AIDS research and human retroviruses最新文献

{"title":"Comparing Gold-Standard Sanger Sequencing with Two Next-Generation Sequencing Platforms of HIV-1 <i>gp160</i> Single Genome Amplicons.","authors":"David J Nolan, Jonathan DaRoza, Robin Brody, Krishna Ganta, Katherine Luzuriaga, Chris Huston, Simon Rosenthal, Susanna L Lamers, Rebecca Rose","doi":"10.1089/AID.2024.0012","DOIUrl":"10.1089/AID.2024.0012","url":null,"abstract":"<p><p>Our goal was to assess the accuracy of next generation sequencing (NGS) compared with Sanger. We performed single genome amplification (SGA) of HIV-1 <i>gp160</i> on extracted tissue DNA from two HIV+ individuals. Amplicons (<i>n</i> = 30) were sequenced with Sanger or reamplified with barcoded primers and pooled before sequencing using Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PB). For each amplicon, a consensus sequence for NGS reads was obtained by (1) mapping reads to the Sanger sequence when available (\"reference-based\") or (2) mapping reads to a \"pseudo-reference\" sequence, i.e., a consensus sequence of a subset of NGS reads (\"reference-free\"). PB reads were clustered based on genetic similarity. A Sanger consensus sequence was obtained for 23/30 amplicons, for which all NGS consensus sequences were identical (<i>n</i> = 9) or nearly identical (<i>n</i> = 14) compared with Sanger. For the nine mismatches between Sanger/NGS, the nucleotide in the NGS sequence matched all other sequences from that patient. Of the 7/30 amplicons without a Sanger sequence, NGS sequences had ≥35 ambiguous calls in five amplicons and 0 ambiguities in two amplicons. Analysis of the electropherograms showed failure of a single sequencing primer for the latter two amplicons (consistent with a single template) and overlapping peaks for the other five (consistent with multiple templates). Clustering results closely followed the Sanger/NGS consensus results, where amplicons derived from a single template also had a single cluster and vice versa (with one exception, which could be the result of barcode misidentification). Representative sequences from the clusters contained 2-13 differences compared with Sanger/NGS. In summary, we show that both ONT and PB can produce amplicon consensus sequences with similar or higher accuracy compared with Sanger and, importantly, without the need for a known reference sequence. Clustering could be useful in some circumstances to predict or confirm the presence of multiple starting templates.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"659-669"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465488","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":"Knockdowns of CD3zeta Chain in Primary NK Cells Illustrate Modulation of Antibody-Dependent Cellular Cytotoxicity Against Human Immunodeficiency Virus-1.","authors":"Sho Sugawara, Esther Lee, Melissa A Craemer, Alayna Pruitt, Harikrishnan Balachandran, Simon B Gressens, Kyle Kroll, Cordelia Manickam, Yuxing Li, Stephanie Jost, Griffin Woolley, R Keith Reeves","doi":"10.1089/AID.2023.0114","DOIUrl":"10.1089/AID.2023.0114","url":null,"abstract":"<p><p>Multifaceted natural killer (NK) cell activities are indispensable for controlling human immunodeficiency virus (HIV)-1 transmission and pathogenesis. Among the diverse functions of NK cells, antibody-dependent cellular cytotoxicity (ADCC) has been shown to predict better HIV-1 protection. ADCC is initiated by the engagement of an Fc γ receptor CD16 with an Fc portion of the antibody, leading to phosphorylation of the CD3 ζ chain (CD3ζ) and Fc receptor γ chain (FcRγ) as well as downstream signaling activation. Though CD3ζ and FcRγ were thought to have overlapping roles in NK cell ADCC, several groups have reported that CD3ζ-mediated signals trigger a more robust ADCC. However, few studies have illustrated the direct contribution of CD3ζ in HIV-1-specific ADCC. To further understand the roles played by CD3ζ in HIV-1-specific ADCC, we developed a CD3ζ knockdown system in primary human NK cells. We observed that HIV-1-specific ADCC was inhibited by CD3ζ perturbation. In summary, we demonstrated that CD3ζ is important for eliciting HIV-1-specific ADCC, and this dynamic can be utilized for NK cell immunotherapeutics against HIV-1 infection and other diseases.