HIV Type 1 Coreceptor Tropism, CCR5 Genotype, and Integrase Inhibitor Resistance Profiles in Vietnam: Implications for the Introduction of New Antiretroviral Regimens

Luu, Quynh Phuong; Dean, Jonathan; Diem, Trinh Thi; Carr, Michael J.; Dunford, Linda; Coughlan, Suzie; Connell, Jeff; Nguyen, Hien Tran; Hall, William W.; Thi, Lan Anh Nguyen

doi:10.1089/aid.2011.0396

Cited by 5 publications

(3 citation statements)

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“…A previous report found a switch from R5 to X4 viruses during effective ART in about 50% of patients who harboured R5 viruses at baseline [23]. Reports from other countries with limited CRF01_AE samples also demonstrated a high prevalence of X4 tropism in HIV-1 CRF01_AE: 31 and 40% of patients harboured X4 virus in studies from Singapore and Vietnam, respectively [24,25] . Sequence compiling in China showed that 22% of patients harboured X4 and 40% R5X4 [26].…”

Section: Discussionmentioning

confidence: 81%

Coreceptor tropism determined by genotypic assay in HIV‐1 circulating in Thailand, where CRF01_AE predominates

et al. 2013

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ObjectivesChemokine (C-C motif) receptor 5 (CCR5) inhibitors are a novel class of antiretroviral agents that are promising for treatment of patients who harbour the HIV-1 R5 strain. Data on coreceptor tropism in non-B HIV-1 subtypes are limited. We studied coreceptor tropism in HIV-1 circulating in Thailand, where CRF01_AE predominates, using a genotypic assay. MethodsWe compiled V3 sequences of HIV-1 strains circulating in Thailand during 2010-2012. Coreceptor tropism was predicted based on V3 sequences using GENO2PHENO version 2.5 (http://coreceptor.bioinf.mpi-inf.mpg.de). ResultsOne hundred and fifty-five HIV-1-infected patients were enrolled in this study. Ninety-nine patients (63.9%) were antiretroviral-naïve, and the remainder had virological failure. The median (interquartile range) CD4 cell count and HIV-1 RNA were 220 (74-379) cells/μL and 75 374 (14 127-226 686) HIV-1 RNA copies/mL, respectively. Of the sequences obtained from these patients, 119 (76.8%) were CRF01_AE and 22 (14.2%) were subtype B. At a false positive rate of < 5%, 61 (39.4%) HIV-1-infected individuals were predicted to harbour the X4 phenotype. X4 viruses were detected more frequently in the treatment-failure group compared with the treatment-naïve group (30.3 vs. 55.4%, respectively; P = 0.002). Those with CRF01_AE had a higher proportion of X4 viruses compared with non-AE subtypes (47.9 vs. 11.1%, respectively; P < 0.001). By multivariate logistic regression, CRF01_AE and treatment failure were independently associated with predicted X4 phenotype [odds ratio (OR) 7.93; 95% confidence interval (CI) 2.57-24.50; P < 0.001, and OR 3.10; 95% CI 1.50-6.42; P = 0.002, respectively]. ConclusionsCRF01_AE and treatment failure are associated with the predicted X4 phenotype. In regions where CRF01_AE predominates, use of CCR5 inhibitors must be considered with caution. The phenotypic assay and its correlation with genotypes should be further investigated in CRF01_AE.Keywords: CCR5, coreceptor, CXCR4, genotypic testing, HIV-1, Thailand, tropism Accepted 26 September 2013 IntroductionHIV-1 infection requires entry into the target cells as a first step to establish infection. The chemokine receptors chemokine (C-C motif) receptor 5 (CCR5) and chemokine (C-X-C motif) receptor 4 (CXCR4) are usually the main Coreceptor tropism testing should be performed prior to initiation of therapy with CCR5 inhibitors. HIV-1 tropism can be assessed with either phenotypic or genotypic methods. The Trofile assay (Monogram Biosciences, South San Francisco, CA) generates pseudovirions from the patient-derived envelope (env) gene [8]. These virions are used to infect human cell lines expressing either CCR5 or CXCR4. The enhanced sensitivity Trofile assay (ESTA) can detect X4 clones with 100% sensitivity when these clones make up 0.3% of the population. However, its use is limited by its restricted availability and long turnaround time. Genotypic testing of coreceptor usage is based on sequencing of the V3-encoding region of the HIV-1 env gene [9]. Various algorithms ...

