Dataset Information

What Should We Do When HIV-positive Children Fail First-line Combination Antiretroviral Therapy? A Comparison of 4 ART Management Strategies.

ABSTRACT: BACKGROUND:Managing virologic failure (VF) in HIV-infected children is especially difficult in resource-limited settings, given limited availability of alternative drugs, concerns around adherence, and the development of HIV resistance mutations. We aimed to evaluate 4 management strategies for children following their first episode of VF by comparing their immunologic and virologic outcomes. METHODS:We included children (< 16 years of age) with VF from 8 International Epidemiologic Database to Evaluate AIDS Southern Africa cohorts, initiating combination antiretroviral therapy (cART) between 2004 and 2010, who followed one of the 4 management strategies: continuing on their failing regimen; switching to a second-line regimen; switching to a holding regimen (either lamivudine monotherapy or other non-cART regimen); discontinuing all ART. We compared the effect of management strategy on the 52-week change in CD4% and log10VL from VF, using inverse probability weighting of marginal structural linear models. RESULTS:Nine hundred eighty-two patients were followed over 54,168 weeks. Relative to remaining on a failing regimen, switching to second-line showed improved immunologic and virologic responses 52 weeks after VF with gains in CD4% of 1.5% (95% confidence interval [CI], 0.2-2.8) and declines in log10VL of -1.4 copies/mL (95% CI, -2.0, -0.8), while switching to holding regimens or discontinuing treatment had worse immunologic (-5.4% (95% CI, -12.1, 1.3) and -5.6% (95% CI, -15.4, 4.1) and virologic outcomes (0.2 (95% CI, -3.6, 4.1) and 0.8 (95% CI, -0.6, 2.1), respectively. CONCLUSIONS:The results provide useful guidance for managing children with VF. Consideration should be given to switching children failing first-line cART to second-line, given the improved virologic and immune responses when compared with other strategies.

SUBMITTER: Patten G

PROVIDER: S-EPMC6355383 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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What Should We Do When HIV-positive Children Fail First-line Combination Antiretroviral Therapy? A Comparison of 4 ART Management Strategies.

Patten Gabriela G Schomaker Michael M Davies Mary-Ann MA Rabie Helena H van Zyl Gert G Technau Karl K Eley Brian B Boulle Andrew A Van Dyke Russell B RB Patel Kunjal K Sipambo Nosisa N Wood Robin R Tanser Frank F Giddy Janet J Cotton Mark M Nuttall James J Essack Gadija G Karalius Brad B Seage George G Sawry Shobna S Egger Matthias M Fairlie Lee L

The Pediatric infectious disease journal 20190401 4

<h4>Background</h4>Managing virologic failure (VF) in HIV-infected children is especially difficult in resource-limited settings, given limited availability of alternative drugs, concerns around adherence, and the development of HIV resistance mutations. We aimed to evaluate 4 management strategies for children following their first episode of VF by comparing their immunologic and virologic outcomes.<h4>Methods</h4>We included children (< 16 years of age) with VF from 8 International Epidemiolog ...[more]

PMID: 30882732

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Project description:Multiple factors make adherence to antiretroviral therapy (ART) a complex process. This study aims to describe the barriers and facilitators to adherence for patients receiving first-line and second-line ART, identify different adherence strategies utilized and make recommendations for an improved adherence strategy. This mixed method parallel convergent study will be conducted in seven high volume public health facilities in Gauteng and one in Limpopo province in South Africa. The study consists of four phases; a retrospective secondary data analysis of a large cohort of patients on ART (using TIER.Net, an ART patient and data management system for recording and monitoring patients on ART and tuberculosis (TB)) from seven Johannesburg inner-city public health facilities (Gauteng province); a secondary data analysis of the Intensified Treatment Monitoring Accumulation (ITREMA) trial (a randomized control trial which ran from June 2015 to January 2019) conducted at the Ndlovu Medical Center (Limpopo province); in-depth interviews with people living with Human Immunodeficiency Virus (PLHIV) who are taking ART (in both urban and rural settings); and a systematic review of the impact of treatment adherence interventions for chronic conditions in sub-Saharan Africa. Data will be collected on demographics, socio-economic status, treatment support, retention in care status, disclosure, stigma, clinical markers (CD4 count and viral load (VL)), self-reported adherence information, intrapersonal, and interpersonal factors, community networks, and policy level factors. The systematic review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting and Population, Interventions, Comparisons and Outcomes (PICO) criteria. Analyses will involve tests of association (Chi-square and t-test), thematic analysis (deductive and inductive approaches) and network meta-analysis. Using an integrated multilevel socio-ecological framework this study will describe the factors associated with adherence for PLHIV who are taking first-line or second-line ART. Implementing evidence-based adherence approaches, when taken up, will improve patient's overall health outcomes. Our study results will provide guidance regarding context-specific intervention strategies to improve ART adherence.