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"631-636"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747177","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":"Strengthening the Application of the DAIDS GCLP Guidelines: The Implementation of an Integrated Laboratory Oversight Framework.","authors":"Loc Nguyen, Anne Leach, Estelle Piwowar-Manning, Mark Marzinke, Allan Levesque, Claudine Gregorio, Kristen Skinner, Tiri Towindo, Heidi Hanes, Kwabena Sarpong, Christian Kasongo, Natasha Samsunder, Grace Aldrovandi, Kathie G Ferbas, Andries Engelbrecht, Michael Stirewalt, Emily Anyango, Sasiwimol Ubolyam, Pamela Lankford-Turner, Marcella Sarzotti-Kelsoe","doi":"10.1089/AID.2024.0042","DOIUrl":"10.1089/AID.2024.0042","url":null,"abstract":"<p><p>The Division of AIDS (DAIDS) Good Clinical Laboratory Practice (GCLP) Guidelines establish a framework to guide the oversight of laboratories supporting DAIDS-sponsored clinical research or trials. Compliance with these guidelines promotes data reliability, validity, and safety of the clinical research or trial participants and laboratory staff and ensures adherence to regulatory requirements. Acknowledgment and adoption of the DAIDS GCLP Guidelines are critical in building laboratory capacity and preparedness for conducting clinical trials. In collaboration with DAIDS, laboratory experts support the implementation of the DAIDS Integrated Laboratory Oversight Framework (Framework) activities. This article describes the implementation of the GCLP Guidelines, the Framework activities, and the coordinated efforts to strengthen laboratory performance. The Framework activities include four components: Quality Assurance Oversight, GCLP Audits, GCLP Training, and Laboratory Quality Improvement. Comparison of GCLP Guidelines with other regulations or standards, including U.S. Clinical Laboratory Improvement Amendments regulation 42 CFR 493, College of American Pathologists, World Health Organization GCLP, and International Organization for Standardization, ISO 15189:2012 standards, highlighted the differences and similarities to guide integration and harmonization efforts. Processes related to the Framework activities are outlined in detail, including key data derived from the managed activities of over 175 laboratories worldwide. Via the evolution of the DAIDS GCLP Guidelines and laboratory oversight workflows, the laboratories participating in DAIDS-sponsored clinical research and trials have successfully participated in internal and external regulatory audits. The collaborative and integrated oversight approach promotes knowledge-sharing and accountability to support the implementation of the DAIDS GCLP Guidelines and compliance monitoring. Lessons learned have helped with the implementation of the DAIDS integrated laboratory oversight approach and quality oversight programs at multiple laboratories worldwide.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"622-630"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970413","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":"Cardiovascular Safety of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate in Virologically Suppressed PLWHIV: A Comparative Analysis of CVD Scores.","authors":"Arturo Ciccullo, Valentina Iannone, Damiano Farinacci, Rebecca Jo Steiner, Francesca Lombardi, Andrea Carbone, Pierluigi Francesco Salvo, Gianmaria Baldin, Alberto Borghetti, Simona Di Giambenedetto","doi":"10.1089/aid.2024.0066","DOIUrl":"10.1089/aid.2024.0066","url":null,"abstract":"<p><p>The Aim of this study is to assess the cardiovascular safety of doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF). We analyzed data from 37 virologically suppressed people living with HIV starting DOR/3TC/TDF, collecting viro-immunological and metabolic parameters as well as the 10-year risk of cardiovascular disease (10Y-CD) using both the Framingham risk score and D:A:D score.After 48 weeks, we observed a significant reduction in 10Y-CD both via the Framingham score (-0.7, <i>p</i> = .021) and the D:A:D score (-0.41, <i>p</i> = .012). After 96 weeks, we registered a significant reduction in 10Y-CD calculated via the D:A:D score (-0.98, <i>p</i> = .009). Regarding serum lipid markers, after 48 weeks we observed a significant reduction in total cholesterol (-17 mg/dL, <i>p</i> < .001), triglycerides (-21 mg/dL, <i>p</i> = .015), and LDL cholesterol (-8 mg/dL, <i>p</i> = .022). After 96 weeks, we registered a significant reduction in total cholesterol (-19 mg/dL, <i>p</i> < .001). DOR/3TC/TDF has shown a favorable metabolic profile, with a significant reduction in 10Y-CD, independently from the use of lipid-lowering drugs.