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Prevalence and Correlates of Pre-Treatment HIV Drug Resistance among HIV-Infected Children in Ethiopia.

ABSTRACT: Pediatric human immunodeficiency virus (HIV) care in resource-limited settings remains a major challenge to achieving global HIV treatment and virologic suppression targets, in part because the administration of combination antiretroviral therapies (cART) is inherently complex in this population and because viral load and drug resistance genotyping are not routinely available in these settings. Children may also be at elevated risk of transmission of drug-resistant HIV as a result of suboptimal antiretroviral administration for prevention of mother-to-child transmission. We investigated the prevalence and the correlates of pretreatment HIV drug resistance (PDR) among HIV-infected, cART-naive children in Ethiopia. We observed an overall PDR rate of 14%, where all cases featured resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs): ~9% of participants harbored resistance solely to NNRTIs while ~5% harbored resistance to both NNRTIs and nucleoside reverse transcriptase inhibitors (NRTIs). No resistance to protease inhibitors was observed. No sociodemographic or clinical parameters were significantly associated with PDR, though limited statistical power is noted. The relatively high (14%) rate of NNRTI resistance in cART-naive children supports the use of non-NNRTI-based regimens in first-line pediatric treatment in Ethiopia and underscores the urgent need for access to additional antiretroviral classes in resource-limited settings.

SUBMITTER: Tadesse BT

PROVIDER: S-EPMC6784098 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Prevalence and Correlates of Pre-Treatment HIV Drug Resistance among HIV-Infected Children in Ethiopia.

Tadesse Birkneh Tilahun BT Tsai Olivia O Chala Adugna A Chaka Tolossa Eticha TE Eromo Temesgen T Lapointe Hope R HR Baraki Bemuluyigza B Shahid Aniqa A Tadesse Sintayehu S Makonnen Eyasu E Brumme Zabrina L ZL Aklillu Eleni E Brumme Chanson J CJ

Viruses 20190919 9

Pediatric human immunodeficiency virus (HIV) care in resource-limited settings remains a major challenge to achieving global HIV treatment and virologic suppression targets, in part because the administration of combination antiretroviral therapies (cART) is inherently complex in this population and because viral load and drug resistance genotyping are not routinely available in these settings. Children may also be at elevated risk of transmission of drug-resistant HIV as a result of suboptimal ...[more]

PMID: 31546824

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Project description:IntroductionPre-treatment HIV drug resistance (PDR) is an increasing problem in sub-Saharan Africa. Children are an especially vulnerable population to develop PDR given that paediatric second-line treatment options are limited. Although monitoring of PDR is important, data on the paediatric prevalence in sub-Saharan Africa and its consequences for treatment outcomes are scarce. We designed a prospective paediatric cohort study to document the prevalence of PDR and its effect on subsequent treatment failure in Nigeria, the country with the second highest number of HIV-infected children in the world.MethodsHIV-1-infected children ≤12 years, who had not been exposed to drugs for the prevention of mother-to-child transmission (PMTCT), were enrolled between 2012 and 2013, and followed up for 24 months in Lagos, Nigeria. Pre-antiretroviral treatment (ART) population-based pol genotypic testing and six-monthly viral load (VL) testing were performed. Logistic regression analysis was used to assess the effect of PDR (World Health Organization (WHO) list for transmitted drug resistance) on subsequent treatment failure (two consecutive VL measurements >1000 cps/ml or death).ResultsOf the total 82 PMTCT-naïve children, 13 (15.9%) had PDR. All 13 children harboured non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations, of whom seven also had nucleoside reverse transcriptase inhibitor resistance. After 24 months, 33% had experienced treatment failure. Treatment failure was associated with PDR and a higher log VL before treatment initiation (adjusted odds ratio (aOR) 7.53 (95%CI 1.61-35.15) and 2.85 (95%CI 1.04-7.78), respectively).DiscussionPDR was present in one out of six Nigerian children. These high numbers corroborate with recent findings in other African countries. The presence of PDR was relevant as it was the strongest predictor of first-line treatment failure.ConclusionsOur findings stress the importance of implementing fully active regimens in children living with HIV. This includes the implementation of protease inhibitor (PI)-based first-line ART, as is recommended by the WHO for all HIV-infected children <3 years of age. Overcoming practical barriers to implement PI-based regimens is essential to ensure optimal treatment for HIV-infected children in sub-Saharan Africa. In countries where individual VL or resistance testing is not possible, more attention should be given to paediatric PDR surveys.

