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1.
PeerJ ; 12: e18058, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39346056

RESUMEN

The Tropical Indo-Pacific (TIP) includes about two thirds of the world's tropical oceans and harbors an enormous number of marine species. The distributions of those species within the region is affected by habitat discontinuities and oceanographic features. As well as many smaller ones, the TIP contains seven large recognized biogeographic barriers that separate the Red Sea and Indian Ocean, the Indian from the Pacific Ocean, the central and eastern Pacific, the Hawaiian archipelago, the Marquesas and Easter Islands. We examined the genetic structuring of populations of Cirrhitichthys oxycephalus, a small cryptic species of reef fish, across its geographic range, which spans the longitudinal limits of the TIP. We assessed geographic variation in the mitochondrial cytb gene and the nuclear RAG1 gene, using 166 samples collected in 46 localities from the western to eastern edges of the TIP. Sequences from cytb show three well-structured groups that are separated by large genetic distances (1.58-2.96%): two in the Tropical Eastern Pacific (TEP), one at Clipperton Atoll another occupying the rest of that region and the third that ranges across the remainder of the TIP, from the central Pacific to the Red Sea and South Africa. These results indicate that the ~4,000 km wide Eastern Pacific Barrier between the central and eastern Pacific is an efficient barrier separating the two main groups. Further, the ~950 km of open ocean that isolates Clipperton Atoll from the rest of the TEP is also an effective barrier. Contrary to many other cases, various major and minor barriers from the Central Indo-Pacific to the Red Sea are not effective against dispersal by C. oxycephalus, although this species has not colonized the Hawiian islands and Easter Island. The nuclear gene partially supports the genetic structure evident in cytb, although all haplotypes are geographically mixed.


Asunto(s)
Variación Genética , Animales , Océano Pacífico , Variación Genética/genética , Océano Índico , Citocromos b/genética , Arrecifes de Coral , Filogenia , Filogeografía
2.
Phys Rev Lett ; 132(6): 062702, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38394565

RESUMEN

The cross section of the ^{13}C(α,n)^{16}O reaction is needed for nuclear astrophysics and applications to a precision of 10% or better, yet inconsistencies among 50 years of experimental studies currently lead to an uncertainty of ≈15%. Using a state-of-the-art neutron detection array, we have performed a high resolution differential cross section study covering a broad energy range. These measurements result in a dramatic improvement in the extrapolation of the cross section to stellar energies potentially reducing the uncertainty to ≈5% and resolving long standing discrepancies in higher energy data.

3.
Public Health ; 227: 49-53, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38104419

RESUMEN

OBJECTIVES: The World Health Organization has declared that COVID-19 is no longer a public health emergency of international concern. Nevertheless, it remains a public health issue, and seasonal vaccinations, at the same time of year as influenza vaccinations, will be necessary. When the first vaccines were administered in 2020, decision-makers had to make assumptions about the best methods to communicate and administer vaccines to increase uptake. Now, a body of evidence can inform these decisions. STUDY DESIGN: A narrative review written by three behavioural scientists who design research for policy. METHODS: We searched the PubMed database for: (i) reviews of interventions to increase uptake of COVID-19 or influenza vaccines and (ii) empirical studies on uptake of COVID-19 and influenza vaccines. In addition, registered trials gathered by a Cochrane scoping review of interventions to increase uptake of COVID-19 vaccines were searched for updated results. RESULTS: Results centre around two aspects of a vaccination campaign of interest to policymakers: communication and administration. Results suggest that communications highlighting the personal benefits of vaccination are likely to be more effective than those highlighting collective benefits. The efficacy of vaccination may be underestimated and stressing efficacy as a strong personal benefit may increase uptake. Keeping vaccines free, sending personalised messages, reminders and prebooked appointment times may also increase uptake. CONCLUSIONS: There is now a body of evidence from behavioural science that suggests how vaccination campaigns for COVID-19 can be structured to increase uptake. These recommendations may be useful to policymakers considering seasonal vaccination campaigns and to researchers generating hypotheses for country-specific trials.


