Therapeutic Immune Recovery and Reduction of CXCR4-Tropic HIV-1

Bader, Joëlle; Däumer, Martin; Schöni‐Affolter, Franziska; Böni, Jürg; Gorgievski-Hrisoho, Meri; Martinetti, Gladys; Thielen, Alexander; Klimkait, Thomas

doi:10.1093/cid/ciw737

Cited by 15 publications

(11 citation statements)

References 30 publications

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“…After 18 months of ART, none of the clones in any of the subtypes were predicted as CXCR4-using (Table 2). This finding is consistent with a previous study in which antiretroviral therapy preferentially suppressed the X4 virus (15). The dramatic decline in HIV DNA in CRF01_AE may be associated with its frequent CXCR4-using.…”

Section: Discussionsupporting

confidence: 93%

“…CXCR4-using virus is reportedly more sensitive to ART: a higher ratio of chemokine receptor CCR5-using virus after 24 weeks of ART has been reported (14). In a recent study, CXCR4-using virus declined sharply in most patients after successful ART (15). However, no study has reported changes in amounts of HIV DNA and associated co-receptors usage of different subtypes in patients receiving relatively long-term ART.…”

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confidence: 99%

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After 18 months of antiretroviral therapy, total HIV DNA decreases more pronouncedly in patients infected by CRF01_AE than in those infected by subtype B and CRF07_BC

Jiao

et al. 2018

Microbiology and Immunology

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Whether the amount of HIV DNA is associated with the subtype of HIV-1 after antiretroviral therapy (ART) has not been reported. In the present study, the amount of HIV DNA and RNA and CD4+T counts in blood and semen prior to and after 18 months of ART were compared in 48 patients infected by CRF01_AE, subtype B or CRF07_BC of HIV-1. Viral RNA was suppressed and CD4 cell count recovery achieved in all patients. The level of HIV DNA were similar before ART; however, patients with CRF01_AE had less HIV DNA after ART than those with subtype B and CRF07_BC infection. According to prediction of co-receptor usage by Geno2Pheno and PSSM in combination, more than 35.6% of clones for CRF01_AE were predicted as CXCR4-using before ART, whereas less than 6% of those for subtype B and CRF07_BC were predicted as CXCR4-using. After 18 months of ART, no CXCR4-using clones were predicted in any of the subtypes. Despite more HIV RNA and fewer CD4 + T cells in patients with CRF01_AE before therapy, no significant differences (P > 0.05) in viral RNA or CD4 cell counts were observed between the subtypes after 18 months of ART. Thus, 18 months of antiretroviral therapy was more efficient in patients with CRF01_AE. Considering that successful ART dramatically reduces the viral load in both blood and semen, risks of sexual transmission of HIV were reduced, contributing to prevention of rapid spread of HIV among men who have sex with men in the region.

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

After 18 months of antiretroviral therapy, total HIV DNA decreases more pronouncedly in patients infected by CRF01_AE than in those infected by subtype B and CRF07_BC

Jiao

et al. 2018

Microbiology and Immunology

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“…In contrary, the prediction in patients failing ART seemed to have a better concordance, although only few patients were analysed. A preferential X4-tropic dependent elimination during ART has been reported [ 14 ]. Also, we found that a switch from X4 to R5 viruses at failure month six was more common with C-PSSM.…”

Section: Discussionmentioning

confidence: 99%

“…Also, R5 and X4 viruses exhibit distinct biological properties, e.g. with regard the replication kinetics, and a preferential selection of X4 virus has been reported in HIV-1B patients on antiretroviral therapy (ART)[ 14 ]. However, no study has evaluated the impact of the viral co-receptor tropism on the outcome of non-maraviroc containing ART in low-middle income countries.…”

Section: Introductionmentioning

confidence: 99%

Prediction of coreceptor usage by five bioinformatics tools in a large Ethiopian HIV-1 subtype C cohort

