Relevance of Early Detection of HIV Type 1 SI/CXCR4-Using Viruses in Vertically Infected Children

Crudeli, Cintia M.; Aulicino, Paula; Rocco, Carlos; Bologna, Rosa; Mangano, Andrea; Sen, Luisa

doi:10.1089/aid.2011.0111

Cited by 11 publications

(20 citation statements)

References 58 publications

(65 reference statements)

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“…Previous studies have presented the concordance between genotypic tropism testing based on plasma viral RNA and proviral DNA and reported the concordance rates ranging from 79% to 97% . Many studies determined the prevalence of HIV‐1 coreceptor usage in HIV‐1 infected children; they have shown that either R5 or X4 viruses can be highly observed using proviral DNA or plasma RNA . Moreover, the HIV‐1 coreceptor usage in children may be influenced by age, HIV‐1 subtypes, or antiretroviral receiving.…”

Section: Discussionmentioning

confidence: 99%

“…HIV‐1 coreceptor usage has been broadly studied in HIV‐1 infected adults and few studies in the newborns or pediatric patients have been performed. Epidemiologic studies of HIV‐1 coreceptor usage among children in Uganda, Argentina, France, Spain, Italy, and India have shown that the distribution of HIV‐1 coreceptor usage is likely to be different because the majority of HIV‐1 infected children harbored R5 viruses, but some harbored X4 viruses . However, no data about HIV‐1 coreceptor usage in HIV‐1 infected children in Thailand have been reported.…”

Section: Introductionmentioning

confidence: 99%

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HIV‐1 coreceptor usage in perinatally infected Thai children

Samleerat

Hongjaisee

Phiayura

et al. 2017

Journal of Medical Virology

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HIV-1 coreceptor usage in children who were born to HIV-1 infected mothers in Thailand is not well characterized. Here, the prevalence of coreceptor usage and genotype among HIV-1 infected children in Thailand were observed. Proviral DNA from 284 HIV-1 infected children who received HIV-1 early infant diagnosis between 2007 and 2013 under the National AIDS Program were studied. Genotypic tropism testing was performed based on amplification of the V3 region in a triplicate nested-PCR following by DNA sequencing. HIV-1 coreceptor usage was determined using Geno2pheno with a false positive rate of 10%. Samples from 267 children were successfully amplified and coreceptor usage could be determined. Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving were observed. The only significant difference was found in N-linked glycosylation characteristic. This evidence showed that X4 viruses can be highly observed at an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HIV‐1 coreceptor usage in perinatally infected Thai children

Samleerat

Hongjaisee

Phiayura

et al. 2017

Journal of Medical Virology

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“…Despite of that only a limited number of studies have explored the relationships between the diversity of the CCR5 encoding gene and the prevalence of X4 tropic viruses. Crudeli et al demonstrated that people who were CCR5 -δ32 heterozygotes (HHG*2) had higher rates of X4 tropic viruses than those not having this genotype in the acute phase of infection 10 . Altamirano et al demonstrated that all wild type homozygotes for CCR5 SNP G303A had NSI virus while all SI variants were found in individuals with A/A or A/G genotypes (HHE-HHF*2) 11 .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Crudeli et al demonstrated that the presence of SI viruses was associated with CCR5 -Δ32 genotype (i.e. HHG*2) at the acute phase but not in the later stages of HIV infection 10 . Another study has shown that CCR5 HHE/HHF*2 was associated with the presence of SI viruses 11 .…”

Section: Introductionmentioning

confidence: 99%

Association Between HIV-1 Tropism and CCR5 Human Haplotype E in a Caucasian Population

Huik

Avi

Uibopuu

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background The influence of the diversity of CCR5 on HIV susceptibility and disease progression has been clearly demonstrated but how the variability of this gene influences the HIV tropism is poorly understood. We investigated whether CCR5 haplotypes are associated with HIV tropism in a Caucasian population. Methods We evaluated 161 HIV-positive subjects in a cross-sectional study. CCR5 haplotypes were derived after genotyping nine CCR2-CCR5 polymorphisms. The HIV subtype was determined by phylogenetic analysis using the Maximum Likelihood method and viral tropism by the genotypic tropism assay (geno2pheno). Associations between CCR5 haplotypes and viral tropism were determined using logistic regression analyses. Samples from 500 blood donors were used to evaluate the representativeness of HIV-positives in terms of CCR5 haplotype distribution. Results The distribution of CCR5 haplotypes was similar in HIV-positive subjects and blood donors. The majority of viruses (93.8%) belonged to HIV-1 CRF06_cpx; 7.5% were X4, and the remaining were R5 tropic. X4 tropic viruses were overrepresented among people with CCR5 human haplotype E (HHE) compared to those without this haplotype (13.0% vs 1.4%; p=0.006). People possessing CCR5 HHE had eleven times increased odds (OR=11.00; 95% CI 1.38 to 87.38) of having X4 tropic viruses than those with non-HHE. After adjusting for antiretroviral therapy (ARV), neither the presence of HHE nor the use of ARV were associated with X4 tropic viruses. Conclusions Our results suggest that CCR5 HHE as well as ARV treatment might be associated with the presence of HIV-1 X4 tropic viruses.

