART patients who met either the clinical or immunologic criteria for treatment failure was 34.4% (95% CI 33.2-35.7), 33.1% (95% CI 24.7-42.3) for the 40 patients on second-line/subsequent regimens, and 33.4% (95% CI 33.1-35.6) for any ART. PPV, regardless of criteria, for first-line ART patients was lowest among patients over 44 years old and highest for patients aged 15 to 34 years. PPV of immunological and clinical criteria for correctly identifying treatment failure was similarly low for adult patients receiving either first-line or second-line/subsequent ART regimens. Our data confirm the inadequacy of clinical and immunologic criteria to correctly identify treatment failure and support the implementation of routine VL testing.
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Project description:The plasma kynurenine/tryptophan (KT) ratio, a marker of adaptive immune defects, strongly predicts mortality during treated human immunodeficiency virus (HIV) disease in Ugandans as compared to US-based populations. Here, the KT ratio and T-cell and plasma biomarkers of immune activation were measured among 535 HIV-infected Ugandans prior to ART initiation and at month 6 of viral suppression. The month 6 KT ratio (adjusted hazard ratio [aHR], 2.74), soluble CD14 level (aHR, 2.32), interleukin 6 level (aHR, 2.34), and D-dimer level (aHR, 1.95) were associated with mortality occurring ≥6 months after ART initiation. The KT ratio remained significantly predictive of mortality even after adjustment for the additional biomarkers, suggesting an independent contribution to clinical outcomes in resource-limited settings.
| S-EPMC5853335 | biostudies-literature
Project description:BackgroundAccess to routine virologic monitoring, critical to ensuring treatment success, remains limited in low- and middle-income countries. We report on implementation of routine viral load (VL) monitoring and risk factors for virologic failure among HIV-infected children on antiretroviral treatment (ART) in Western Kenya.MethodsRoutine VL testing was introduced in western Kenya in November 2013. We performed a case-control study among 1190 HIV-infected children ≤15 years on ART who underwent routine VL testing June 2014-May 2015. A random sample of 98 cases (virologic failure define as VL >1000 cps/mL) and 201 controls (VL <1000 cps/mL) from five facilities in three high HIV prevalence counties in Kenya were followed for a minimum of 12 months. Data from patient charts were analyzed using logistic regression to determine factors associated with failure to attain virologic suppression at initial routine and subsequent VL testing among cases.ResultsOverall, 1190 (94%) children with a median age of 8 years underwent routine VL testing of whom (37%) had virological failure. Among the 299 cases and controls, WHO stage, baseline CD4 count and time since ART initiation were not associated with virologic failure during the follow-up period. In multivariable analysis, unsuppressed children at initial test were more likely to be male (adjusted Odds Ratio (aOR) 2.1, 95% Confidence Interval (CI) 2.1-3.6) and have had an ART regimen change (aOR 2.0, CI 1.0-3.7) than controls. Of the two-thirds of children 201/299 who had a subsequent VL performed, VL suppression was greater among those suppressed at initial test 126/135 (93.3%) compared to children with virologic failure 15/66 (22.7%, p<0.0001). Among those failing at first test who achieved viral suppression in follow up, 12/15 (80%) were on a protease inhibitor (PI)-based regimen. In the multivariable analysis of children with subsequent VL testing, children on PI-based 2nd line regimens were 10-fold more likely to achieve viral suppression than children on first-line NNRTI-based ART (adjusted Odds Ratio [aOR] 0.1; 95%CI 0.0-0.4).ConclusionCoverage of initial routine viral load testing among children on ART in western Kenya is high. However, subsequent testing and virologic suppression are low in children with virologic failure on initial routine viral load test. There is an urgent need to improve management and viral load monitoring of children living with HIV experiencing treatment failure to ensure improved long-term outcomes.
