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High levels of pre-treatment HIV drug resistance and treatment failure in Nigerian children.

ABSTRACT: Pre-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.HIV-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).Of 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).PDR 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.Our 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.

SUBMITTER: Boerma RS

PROVIDER: S-EPMC5106466 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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High levels of pre-treatment HIV drug resistance and treatment failure in Nigerian children.

Boerma Ragna S RS Boender T Sonia TS Sigaloff Kim C E KC Rinke de Wit Tobias F TF van Hensbroek Michael Boele MB Ndembi Nicaise N Adeyemo Titilope T Temiye Edamisan O EO Osibogun Akin A Ondoa Pascale P Calis Job C JC Akanmu Alani Sulaimon AS

Journal of the International AIDS Society 20161110 1

<h4>Introduction</h4>Pre-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 subsequ ...[more]

PMID: 27836020

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Project description:BackgroundIn order to assess the level of transmitted and/or pre-treatment antiretroviral drug resistance to HIV-1, the World Health Organization (WHO) recommends that regular surveys are conducted. This study's objective was to assess the frequency of HIV-1 antiretroviral drug resistance in patients initiating antiretroviral treatment (ART) in the public sector throughout South Africa.MethodsA prospective cross-sectional survey was conducted using probability proportional to size sampling. This method ensured that samples from each province were proportionally collected, based on the number of patients receiving ART in each region. Samples were collected between March 2013 and October 2014. Pol sequences were obtained using RT-PCR and Sanger sequencing and submitted to the Stanford Calibrated Population Resistance tool v6.0.ResultsA total of 277 sequences were available for analysis. Most participants were female (58.8%) and the median age was 34 years (IQR: 29-42). The median baseline CD4-count was 149 cells/mm3 (IQR: 62-249) and, based on self-reporting, participants had been diagnosed as HIV-positive approximately 44 days prior to sample collection (IQR: 23-179). Subtyping revealed that 98.2% were infected with HIV-1 subtype C. Overall, 25 out of 277 patients presented with ?1 surveillance drug resistance mutation (SDRM, 9.0%, 95% CI: 6.1-13.0%). Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were the most numerous mutations detected (n = 23). Only two patients presented with a protease inhibitor (PI) mutation. In four patients ?4 SDRMs were detected, which might indicate that these patients were not truly ART-naïve or were infected with a multi-resistant virus.ConclusionsThese results show that the level of antiretroviral drug resistance in ART-naïve South Africans has reached moderate levels, as per the WHO classification. Therefore, regular surveys of pre-treatment drug resistance levels in all regions of South Africa is highly recommended to monitor the changing levels of pre-treatment antiretroviral drug resistance.

Project description:BackgroundThe expansion of access to antiretroviral therapy (ART) has been accompanied by an increase in pre-treatment drug resistance (PDR). While it is critical to monitor the increasing prevalence of PDR across countries and populations to inform optimal regimen selection, the completeness of reporting is often suboptimal, limiting the interpretation and generalizability of the results. Indeed, there is no formal guidance on how studies investigating the prevalence of drug resistance should be reported. Thus, we sought to determine the completeness of reporting in studies of PDR and the factors associated with sub-optimal reporting to ascertain the need for guidelines.MethodsAs part of a systematic review on the global prevalence of PDR in key populations (men who have sex with men, sex workers, transgender people, people who inject drugs and people in prisons), we searched 10 electronic databases until January 2019. We extracted information on selected study characteristics useful for interpreting prevalence data. Data were extracted in duplicate. Analyses of variance and correlation were used to explore factors that may explain the number of items reported.ResultsWe found 650 studies of which 387 were screened as full text and 234 were deemed eligible. The included studies were published between 1997 and 2019 and included a median of 239 (quartile 1 = 101; quartile 3 = 778) participants. Most studies originated from high-income countries (125/234; 53.0%). Of 23 relevant data items, including study design, setting, participant sociodemographic characteristics, HIV risk factors, type of resistance test conducted, definition of resistance, the mean (standard deviation) number of items reported was 13 (2.2). We found that more items were reported in studies published more recently (r = 0.20; p < 0.002) and in studies at low risk of bias (F [2231] = 8.142; p < 0.001).ConclusionsIncomplete reporting in studies on PDR makes characterising levels of PDR in subpopulations across countries challenging. Hence, guidelines are needed to define a minimum set of variables to be included in such studies.

Dataset Information

High levels of pre-treatment HIV drug resistance and treatment failure in Nigerian children.

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High levels of pre-treatment HIV drug resistance and treatment failure in Nigerian children.

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