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520714","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":"Long-Term Follow-Up of Persons Living with Perinatally Acquired HIV Infection at a Large HIV Treatment Clinic in Trinidad.","authors":"Jonathan Edwards, Gregory Boyce, Nyla Lyons, Selena Todd, Wendy Samaroo Francis, Elise Raeburn, Robert Jeffrey Edwards","doi":"10.1089/aid.2024.0052","DOIUrl":"https://doi.org/10.1089/aid.2024.0052","url":null,"abstract":"<p><p>Data on persons with perinatally acquired HIV infection in the Caribbean are limited; thus, a chart review was conducted among these clients at an adult HIV treatment clinic in Trinidad over the period January 01, 2011-June 30, 2023. Sociodemographic, clinical, and laboratory data were extracted and analyzed using RStudio version 2021.09.0. Fifty-four study participants were followed up, age range 18-29 years, and there were 27 (50%) males. Eighteen participants (33.3%) were institutionalized until the age of 18 years, while 36 (66.7%) lived with caregivers/relatives and attended outpatient pediatric clinic. The transition from the sheltered environment of pediatric care to the adult HIV clinic was turbulent for some participants as they experienced HIV-related stigma, which may result in poor HIV outcomes. At the initial clinic visit, 28 (51.9%) study participants were virally suppressed (HIV viral load <1,000 copies/mL), which included 12 (66.7%) of 18 who were institutionalized as compared to 16 (44.4%) of 38 who lived with caregivers/relatives (<i>p</i> = 0.387). Data from their last clinic visit showed 31 (57.4%) participants were virally suppressed; 13 (24.1%) were lost to follow-up from care, and there were 6 (11.1%) deaths; 29 (53.7%) were on antiretroviral therapy single-tablet regimens (STRs) and 25 (46.3%) on complex multiple-tablet regimens (MTRs). Institutionalized clients and those on STRs were more likely to be virally suppressed than those living with relatives (<i>p</i> = 0.043) and those on MTR (<i>p</i> < 0.001), respectively. Reported deaths were higher among clients who lived with caregivers/relatives and those on MTR. Participants of younger age were less likely to achieve viral suppression (<i>p</i> = 0.02). Comprehensive programs that include STRs, the engagement of caregivers/relatives and health workers, life skills, and enhanced psychosocial interventions for youths living with perinatally acquired HIV are important to support the transition to adult care and reduce the complex challenges of living with a stigmatizing disease.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455853","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 Climate Change Burden on Immune Health: Are Persons Living with HIV More at Risk?","authors":"Griffin Woolley, Kyle Kroll, Kate Hoffman, Ashley Ward, Amy Corneli, Sarah V Mudrak, M Umar Qureshi, N Lance Okeke, Cliburn Chan, Akhenaton-Andrew D Jones, Georgia D Tomaras, R Keith Reeves","doi":"10.1089/AID.2024.0050","DOIUrl":"10.1089/AID.2024.0050","url":null,"abstract":"<p><p>Climate change poses one of the most significant modern threats to overall human health,especially for vulnerable populations including persons living with HIV (PLWH). In this perspective, we specifically explore the concept of immune resilience in human health and how climate change phenomena - including extreme weather events, food insecurity, pollution, and emerging diseases - may exacerbate immune dysfunction and comorbidities faced by PLWH and hinder access to HIV treatment and prevention services. Multidisciplinary, collaborative efforts are urgently needed to quantify these impacts, develop mitigation strategies, and strengthen policies and funding to bolster immune resilience for PLWH in the face of accelerating climate change.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"549-554"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955774","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":"Study APV20002: Safety and Efficacy Results Through Week 684 for Pediatric Participants Living with HIV-1 Treated with Ritonavir-Boosted Fosamprenavir Oral Solution-Based Antiretroviral Therapy.","authors":"Lisa L Ross, Mark F Cotton, Haseena Cassim, Harmony P Garges, Sven C van Dijkman, Kishen Morarji, Supriya Karthika, Susan Danehower, Jacob Radford, David Butcher","doi":"10.1089/AID.2024.0020","DOIUrl":"10.1089/AID.2024.0020","url":null,"abstract":"<p><p>APV20002 was a multicenter, international, open-label study that began in 2003 investigating the pharmacokinetics, efficacy, and safety of ritonavir-boosted fosamprenavir (FPV/r) oral solution (OS) in combination with nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) in participants living with HIV-1 aged 4 weeks to <2 years with a primary endpoint at Week 48 (48W). Participants in APV20002 could continue in the study post-48W