AIDS research and human retroviruses最新文献

{"title":"Machine Learning Revealed a Novel Ferroptosis-Based Classification for Diagnosis in Antiretroviral Therapy-Treated HIV Patients with Defective Immune Recovery.","authors":"Ruoyang Du, Jianfeng Huang","doi":"10.1089/AID.2022.0138","DOIUrl":"10.1089/AID.2022.0138","url":null,"abstract":"<p><p>Despite virological suppression, the CD4⁺ T lymphocytes are not restored in some HIV-infected patients after antiretroviral therapy. These individuals are known as immune non-responders (INRs). INRs are at high risk of developing AIDS and non-AIDS-related events and have a shorter life expectancy. Hence, it is vital to identify INRs early and prevent their complications, but there are still no specific diagnostic indicators or models. Ferroptosis has lately been reported as a type of programmed cell death, which plays an indispensable part in diverse diseases. However, its particular regulatory mechanisms remain unclear and its function in the pathogenic process of defective immunological recovery is still unknown. Blood is mainly used for rapid diagnosis because it enables quick testing. To investigate the role of ferroptosis-related genes (FRGs) in early detection of INRs, we scrutinized Gene Expression Omnibus datasets of peripheral blood samples to estimate their effectiveness. To our knowledge, for the first time, gene expression data were utilized in this study to discover six FRGs that were explicitly expressed in peripheral blood from INRs. Later on, multiple machine-supervised learning algorithms were employed, and a superlative diagnostic model for INRs was built with the random forest algorithm, which displayed satisfactory diagnostic efficiency in the training cohort (area under the curve [AUC] = 0.99) and one external validation cohort (AUC = 0.727). Our findings suggest that FRGs are implicated in the development of defective immune recovery, presenting a potential route for early detection and potential biological targets for the most effective treatment of defective immune recovery.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"90-100"},"PeriodicalIF":1.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9767343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short Cycle, Intermittent Therapy: A Valuable Option in Selected, Virologically Suppressed People Living with HIV.","authors":"Massimiliano Lanzafame, Emanuela Lattuada, Dora Luise, Andrea Delama, Daniela Fait, Sandro Vento","doi":"10.1089/AID.2022.0168","DOIUrl":"10.1089/AID.2022.0168","url":null,"abstract":"<p><p>The use of long-acting antiretroviral regimens will not be suitable for all people living with HIV for various reasons (previous virological failure with drugs of the same class, side effects, logistic difficulties, and costs). We think that short-cycle therapies could represent a feasible and valuable option for antiretroviral treatment optimization in selected individuals. So here we review clinical evidence about efficacy of short-cycle therapy in suppressed HIV-infected patients.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"69-72"},"PeriodicalIF":1.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10115173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pentraxin 3 as an Immune Recovery Marker in HIV Infection After Combination Antiretroviral Therapy.","authors":"Eun Hwa Lee, Jung Ah Lee, Chang Hyup Kim, Ki Hyun Lee, Jinnam Kim, Jung Ho Kim, Jin Young Ahn, Nam Su Ku, Jun Yong Choi, Joon-Sup Yeom, Su Jin Jeong","doi":"10.1089/AID.2023.0002","DOIUrl":"10.1089/AID.2023.0002","url":null,"abstract":"<p><p>Human immunodeficiency virus (HIV) infection causes chronic inflammation in affected individuals. Chronic inflammation may hinder immunological recovery. Treatment with combination antiretroviral therapy (cART) is insufficient to reduce inflammation. Pentraxin 3 (PTX3) is an inflammatory marker associated with cardiovascular disease, malignancy, and acute infection. This study evaluated the usefulness of serum PTX3 levels in measuring inflammation levels, which may be associated with the probability of immune recovery in people living with HIV (PLH). In this single-center prospective study, we measured serum PTX3 levels in PLH treated with cART. Clinical information on HIV status, type of cART administered, and CD4⁺ and CD8⁺ T cell counts at the initial diagnosis of HIV and at study enrollment was obtained from each participant. PLH were divided into good and poor responder groups according to their CD4⁺ T cell counts at enrollment. A total of 198 PLH were enrolled in this study. A total of 175 and 23 participants were assigned to the good and poor responder groups, respectively. The poor responder group exhibited higher PTX3 levels (0.53 ng/mL vs. 1.26 ng/mL, <i>p</i> = .032). Logistic regression analysis demonstrated that low body mass index [odds ratio (OR) = 0.8, <i>p</i> = .010], low initial CD4⁺ T cell counts at diagnosis (OR = 0.994, <i>p</i> = .001), and high PTX3 levels (OR = 1.545, <i>p</i> = .006) are clinical factors that were significantly associated with poor immune recovery in PLH. According to the Youden index, PTX3 levels >1.25 ng/mL are associated with poor immune recovery. PLH should be clinically, virologically, and immunologically evaluated. Serum PTX level is a useful inflammatory marker associated with immune recovery in PLH treated with cART.