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9 pages, 554 KiB  
Article
Pittsburgh Sleep Quality Index (PSQI) Changes in Virologically Suppressed People Living with HIVSwitching to Long-Acting Cabotegravir and Rilpivirine
by Nicolò De Gennaro, Mariacristina Poliseno, Angelo Dargenio, Flavia Balena, Deborah Fiordelisi, Vito Spada, Greta Romita, Giacomo Guido, Francesco Di Gennaro, Giuseppe Bruno, Mariantonietta Purgatorio, Giovanni Battista Buccoliero and Annalisa Saracino
Biomedicines 2024, 12(9), 1995; https://doi.org/10.3390/biomedicines12091995 - 2 Sep 2024
Viewed by 342
Abstract
Background: Limited evidence is available about sleep quality changes associated with the use of Cabotegravir (CAB), a new, long-acting (LA) antiretroviral (ARV) drug belonging to the class of Integrase Strand Transfer Inhibitors (INSTIs). Methods: Pittsburgh Sleep Quality Index (PSQI) was calculated in 53 [...] Read more.
Background: Limited evidence is available about sleep quality changes associated with the use of Cabotegravir (CAB), a new, long-acting (LA) antiretroviral (ARV) drug belonging to the class of Integrase Strand Transfer Inhibitors (INSTIs). Methods: Pittsburgh Sleep Quality Index (PSQI) was calculated in 53 people living with HIV (PLWH) under the care of the outpatient services of two Italian Infectious Diseases Centers in Apuliabefore (M0) and seven months after (M7) the switch to LA CAB. Global scores and relative subitems were compared using paired sample tests. The same analysis was repeated in subgroups of PLWH switching from INSTIs-, Dolutegravir-(DTG), and Bictegravir (BIC)-based regimens. Results: A significant reduction was reported in global mean (±StandardDeviation, SD) PSQI at M7 compared to M0 (4 (±3) vs. 3 (±2), p = 0.01), particularly in the areas of sleep latency and sleep disturbances. The improvement was also significant in PLWH already on INSTIs- (from median 3 to 2 points, p = 0.02) and DTG-based (from median 4 to 2, p = 0.01) ARV regimens, but not among those who switched from BIC-based regimens. Conclusions: PLWH reported improved sleep quality after switching from ARV treatment to LA CAB. Further studies are needed to give deeper insights into this phenomenon. Full article
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13 pages, 730 KiB  
Article
Development and Optimization of Oligonucleotide Ligation Assay (OLA) Probes for Detection of HIV-1 Resistance to Dolutegravir
by Ingrid A. Beck, Ceejay L. Boyce, Marley D. Bishop, Yen L. Vu, Amanda Fung, Sheila Styrchak, Nuttada Panpradist, Barry R. Lutz and Lisa M. Frenkel
Viruses 2024, 16(7), 1162; https://doi.org/10.3390/v16071162 - 19 Jul 2024
Viewed by 756
Abstract
The WHO currently recommends dolutegravir (DTG)-based ART for persons living with HIV infection in resource-limited-settings (RLS). To expand access to testing for HIV drug resistance (DR) to DTG in RLS, we developed probes for use in the oligonucleotide ligation assay (OLA)-Simple, a near-point [...] Read more.
The WHO currently recommends dolutegravir (DTG)-based ART for persons living with HIV infection in resource-limited-settings (RLS). To expand access to testing for HIV drug resistance (DR) to DTG in RLS, we developed probes for use in the oligonucleotide ligation assay (OLA)-Simple, a near-point of care HIV DR kit. Genotypic data from clinical trials and case reports were used to determine the mutations in HIV-1 integrase critical to identifying individuals with DTG-resistance at virologic failure of DTG-based ART. Probes to detect G118R, Q148H/K/R, N155H and R263K in HIV-1 subtypes A, B, C, D and CRF01_AE were designed using sequence alignments from the Los Alamos database and validated using 61 clinical samples of HIV-1 subtypes A, B, C, D, CRF01_AE genotyped by PacBio (n = 15) or Sanger (n = 46). Initial OLA probes failed to ligate for 16/244 (6.5%) codons (9 at G118R and 7 at Q148H/K/R). Probes revised to accommodate polymorphisms interfering with ligation at codons G118R and Q148R reduced indeterminates to 3.7% (5 at G118R and 4 at Q148H/K/R) and detected DTG-mutations with a sensitivity of 96.5% and 100% specificity. These OLA DTG resistance probes appear highly sensitive and specific across HIV-1 subtypes common in RLS with high burden of HIV infection. Full article
(This article belongs to the Special Issue Antiviral Resistance Mutations)
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11 pages, 765 KiB  
Article
Full-Spectrum Surveillance of Pre-Treatment HIV Drug Resistance in Southeastern China
by Jiafeng Zhang, Baochang Sun, Zihang Sheng, Xiaobei Ding, Qin Fan, Gang Huang, Zhihong Guo, Ping Zhong, Lingjie Liao, Hui Xing, Yan Xia, Chengliang Chai and Jianmin Jiang
Pharmaceuticals 2024, 17(7), 900; https://doi.org/10.3390/ph17070900 - 6 Jul 2024
Viewed by 698
Abstract
HIV drug resistance compromises the ability of anti-retroviral therapy (ART) to suppress viral replication, resulting in treatment failure. This study investigates the prevalence of pre-treatment drug resistance (PDR) in newly diagnosed individuals in a prosperous city (Wenzhou) in Southeastern China. A cross-sectional investigation [...] Read more.