Asunto(s)
COVID-19 , Vacunas contra la Influenza , Gripe Humana , Humanos , Vacunas contra la COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , Vacunación , Comunicación , Gripe Humana/prevención & control
4.
Trials ; 24(1): 799, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38082326

RESUMEN

BACKGROUND: Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. METHODS: ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. DISCUSSION: RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.


Asunto(s)
Lesión Renal Aguda , Anemia , Procedimientos Quirúrgicos Cardíacos , Humanos , Estudios Prospectivos , Eritrocitos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Glutatión/farmacología , Hipoxia , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase III como Asunto
5.
Zookeys ; 1180: 159-180, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37780890

RESUMEN

Tropical deep reefs (~40-300 m) are diverse ecosystems that serve as habitats for diverse communities of reef-associated fishes. Deep-reef fish communities are taxonomically and ecologically distinct from those on shallow reefs, but like those on shallow reefs, they are home to a species-rich assemblage of small, cryptobenthic reef fishes, including many species from the family Gobiidae (gobies). Here we describe two new species of deep-reef gobies, Varicusprometheussp. nov. and V.roatanensissp. nov., that were collected using the submersible Idabel from rariphotic reefs off the island of Roatan (Honduras) in the Caribbean. The new species are the 11th and 12th species of the genus Varicus, and their placement in the genus is supported by morphological data and molecular phylogenetic analyses. Additionally, we also collected new specimens of the closely-related genus and species Pinnichthysaimoriensis during submersible collections off the islands of Bonaire and St. Eustatius (Netherland Antilles) and included them in this study to expand the current description of that species and document its range extension from Brazil into the Caribbean. Collectively, the two new species of Varicus and new records of P.aimoriensis add to our growing knowledge of cryptobenthic fish diversity on deep reefs of the Caribbean.

6.
Mol Cell Endocrinol ; 578: 112049, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37666445

RESUMEN

Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are oocyte-specific paracrine factors which regulate ovarian cumulus cell (CC) functions. This study aimed to investigate if BMP15 and GDF9 bound to CCs can be characterized, quantified, and show an association with IVF outcomes in infertile women. BMP15 and GDF9 ELISAs were validated and applied to discarded CC extracts. Pooled CCs from individual patients were collected from 120 (cohort 1; BMP15 only) and 81 infertility patients (cohort 2; BMP15 and GDF9) undergoing superovulation. BMP15 and GDF9 levels expressed per CC DNA were correlated with maternal age, clinical and embryology data. Total BMP15 and GDF9 were highly correlated with each other (r = 0.9, p < 0.001). The GDF9:BMP15 ratio was unrelated to oocyte number or age. BMP15/CC DNA and GDF9/CC DNA were unaffected by the type of superovulation and were not related to oocyte/embryo outcomes.

7.
Cell Biochem Biophys ; 81(2): 243-251, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37115367

RESUMEN

A description is given of a sequence of events which would have led to the appearance of the organic compounds and living cells present on Earth, one of which is human cells. The evolutionary events involved are proposed as having taken place in phosphate ion-dominated aqueous pools formed in regions associated with volcanoes. The mechanism involved the unique molecular structure variations and chemical properties of polyphosphoric acid and compounds of this acid producing urea as the first organic compound formed on Earth and derivatives of urea giving rise to DNA and RNA. The occurrence of the process in present times is considered possible.