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Project description:OBJECTIVE:The objective of this analysis was to examine trends in malaria parasite prevalence and related socioeconomic inequalities in malaria indicators from 2006 to 2013 during a period of intensification of malaria control interventions in Siaya County, western Kenya. METHODS:Data were analysed from eight independent annual cross-sectional surveys from a combined sample of 19 315 individuals selected from 7253 households. Study setting was a health and demographic surveillance area of western Kenya. Data collected included demographic factors, household assets, fever and medication use, malaria parasitaemia by microscopy, insecticide-treated bed net (ITN) use and care-seeking behaviour. Households were classified into five socioeconomic status and dichotomised into poorest households (poorest 60%) and less poor households (richest 40%). Adjusted prevalence ratios (aPR) were calculated using a multivariate generalised linear model accounting for clustering and cox proportional hazard for pooled data assuming constant follow-up time. RESULTS:Overall, malaria infection prevalence was 36.5% and was significantly higher among poorest individuals compared with the less poor (39.9% vs 33.5%, aPR=1.17; 95% CI 1.11 to 1.23) but no change in prevalence over time (trend p value <0.256). Care-seeking (61.1% vs 62.5%, aPR=0.99; 95% CI 0.95 to 1.03) and use of any medication were similar among the poorest and less poor. Poorest individuals were less likely to use Artemether-Lumefantrine or quinine for malaria treatment (18.8% vs 22.1%, aPR=0.81, 95% CI 0.72 to 0.91) while use of ITNs was lower among the poorest individuals compared with less poor (54.8% vs 57.9%; aPR=0.95; 95% CI 0.91 to 0.99), but the difference was negligible. CONCLUSIONS:Despite attainment of equity in ITN use over time, socioeconomic inequalities still existed in the distribution of malaria. This might be due to a lower likelihood of treatment with an effective antimalarial and lower use of ITNs by poorest individuals. Additional strategies are necessary to reduce socioeconomic inequities in prevention and control of malaria in endemic areas in order to achieve universal health coverage and sustainable development goals.
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Project description:HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15-59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively. HIV-1 pol sequences were scored for drug resistance mutations using Stanford HIVdb and WHO 2009 mutation guidelines. HIV-1 subtyping was computed in MEGA6. Eighty seven (93.5%) of the eligible samples were successfully sequenced. Of these, 8 had at least one TDR mutation, resulting in a TDR prevalence of 9.2% (95% CI 4.7-17.1). No TDR was observed among persons with AHI (n = 7). TDR prevalence was 4.6% (95% CI 1.8-11.2) for nucleoside reverse transcriptase inhibitors (NRTIs), 6.9% (95% CI 3.2-14.2) for non- nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.2% (95% CI 0.2-6.2) for protease inhibitors. Three (3.4% 95% CI 0.8-10.1) persons had dual-class NRTI/NNRTI resistance. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6%) and M184V (2.3%); only M46I/L (1.1%) occurred in the protease. All the eight persons were predicted to have different grades of resistance to the ARV regimens, ranging from potential low-level to high-level resistance. HIV-1 subtype distribution was heterogeneous: A (57.5%), C (6.9%), D (21.8%), G (2.3%), and circulating recombinant forms (11.5%). Only low CD4 count was associated with TDR (p = 0.0145). Our findings warrant the need for enhanced HIV-1 TDR monitoring in order to inform on population-based therapeutic guidelines and public health interventions.