HIV drug resistance compromises the ability of anti-retroviral therapy (ART) to suppress viral replication, resulting in treatment failure. This study investigates the prevalence of pre-treatment drug resistance (PDR) in newly diagnosed individuals in a prosperous city (Wenzhou) in Southeastern China. A cross-sectional investigation was carried out among 473 newly diagnosed ART-naive HIV-1-infected individuals between January and December 2022. The protease–reverse transcriptase (PR-RT) region and integrase (IN) region of HIV-1 were amplified by two separately nested PCRs, followed by sequencing. Drug resistance mutations (DRMs) and drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were analyzed. The PDR prevalence was 6.5% [95% CI: 4.4–9.1] for any anti-retroviral drug, 0.9% [95% CI: 0.3–2.3] for NRTIs, 4.1% [95% CI: 2.5–6.5] for NNRTIs, 1.8% [95% CI: 0.8–3.6] for PIs and 0.5% [95% CI: 0.1–1.8] for INSTIs. According to the subtyping results of the PR-RT region, 11 different subtypes and 31 unique recombinant forms (URFs) were found. CRF07_BC was the dominant subtype (53.7%, 233/434), followed by CRF01_AE (25.3%, 110/434). V179D (1.6%) and K103N (1.4%) were the most predominant types of NNRTI DRMs. Q58E (1.2%) and M184V (0.7%) were the most frequent PI DRMs and NRTI DRMs, respectively. The INSTI-related DRMs Y143S (causes high-level resistance to RAL) and G163K (causes low-level resistance to EVG and RAL) were found in one patient each. Given the relatively high PDR prevalence of NNRTI (4.1%), non-NNRTI-based ART may be preferred in the future. It is recommended to include genotypic resistance testing before starting ART in regions where feasible. Full article
(This article belongs to the Section Pharmacology)
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8 pages, 245 KiB  
Article
Reversibility of Neuropsychiatric Adverse Events after Switching to Darunavir/Cobicistat or Doravirine in Men on INSTI-Based Regimen
by José Antonio Mata-Marín, Carina Aurora Juárez-Contreras, Mara Soraya Rodríguez-Evaristo, Olivia Concepción Martínez-Carrizales, Ericka Pompa-Mera, Alberto Chaparro Sánchez, Salma Triana-González, Ana Luz Cano-Díaz and Jesús Enrique Gaytán-Martínez
Viruses 2024, 16(7), 1083; https://doi.org/10.3390/v16071083 - 5 Jul 2024
Viewed by 661
Abstract
Integrase strand transfer inhibitors (INSTI) are associated with neuropsychiatric adverse events (NPAEs). The aim of this study was to evaluate improvements in NPAEs after switching an INSTI-based regimen to darunavir/cobicistat (DRV/c) or doravirine (DOR). Methods: A prospective cohort study was conducted to [...] Read more.
Integrase strand transfer inhibitors (INSTI) are associated with neuropsychiatric adverse events (NPAEs). The aim of this study was to evaluate improvements in NPAEs after switching an INSTI-based regimen to darunavir/cobicistat (DRV/c) or doravirine (DOR). Methods: A prospective cohort study was conducted to evaluate the reversibility of NPAEs via the Patient Health Questionnaire (PHQ-9), the Insomnia Severity Index (ISI), and the Hospital Anxiety and Depression Scale (HADS-A and D) in patients who started antiretroviral therapy with dolutegravir (DTG) or bictegravir (BIC). These patients were switched to DRV/c or DOR. Scales were compared at the moment of the switch and 12 weeks later. Results: We included 1153 treatment-naïve men, 676 (58.7%) with BIC and 477 (41.3%) with DTG. A total of 32 (2.7%) experienced NPAEs that led to discontinuation. Insomnia was found in 20 patients; depression via PHQ-9 in 21 patients, via HADS-D in 5 patients, and anxiety via HADS-A in 12 patients. All of them were evaluated by a psychiatrist at the moment of the symptoms; 7 (21.8%) started psychotropic drugs. After 12 weeks of follow-up, PHQ-9, ISI, HADS-A, and HADS-D decreased, with a p-value ≤ 0.05. Conclusions: NPAEs seem to improve after switching to a DRV/c- or DOR-based regimen after the first 4 and 12 weeks. Full article
(This article belongs to the Special Issue HIV and Drugs of Abuse, 3rd Edition)
16 pages, 2250 KiB  
Article
Cell Culture Evaluation Hints Widely Available HIV Drugs Are Primed for Success if Repurposed for HTLV-1 Prevention
by Mphatso D. Kalemera, Allison K. Maher, Margarita Dominguez-Villar and Goedele N. Maertens
Pharmaceuticals 2024, 17(6), 730; https://doi.org/10.3390/ph17060730 - 5 Jun 2024
Viewed by 890
Abstract
With an estimated 10 million people infected, the deltaretrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is the second most prevalent pathogenic retrovirus in humans after HIV-1. Like HIV-1, HTLV-1 overwhelmingly persists in a host via a reservoir of latently infected CD4+ [...] Read more.