Project description:BackgroundThe Ethiopian epidemic is currently on the wane. However, the situation for infected children is in some ways lagging behind due to low treatment coverage and deficient prevention of mother-to-child transmission. Too few studies have examined HIV infected children presenting to care in low-income countries in general. Considering the presence of local variations in the nature of the epidemic a study in Ethiopia could be of special value for the continuing fight against HIV. The aim of this study is to describe the main characteristics of children with HIV presenting to care at a district hospital in a resource-limited area in southern Ethiopia. The aim was also to analyse factors affecting pre-ART loss to follow-up, time to ART-initiation and disease stage upon presentation.MethodsThis was a prospective cohort study. The data analysed were collected in 2009 for the period January 2003 through December 2008 at Arba Minch Hospital and additional data on the ART-need in the region were obtained from official reports.ResultsThe pre-ART loss to follow-up rate was 29.7%. Older children (10-14 years) presented in a later stage of their disease than younger children (76.9% vs. 45.0% in 0-4 year olds, chi-square test, ?2?=?8.8, P?=?0.01). Older girls presented later than boys (100.0% vs. 57.1%, Fisher's exact test, P?=?0.02). Children aged 0-4 years were more likely to be lost to follow-up (40.0 vs. 21.8%, chi-square test, ?2?=?5.4, P?=?0.02) and had a longer time to initiate ART (Cox regression analysis, HR: 0.50, 95% CI: 0.25-0.97, P?=?0.04, controlling for sex, place of residence, enrollment phase and WHO clinical stage upon presentation). Neither sex was overrepresented in the sample. Tuberculosis prevalence upon presentation and previous history of tubercolosis were 14.5% and 8% respectively.ConclusionsThe loss to follow-up is alarmingly high and children present too late. Further research is needed to explore specific causes and possible solutions.

Project description:BackgroundThe development of pretreatment drug resistance (PDR) is becoming an obstacle to the success of antiretroviral therapy (ART). Besides, data from developing settings including Ethiopia is still limited. Therefore, this study was aimed to assess HIV-1 genetic diversity and PDR mutations among ART-naive recently diagnosed HIV-1 infected individuals in Addis Ababa, Ethiopia.MethodsInstitutional based cross-sectional study was conducted from June to December 2018 in Addis Ababa among ART-naive recently diagnosed individuals. Partial HIV-1 pol region covering the entire protease (PR) and partial reverse transcriptase (RT) regions of 51 samples were amplified and sequenced using an in-house assay. Drug resistance mutations were examined using calibrated population resistance (CPR) tool version 6.0 from the Stanford HIV drug resistance database and the International Antiviral Society-USA (IAS-USA) 2019 mutation list.ResultsAccording to both algorithms used, 9.8% (5/51) of analyzed samples had at least one PDR Mutation. PDR mutations to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) were the most frequently detected (7.8% and 9.8%, according to the CPR tool and IAS-USA algorithm, respectively). The most frequently observed NNRTIs-associated mutations common to both algorithms were K103N (2%), Y188L (2%), K101E (2%), and V106A (2%), while E138A (2%) was observed according to IAS-USA only. Y115F and M184V (mutations that confer resistance to NRTIs) dual mutations were detected according to both criteria in a single study participant (2%). PDR mutation to protease inhibitors was found to be low (only G73S; 2% according to the CPR tool). Phylogenetic analysis showed that 98% (50/51) of the study participants were infected with HIV-1C virus while one individual (2%) was infected with HIV-1A1 virus.ConclusionsThis study showed an increased level of PDR and persistence HIV-1C clade homogeneity after 15 years of the rollout of ART and 3 decades of HIV-1C circulation in Ethiopia, respectively. Therefore, we recommend routine baseline genotypic drug resistance testing for all newly diagnosed HIV infected patients before initiating treatment. This will aid the selection of appropriate therapy in achieving the 90% of patients having an undetectable viral load in consonance with the UN target.

Dataset Information

Prevalence and Correlates of Pre-Treatment HIV Drug Resistance among HIV-Infected Children in Ethiopia.

Publications

Prevalence and Correlates of Pre-Treatment HIV Drug Resistance among HIV-Infected Children in Ethiopia.

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