Asunto(s)
ARN , Urea , Humanos , Biofisica
10.
Clin Ter ; 174(2): 152-158, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36920133

RESUMEN

Abstract: Working night shifts has been associated with negative mental health consequences such as depression, anxiety, and sleep problems. The objectives of this study were to determine the lifestyle behaviors (prevalence of nicotine, caffeine, cannabis, sleep-promoting medication, and alcohol use) and the association between job stress, sleep quality, anxiety, and depression among registered nurses working night shifts in the Canadian province of Saskatchewan in the COVID-19 era. Twenty-two registered nurses ranging from ages 25-65 that work permanent or rotating night shifts participated in an online survey from April 11th to July 15th, 2022. The results showed a strong positive association between sleep disturbance, and depression r (19) = 0.50, [p = 0.029, 95% CI, 0.06, 0.78]. A positive correlation was found between higher levels of reported anxiety and sleep disturbance r (19) = 0.69, [p = 0.001, 95% CI, 0.34, 0.87]. There was a positive correlation between depression and occupational exhaustion r (17) = 0.56, [p = 0.021, 95% CI, 0.10, 0.82]. Anxiety was significantly related to occupational exhaustion r (17) = 0.65, [p = 0.005, 95% CI, 0.24, 0.86] and depersonalization r (17) = 0.52, [p = 0.005, 95% CI, 0.06, 0.80], but not significantly related to personal accomplishment r (17) = -0.34, [p = 0.185, 95% CI, -0.70, 0.17]. In conclusion, a sample of Canadian nurses working night shifts in the province of Saskatchewan during the COVID-19 pandemic showed a significant positive relationship among sleep disturbance, anxiety, and depression. Furthermore, most nurses reported using at least one or more of the following substances: sleep-promoting medication, nicotine, alcohol, and cannabis.


Asunto(s)
COVID-19 , Enfermeras y Enfermeros , Humanos , Adulto , Persona de Mediana Edad , Anciano , Tolerancia al Trabajo Programado , Proyectos Piloto , Nicotina , Pandemias , Canadá/epidemiología , COVID-19/epidemiología , Sueño , Encuestas y Cuestionarios , Estilo de Vida
11.
Ecol Evol ; 13(1): e9675, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36726876

RESUMEN

Interoceanic canals can facilitate biological invasions as they connect the world's oceans and remove dispersal barriers between bioregions. As a consequence, multiple opportunities for biotic exchange arise and the resulting establishment of migrant species often causes adverse ecological and economic impacts. The Panama Canal is a key region for biotic exchange as it connects the Pacific and Atlantic Oceans in Central America. In this study, we used two complementary methods (environmental DNA (eDNA) metabarcoding and gillnetting) to survey fish communities in this unique waterway. Using COI (cytochrome oxidase subunit I) metabarcoding, we detected a total of 142 fish species, including evidence for the presence of sixteen Atlantic and eight Pacific marine fish in different freshwater sections of the Canal. Of these, nine are potentially new records. Molecular data did not capture all species caught with gillnets, but generally provided a more complete image of the known fish fauna as more small-bodied fish species were detected. Diversity indices based on eDNA surveys revealed significant differences across different sections of the Canal reflecting in part the prevailing environmental conditions. The observed increase in the presence of marine fish species in the Canal indicates a growing potential for interoceanic fish invasions. The potential ecological and evolutionary consequences of this increase in marine fishes are not only restricted to the fish fauna in the Canal as they could also impact adjacent ecosystems in the Pacific and Atlantic Oceans.

12.
Nat Hazards (Dordr) ; 116(2): 1355-1402, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36776703

RESUMEN

Modern civilization has no collective experience with possible wide-ranging effects from a medium-sized asteroid impactor. Currently, modeling efforts that predict initial effects from a meteor impact or airburst provide needed information for initial preparation and evacuation plans, but longer-term cascading hazards are not typically considered. However, more common natural disasters, such as volcanic eruptions, earthquakes, wildfires, dust storms, and hurricanes, are likely analogs that can provide the scope and scale of these potential effects. These events, especially the larger events with cascading effects, are key for understanding the scope and complexity of mitigation, relief, and recovery efforts for a medium-sized asteroid impact event. This paper reviews the initial and cascading effects of these natural hazards, describes the state of the art for modeling these hazards, and discusses the relevance of these hazards to expected long-term effects of an asteroid impact. Emergency managers, resource managers and planners, and research scientists involved in mitigation and recovery efforts would likely derive significant benefit from a framework linking multiple hazard models to provide a seamless sequence of related forecasts.

