Prevalence of Transmitted HIV-1 Drug Resistance Mutations in Children and Adolescents in São Paulo, Brazil

Almeida, Flávia Jacqueline; Rodrigues, Rosangela; Zaparoli, Mayra Simioni; Berezin, Eitan Naaman; Sáfadi, Marco Aurélio Palazzi; Ferreira, João Leandro de Paula; Lança, André Minhoto; Brígido, Luis Fernando de Macedo

doi:10.1097/inf.0b013e3182684d8e

Cited by 15 publications

(8 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, there are several limitations with this approach, including: no phenotypic confirmation, inability to detect minority viral populations, and determinants of X4 tropism residing outside of the V3 region [9]. In the only other study of the ESTA ™ assay in PHIV children, 36 cART-experienced PHIV Spanish children (median age: 14.6 years, range: 10.9–17.0) had an overall prevalence of X4-tropism of 33%, substantially lower than our finding [5]. In general, we demonstrated higher prevalence rates of X4/DM virus using the ESTA ™ assay than those that have used genotypic testing in PHIV children and youth [6, 7].…”

Section: Discussioncontrasting

confidence: 54%

“…The presence of X4 or dual-mixed (DM), X4 and R5-tropic HIV, precludes the response to therapy with a R5 antagonist [4]. The few pediatric studies in the literature have reported X4 or DM prevalence rates of 19–33% in cohorts of children on and off antiretroviral therapy[5–7]. However, these studies have primarily used genotypic assays to assess HIV tropism, which may be less accurate and less clinically relevant than phenotypic tropism assays [8].…”

Section: Introductionmentioning

confidence: 99%

“…Genotypic assays have specificities ~90%, but are relatively insensitive (sensitivity ~50%–70%) for detecting X4- or DM-tropic HIV; while phenotypic assays have sensitivities and specificities above 95% [8, 10]. Studies have reported variability in concordance of tropism results by genotypic and phenotypic assays [5, 11, 12]. Thus, studies, preferably using phenotypic assays, are needed to evaluate the R5 antagonist activity in PHIV-infected children.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Phenotypic Coreceptor Tropism in Perinatally HIV-infected Youth Failing Antiretroviral Therapy

Agwu

Yao

Eshleman

et al. 2016

Pediatric Infectious Disease Journal

View full text Add to dashboard Cite

Background Perinatally HIV-infected (PHIV) children and youth are often heavily treatment-experienced, with resultant antiretroviral (ARV) resistance and limited treatment options. For those with virologic failure (VF), new agents such as CCR5 (R5) antagonists may be useful; however, reports of R5 antagonist susceptibility in children have mostly relied on genotypic testing, which may not accurately reflect the phenotypic tropism of the viral populations. We characterized phenotypic co-receptor usage among PHIV children and youth with VF on ARV treatment (ART) to identify predictors of CXCR4 (X4) tropism which preclude R5 antagonist use. Methods Plasma samples with >1,000 HIV RNA copies/mL were obtained from 73 PHIV-infected ART-treated children and youth (age 9–21 years) enrolled in the multi-center Pediatric HIV/AIDS Cohort Study. Samples were analyzed using the Trofile™ phenotypic assay. Multiple logistic regression was performed to identify factors associated with detectable X4-tropism. Results Tropism results were obtained for 59 (81%) of the 73 children and youth; 32 (54%) had X4-tropism. Persistent viremia (≥80% of HIV RNA measurements >400 copies/mL) was associated with detectable X4-tropism (adjusted odds ratio (aOR) 6.6, 95% CI 1.4, 31.4), while longer cumulative nucleoside reverse transcriptase inhibitor (NRTI) use was associated with lower risk of X4-tropism (aOR 0.6, 95% CI 0.5, 0.9). Conclusions Using a phenotypic assay, >50% of PHIV children and youth with VF had X4-tropism, similar to that in treatment-experienced adults, and higher than the 30% reported for children using genotypic assays. Persistent viremia and shorter NRTI exposure are associated with X4-tropism in children and youth and may help target phenotypic testing to those most likely to benefit from R5 antagonist.