Project description:IntroductionThere are a limited number of paediatric antiretroviral drug options. Characterising the long term safety and durability of different antiretrovirals in children is important to optimise management of HIV infected children and to determine the estimated need for alternative drugs in paediatric regimens. We describe first-line antiretroviral therapy (ART) durability and reasons for discontinuations in children at two South African ART programmes, where lopinavir/ritonavir has been recommended for children <3 years old since 2004, and abacavir replaced stavudine as the preferred nucleoside reverse transcriptase inhibitor in 2010.MethodsWe included children (<16 years at ART initiation) who initiated ?3 antiretrovirals between 2004-2014 with ?1 follow-up visit on ART. We estimated the incidence of first antiretroviral discontinuation using Kaplan-Meier analysis. We determined the reasons for antiretroviral discontinuations using competing risks analysis. We used Cox regression to identify factors associated with treatment-limiting toxicity.ResultsWe included 3579 children with median follow-up duration of 41 months (IQR 14-72). At ART initiation, median age was 44 months (IQR 13-89) and median CD4 percent was 15% (IQR 9-21%). At three and five years on ART, 72% and 26% of children respectively remained on their initial regimen. By five years on ART, the most common reasons for discontinuations were toxicity (32%), treatment failure (18%), treatment simplification (5%), drug interactions (3%), and other or unspecified reasons (18%). The incidences of treatment limiting toxicity were 50.6 (95% CI 46.2-55.4), 1.6 (0.5-4.8), 2.0 (1.2-3.3), and 1.3 (0.6-2.8) per 1000 patient years for stavudine, abacavir, efavirenz and lopinavir/ritonavir respectively.ConclusionsWhile stavudine was associated with a high risk of treatment-limiting toxicity, abacavir, lopinavir/ritonavir and efavirenz were well-tolerated. This supports the World Health Organization recommendation to replace stavudine with abacavir or zidovudine in paediatric first-line ART regimens in order to improve paediatric first-line ART durability.

Project description:BackgroundFirst-line antiretroviral treatment failure has become a public health concern in high, low and middle-income countries with high mortality and morbidity In Ethiopia, around 710,000 peoples were living with HIV and 420,000 of them were receiving ART in 2017. Little is known about the magnitude of first-line ART treatment failure and its associated factors in Ethiopia, particularly in the study area. Therefore, this study was aimed to find the magnitude of first-line ART treatment failure and its associated factors among adult patients attending ART clinic at Southwest shoa zone public hospitals.MethodsInstitutions based cross-sectional study was employed from February 1 to April 2, 2019. An interviewer administered questionnaire was used to collect data from 350 adult patients on ART using a systematic random sampling technique. The collected data were coded and entered into Epidata version 3 and exported to STATA SE version 14 for analysis. Bivariable and multivariable logistic regression was done to identify factors associated with first-line ART treatment failure. At 95% confidence level strength of association was measured using Odds ratio. Variables with a p-value of ≤ 0.25 in the bivariable analysis were considered as a candidate variable for multivariable analysis. To get the final variables step-wise backward selection procedure was used and those in the final model were selected at a p-value <0.05. Finally, texts, simple frequency tables, and figures were used to present the findings.ResultsIn this study the magnitude of first-line ART treatment failure was 33.42%. Absence of baseline opportunistic infection AOR = 0.362 (95%CI0.178, 0.735), Staying on first-line ART for <5 years AOR = 0.47 (95%CI 0.252, 0.878), Nevirapine containing ART regimen AOR = 3.07 (95%CI 1.677, 5.63), Baseline CD4 count ≥100 cells/mm3 AOR = 0.299 (95%CI 0.152 0.591), absence of opportunistic infections after ART initiation AOR = 0.257 (95%CI 0.142, .467), time taking greater than an one-hour to reach health facility AOR 1.85 (95%CI 1.022 3.367) were significantly associated with first-line ART treatment failure.ConclusionThe magnitude of first-line ART treatment failure was high in the study area. Base-line opportunistic infection, duration on first-line ART, NVP based ART, Baseline CD4 count level, OI after ART initiation, and time it takes to reach health facility were independent determinants of first-line ART treatment failure.