13.
Zootaxa ; 5346(1): 51-73, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38221352

RESUMEN

Centropristes fusculus Poey, 1861 historically has variously and somewhat perplexingly been assigned to Centropristis Cuvier, 1829, Prionodes Jenyns, 1840, and Serranus Cuvier, 1816. Here, we provide evidence from comparisons of morphology, ecology, and sexual systems for its inclusion in Serranus and redescribe the species based on the holotype and 60 specimens from Brazil, the Caribbean, the United States, and Uruguay. Serranus fusculus is a simultaneous hermaphrodite, a sexual system that is relevant to its generic placement. The inclusion of Serranus fusculus in the genus Serranus increases to 33 the number of currently valid Serranus species, of which two are found in the Western Indian Ocean, six in the eastern Pacific and 25 in the Atlantic Ocean (15 restricted to the western Atlantic and 10 to the eastern and Central Atlantic). An identification key to western Atlantic species of the genus is provided.


Asunto(s)
Lubina , Animales , Lubina/clasificación
15.
Phys Rev Lett ; 128(16): 162701, 2022 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-35522496

RESUMEN

The ^{18}O(α,γ)^{22}Ne reaction is an essential part of a reaction chain that produces the ^{22}Ne(α,n)^{25}Mg neutron source for both the weak and main components of the slow neutron-capture process. At temperatures of stellar helium burning, the astrophysically relevant resonances in the ^{18}O(α,γ)^{22}Ne reaction that dominate the reaction rate occur at α particle energies E_{lab} of 472 and 569 keV. However, previous experiments have shown the strengths of these two resonances to be very weak, and only upper limits or partial resonance strengths could be obtained. This Letter reports the first direct measurement of the total resonance strength for the 472- and 569-keV resonances, 0.26±0.05 and 0.63±0.30 µeV, respectively. New resonance strengths for the resonances at α particle energies of 662.1, 749.9, and 767.6 keV are also provided. These results were achieved in an experiment optimized for background suppression and detection efficiency. The experiment was performed at the Sanford Underground Research Facility, in the 4850-foot underground cavity dedicated to the Compact Accelerator System for Performing Astrophysical Research. The experimental end station used the γ-summing High EffiCiency TOtal absorption spectrometeR. Compared to previous works, the results decrease the stellar reaction rate by as much as ≈46_{-11}^{+6}% in the relevant temperature range of stellar helium burning.

16.
Mol Phylogenet Evol ; 173: 107496, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35569809

RESUMEN

The Panamic Clingfish Gobiesox adustus is widely distributed in the Tropical Eastern Pacific (TEP), from the central Gulf of California, Mexico to Ecuador, including the oceanic Revillagigedo Archipelago, and Isla del Coco. This cryptobenthic species is restricted to very shallow rocky-reef habitats. Here, we used one mitochondrial and three nuclear DNA markers from 155 individuals collected across the distribution range of the species in order to evaluate if geographically structured populations exist and to elucidate its evolutionary history. Phylogenetic analyses recovered a monophyletic group, with four well-supported, allopatric subgroups. Each subgroup corresponded to one of the following well-known biogeographic regions/provinces: 1) the Revillagigedo Archipelago, 2) the Cortez + Mexican provinces (Mexico), 3) the Panamic province (from El Salvador to Ecuador), and 4) Isla del Coco. A molecular-clock analysis showed a mean date for the divergence between clade I (the Revillagigedos and Cortez + Mexican provinces) and clade II (Panamic province and Isla del Coco) in the Pliocene, at ca. 5.33 Mya. Within clade I, the segregation between the Revillagigedos and Cortez + Mexican province populations was dated at ca. 1.18 Mya, during the Pleistocene. Within clade II, the segregation between samples of Isla del Coco and the Panamic province samples was dated at ca. 0.77 Mya, during the Pleistocene. The species tree, Bayesian species delimitation tests (BPP and STACEY), the ΦST, AMOVA, and the substantial genetic distances that exist between those four subgroups, indicate that they are independent evolutionary units. These cladogenetic events seem to be related to habitat discontinuities, and oceanographic and geological processes that produce barriers to gene flow for G. adustus, effects of which are enhanced by the intrinsic ecological characteristics of this species.