et al. 2017

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BackgroundGenotypic tropism testing (GTT) has been developed largely on HIV-1 subtype B. Although a few reports have analysed the utility of GTT in other subtypes, more studies using HIV-1 subtype C (HIV-1C) are needed, considering the huge contribution of HIV-1C to the global epidemic.MethodsPlasma was obtained from 420 treatment-naïve HIV-1C infected Ethiopians recruited 2009–2011. The V3 region was sequenced and the coreceptor usage was predicted by five tools: Geno2Pheno clinical–and clonal–models, PhenoSeq-C, C-PSSM and Raymond’s algorithm. The impact of baseline tropism on antiretroviral treatment (ART) outcome was evaluated.ResultsOf 352 patients with successful baseline V3 sequences, the proportion of predicted R5 virus varied between the methods by 12.5% (78.1%-90.6%). However, only 58.2% of the predictions were concordant and only 1.7% were predicted to be X4-tropic across the five methods. Compared pairwise, the highest concordance was between C-PSSM and Geno2Pheno clonal (86.4%). In bivariate intention to treat (ITT) analysis, R5 infected patients achieved treatment success more frequently than X4 infected at month six as predicted by Geno2Pheno clinical (77.8% vs 58.7%, P = 0.004) and at month 12 by C-PSSM (61.9% vs 46.6%, P = 0.038). However, in the multivariable analysis adjusted for age, gender, baseline CD4 and viral load, only tropism as predicted by C-PSSM showed an impact on month 12 (P = 0.04, OR 2.47, 95% CI 1.06–5.79).ConclusionEach of the bioinformatics models predicted R5 tropism with comparable frequency but there was a large discordance between the methods. Baseline tropism had an impact on outcome of first line ART at month 12 in multivariable ITT analysis but only based on prediction by C-PSSM which thus possibly could be used for predicting outcome of ART in HIV-1C infected Ethiopians.

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“…Previously we 47 and others 44 found that X4 variants are prevalent in low-level viremias of otherwise ART-suppressed participants. The presence of X4 variants in the plasma rebound might reflect the late disease stage of participants [48][49][50] or it could indicate a previously unappreciated latent reservoir in naive T cells or those of the myeloid lineage that express high concentrations of the CXCR4 receptor. 42,[51][52][53][54][55] The number of women in our study of rebound virus was limited because most in this cohort experienced ART suppression.…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic Analyses Comparing HIV Sequences from Plasma at Virologic Failure to Cervix Versus Blood Sequences from Antecedent Antiretroviral Therapy Suppression

Bull

McKernan

Styrchak

et al. 2019

AIDS Research and Human Retroviruses

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Identifying tissue sources of HIV that rebound following ''failure'' of antiretroviral therapy (ART) is critical to evaluating cure strategies. To assess the role of the uterine cervix and peripheral blood mononuclear cells (PBMC) as viral reservoirs, nearest-neighbor phylogenetic analyses compared genetic relatedness of tissue sequences during ART suppression to those detected in plasma at viral rebound. Blood and genital tract specimens from a natural history cohort of HIV-infected women were collected over 5 years. HIV DNA sequences extracted from PBMC and cervical biopsies during ART suppression and plasma RNA from rebound (defined as HIV RNA >3 log 10 copies/mL) were derived by single-genome amplification. Phylogenetic and nearest-neighbor analyses of HIV env sequences and drug resistance in pol sequences were compared between tissues. Nine instances of plasma viral rebound (median HIV RNA 3.6 log 10 c/mL; IQR: 3.1-3.8) were detected in 7 of 57 women. Nearest-neighbor analyses found rebound plasma sequences were closer to uterine cervical sequences in 4/9 (44%), closer to PBMC in 3/9 (33%), and ambiguous in 2/9 (22%) cases. Rebound plasma clades (n = 27) shared identical sequences in seven instances with the cervix versus two with PBMC. Novel drug resistance mutations were detected in 4/9 (44%) rebounds. The observed tendency for greater sharing of identical HIV variants and greater nearest-neighbor association between rebounding plasma and uterine cervical versus PBMC sequences suggests that the uterine cervix may be a relevant HIV reservoir. The cervix, a readily accessible tissue in women that can be repeatedly sampled, could help assess the HIV reservoir when evaluating cure strategies.

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Therapeutic Immune Recovery and Reduction of CXCR4-Tropic HIV-1

Cited by 15 publications

References 30 publications

After 18 months of antiretroviral therapy, total HIV DNA decreases more pronouncedly in patients infected by CRF01_AE than in those infected by subtype B and CRF07_BC

After 18 months of antiretroviral therapy, total HIV DNA decreases more pronouncedly in patients infected by CRF01_AE than in those infected by subtype B and CRF07_BC

Prediction of coreceptor usage by five bioinformatics tools in a large Ethiopian HIV-1 subtype C cohort

Phylogenetic Analyses Comparing HIV Sequences from Plasma at Virologic Failure to Cervix Versus Blood Sequences from Antecedent Antiretroviral Therapy Suppression

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