Drug resistance prevalence and HIV-1 variant characterization in the naive and pretreated HIV-1-infected paediatric population in Madrid, Spain

Mulder, Miguel de; Yebra, Gonzalo; Martín, Leticia; Muñoz‐Fernández, María Ángeles; Ory, Santiago Jiménez de; Holguín, África; José, Ma Isabel De; González-Tomé, María Isabel; Gurbindo, María Dolores; Navarro, Marı́a Luisa; Saavedra-Lozano, Jesús; Delgado, Rafaël; Martín-Fontelos, Pablo; Guillén, Sara; Martínez, J; Roa, M.A.; Beceiro, José; Navas, Adriana; Gonzalez-Granados, I.; Prieto, Luís; Mellado, María José; Rojo, Pablo; Blázquez, Daniel; Ramos, José Tomás

doi:10.1093/jac/dkr305

Cited by 16 publications

(33 citation statements)

References 36 publications

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“…Although a participant might be adherent, their medications may not be taken as directed with respect to the timing of doses and timing of food consumption, which could reduce medication effectiveness (24). Children who have developed resistance would also not be expected to achieve viral suppression despite high levels of adherence; high prevalence of viral resistance has been identified in several cohorts of perinatally-infected children [38–40]. Finally, children have greater difficulty in achieving optimal viral suppression than adults, which has been attributed to higher baseline viral load and differences in viral dynamics (41).…”

Section: Discussionmentioning

confidence: 99%

Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America

Duarte

Harris

Tassiopoulos

et al. 2015

The Brazilian Journal of Infectious Diseases

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Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of HIV-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with HIV viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable' viral load (<400 copies/mL). At enrollment, 90.8% of participants were perfectly (100%) adherent, compared to 87.6% at the 6-month and 92.0% at the 12-month visit; the proportion with perfect adherence did not differ over time (p=0.1). Perfect adherence was associated with a higher probability of undetectable viral load at the 12-month visit (odds ratio=4.1, 95% confidence interval: 1.8–9.1; p<0.001), but not at enrollment or the 6-month visit (p>0.3). Last time missed any antiretroviral therapy dose was reported as "never" for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p<0.001 for test of trend). The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p≤0.005), but not at the 6-month visit (p=0.2). While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population.

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Section: Discussionmentioning

confidence: 99%

Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America

Duarte

Harris

Tassiopoulos

et al. 2015

The Brazilian Journal of Infectious Diseases

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“…4 In Western Europe, a previously subtype B-restricted area where pure non-B subtypes and CRFs are rapidly spreading, [5][6][7] BC recombinants have been rarely reported. 8,9 In a recent Italian study, 10 in which an 11.4% prevalence (417 patients of 3670 evaluated) was reported for non-B subtypes in the period 1980-2008, only three strains (0.71% of non-B variants) derived from subtypes B and C were identified.…”

Section: Introductionmentioning

confidence: 99%

An outbreak of HIV-1 BC recombinants in Southern Italy

Monno

Brindicci

Lai

et al. 2012

Journal of Clinical Virology

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“…Partial sequences of the pol gene from pediatric patients are described in [34], and sequences from adult patients were collected from different sources [33–35]. Sequences encompassed 334 amino acids: the 297 amino acids of the viral protease ( PR ), and a fragment coding for the first 37 amino acids of the reverse transcriptase ( RT ) (1,002 nucleotides, positions 2,255–3,256 of HXB2 subtype B reference strain, GenBank accession number K03455).…”

Section: Methodsmentioning

confidence: 99%

“…This well described pediatric cohort has a number of characteristics that made it suitable to address the objectives of the present work. First, it includes patients with detailed follow up information of infection [30–32] and ART resistance [33–36]. This means that data on the above-mentioned clinical parameters, as well as virus sequences of the pol gene and frequency of drug resistance mutations, are available for a large number of individuals [34–36].…”

Section: Introductionmentioning

confidence: 99%

“…This means that data on the above-mentioned clinical parameters, as well as virus sequences of the pol gene and frequency of drug resistance mutations, are available for a large number of individuals [34–36]. Second, the pediatric cohort includes patients of all ages, from new-borns to 21 years-old patients, many of which were infected perinatally [33]. This allowed analysing the effect of exposure time/age in the genetic diversity of HIV-1B populations.…”

Section: Introductionmentioning

confidence: 99%

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Clinical Determinants of HIV-1B Between-Host Evolution and their Association with Drug Resistance in Pediatric Patients

et al. 2016

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Understanding the factors that modulate the evolution of virus populations is essential to design efficient control strategies. Mathematical models predict that factors affecting viral within-host evolution may also determine that at the between-host level. Although HIV-1 within-host evolution has been associated with clinical factors used to monitor AIDS progression, such as patient age, CD4 cells count, viral load, and antiretroviral experience, little is known about the role of these clinical factors in determining between-host HIV-1 evolution. Moreover, whether the relative importance of such factors in HIV-1 evolution vary in adult and children patients, in which the course of infection is different, has seldom been analysed. To address these questions, HIV-1 subtype B (HIV-1B) pol sequences of 163 infected children and 450 adults of Madrid, Spain, were used to estimate genetic diversity, rates of synonymous and non-synonymous mutations, selection pressures and frequency of drug-resistance mutations (DRMs). The role and relative importance of patient age, %CD4, CD4/mm3, viral load, and antiretroviral experience in HIV-1B evolution was analysed. In the pediatric HIV-1B population, three clinical factors were primary predictors of virus evolution: Higher HIV-1B genetic diversity was observed with increasing children age, decreasing CD4/mm3 and upon antiretroviral experience. This was mostly due to higher rates of non-synonymous mutations, which were associated with higher frequency of DRMs. Using this data, we have also constructed a simple multivariate model explaining between 55% and 66% of the variance in HIV-1B evolutionary parameters in pediatric populations. On the other hand, the analysed clinical factors had little effect in adult-infecting HIV-1B evolution. These findings highlight the different evolutionary dynamics of HIV-1B in children and adults, and contribute to understand the factors shaping HIV-1B evolution and the appearance of drug-resistance mutation in pediatric patients.

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Drug resistance prevalence and HIV-1 variant characterization in the naive and pretreated HIV-1-infected paediatric population in Madrid, Spain

Cited by 16 publications

References 36 publications

Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America

Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America

An outbreak of HIV-1 BC recombinants in Southern Italy

Clinical Determinants of HIV-1B Between-Host Evolution and their Association with Drug Resistance in Pediatric Patients

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