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"110-113"},"PeriodicalIF":1.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9882872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Cytokine Expression and Immune Reconstitution in Early and Delayed Anti-HIV 96-Weeks Treatment: A Retrospective Study.","authors":"Chao Li, Jian-Ping Sun, Ni Wang, Ping Yan, Rui Wang, Bin Su, Tong Zhang, Hao Wu, Hui Chen, Zhen Li, Xiao-Jie Huang","doi":"10.1089/AID.2022.0089","DOIUrl":"10.1089/AID.2022.0089","url":null,"abstract":"<p><p>HIV is an immunodeficiency disease with emergence of inadequate corresponding reconstruction therapies. Pyroptosis of CD4⁺T cell is mainly caused by immune activation and inflammation that cannot be reduced by successful antiretroviral therapy (ART) alone. Coinfections because of CD4⁺T cell reconstitution failure can occur. Anti-inflammatory treatment determines the success of immune reconstitution. In our experiment, only a few cytokines could recover to normal level following a 2-year antiretroviral treatment in early ART initiation, which is consistent with current findings about adjuvant HIV anti-inflammatory therapy. Early infection is often accompanied by a more severe inflammatory response. Innate immunity cytokines like granulocyte macrophage-colony stimulating factor, IFN-γ induced protein 10 kDa, and tumor necrosis factor-α exhibited the most elevated levels among all kinds of inflammatory cytokines. The correlation analysis showed at least eight cytokines contributing to the changes of CD4/CD8 ratio.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"101-109"},"PeriodicalIF":1.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9544424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Associated with Low-Level Viremia in People Living with HIV in the Italian Antiviral Response Cohort Analysis Cohort: A Case-Control Study.","authors":"Francesca Lombardi, Elena Bruzzesi, Yagai Romeo Bouba, Domenico Di Carlo, Valentino Costabile, Martina Ranzenigo, Franco Maggiolo, Antonella Castagna, Anna Paola Callegaro, Alessia Zoncada, Stefania Paolucci, Valeria Micheli, Silvia Renica, Antonia Bezencheck, Barbara Rossetti, Maria Mercedes Santoro","doi":"10.1089/AID.2023.0015","DOIUrl":"10.1089/AID.2023.0015","url":null,"abstract":"<p><p>Despite effective antiretroviral therapies (ARTs), a subset of people living with HIV (PLWH) still experience low-level viremia (LLV, i.e., 50-1,000 copies/mL). The present study compared PLWH experiencing LLV with those maintaining virological suppression (VS) and explored the potential impact of preexisting drug resistance and other factors on LLV. We conducted a retrospective, 1:1 matched case-control study within a cohort of drug-experienced VS subjects from the Italian Antiviral Response Cohort Analysis database, followed in the period 2009-2019. Cases were individuals experiencing LLV, while controls were those who maintained VS. Matching was for calendar year of first ART regimen. Preexisting drug resistance was calculated as cumulative genotypic susceptibility score (GSS) according to regimen administered at the observational period start. To explore the effect of cumulative GSS, treated as a binary variable (≥2 and <2) and other factors on LLV, we performed a logistic regression analysis. Within a main population of 3,455 PLWH, 337 cases were selected. Cases were comparable to the controls for both gender and age. However, cases showed that they had experienced a longer time since HIV diagnosis, a higher number of drugs previously administered, lower baseline CD4⁺ T cell count and a higher zenith viral load (VL). By multivariate analysis, we found that higher zenith VL [adjusted odds ratio (aOR) (95% confidence interval [CI]) 1.30 (1.14-1.48)], a cumulative usage of both PI [aOR (95% CI): 2.03 (1.19-3.48)] and InSTI [aOR (95% CI): 2.23 (1.47-3.38)] and a cumulative GSS <2 [aOR (95% CI) 0.67 (0.46-0.98)], were associated with a higher risk in developing LLV. In current high-efficacy ART era, in drug-experienced PLWH, the predictors of increased risk of LLV were the presence of preexisting drug resistance, higher zenith VL, and previous PI, and InSTI exposure.