With an estimated 10 million people infected, the deltaretrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is the second most prevalent pathogenic retrovirus in humans after HIV-1. Like HIV-1, HTLV-1 overwhelmingly persists in a host via a reservoir of latently infected CD4+ T cells. Although most patients are asymptomatic, HTLV-1-associated pathologies are often debilitating and include adult T-cell leukaemia/lymphoma (ATLL), which presents in mature adulthood and is associated with poor prognosis with short overall survival despite treatment. Curiously, the strongest indicator for the development of ATLL is the acquisition of HTLV-1 through breastfeeding. There are no therapeutic or preventative regimens for HTLV-1. However, antiretrovirals (ARVs), which target the essential retrovirus enzymes, have been developed for and transformed HIV therapy. As the architectures of retroviral enzyme active sites are highly conserved, some HIV-specific compounds are active against HTLV-1. Here, we expand on our work, which showed that integrase strand transfer inhibitors (INSTIs) and some nucleoside reverse transcriptase inhibitors (NRTIs) block HTLV-1 transmission in cell culture. Specifically, we find that dolutegravir, the INSTI currently recommended as the basis of all new combination antiretroviral therapy prescriptions, and the latest prodrug formula of the NRTI tenofovir, tenofovir alafenamide, also potently inhibit HTLV-1 infection. Our results, if replicated in a clinical setting, could see transmission rates of HTLV-1 and future caseloads of HTLV-1-associated pathologies like ATLL dramatically cut via the simple repurposing of already widely available HIV pills in HTLV-1 endemic areas. Considering our findings with the old medical saying “it is better to prevent than cure”, we highly recommend the inclusion of INSTIs and tenofovir prodrugs in upcoming HTLV-1 clinical trials as potential prophylactics. Full article
(This article belongs to the Special Issue HTLV-1: Molecular Insights to Targeted Elimination Strategies)
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18 pages, 2844 KiB  
Article
A Two-Faced Gut Microbiome: Butyrogenic and Proinflammatory Bacteria Predominate in the Intestinal Milieu of People Living with HIV from Western Mexico
by Tonatiuh Abimael Baltazar-Díaz, Jaime F. Andrade-Villanueva, Paulina Sánchez-Álvarez, Fernando Amador-Lara, Tania Holguín-Aguirre, Karina Sánchez-Reyes, Monserrat Álvarez-Zavala, Rocío Ivette López-Roa, Miriam Ruth Bueno-Topete and Luz Alicia González-Hernández
Int. J. Mol. Sci. 2024, 25(9), 4830; https://doi.org/10.3390/ijms25094830 - 29 Apr 2024
Viewed by 1007
Abstract
HIV infection results in marked alterations in the gut microbiota (GM), such as the loss of microbial diversity and different taxonomic and metabolic profiles. Despite antiretroviral therapy (ART) partially ablating gastrointestinal alterations, the taxonomic profile after successful new ART has shown wide variations. [...] Read more.
HIV infection results in marked alterations in the gut microbiota (GM), such as the loss of microbial diversity and different taxonomic and metabolic profiles. Despite antiretroviral therapy (ART) partially ablating gastrointestinal alterations, the taxonomic profile after successful new ART has shown wide variations. Our objective was to determine the GM composition and functions in people living with HIV (PLWHIV) under ART in comparison to seronegative controls (SC). Fecal samples from 21 subjects (treated with integrase strand-transfer inhibitors, INSTIs) and 18 SC were included. We employed 16S rRNA amplicon sequencing, coupled with PICRUSt2 and fecal short-chain fatty acid (SCFA) quantification by gas chromatography. The INSTI group showed a decreased α-diversity (p < 0.001) compared to the SC group, at the expense of increased amounts of Pseudomonadota (Proteobacteria), Segatella copri, Lactobacillus, and Gram-negative bacteria. Concurrently, we observed an enrichment in Megasphaera and Butyricicoccus, both SCFA-producing bacteria, and significant elevations in fecal butyrate in this group (p < 0.001). Interestingly, gut dysbiosis in PLWHIV was characterized by a proinflammatory environment orchestrated by Pseudomonadota and elevated levels of butyrate associated with bacterial metabolic pathways, as well as the evident presence of butyrogenic bacteria. The role of this unique GM in PLWHIV should be evaluated, as well as the use of butyrate-based supplements and ART regimens that contain succinate, such as tenofovir disoproxil succinate. This mixed profile is described for the first time in PLWHIV from Mexico. Full article
(This article belongs to the Special Issue Microbiome and Metabolome in the Gastrointestinal Tract, 2nd Edition)
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15 pages, 1832 KiB  
Article
Applying Next-Generation Sequencing to Track HIV-1 Drug Resistance Mutations Circulating in Portugal
by Victor Pimentel, Marta Pingarilho, Cruz S. Sebastião, Mafalda Miranda, Fátima Gonçalves, Joaquim Cabanas, Inês Costa, Isabel Diogo, Sandra Fernandes, Olga Costa, Rita Corte-Real, M. Rosário O. Martins, Sofia G. Seabra, Ana B. Abecasis and Perpétua Gomes
Viruses 2024, 16(4), 622; https://doi.org/10.3390/v16040622 - 17 Apr 2024
Cited by 1 | Viewed by 1097
Abstract
Background: The global scale-up of antiretroviral treatment (ART) offers significant health benefits by suppressing HIV-1 replication and increasing CD4 cell counts. However, incomplete viral suppression poses a potential threat for the emergence of drug resistance mutations (DRMs), limiting ART options, and increasing HIV [...] Read more.