show abstract

Section: Discussioncontrasting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Phenotypic Coreceptor Tropism in Perinatally HIV-infected Youth Failing Antiretroviral Therapy

Agwu

Yao

Eshleman

et al. 2016

Pediatric Infectious Disease Journal

View full text Add to dashboard Cite

show abstract

“…Other drug families (cell-entry and integrase inhibitors), could be good candidates to control viraemia among pretreated transferred patients in Madrid due to their previous scarce exposure (<1%). However, the presence of X4-tropic variants in over 80% of the cohort of antiretroviral-experienced children and adolescents with vertical HIV-1 infection in Madrid has recently been reported [44]. The authors indicate a very limited role for CCR5 antagonists as part of salvage regimens for highly treatment-experienced vertically infected patients with extensive antiretroviral drug resistance [44].…”

Section: Discussionmentioning

confidence: 95%

High Drug Resistance Prevalence among Vertically HIV-Infected Patients Transferred from Pediatric Care to Adult Units in Spain

Mulder

Yebra²,

Navas

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

BackgroundAntiretroviral treatment (ART) has contributed to increased life expectancy of HIV-1 infected children. In developed countries, an increasing number of children reaching adulthood are transferred to adult units. The objectives were to describe the demographic and clinical features, ART history, antiviral drug resistance and drug susceptibility in HIV-1 perinatally infected adolescents transferred to adult care units in Spain from the Madrid Cohort of HIV-1 infected children.MethodsClinical, virological and immunological features of HIV-1 vertically infected patients in the Madrid Cohort of HIV-infected children were analyzed at the time of transfer. Pol sequences from each patient were recovered before transfer. Resistance mutations according to the InternationaI AIDS Society 2011 list were identified and interpreted using the Stanford algorithm. Results were compared to the non-transferred HIV-1 infected pediatric cohort from Madrid.ResultsOne hundred twelve infected patients were transferred to adult units between 1997 and 2011. They were mainly perinatally infected (93.7%), with a mean nadir CD4+-T-cells count of 10% and presented moderate or severe clinical symptoms (75%). By the time of transfer, the mean age was 18.9 years, the mean CD4+T-cells count was 627.5 cells/ml, 64.2% presented more than 350 CD4+T-cells/ml and 47.3% had ≤200 RNA-copies/ml. Most (97.3%) were ART experienced receiving Highly Active ART (HAART) (84.8%). Resistance prevalence among pretreated was 50.9%, 76.9% and 36.5% for Protease Inhibitors (PI), Nucleoside Reverse Transcriptase Inhibitors (NRTI) and Non-NRTI (NNRTI), respectively. Resistance mutations were significantly higher among transferred patients compared to non-transferred for the PI+NRTI combination (19% vs. 8.4%). Triple resistance was similar to non-transferred pediatric patients (17.3% vs. 17.6%).ConclusionDespite a good immunological and virological control before transfer, we found high levels of resistance to PI, NRTI and triple drug resistance in HIV-1 infected adolescents transferred to adult units.

show abstract

“…MVC), which are only active against viral populations that use the CCR5 co‐receptor for cell entry. The proportion of perinatally infected adolescents with R5 variants, for whom MVC is a potential option, is highly variable within cross‐sectional studies 183, 184. Co‐receptor tropism should be performed within 3 months of the proposed treatment switch that includes MVC for those with detectable viraemia.…”

Section: When To Switch Resistance Testing and Second And Subsequentmentioning

confidence: 99%

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

et al. 2015

View full text Add to dashboard Cite

The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV‐1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short‐term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long‐term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first‐ and second‐line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART ‘pipeline’ of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.

show abstract

Prevalence of Transmitted HIV-1 Drug Resistance Mutations in Children and Adolescents in São Paulo, Brazil

Cited by 15 publications

References 12 publications

Phenotypic Coreceptor Tropism in Perinatally HIV-infected Youth Failing Antiretroviral Therapy

Phenotypic Coreceptor Tropism in Perinatally HIV-infected Youth Failing Antiretroviral Therapy

High Drug Resistance Prevalence among Vertically HIV-Infected Patients Transferred from Pediatric Care to Adult Units in Spain

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

Contact Info

Product

Resources

About