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"80-89"},"PeriodicalIF":1.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9778964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The HIV-1 Capsid-Targeted Inhibitor GSK878 Alters Selection of Target Sites for HIV DNA Integration.","authors":"Kaitlin A Marquis, John Everett, Adrian Cantu, Alexander McFarland, Scott Sherrill-Mix, Mark Krystal, Kyle Parcella, Eric Gillis, Robert A Fridell, Frederic D Bushman","doi":"10.1089/AID.2022.0161","DOIUrl":"10.1089/AID.2022.0161","url":null,"abstract":"<p><p>Decades of effort have yielded highly effective antiviral agents to treat HIV, but viral strains have evolved resistance to each inhibitor type, focusing attention on the importance of developing new inhibitor classes. A particularly promising new target is the HIV capsid, the function of which can be disrupted by highly potent inhibitors that persist long term in treated subjects. Studies with such inhibitors have contributed to an evolving picture of the role of capsid itself-the inhibitors, like certain capsid protein (CA) amino acid substitutions, can disrupt intracellular trafficking to alter the selection of target sites for HIV DNA integration in cellular chromosomes. In this study, we compare effects on HIV integration targeting for two potent inhibitors-a new molecule targeting CA, GSK878, and the previously studied lenacapavir (LEN, formerly known as GS-6207). We find that both inhibitors reduce integration in active transcription units and near epigenetic marks associated with active transcription. A careful study of integration near repeated sequences indicated frequencies were also altered for integration within multiple repeat classes. One notable finding was increased integration in centromeric satellite repeats in the presence of LEN and GSK878, which is of interest because proviruses integrated in centromeric repeats have been associated with transcriptional repression, inducibility, and latency. These data add to the picture that CA protein remains associated with preintegration complexes through the point in infection during which target sites for integration are selected, and specify new aspects of the consequences of disrupting this mechanism.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"114-126"},"PeriodicalIF":1.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9582043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Switching to Dolutegravir/Lamivudine in Virologically Suppressed People Living with HIV-1 Aged Over 65 Years.","authors":"Leonardo Calza, Vincenzo Colangeli, Giorgio Legnani, Silvia Cretella, Isabella Bon, Pierluigi Viale","doi":"10.1089/AID.2023.0046","DOIUrl":"10.1089/AID.2023.0046","url":null,"abstract":"<p><p>Clinical trials of dual regimen dolutegravir/lamivudine (DOL/3TC) demonstrated potent efficacy and favorable safety in both antiretroviral therapy-naïve and -experienced patients, but data on older people are lacking. We aimed to evaluate virological efficacy and safety of DOL/3TC in suppressed older patients over a 12-month period. We performed a retrospective cohort study evaluating people living with HIV (PLWHIV) aged ≥65 years at our HIV Clinic who were switched to DOL/3TC. Eligible patients had baseline HIV-1 RNA <20 copies/mL, and no previous virological failures or known resistance mutations for lamivudine or dolutegravir. Inclusion criteria were met by 72 patients: 59 were men, median age was 69.2 years, and one or more comorbidities were present in 89% of patients. The most common reason for switch was simplification, followed by drug-drug interactions (DDIs) and toxicities. After 12 months, 64 (88.9%, by the intention-to-treat analysis) patients maintained HIV-1 RNA <20 copies/mL, and reasons for treatment failure were virological failure in three cases, adverse events in three, and missing data in two. Genotype resistance testing showed no resistance mutations for lamivudine or dolutegravir in subjects with virological failure. The number of potential DDIs decreased from 92 to 12 after switching to DOL/3TC, and a significant reduction in median total and low-density lipoprotein cholesterol was reported, while median change in body weight was not significant. In this real-life cohort, switching to DOL/3TC was associated with maintenance of virological control and good tolerability among persons aged >65 years, supporting use of this dual regimen in older PLWHIV.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"73-79"},"PeriodicalIF":1.