Background: The global scale-up of antiretroviral treatment (ART) offers significant health benefits by suppressing HIV-1 replication and increasing CD4 cell counts. However, incomplete viral suppression poses a potential threat for the emergence of drug resistance mutations (DRMs), limiting ART options, and increasing HIV transmission. Objective: We investigated the patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) among HIV-1 patients in Portugal. Methods: Data were obtained from 1050 HIV-1 patient samples submitted for HIV drug resistance (HIVDR) testing from January 2022 to June 2023. Evaluation of DRM affecting viral susceptibility to nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) was performed using an NGS technology, the Vela Diagnostics Sentosa SQ HIV-1 Genotyping Assay. Results: About 71% of patients were ART naïve and 29% were experienced. Overall, 20% presented with any DRM. The prevalence of TDR and ADR was 12.6% and 41.1%, respectively. M184V, T215S, and M41L mutations for NRTI, K103N for NNRTI, and M46I/L for PIs were frequent in naïve and treated patients. E138K and R263K mutations against INSTIs were more frequent in naïve than treated patients. TDR and ADR to INSTIs were 0.3% and 7%, respectively. Patients aged 50 or over (OR: 1.81, p = 0.015), originating from Portuguese-speaking African countries (PALOPs) (OR: 1.55, p = 0.050), HIV-1 subtype G (OR: 1.78, p = 0.010), and with CD4 < 200 cells/mm3 (OR: 1.70, p = 0.043) were more likely to present with DRMs, while the males (OR: 0.63, p = 0.003) with a viral load between 4.1 to 5.0 Log10 (OR: 0.55, p = 0.003) or greater than 5.0 Log10 (OR: 0.52, p < 0.001), had lower chances of presenting with DRMs. Conclusions: We present the first evidence on TDR and ADR to INSTI regimens in followed up patients presenting for healthcare in Portugal. We observed low levels of TDR to INSTIs among ART-naïve and moderate levels in ART-exposed patients. Regimens containing PIs could be an alternative second line in patients with intermediate or high-level drug resistance, especially against second-generation INSTIs (dolutegravir, bictegravir, and cabotegravir). Full article
(This article belongs to the Special Issue Antiviral Resistance Mutations)
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12 pages, 706 KiB  
Article
Risk of Cardiovascular Events in People with HIV (PWH) Treated with Integrase Strand-Transfer Inhibitors: The Debate Is Not Over; Results of the SCOLTA Study
by Nicolò Corti, Barbara Menzaghi, Giancarlo Orofino, Marta Guastavigna, Filippo Lagi, Antonio Di Biagio, Lucia Taramasso, Giuseppe Vittorio De Socio, Chiara Molteni, Giordano Madeddu, Elena Salomoni, Giovanni Francesco Pellicanò, Emanuele Pontali, Rita Bellagamba, Benedetto Maurizio Celesia, Antonio Cascio, Eleonora Sarchi, Roberto Gulminetti, Leonardo Calza, Paolo Maggi, Giovanni Cenderello, Alessandra Bandera, Maria Aurora Carleo, Katia Falasca, Sergio Ferrara, Salvatore Martini, Giuliana Guadagnino, Goffredo Angioni, Olivia Bargiacchi, Elena Delfina Ricci, Nicola Squillace and Paolo Bonfantiadd Show full author list remove Hide full author list
Viruses 2024, 16(4), 613; https://doi.org/10.3390/v16040613 - 15 Apr 2024
Viewed by 1216
Abstract
Cardiovascular disease (CVD) is common in people with HIV (PWH), and has great impact in terms of morbidity and mortality. Several intertwined mechanisms are believed to play a role in determining the increased risk of CVD, including the effect of certain antiretrovirals; among [...] Read more.