until FPV OS was locally available in their countries. Children were required to discontinue after reaching >39 kg or if FPV OS had no clinical benefit. Fifty-nine participants were enrolled; 5/59 received a single FPV OS visit for pharmacokinetic determinations. Most (38/54; 70%) were antiretroviral experienced; 39/59 participants had >48 weeks on treatment, 4/39 of whom discontinued after 48 weeks due to an adverse event (AE). At 48W, 88% of participants had HIV-1 RNA <400 copies/mL by Observed analysis; the proportion with HIV-1 RNA <400 copies/mL remained high (84%-100%) through Week 684. The median CD4⁺ cell count was 1,235 cells/mm³ [<i>n</i> = 51] at baseline, 1,690 cells/mm³ (<i>n</i> = 41) at Week 48, and 1,280 cells/mm³ (<i>n</i> = 21) at Week 180. From baseline to Week 684, 54/59 (92%) participants had ≥1 treatment-emergent AE regardless of causality; 42/59 (71%) had a treatment-emergent grade 2-4 AE, predominantly maximum toxicity: grade 2; 21/59 (36%) and 21/59 (36%) had severe or grade 3/4 AEs. From baseline to Week 684, 14/54 (26%) participants met virologic failure (VF) criteria, 9/14 before 48W. HIV from 1/9 VFs through 48W developed treatment-emergent reduced susceptibility to FPV and 1/9 to lamivudine/emtricitabine. Post-48W, 4/5 participants with VF had phenotype results; all were still susceptible to all study drugs at VF. In conclusion, FPV OS-based ART was efficacious and generally well tolerated in this long-running pediatric study through 684 weeks of treatment, with a safety profile consistent with experience in adults and older children.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"606-613"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141553948","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":"<i>In Utero</i> Mother-to-Child Transmission of HIV-1 and the Associated Factors in Rwanda, Africa.","authors":"Gad Rutayisire, Emmanuel Ssemwanga, Roman Ntale, Uwera Marie Grace, Jean Pierre Gashema, Paul Gasana, Enock Wekia, Noah Kiwanuka, Bernard Ssentalo Bagaya","doi":"10.1089/aid.2023.0117","DOIUrl":"10.1089/aid.2023.0117","url":null,"abstract":"<p><p>Mother-to-child transmission (MTCT) of HIV-1 and associated mortality continue to occur at unacceptably high rates, despite the extensive rollout and implementation of Prevention of Mother-to-Child Transmission (PMTCT) Programs, including the modified versions of Option B and B+ in 2010 and 2012, respectively. Maternal HIV viral load (VL) and socio-behavioral factors sustaining MTCT in Rwanda remain largely unexplored. The study examined the effects of socio-behavioral factors on maternal VL and their contribution to <i>in utero</i> transmission of HIV-1 in the context of Rwanda's HIV epidemic. A prospective cohort study was conducted in 862 mother-baby pairs enrolled in 10 PMTCT clinics in Rwanda. VL was determined on plasma and Dried Blood Spots samples, whereas HIV DNA PCR was performed to determine <i>in utero</i> MTCT of HIV of the babies immediately at birth and then at 3 weeks, 4 weeks, 6 months, and 18 months, together with HIV antibody testing to determine other forms of MTCT of HIV. Quantitative data on socio-behavioral factors were collected through a structured questionnaire. Linear regression and univariate analysis of variances using SPSS 25.0 were used to test the hypotheses. We found 22/862 (2.55%) cases of <i>in utero</i> transmission and a total of 32/862 (3.7%) cases of MTCT of HIV-1 over 18 study months. Maternal VL at delivery was significantly associated with the risk of <i>in utero</i> transmission of HIV-1. Socio-behavioral factors associated with elevated maternal VL at delivery included alcohol, smoking, multiple sexual partners, mothers' income, being a casual laborer, and distance to health care services. We report an MTCT rate of 3.7% in our study population over the 18 months, higher than the national average of 1.5%, the majority of which occurred <i>in utero</i>. MTCT cases were attributable to failure to suppress maternal VL.