Project description:BackgroundClinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals.MethodsIn this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3-6 months (when below the threshold) or every 9-12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per μL, 350 cells per μL, and 500 cells per μL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count.Findings47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1·05 (95% CI 0·86-1·29) for threshold 200 and 1·02 (0·91·1·14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1·08 (0·95-1·22) for threshold 200 and 1·03 (0·96-1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2·01 (1·17-3·43) for threshold 200 and 1·24 (0·89-1·73) for threshold 350, and 24 month mean CD4 cell count differences were 0·4 (-25·5 to 26·3) cells per μL for threshold 200 and -3·5 (-16·0 to 8·9) cells per μL for threshold 350.InterpretationDecreasing monitoring to annually when CD4 count is higher than 200 cells per μL compared with higher than 500 cells per μL does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies.FundingNational Institutes of Health.

Project description:IntroductionTenofovir-based first-line antiretroviral therapy (ART) is recommended globally. To evaluate the impact of its incorporation into the World Health Organization (WHO) guidelines, we examined treatment failure and drug resistance among a cohort of patients on tenofovir-based first-line ART at the Academic Model Providing Access to Healthcare, a large HIV treatment programme in western Kenya.MethodsWe determined viral load (VL), drug resistance and their correlates in patients on ≥six months of tenofovir-based first-line ART. Based on enrolled patients' characteristics, we described these measures in those with (prior ART group) and without (tenofovir-only group) prior non-tenofovir-based first-line ART using Wilcoxon rank sum and Fisher's exact tests.ResultsAmong 333 participants (55% female; median age 41 years; median CD4 336 cells/µL), detectable (>40 copies/mL) VL was found in 18%, and VL>1000 copies/mL (WHO threshold) in 10%. Virologic failure at both thresholds was significantly higher in 217 participants in the tenofovir-only group compared with 116 in the prior ART group using both cut-offs (24% vs. 7% with VL>40 copies/mL; 15% vs. 1% with VL>1000 copies/mL). Failure in the tenofovir-only group was associated with lower CD4 values and advanced WHO stage. In 35 available genotypes from 51 participants in the tenofovir-only group with VL>40 copies/mL (69% subtype A), any resistance was found in 89% and dual-class resistance in 83%. Tenofovir signature mutation K65R occurred in 71% (17/24) of the patients infected with subtype A. Patients with K65R had significantly lower CD4 values, higher WHO stage and more resistance mutations.ConclusionsIn this Kenyan cohort, tenofovir-based first-line ART resulted in good (90%) virologic suppression including high suppression (99%) after switch from non-tenofovir-based ART. Lower virologic suppression (85%) and high observed resistance levels (89%) in the tenofovir-only group impact future treatment options, support recommendations for widespread VL monitoring in such resource limited settings to identify early treatment failure and suggest consideration of individualized resistance testing to design effective subsequent regimens.

Dataset Information

What Should We Do When HIV-positive Children Fail First-line Combination Antiretroviral Therapy? A Comparison of 4 ART Management Strategies.

Publications

What Should We Do When HIV-positive Children Fail First-line Combination Antiretroviral Therapy? A Comparison of 4 ART Management Strategies.

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