Cardiovascular disease (CVD) is common in people with HIV (PWH), and has great impact in terms of morbidity and mortality. Several intertwined mechanisms are believed to play a role in determining the increased risk of CVD, including the effect of certain antiretrovirals; among these, the role of integrase strand-transfer inhibitors (INSTIs) is yet to be fully elucidated. We conducted a multicenter, observational study comprising 4984 PWH evaluating the antiretroviral therapy (ART)-related nature of CVD in real life settings, both in naïve vs. treatment-experienced people. A comparison was conducted between INSTIs vs. either protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) considering demographic, baseline clinical characteristics, incidence of CVD in both 2-year and complete follow-up periods. Among 2357 PWH exposed to INSTIs, 24 people experienced CVD; the corresponding figure was 12 cases out of 2599 PWH exposed to other ART classes. At univariate and multivariate analysis, a tendency towards an increased risk of CVD was observed in the 2-year follow-up period in PWH exposed to INSTIs in the absence, however, of statistical significance. These findings leave open the hypothesis that INSTIs may play a role, albeit minimal, in determining an increased risk of CVD in PWH. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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19 pages, 362 KiB  
Review
HIV Infection, Antiretroviral Drugs, and the Vascular Endothelium
by Georgette D. Kanmogne
Cells 2024, 13(8), 672; https://doi.org/10.3390/cells13080672 - 12 Apr 2024
Cited by 1 | Viewed by 1418
Abstract
Endothelial cell activation, injury, and dysfunction underlies the pathophysiology of vascular diseases and infections associated with vascular dysfunction, including human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome. Despite viral suppression with combination antiretroviral therapy (ART), people living with HIV (PLWH) are prone to [...] Read more.
Endothelial cell activation, injury, and dysfunction underlies the pathophysiology of vascular diseases and infections associated with vascular dysfunction, including human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome. Despite viral suppression with combination antiretroviral therapy (ART), people living with HIV (PLWH) are prone to many comorbidities, including neurological and neuropsychiatric complications, cardiovascular and metabolic diseases, premature aging, and malignancies. HIV and viral proteins can directly contribute to the development of these comorbidities. However, with the continued high prevalence of these comorbidities despite viral suppression, it is likely that ART or some antiretroviral (ARVs) drugs contribute to the development and persistence of comorbid diseases in PLWH. These comorbid diseases often involve vascular activation, injury, and dysfunction. The purpose of this manuscript is to review the current literature on ARVs and the vascular endothelium in PLWH, animal models, and in vitro studies. I also summarize evidence of an association or lack thereof between ARV drugs or drug classes and the protection or injury/dysfunction of the vascular endothelium and vascular diseases. Full article
15 pages, 3656 KiB  
Article
Cardiometabolic Differences in People Living with HIV Receiving Integrase Strand Transfer Inhibitors Compared to Non-nucleoside Reverse Transcriptase Inhibitors: Implications for Current ART Strategies
by Wilhelm A. J. W. Vos, Nadira Vadaq, Vasiliki Matzaraki, Twan Otten, Albert L. Groenendijk, Marc J. T. Blaauw, Louise E. van Eekeren, Kees Brinkman, Quirijn de Mast, Niels P. Riksen, Anton F. H. Stalenhoef, Jan van Lunzen, Andre J. A. M. van der Ven, Willem L. Blok and Janneke E. Stalenhoef
Viruses 2024, 16(4), 582; https://doi.org/10.3390/v16040582 - 10 Apr 2024
Viewed by 1246
Abstract
In people living with HIV (PLHIV), integrase strand transfer inhibitors (INSTIs) are part of the first-line combination antiretroviral therapy (cART), while non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are alternatives. Distinct cART regimens may variably influence the risk for non-AIDS comorbidities. We aimed to [...] Read more.