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"575-580"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069979","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 Global Impact of Diversifying PrEP Options: Results of an International Discrete Choice Experiment of Existing and Potential PrEP Strategies with Gay and Bisexual Men and Physicians.","authors":"Christine Tagliaferri Rael, Rebecca Giguere, Ewa Bryndza Tfaily, Sara Sutton, Elizabeth Horn, Robert J Schieffer, Craig Hendrix, Richard T D'Aquila, Thomas J Hope","doi":"10.1089/AID.2023.0120","DOIUrl":"10.1089/AID.2023.0120","url":null,"abstract":"<p><p>To improve current and future use of existing (oral, injectable) and potential future (implants, douches) pre-exposure prophylaxis (PrEP) products, we must understand product preferences relative to one another, among gay and bisexual men (GBM), and physicians who prescribe PrEP. We completed an online discrete choice experiment (DCE) with separate groups of GBM and/or physicians from the United States, South Africa, Spain, and Thailand. Participants were presented information on PrEP products, including daily pills, event-driven pills (2-1-1 regimen), injections, subdermal implants (dissolvable, removable), and rectal douches. Next, they completed a choice exercise in which they were shown 10 screens, each presenting 3 of the aforementioned products at a time with 11 attributes for physicians and 10 attributes for GBM. For the attributes that were not constant, one level was shown per screen for each product. Participants selected the product they preferred most and rated their likelihood to select (GBM) or recommend (physicians) that product. Data were modeled using hierarchical Bayes estimation; resulting model coefficients were used to develop attribute importance measures and product preferences. For GBM across all countries, if all aforementioned PrEP products were on the market at the same time, over 90% of GBM would use some form of PrEP; 100% of physicians would recommend at least one of the PrEP products. There were variations in product preference by country. GBM in the United States and Thailand preferred the injection (21.7%, 22.9%, respectively), while the dissolvable implant was preferred in South Africa and Spain (19.9%, 19.8%, respectively). In the United States, South Africa, and Spain (where physician data were available), physicians were most likely to recommend the dissolvable implant (37.2%, 40.6%, 38.3%, respectively).</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"591-605"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955784","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":"The Effect of Efavirenz on Reward Processing in Asymptomatic People Living with HIV: A Randomized Controlled Trial.","authors":"Patrick G A Oomen, Charlotte S Hakkers, Joop E Arends, Guido E L van der Berk, Pascal Pas, Andy I M Hoepelman, Berend J van Welzen, Stefan du Plessis","doi":"10.1089/AID.2022.0069","DOIUrl":"10.1089/AID.2022.0069","url":null,"abstract":"<p><p>Functional magnetic resonance imaging (fMRI) studies have demonstrated that HIV-infection affects the fronto-striatal network. It has not been examined what impact efavirenz (EFV), an antiretroviral drug notorious for its neurocognitive effects, has on the reward system: a key subcomponent involved in depressive and apathy symptoms. Therefore, this study aims to investigate the effect of EFV on reward processing using a monetary incentive delay (MID) task. In this multicenter randomized controlled trial, asymptomatic adult participants stable on emtricitabine/tenofovirdisoproxil fumarate (FTC/TDF)/EFV were randomly assigned in a 2:1 ratio to switch to FTC/TDF/rilpivirine (RPV) (<i>n</i> = 30) or continue taking FTC/TDF/EFV (<i>n</i> = 13). At baseline and 12 weeks after therapy switch, both groups performed an MID task. Behavior and functional brain activity related to reward anticipation and reward outcome were assessed with blood-oxygen-level-dependent fMRI. Both groups were matched for age, education level, and time since HIV diagnosis and on EFV. At the behavioral level, both groups had faster response times and better response accuracy during rewarding versus nonrewarding trials, with no improvement resulting from switching FTC/TDF/EFV to FTC/TDF/RPV. No significant change in activation related to reward anticipation in the ventral striatum was found after switching therapy. Both groups had significantly higher activation levels over time, consistent with a potential learning effect. Similar activity related to reward outcome in the orbitofrontal cortex was found. Discontinuing FTC/TDF/EFV was not found to improve activity related to reward anticipation in asymptomatic people living with HIV, with similar cortical functioning during reward outcome processing. It is therefore likely that EFV does not affect motivational control. Further research is needed to determine whether EFV affects motivational control in HIV populations with different characteristics.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"581-590"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9126463","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}