Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic

Sebunya, Robert; Musiime, Victor; Kitaka, Sabrina Bakeera; Ndeezi, Grace

doi:10.1186/1742-6405-10-25

Cited by 50 publications

(77 citation statements)

References 33 publications

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“…Sebunya et al found that Ugandan children who never experienced ART failure were more likely to have a grandmother as their primary caregiver and suggest that grandparents often reside in rural settings and have more time to offer care to the children, facilitating adherence [16]. Stigma and discrimination can contribute to non-adherence and non-disclosure, thereby potentially increasing the risk of treatment failure.…”

Section: Resultsmentioning

confidence: 94%

“…When patients initiating ART fail to achieve viral suppression by 24 weeks of treatment, the possibility of suboptimal adherence and other factors must be considered. Treatment failure, as measured by detectable viral load (VL) during chronic care, has been shown to be associated with non-adherence [14][15][16], although this has not been consistently observed [17]. In a study from Zambia, Haberer et al demonstrated that older children (9-15 years) who were unaware of their HIV diagnosis were at risk of treatment failure due to poor adherence [18].…”

Section: Resultsmentioning

confidence: 98%

“…In the case where a PI-based first-line regimen is not affordable, the subsequent NVP-containing regimen within 6-12 months of prior exposure to single-dose NVP may have a negative impact upon virological response and result in treatment failure [23]. In a study done in Uganda by Sebunya et al, patients were twice as likely to fail a NVP-NNRTI regimen compared to an efavirenz (EFV)-NNRTI regimen [16]. This was confirmed in other studies [29].…”

Section: Drug Regimenmentioning

confidence: 99%

“…ART given for prevention of mother-to-child transmission (PMTCT) may result in direct transmission of HIV drugresistant virus, and in most of the resource-limited settings the PMTC regimen rests primarily on NVP. NVP resistance increases the risk of treatment failure when the child starts Poor adherence sdNVP-based first-line regimen prior exposure to sd-NVP [16] Emmett et al [14] Gebremedhin et al Workneh et al NVP-based ART [5,28]. For this reason, when feasible, a boosted protease inhibitor (PI)-based regimen is recommended as firstline therapy by all pediatric guidelines for children at high risk of non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance [22,46].…”

Section: Drug Regimenmentioning

confidence: 99%

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Tackling virological failure in HIV-infected children living in Africa

Jenabian

Costiniuk

Bouassa

et al. 2015

Expert Review of Anti-infective Therapy

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Drug resistance in HIV-infected children is one of the main contributors to antiretroviral treatment (ART) failure, especially in developing countries. Sub-Saharan Africa has the largest burden of pediatric HIV infection in the world. Herein, we systematically review the current status of ART failure in HIV-infected African children. A literature search for publications within 10 years was performed through PubMed to identify relevant articles. Included studies examined the impact of timing of ART initiation, criteria for diagnosing therapeutic failure, predictors of therapeutic failure, management strategies and future directions to minimize failure rates in these pediatric populations. Although there is scale-up of ART programs in Africa, novel therapeutic and management strategies are needed to overcome current challenges.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 98%

Section: Drug Regimenmentioning

confidence: 99%

Section: Drug Regimenmentioning

confidence: 99%

See 2 more Smart Citations

Tackling virological failure in HIV-infected children living in Africa

Jenabian

Costiniuk

Bouassa

et al. 2015

Expert Review of Anti-infective Therapy

View full text Add to dashboard Cite

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“…The efficacy of first-line ART has been reported in an earlier meta-analysis, in which the pooled estimate for viral suppression was 70% by 12 months [5]. Despite this relative success, children are failing treatment and needing second-line regimens [6,7]. Paediatric treatment options are limited for many reasons, including the limited drug approval for children, lack of affordable paediatric formulations and lack of appropriate fixed-dose combination formulations [8], often resulting in children remaining on first-line ART, despite failure [9].…”