In people living with HIV (PLHIV), integrase strand transfer inhibitors (INSTIs) are part of the first-line combination antiretroviral therapy (cART), while non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are alternatives. Distinct cART regimens may variably influence the risk for non-AIDS comorbidities. We aimed to compare the metabolome and lipidome of INSTI and NNRTI-based regimens. The 2000HIV study includes asymptomatic PLHIV (n = 1646) on long-term cART, separated into a discovery cohort with 730 INSTI and 617 NNRTI users, and a validation cohort encompassing 209 INSTI and 90 NNRTI users. Baseline plasma samples from INSTI and NNRTI users were compared using mass spectrometry-based untargeted metabolomic (n = 500) analysis. Perturbed metabolic pathways were identified using MetaboAnalyst software. Subsequently, nuclear magnetic resonance spectroscopy was used for targeted lipoprotein and lipid (n = 141) analysis. Metabolome homogeneity was observed between the different types of INSTI and NNRTI. In contrast, higher and lower levels of 59 and 45 metabolites, respectively, were found in the INSTI group compared to NNRTI users, of which 77.9% (81/104) had consistent directionality in the validation cohort. Annotated metabolites belonged mainly to ‘lipid and lipid-like molecules’, ‘organic acids and derivatives’ and ‘organoheterocyclic compounds’. In pathway analysis, perturbed ‘vitamin B1 (thiamin) metabolism’, ‘de novo fatty acid biosynthesis’, ‘bile acid biosynthesis’ and ‘pentose phosphate pathway’ were detected, among others. Lipoprotein and lipid levels in NNRTIs were heterogeneous and could not be compared as a group. INSTIs compared to individual NNRTI types showed that HDL cholesterol was lower in INSTIs compared to nevirapine but higher in INSTIs compared to doravirine. In addition, LDL size was lower in INSTIs and nevirapine compared to doravirine. NNRTIs show more heterogeneous cardiometabolic effects than INSTIs, which hampers the comparison between these two classes of drugs. Targeted lipoproteomic and lipid NMR spectroscopy showed that INSTI use was associated with a more unfavorable lipid profile compared to nevirapine, which was shifted to a more favorable profile for INSTI when substituting nevirapine for doravirine, with evidently higher fold changes. The cardiovascular disease risk profile seems more favorable in INSTIs compared to NNRTIs in untargeted metabolomic analysis using mass-spectrometry. Full article
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15 pages, 2989 KiB  
Article
Spatial Analysis of Exposure of Roads to Flooding and Its Implications for Mobility in Urban/Peri-Urban Accra
by Gerald Albert Baeribameng Yiran, Martin Oteng Ababio, Albert Nii Moe Allotey, Richard Yao Kofie and Lasse Møller-Jensen
ISPRS Int. J. Geo-Inf. 2024, 13(4), 111; https://doi.org/10.3390/ijgi13040111 - 27 Mar 2024
Viewed by 1972
Abstract
Climate change seriously threatens human systems, properties and livelihoods. Global projections suggest a continuous increase in the frequency and severity of weather events, with severe outcomes. Although the trends and impacts are highly variable depending on location, most studies tend to concentrate on [...] Read more.
Climate change seriously threatens human systems, properties and livelihoods. Global projections suggest a continuous increase in the frequency and severity of weather events, with severe outcomes. Although the trends and impacts are highly variable depending on location, most studies tend to concentrate on either the urban or rural areas, with little focus on peri-urban areas. Yet, in Sub-Saharan Africa, peri-urban areas display unique characteristics: inadequate infrastructure, unplanned development, weak governance, and environmental degradation, all of which exacerbate flood impact and thus need academic attention. This study contributes to filling this gap by assessing the flood vulnerability of roads in peri-urban Accra and its implications for mobility. Based on the fieldwork, the study delineated and analysed potential zones within the research locations. The researchers calculated roads’ absolute and relative lengths, using a spatial overlay (intersection) of potentially flooded roads with the total road network within the grid cells of 500 m by 500 m. These measures were adopted and used as exposure measures. The findings revealed that over 80% of roads with lengths between 100 m and 500 m were exposed to floods. Some areas had higher exposure indices, with absolute road lengths ranging from 1.5 km to 3.2 km and relative road lengths between 0.8 and 1.0. There were significant variations in road exposure between and within neighbourhoods. Depending on the depth and duration of the floodwater, residents may be unable to access their homes or carry out their daily activities. In conclusion, this study highlights the differential vulnerability of peri-urban areas to road flooding and recommends targeted provision of flood-resilient infrastructure to promote sustainable development. Full article
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23 pages, 583 KiB  
Review
Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review
by Carolyn Chu, Kaiming Tao, Vinie Kouamou, Ava Avalos, Jake Scott, Philip M. Grant, Soo-Yon Rhee, Suzanne M. McCluskey, Michael R. Jordan, Rebecca L. Morgan and Robert W. Shafer
Viruses 2024, 16(3), 399; https://doi.org/10.3390/v16030399 - 4 Mar 2024
Cited by 3 | Viewed by 2524
Abstract
Background: Dolutegravir (DTG) is a cornerstone of global antiretroviral (ARV) therapy (ART) due to its high efficacy and favorable tolerability. However, limited data exist regarding the risk of emergent integrase strand transfer inhibitor (INSTI) drug-resistance mutations (DRMs) in individuals receiving DTG-containing ART. Methods: [...] Read more.