Asunto(s)
Evolución Biológica , Peces , Animales , Teorema de Bayes , ADN Mitocondrial/genética , Peces/genética , Humanos , Filogenia , Filogeografía
17.
Zootaxa ; 5093(2): 101-141, 2022 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-35390813

RESUMEN

The hamlets (Hypoplectrus spp., Perciformes: Serranidae) constitute a distinctive model system for the study of a variety of ecological and evolutionary processes including the evolution and maintenance of simultaneous hermaphroditism and egg trading, sex allocation, sexual selection, social-trap, mimicry, dispersal, speciation, and adaptive radiation. Addressing such fundamental and complex processes requires a good knowledge of the taxonomy and natural history of the hamlets. Here, we review the taxonomy of the hamlets, from early ichthyological studies to the most recent species description in 2018. We report a total of 72 different binomial names for Hypoplectrus, synonymized or invalidated down to 17 unambiguously recognized species today. In addition, we redescribe Hypoplectrus affinis (Poey, 1861) as a valid species. In Bocas del Toro (Panama), this hamlet is distinct from eight sympatric congeners in terms of colour pattern, body size and behaviour. Whole-genome analysis and spawning observations indicate that it is genetically distinct from sympatric congeners and reproductively isolated through assortative pairing. Based on the colour pattern we detail in its redescription, live-fish photographs, videos, and earlier reports, H. affinis occurs in Panama, Nicaragua, Mexico, the Florida Keys, Cuba, Grand Cayman, Jamaica, the Dominican Republic, Los Roques (Venezuela), Bonaire, and Tobago. We conclude with a discussion of pending taxonomic issues in this group and the species status of the hamlets in general.


Asunto(s)
Lubina , Perciformes , Animales , Genoma , Perciformes/genética , Simpatría
18.
Mol Phylogenet Evol ; 166: 107316, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34537324

RESUMEN

Marine species that are widely distributed in the Tropical Eastern Pacific (TEP) has served as a model for studying biogeographic patterns resulting from the effects of intraregional habitat discontinuities and oceanographic processes on the diversification and evolution of cryptobenthic reef fishes. Tomicodon petersii, a clingfish (Gobiesocidae) endemic to the TEP, is found on very shallow rocky reefs from central Mexico to northern Peru, and in the Cocos and Galapagos islands. We evaluated the effect of likely biogeographic barriers in different parts of the TEP on the diversification process of this species. We used one mitochondrial and three nuclear DNA markers from 112 individuals collected across the distribution range of T. petersii. Our phylogenetic results showed the samples constituted a monophyletic group, with three well-supported, allopatric subgroups: in the Mexican province, the Panamic province (from El Salvador to Ecuador), and the Galapagos Islands. The split between the Mexican and more southerly clades was estimated to occur at the end of the Miocene ca. 5.74 Mya, and the subsequent cladogenetic event separating the Galapagos population from the Panamic population at the junction of the Pliocene and Pleistocene, ca. 2.85 Mya. The species tree, Bayesian species delimitation tests (BPP), STACEY, and substantial genetic distances separating these three populations indicate that these three independent evolutionary units likely include two unnamed species. The cladogenetic events that promoted the formation of those genetically differentiated groups are consistent with disruptive effects on gene flow of habitat discontinuities and oceanographic processes along the mainland shoreline in the TEP and of ocean-island isolation, in conjunction with the species intrinsic life-history characteristics.