Section: Introductionmentioning

confidence: 99%

Determinants of durability of first-line antiretroviral therapy regimen and time from first-line failure to second-line antiretroviral therapy initiation

Desmonde

Eboua

Malateste

et al. 2015

Aids

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Background We described reasons for switching to second-line antiretroviral treatment (ART) and time to switch in HIV-infected children failing first-line ART in West Africa. Methods We included all children aged 15 years or less, starting ART (at least three drugs) in the paediatric IeDEA clinical centres in five West-African countries. We estimated the incidence of switch (at least one a drug class change) within 24 months of ART and associated factors were identified in a multinomial logistic regression. Among children with clinical-immunological failure, we estimated the 24-month probability of switching to a second-line and associated factors, using competing risks. Children who switched to second-line ART following the withdrawal of nelfinavir in 2007 were excluded. Results Overall, 2820 children initiated ART at a median age of 5 years; 144 (5%) were on nelfinavir. At 24-month post-ART initiation, 188 (7%) had switched to second-line. The most frequent reasons were drug stock outs (20%), toxicity (18%), treatment failure (16%) and poor adherence (8%). Over the 24-month follow-up period, 322 (12%) children failed first-line ART after a median time of 7 months. Of these children, 21 (7%) switched to second-line after a median time of 21 weeks in failure. This was associated with older age [subdistribution hazard ratio (sHR) 1.21, 95% confidence interval (95% CI) 1.10–1.33] and longer time on ART (sHR 1.16, 95% CI 1.07–1.25). Conclusion Switches for clinical failure were rare and switches after an immunological failure were insufficient. These gaps reveal that it is crucial to advocate for both sustainable access to first-line and alternative regimens to provide adequate roll-out of paediatric ART programmes.

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Prediction‐driven pooled testing methods: Application to HIV treatment monitoring in Rakai, Uganda

Brand

May

Nakigozi

et al. 2021

Statistics in Medicine

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Chronic medical conditions often necessitate regular testing for proper treatment. Regular testing of all afflicted individuals may not be feasible due to limited resources, as is true with HIV monitoring in resource-limited settings. Pooled testing methods have been developed in order to allow regular testing for all while reducing resource burden. However, the most commonly used methods do not make use of covariate information predictive of treatment failure, which could improve performance. We propose and evaluate four prediction-driven pooled testing methods that incorporate covariate information to improve pooled testing performance. We then compare these methods in the HIV treatment management setting to current methods with respect to testing efficiency, sensitivity, and number of testing rounds using simulated data and data collected in Rakai, Uganda. Results show that the prediction-driven methods increase efficiency by up to 20% compared with current methods while maintaining equivalent sensitivity and reducing number of testing rounds by up to 70%. When predictions were incorrect, the performance of prediction-based matrix methods remained robust. The best performing method using our motivating data from Rakai was a prediction-driven hybrid method, maintaining sensitivity over 96% and efficiency over 75% in likely scenarios. If these methods perform similarly in the field, they may contribute to improving mortality and reducing transmission in resource-limited settings. Although we evaluate our proposed pooling methods in the HIV treatment setting, they can be applied to any setting that necessitates testing of a quantitative biomarker for a threshold-based decision. K E Y W O R D Smatrix-based testing, mini pool, pooled testing, prediction-based testing, treatment failure INTRODUCTIONProper management of treatable, chronic medical conditions often relies on measurement of one or more biomarkers to assess the effectiveness of current treatment and disease progression. Based on regular blood testing, a patient withThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic

Cited by 50 publications

References 33 publications

Tackling virological failure in HIV-infected children living in Africa

Tackling virological failure in HIV-infected children living in Africa

Determinants of durability of first-line antiretroviral therapy regimen and time from first-line failure to second-line antiretroviral therapy initiation

Prediction‐driven pooled testing methods: Application to HIV treatment monitoring in Rakai, Uganda

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