Background: Dolutegravir (DTG) is a cornerstone of global antiretroviral (ARV) therapy (ART) due to its high efficacy and favorable tolerability. However, limited data exist regarding the risk of emergent integrase strand transfer inhibitor (INSTI) drug-resistance mutations (DRMs) in individuals receiving DTG-containing ART. Methods: We performed a PubMed search using the term “Dolutegravir”, last updated 18 December 2023, to estimate the prevalence of VF with emergent INSTI DRMs in people living with HIV (PLWH) without previous VF on an INSTI who received DTG-containing ART. Results: Of 2131 retrieved records, 43 clinical trials, 39 cohorts, and 6 cross-sectional studies provided data across 6 clinical scenarios based on ART history, virological status, and co-administered ARVs: (1) ART-naïve PLWH receiving DTG plus two NRTIs; (2) ART-naïve PLWH receiving DTG plus lamivudine; (3) ART-experienced PLWH with VF on a previous regimen receiving DTG plus two NRTIs; (4) ART-experienced PLWH with virological suppression receiving DTG plus two NRTIs; (5) ART-experienced PLWH with virological suppression receiving DTG and a second ARV; and (6) ART-experienced PLWH with virological suppression receiving DTG monotherapy. The median proportion of PLWH in clinical trials with emergent INSTI DRMs was 1.5% for scenario 3 and 3.4% for scenario 6. In the remaining four trial scenarios, VF prevalence with emergent INSTI DRMs was ≤0.1%. Data from cohort studies minimally influenced prevalence estimates from clinical trials, whereas cross-sectional studies yielded prevalence data lacking denominator details. Conclusions: In clinical trials, the prevalence of VF with emergent INSTI DRMs in PLWH receiving DTG-containing regimens has been low. Novel approaches are required to assess VF prevalence with emergent INSTI DRMs in PLWH receiving DTG in real-world settings. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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13 pages, 1328 KiB  
Article
Comparison of Integrase Strand Transfer Inhibitors (INSTIs) and Protease-Boosted Inhibitors (PIs) on the Reduction in Chronic Immune Activation in a Virally Suppressed, Mainly Male Population Living with HIV (PLWH)
by Thomas Nitsotolis, Konstantinos G. Kyriakoulis, Anastasios Kollias, Alexia Papalexandrou, Helen Kalampoka, Elpida Mastrogianni, Dimitrios Basoulis and Mina Psichogiou
Medicina 2024, 60(2), 331; https://doi.org/10.3390/medicina60020331 - 15 Feb 2024
Viewed by 1391
Abstract
Background and Objectives: The success of combined antiretroviral therapy (cART) has led to a dramatic improvement in the life expectancy of people living with HIV (PLWH). However, there has been an observed increase in cardiometabolic, bone, renal, hepatic, and neurocognitive manifestations, as well [...] Read more.
Background and Objectives: The success of combined antiretroviral therapy (cART) has led to a dramatic improvement in the life expectancy of people living with HIV (PLWH). However, there has been an observed increase in cardiometabolic, bone, renal, hepatic, and neurocognitive manifestations, as well as neoplasms, known as serious non-AIDS events/SNAEs, compared to the general population of corresponding age. This increase is linked to a harmful phenomenon called inflammaging/immunosenescence, which is driven by chronic immune activation and intestinal bacterial translocation. In this study, we examined immunological and metabolic parameters in individuals receiving current cART. Materials and Methods: The study was conducted at Laiko General Hospital in Athens, Greece. Plasma concentrations of sCD14, IL-6, SuPAR, I-FABP, and LBP were measured in virally suppressed PLWH under cART with at least 350 CD4 lymphocytes/μL. We compared these levels between PLWH receiving integrase strand transfer inhibitors (INSTIs) and protease inhibitors (PIs) and attempted to correlate them with chronic immune activation and metabolic parameters. Results: Data from 28 PLWH were analyzed, with a mean age of 52 and 93% being males. Among the two comparison groups, IL-6 levels were higher in the PIs group (5.65 vs. 7.11 pg/mL, p = 0.03). No statistically significant differences were found in the other measured parameters. A greater proportion of PLWH under INSTIs had normal-range LBP (33% vs. 0%, p = 0.04). When using inverse probability of treatment weighting, no statistically significant differences in the measured parameters were found between the two groups (sCD14 p = 0.511, IL-6 p = 0.383, SuPAR p = 0.793, I-FABP p = 0.868, and LBP p = 0.663). Glucose levels were found to increase after viral suppression in the entire sample (92 mg/dL vs. 98 mg/dL, p = 0.009). Total (191 mg/dL vs. 222 mg/dL, p = 0.005) and LDL cholesterol (104 mg/dL vs. 140 mg/dL, p = 0.002) levels were higher in the PIs group. No significant differences were observed in liver and renal function tests. Conclusions: Further investigation is warranted for PLWH on cART-containing INSTI regimens to explore potential reductions in chronic immune activation and intestinal bacterial translocation. Full article
(This article belongs to the Section Infectious Disease)
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18 pages, 2842 KiB  
Systematic Review
HIV-1 Drug Resistance Detected by Next-Generation Sequencing among ART-Naïve Individuals: A Systematic Review and Meta-Analysis
by Fei Ouyang, Defu Yuan, Wenjing Zhai, Shanshan Liu, Ying Zhou and Haitao Yang
Viruses 2024, 16(2), 239; https://doi.org/10.3390/v16020239 - 2 Feb 2024
Cited by 2 | Viewed by 1829
Abstract
Background: There are an increasing number of articles focused on the prevalence and clinical impact of pretreatment HIV drug resistance (PDR) detected by Sanger sequencing (SGS). PDR may contribute to the increased likelihood of virologic failure and the emergence of new resistance mutations. [...] Read more.