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Section: Discussionmentioning

confidence: 81%

Coreceptor tropism determined by genotypic assay in HIV‐1 circulating in Thailand, where CRF01_AE predominates

et al. 2013

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“…The global prevalence of CRF01-AE is 5%, and it is responsible for up to 4% of the HIV-1 infections in Europe according to the SPREAD study (13). Previous studies have employed either phenotypic or genotypic prediction of coreceptor usage by HIV-1 CRF01-AE, but the correlation between the two methods has not been investigated (14)(15)(16)(17).…”

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confidence: 99%

Genotypic Prediction of HIV-1 CRF01-AE Tropism

et al. 2013

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f HIV-1 subtype CRF01-AE predominates in south Asia and has spread throughout the world. The virus tropism must be determined before using CCR5 antagonists. Genotypic methods could be used, but the prediction algorithms may be inaccurate for non-B subtypes like CRF01-AE and the correlation with the phenotypic approach has not been assessed. We analyzed 61 CRF01-AE V3 clonal sequences of known phenotype from the GenBank database. The sensitivity of the Geno2pheno10 genotypic algorithm was 91%, but its specificity was poor (54%). In contrast, the combined 11/25 and net charge rule was highly specific (98%) but rather insensitive (64%). We thus identified subtype CRF01-AE determinants in the V3 region that are associated with CXCR4 use and developed a new simple rule for optimizing the genotypic prediction of CRF01-AE tropism. The concordance between the predicted CRF01-AE genotype and the phenotype was 95% for the clonal data set. We then validated this algorithm by analyzing the data from 44 patients infected with subtype CRF01-AE, whose tropism was determined using a recombinant phenotypic entry assay and V3-loop bulk sequencing. The CRF01-AE genotypic tool was 70% sensitive and 96% specific for predicting CXCR4 use, and the concordance between genotype and phenotype was 84%, approaching the concordance obtained for predicting the tropism of HIV-1 subtype B. Genotypic predictions that use a subtype CRF01-AE-specific algorithm appear to be preferable for characterizing coreceptor usage both in pathophysiological studies and for ensuring the appropriate use of CCR5 antagonists.

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“…On the other hand, an IDU-associated virus already transmitted through heterosexual contact may regain some of this transmission efficacy. Though it is difficult to speculate on mechanisms that might bring about this potential difference, some unique characteristics of HIV strains in Vietnam, such as the dominance of CXCR4 tropism observed in our study or a previous report [ 23 ], may have contributed to the apparent lower sexual transmission efficacy among stable couples in northern Vietnam. However, only half of the HIV env sequences could be successfully evaluated, and sequence data of the V3 loop alone cannot determine co-receptor tropism of CRF01_AE stains [ 24 ].…”

Section: Discussionmentioning

confidence: 66%

High Proportion of HIV Serodiscordance among HIV-Affected Married Couples in Northern Vietnam

et al. 2015

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IntroductionLittle is known about the state of HIV transmission among married couples in Vietnam. This study aims to clarify HIV serostatus in this group and elucidate risk factors for intra-marital HIV transmission.MethodsIn 2012, we enrolled a group of HIV-positive married men registered at the HIV outpatient clinic of a referral hospital in northern Vietnam, along with their wives. Sociodemographic, behavioural and clinical data were collected from men and wives. HIV serodiscordant couples were followed until March 2014 to determine seroconversion rate. A phylogenetic analysis was performed based on env V3 sequence to detail cluster formation among men.ResultsOf the 163 HIV-positive men enrolled in the study, 101 (62.0%) had wives testing HIV-negative. Half of men reported injecting drug use (IDU) as a likely transmission route. Couples reported a high incidence of unprotected sexual intercourse prior to diagnosis; the median (inter quartile range) was 4 (4–8) times per month. Only 17 couples (10.4%) reported using condoms during at least half these instances. Multivariable analysis revealed IDU history among men was independently associated with HIV-negative wives (adjusted OR 0.31; 95% CI 0.10–0.95, p=0.041). Phylogenetic analysis of 80 samples indicated CRF01_AE. Of these, 69 (86.3%) clustered with IDU-associated viruses from Vietnam. No HIV seroconversion was identified during a follow-up of 61 serodiscordant couples, with 126.5 person-years of observation during which HIV-infected men were on antiretroviral drug therapy (ART).ConclusionHigh HIV serodiscordance was observed among HIV-affected married couples in northern Vietnam. A large number of at-risk wives therefore remain HIV-negative and can be protected with measures including proper use of ART if couples are made aware of the serodiscordance through screening.

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HIV Type 1 Coreceptor Tropism, CCR5 Genotype, and Integrase Inhibitor Resistance Profiles in Vietnam: Implications for the Introduction of New Antiretroviral Regimens

Cited by 5 publications

References 14 publications

Coreceptor tropism determined by genotypic assay in HIV‐1 circulating in Thailand, where CRF01_AE predominates

Coreceptor tropism determined by genotypic assay in HIV‐1 circulating in Thailand, where CRF01_AE predominates

Genotypic Prediction of HIV-1 CRF01-AE Tropism

High Proportion of HIV Serodiscordance among HIV-Affected Married Couples in Northern Vietnam

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