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“…In the study by D'Aquila et al, syncythium-inducing viruses, reflecting infection with X4 tropic populations, were more common among CCR5 Δ32/wild type (wt) heterozygotes compared with CCR5 wt/wt [22]. Infection with X4 isolates was found to be more frequent among CCR5 Δ32/wt children with acute HIV infection; however, this association was lost in cases of chronic infection [23]. Also, Brumme et al reported that CCR5 Δ32/wt heterozygosity was associated with a 2.5 times higher risk of harbouring X4 variants [24].…”

Section: Introductionmentioning

confidence: 99%

Association of chemokine receptor gene variants with HIV‐1 genotype predicted tropism

et al. 2014

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ObjectivesAs a switch from chemokine (C-C motif) receptor 5 [CCR5 (R5)] to chemokine (C-X-C motif) receptor 4 [CXCR4 (X4)] HIV-1 tropism is associated with symptomatic and AIDS stages of infection, while chemokine receptor gene variants modify the tempo of HIV disease progression, we aimed to analyse the association between pretreatment HIV-1 tropism and chemokine polymorphisms known to restrict disease progression. MethodsV3 genotype tropism prediction was performed in a group of 221 treatment-naïve patients, with subsequent CCR5 Δ32 (rs333), CCR2 V64I (rs1799864), CCR5 promoter (−627 C/T; rs1799988) and CX3CR1 V249I (rs3732378) genotyping performed in 206 patients. Alleles with a protective effect were assigned positive values while risk alleles were assigned negative values to calculate genetic scores. χ 2 tests, Mann−Whitney U-tests and logistic and linear regression models were used for statistical analyses. ResultsR5 tropism was found in 85.5% of patients (n = 189) using a false positive rate (FPR) of 5.75% and in 72.8% of patients (n = 161) using an FPR of 10%. A higher frequency of the 5.75% FPR predicted R5 tropism was associated with the CX3CR1 A allele (P = 0.027). Lower additive genetic scores were associated with an increased frequency of 5.75% FPR predicted R5 tropism (P = 0.0059), with the trend confirmed by logistic regression [odds ratio (OR) 0.5819; 95% confidence interval (CI) 0.3457-0.9795; P = 0.0416]. Viral load tended to increase with decreasing genetic score in the logistic regression analysis (slope = −0.127 ± 0.076; P = 0.095; r 2 = 0.161). ConclusionsThe CX3CR1 A allele and lower genetic scores may restrict the switch of HIV-1 tropism from R5 to X4. This effect may be associated with the amount of co-receptor on the cell surface. Chemokine receptor gene polymorphisms influence both disease progression and tropism variability.Keywords: chemokine receptor variants, chemokines, HIV tropism, host genetics. Accepted 26 February 2014 IntroductionStudies on the interaction of HIV with chemokine receptors have resulted in the identification of the chemokine (C-C motif) receptor 5 [CCR5 (R5)], chemokine (C-X-C motif) receptor 4 [CXCR4 (X4)] and dual-mixed (D/M) tropic viral populations. R5 is associated with early stages of infection and is preferentially transmitted, while X4 HIV-1 tropism has been associated with symptomatic and AIDS stages of infection, severe immunodeficiency and a lower lymphocyte CD4 nadir [1,2]. Sequencing of the third hypervariable loop and association of sequence data with phenotypic tropism analyses have led to the development of efficient tropism prediction tools based on the genetic sequence [3][4][5][6]. Currently, it is required to identify HIV-1 tropism prior to CCR5 inhibitor use, and according to European guidelines both genotypic and phenotypic prediction tools may be used [7]. From the perspective of host genetic variability, several chemokine receptor genes associated with differences in cell surface HIV co-receptor expression have been associated with modi...

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Relevance of Early Detection of HIV Type 1 SI/CXCR4-Using Viruses in Vertically Infected Children

Cited by 11 publications

References 58 publications

HIV‐1 coreceptor usage in perinatally infected Thai children

HIV‐1 coreceptor usage in perinatally infected Thai children

Association Between HIV-1 Tropism and CCR5 Human Haplotype E in a Caucasian Population

Association of chemokine receptor gene variants with HIV‐1 genotype predicted tropism

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