Background: There are an increasing number of articles focused on the prevalence and clinical impact of pretreatment HIV drug resistance (PDR) detected by Sanger sequencing (SGS). PDR may contribute to the increased likelihood of virologic failure and the emergence of new resistance mutations. As SGS is gradually replaced by next-generation sequencing (NGS), it is necessary to assess the levels of PDR using NGS in ART-naïve patients systematically. NGS can detect the viral variants (low-abundance drug-resistant HIV-1 variants (LA-DRVs)) of virus quasi-species at levels below 20% that SGS may fail to detect. NGS has the potential to optimize current HIV drug resistance surveillance methods and inform future research directions. As the NGS technique has high sensitivity, it is highly likely that the level of pretreatment resistance would be underestimated using conventional techniques. Methods: For the systematic review and meta-analysis, we searched for original studies published in PubMed, Web of Science, Scopus, and Embase before 30 March 2023 that focused exclusively on the application of NGS in the detection of HIV drug resistance. Pooled prevalence estimates were calculated using a random effects model using the ‘meta’ package in R (version 4.2.3). We described drug resistance detected at five thresholds (>1%, 2%, 5%, 10%, and 20% of virus quasi-species). Chi-squared tests were used to analyze differences between the overall prevalence of PDR reported by SGS and NGS. Results: A total of 39 eligible studies were selected. The studies included a total of 15,242 ART-naïve individuals living with HIV. The prevalence of PDR was inversely correlated with the mutation detection threshold. The overall prevalence of PDR was 29.74% at the 1% threshold, 22.43% at the 2% threshold, 15.47% at the 5% threshold, 12.95% at the 10% threshold, and 11.08% at the 20% threshold. The prevalence of PDR to INSTIs was 1.22% (95%CI: 0.58–2.57), which is the lowest among the values for all antiretroviral drugs. The prevalence of LA-DRVs was 9.45%. At the 2% and 20% detection threshold, the prevalence of PDR was 22.43% and 11.08%, respectively. Resistance to PIs and INSTIs increased 5.52-fold and 7.08-fold, respectively, in those with a PDR threshold of 2% compared with those with PDR at 20%. However, resistance to NRTIs and NNRTIs increased 2.50-fold and 2.37-fold, respectively. There was a significant difference between the 2% and 5% threshold for detecting HIV drug resistance. There was no statistically significant difference between the results reported by SGS and NGS when using the 20% threshold for reporting resistance mutations. Conclusion: In this study, we found that next-generation sequencing facilitates a more sensitive detection of HIV-1 drug resistance than SGS. The high prevalence of PDR emphasizes the importance of baseline resistance and assessing the threshold for optimal clinical detection using NGS. Full article
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12 pages, 1340 KiB  
Article
Comprehensive Analysis of HIV-1 Integrase Resistance-Related Mutations in African Countries
by Francesco Branda, Marta Giovanetti, Leonardo Sernicola, Stefania Farcomeni, Massimo Ciccozzi and Alessandra Borsetti
Pathogens 2024, 13(2), 102; https://doi.org/10.3390/pathogens13020102 - 24 Jan 2024
Viewed by 1564
Abstract
The growing emergence of non-nucleoside reverse transcriptase inhibitor (NNRTI) HIV drug resistance in sub-Saharan Africa (SSA) led to the World Health Organization (WHO) recommending, in 2018, a transition to dolutegravir (DTG) as a first-line antiretroviral therapy (ART) in SSA. The broad HIV-1 genetic [...] Read more.
The growing emergence of non-nucleoside reverse transcriptase inhibitor (NNRTI) HIV drug resistance in sub-Saharan Africa (SSA) led to the World Health Organization (WHO) recommending, in 2018, a transition to dolutegravir (DTG) as a first-line antiretroviral therapy (ART) in SSA. The broad HIV-1 genetic diversity in SSA could shape DTG effectiveness and the pattern of drug resistance mutations (DRMs) in this region. This study evaluated HIV-1 integrase (IN) DRMs and conserved regions among published groups M, N, O, and P HIV-1 sequences spanning forty years of the HIV epidemic during the transition of DTG-based ART. Overall, we found low levels of integrase strand transfer inhibitor (INSTI)-DRMs (<1%) across HIV groups between the years 1983 and 2023; however, it was unexpected to detect DRMs at statistically significantly higher frequencies in pre-INSTI (1983–2007) than in the INSTI (2008–2023) era. The variability of accessory INSTI-DRMs depended on the HIV subtypes, with implications for susceptibility to DTG. Our findings provide new perspectives on the molecular epidemiology and drug resistance profiles of INSTIs in SSA, emphasizing the need for ongoing surveillance and customized treatment approaches to address the continent’s varied HIV subtypes and changing resistance patterns. Full article
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