| S-EPMC5298248 | biostudies-literature
Project description:BackgroundWhile progress has been made in reducing neonatal mortality in Guatemala, stillbirth and maternal mortality rates remain high, especially among the indigenous populations, which have among the highest adverse pregnancy-related mortality rates in Guatemala.MethodsWe conducted a prospective study in the Western Highlands of Guatemala from 2010 through 2013, enrolling women during pregnancy with follow-up through 42-days postpartum. All pregnant women were identified and enrolled by study staff in the clusters in the Chimaltenango region for which we had 4 years of data. Enrolment usually occurred during the antenatal period; women were also visited following delivery and 42-days postpartum to collect outcomes. Measures of antenatal and delivery care were also obtained.ResultsApproximately four thousand women were enrolled annually (3,869 in 2010 to 4,570 in 2013). The stillbirth rate decreased significantly, from 22.0 per 1000 births (95% CI 16.6, 29.0) in 2010 to 16.7 (95% CI 13.5, 20.6) in 2013 (p-value 0.0223). The perinatal mortality rate decreased from 43.9 per 1,000 births (95% CI 36.0, 53.6) to 31.6 (95% CI 27.2, 36.7) (p-value 0.0003). The 28-day neonatal mortality rate decreased from 28.9 per 1000 live births (95% CI 25.2, 33.2) to 21.7 (95% CI 17.5, 26.9), p-value 0.0004. The maternal mortality rate was 134 per 100,000 in 2010 vs. 113 per 100,000 in 2013. Over the same period, hospital birth rates increased from 30.0 to 50.3%.ConclusionsIn a relatively short time period, significant improvements in neonatal, fetal and perinatal mortality were noted in an area of Guatemala with a history of poor pregnancy outcomes. These changes were temporally related to major increases in hospital-based delivery with skilled birth attendants, as well as improvements in the quality of delivery care, neonatal care, and prenatal care.
| S-EPMC4464607 | biostudies-literature
Project description:BackgroundPre-antiretroviral-treatment drug resistance (PDR) is a predictor of human immunodeficiency virus (HIV) treatment failure. We determined PDR prevalence and correlates in a Kenyan cohort.MethodsWe conducted a cross-sectional analysis of antiretroviral (ARV) treatment-eligible HIV-infected participants. PDR was defined as ≥2% mutant frequency in a participant's HIV quasispecies at pol codons K103N, Y181C, G190A, M184 V, or K65R by oligonucleotide ligation assay and Illumina sequencing. PDR prevalence was calculated by demographics and codon, stratifying by prior ARV experience. Poisson regression was used to estimate prevalence ratios.ResultsPDR prevalences (95% confidence interval [CI]) in 815 ARV-naive adults, 136 ARV-experienced adults, and 36 predominantly ARV-naive children were 9.4% (7.5%-11.7%), 12.5% (7.5%-19.3%), and 2.8% (0.1%-14.5%), respectively. Median mutant frequency within an individual's HIV quasispecies was 67%. PDR prevalence in ARV-naive women 18-24 years old was 21.9% (9.3%-40.0%). Only age in females associated with PDR: A 5-year age decrease was associated with adjusted PDR prevalence ratio 1.20 (95% CI, 1.06-1.36; P = .004).ConclusionsThe high PDR prevalence may warrant resistance testing and/or alternative ARVs in high HIV prevalence settings, with attention to young women, likely to have recent infection and higher rates of resistance.Clinical trials registrationNCT01898754.
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Project description:To explore immunologic risk factors for death within 90 days of highly active antiretroviral therapy (HAART) initiation, CD4(+) and CD8(+) T cell subsets were measured by flow cytometry and characterized by logistic regression in 149 Zambian children between 9 months and 10 years of age enrolled in a prospective, observational study of the impact of HAART on measles immunity. Of 21 children who died during follow-up, 17 (81%) had known dates of death and 16 (76%) died within 90 days of initiating HAART. Young age and low weight-for-age z-scores were associated with increased risks of mortality within 90 days of starting HAART, whereas CD4(+) T cell percentage was not associated with mortality. After adjusting for these factors, each 10% increase in CD8(+) effector T cells increased the odds of overall mortality [OR=1.43 (95% CI: 1.08, 1.90)] and was marginally associated with early mortality [OR=1.29 (95% CI: 0.97, 1.72)]. Conversely, each 10% increase in CD4(+) central memory T cells decreased the odds of overall [OR=0.06 (95% CI: 0.01, 0.59)] and early mortality [OR=0.09 (95% CI: 0.01, 0.97)]. Logistic regression prediction models demonstrated areas under the receiver-operator characteristic curves of ?85% for early and overall mortality, with bootstrapped sensitivities of 82-85% upon validation, supporting the predictive accuracy of the models. CD4(+) and CD8(+) T cell subsets may be more accurate predictors of early mortality than CD4(+) T cell percentages and could be used to identify children who would benefit from more frequent clinical monitoring after initiating HAART.
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