Asunto(s)
Peces , Especiación Genética , Animales , Teorema de Bayes , ADN Mitocondrial/genética , Ecosistema , Peces/genética , Filogenia
19.
Zookeys ; 1103: 79-122, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36761789

RESUMEN

The US Virgin Islands (USVI) include St. John and St. Thomas on the Puerto Rican Platform (PRP) and St. Croix, isolated by 2000 m deep water 45 km south of that platform. Previous inventories of the marine fishes of these islands include a comprehensive 2014 checklist of the fishes of St. Croix and a list of the fishes of the PRP produced in 2000. The latter list noted the locations of many records of the plateau's fishes, allowing the construction of a combined inventory for St. John and St. Thomas. Those two islands are treated here as a single faunal unit because they are only 3.5 km apart on a shared shallow shelf with various islets and reefs in between. Here we provide updated information on those two USVI (St. Croix and St. John-Thomas) marine fish faunas. The additions to the St. Croix and St. John-Thomas inventories presented here are based on a combination of information from the two sources indicated above, more recent publications dealing with those faunas, a review of location records on various online sources of biogeographic data, and voucher photographs taken of fishes in the field by authors of this paper and other citizen scientists. This assessment increased the known fauna of St. Croix by 7.5% to 585 species. The inventory for St. John-Thomas increased by 39.9% from 401 species on the 2000 PRP list to 561 with the inclusion of records from other sources. On-site mtDNA (COI) barcodes are available for approximately one-third of the species of the St. John-Thomas fauna, but for only one species collected at St. Croix. A set of underwater photographs of 372 species (34 of them representing the sole record of a species) from St. John-Thomas and of 11 shallow-water species added to the St. Croix fauna is included. These represent occurrence vouchers and also are intended to facilitate future work that builds on the present compendium.

20.
Antivir Chem Chemother ; 29: 20402066211030380, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34343443

RESUMEN

Viruses from 15 of 35 maraviroc-treated participants with virologic failure and CCR5-tropic (R5) virus in the MOTIVATE studies at Week 24 had reduced maraviroc susceptibility. On-treatment amino acid changes were observed in the viral envelope glycoprotein 120 third variable (V3)-loop stems and tips and differed between viruses. No amino acid change reliably predicted reduced susceptibility, indicating that resistance was genetic context-dependent. Through Week 24, poor adherence was associated with maraviroc-susceptible virologic failure, whereas reduced maraviroc susceptibility was associated with suboptimal background regimen activity, highlighting the importance of overall regimen activity and good adherence. Predictive values of pretreatment V3-loop sequences containing these Week 24 mutations or other variants present at >3% in pretreatment viruses of participants with virologic failure at Week 48 were retrospectively assessed. Week 48 clinical outcomes were evaluated for correlates with pretreatment V3-loop CCR5-tropic sequences from 704 participants (366 responders; 338 virologic failures [83 with R5 virus with maraviroc susceptibility assessment]). Seventy-five amino acid variants with >3% prevalence were identified among 23 V3-loop residues. Previously identified variants associated with resistance in individual isolates were represented, but none were associated reliably with virologic failure alone or in combination. Univariate analysis showed virologic-failure associations with variants 4L, 11R, and 19S (P < 0.05). However, 11R is a marker for CXCR4 tropism, whereas neither 4L nor 19S was reliably associated with reduced maraviroc susceptibility in R5 failure. These findings from a large study of V3-loop sequences confirm lack of correlation between V3-loop genotype and clinical outcome in participants treated with maraviroc.Clinical trial registration numbers (ClinicalTrials.gov): NCT00098306 and NCT00098722.


Asunto(s)
Infecciones por VIH , VIH-1 , Genotipo , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Humanos , Maraviroc , Receptores CCR5/genética , Estudios Retrospectivos , Tropismo Viral
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