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9744897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Characteristics of the New HIV-1 CRF07_BC K₂₈E₃₂ Variant.","authors":"Yingying Ma, Zhenzhou Wan, Min Zhang, Chiyu Zhang","doi":"10.1089/AID.2022.0182","DOIUrl":"10.1089/AID.2022.0182","url":null,"abstract":"<p><p>Accompanied with the appearance and prevalence of the new K₂₈E₃₂ variant among men who have sex with men, HIV-1 circulating recombinant form 07_BC (CRF07_BC) was becoming the most predominant subtype circulating in China. The K₂₈E₃₂ variant with five specific mutations in reverse transcriptase coding region appears to have significantly higher <i>in vitro</i> HIV-1 replication ability than the wild-type strain. In this study, we characterized the special mutations/substitutions in the K₂₈E₃₂ variant at the genomic level. Ten specific mutations that rarely appeared in other six main HIV-1 subtypes/CRFs (A-D, CRF01_AE, and CRF02_AG) were identified in the coding genes/regions of the K₂₈E₃₂ variant, including S77L and a novel seven-amino acid detection (32DKELYPL38) (p6Δ7) in p6, I135L in integrase, T189S in Vif, H/Y15L/F in Vpr, I264V/A and LV/LI328-329VG in gp41, and H82C and S97P in Rev. The special locations of the novel p6Δ7, and gp41 mutations I264V/A and LV/LI328-329VG in crucial protein functional domains suggest that these mutations might be functionally important to the K₂₈E₃₂ variant. Furthermore, eight specific substitutions were identified in Rev responsive element (RRE) of the K₂₈E₃₂ variant, and were revealed to increase the stability of RRE structure with a lower minimum free energy. Whether these mutations/substitutions contribute to improved transmissibility of the CRF07_BC K₂₈E₃₂ variant needs to be further confirmed.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"42-53"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10112887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgment of Reviewers 2023.","authors":"","doi":"10.1089/aid.2024.29005.ack","DOIUrl":"https://doi.org/10.1089/aid.2024.29005.ack","url":null,"abstract":"","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":"40 1","pages":"66-67"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Problematic Cannabis Use Is Associated with Reduced Rectal Microbial Species Richness and Diversity Among a Pilot Sample of Young Sexual and Gender Minorities.","authors":"Ethan Morgan, Jennifer A Manuzak, Courtney Broedlow, Hannah Hudson, Richard D'Aquila, Adam W Carrico, Nichole R Klatt, Brian Mustanski","doi":"10.1089/aid.2022.0143","DOIUrl":"10.1089/aid.2022.0143","url":null,"abstract":"<p><p>Compared to young heterosexual men, young sexual and gender minorities (YSGM) have elevated systemic inflammation and unique intestinal microbial profiles, influenced by HIV infection and substance use. However, links between cannabis use and microbial dysbiosis in this population have not been well described. In this pilot study, we aimed to characterize the complex interrelationships between cannabis use and microbial community structure in YSGM in relationship to HIV status. Cannabis use was assessed by self-administered Cannabis Use Disorder Identification Test (CUDIT) questionnaires and rectal microbial community alpha-diversity metrics were assessed via 16S ribosomal ribonucleic acid (rRNA) sequencing in a subset of YSGM (<i>n</i> = 42) in the RADAR cohort (aged 16-29) in Chicago. Multivariable regression models were used to assess the relationship between cannabis use and microbiome alpha-diversity metrics, adjusting for HIV status and other risk characteristics, including inflammation, which was evaluated by plasma levels of C-reactive protein (CRP). Problematic cannabis use, but not general use, was significantly inversely associated with microbial community richness (Adj. Beta = -8.13; 95% confidence interval [CI]: -15.68 to -0.59) and Shannon diversity (Adj. Beta = -0.04; 95% CI: -0.07 to 0.009). No significant association was observed between CUDIT score and community evenness, nor was any significant moderation observed by HIV status. We observed that problematic cannabis use was associated with reduced microbial community richness and Shannon diversity, adjusting for within population differences in inflammation and HIV status. Future research should aim to assess how cannabis use contributes to microbiome-related health factors among YSGM and if decreasing cannabis use can restore gut microbial community structure.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"1-6"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9752945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}