Dual-Emissive Iridium(III) Complexes and Their Applications in Biological Sensing and Imaging.

Phosphorescent iridium(III) complexes are widely recognized for their unique properties in the excited triplet state, making them crucial for various applications including biological sensing and imaging. Most of these complexes display single phosphorescence emission from the lowest-lying triplet state after undergoing highly efficient intersystem crossing (ISC) and ultrafast internal conversion (IC) processes. However, in cases where these excited-state processes are restricted, the less common phenomenon of dual emission has been observed. This dual emission phenomenon presents an opportunity for developing biological probes and imaging agents with multiple emission bands of different wavelengths. Compared to intensity-based biosensing, where the existence and concentration of an analyte are indicated by the brightness of the probe, the emission profile response involves modifications in emission color. This enables quantification by utilizing the intensity ratio of different wavelengths, which is self-calibrating and unaffected by the probe concentration and excitation laser power. Moreover, dual-emissive probes have the potential to demonstrate distinct responses to multiple analytes at separate wavelengths, providing orthogonal detection capabilities. In this concept, we focus on iridium(III) complexes displaying fluorescence-phosphorescence or phosphorescence-phosphorescence dual emission, along with their applications as biological probes for sensing and imaging.

Understanding Staphylococcus aureus in hyperglycaemia: A review of virulence factor and metabolic adaptations.

Staphylococcus aureus is one of the most commonly detected bacteria in diabetic skin and soft tissue infections. The incidence and severity of skin and soft tissue infections are higher in patients with diabetes, indicating a potentiating mechanism of hyperglycaemia and infection. The goal of this review is to explore the metabolic and virulence factor adaptations of S. aureus under hyperglycaemic conditions. Primary data from identified studies were included and summarised in this paper. Understanding the nexus of hyperglycaemia, metabolism, and virulence factors provides insights into the complexity of diabetic skin and soft tissue infections attributed to S. aureus.

Myrtinols A-F: New Anti-Inflammatory Peltogynoid Flavonoid Derivatives from the Leaves of Australian Indigenous Plant Backhousia myrtifolia.

Our in-house ethnopharmacological knowledge directed our anti-inflammatory investigation into the leaves of Backhousia mytifolia. Bioassay guided isolation of the Australian indigenous plant Backhousia myrtifolia led to the isolation of six new rare peltogynoid derivatives named myrtinols A-F (1-6) along with three known compounds 4-O-methylcedrusin (7), 7-O-methylcedrusin (8) and 8-demethylsideroxylin (9). The chemical structures of all the compounds were elucidated by detailed spectroscopic data analysis, and absolute configuration was established using X-ray crystallography analysis. All compounds were evaluated for their anti-inflammatory activity by assessing the inhibition of nitric oxide (NO) production and tumor necrosis factor- α (TNF-α) in lipopolysaccharide (LPS) and interferon (IFN)-γ activated RAW 264.7 macrophages. A structure activity relationship was also established between compounds (1-6), noting promising anti-inflammatory potential by compounds 5 and 9 with an IC50 value of 8.51 ± 0.47 and 8.30 ± 0.96 µg/mL for NO inhibition and 17.21 ± 0.22 and 46.79 ± 5.87 µg/mL for TNF-α inhibition, respectively.

Dual-emissive Iridium(III) Complexes as Phosphorescent Probes with Orthogonal Responses to Analyte Binding and Oxygen Quenching.

Phosphorescent probes often show sensitive response toward analytes at a specific wavelength. However, oxygen quenching usually occurs at the same wavelength and thus hinders the accurate detection of analytes. In this study, we have developed dual-emissive iridium(III) complexes that exhibit phosphorescence responses to copper(II) ions at a wavelength distinct from that where oxygen quenching occurs. The complexes displayed colorimetric phosphorescence response in aqueous solutions under different copper(II) and oxygen conditions. In cellular imaging, variation in oxygen concentration over a large range from 5 % to 80 % can modulate the intensity and lifetime of green phosphorescence without affecting the response of red phosphorescence toward intracellular copper(II) ions.

Bioorthogonal "Labeling after Recognition" Affording an FRET-Based Luminescent Probe for Detecting and Imaging Caspase-3 via Photoluminescence Lifetime Imaging.

Bis-labeling with a luminescent energy donor/acceptor pair onto biological substrates affords probes which give FRET readouts for the detection of interaction partners. However, the covalently bound luminophores bring about steric hindrance and nonspecific interaction, which probably perturb the biological recognition. Herein, we designed a highly sensitive and specific "labeling after recognition" sensing approach, where luminophore labeling occurred after the biological recognition. Taking the cutting enzyme caspase-3 as an example, we demonstrated the detection of its catalytic activity in solution and apoptotic cells using the tetrapeptide motif Asp-Glu-Val-Asp (DEVD) as the cleavable substrate, and an iridium(III) complex and a rhodamine derivative as the energy donor/acceptor pair. The DEVD tetrapeptide was modified with an azide and a GK-norbornylene groups at the amino and carboxyl terminuses, respectively, which allowed donor/acceptor bis-labeling via two independent catalysis-free bioorthogonal reactions. The phosphorescence lifetime of the iridium(III) complex was quenched upon bis-labeling owing to the intracellular FRET to the rhodamine derivative, and significantly elongated upon the peptide being catalytically cleaved by caspase-3. Interestingly, the sensitivity and efficiency of the lifetime responses were much higher in the "labeling after recognition" sensing approach. Molecular docking analysis showed that the steric hindrance and nonspecific interactions partially inhibited the biological recognition of the DEVD substrate by caspase-3. The imaging of the catalytic activity of caspase-3 in apoptotic cells was demonstrated via photoluminescence lifetime imaging microscopy. Lifetime analysis not only confirmed the occurrence of intracellular bioorthogonal bis-labeling and catalytic cleavage, but also showed the extent to which the two dynamic processes occurred.

Long-Lived Emissive Probes for Time-Resolved Photoluminescence Bioimaging and Biosensing.

In this Review article, we systematically summarize the design and applications of various kinds of long-lived emissive probes for bioimaging and biosensing via time-resolved photoluminescence techniques. The probes reviewed, including lanthanides, transition-metal complexes, organic dyes, carbon and silicon nanoparticles, metal clusters, and persistent phosphores, exhibit longer luminescence lifetimes than that of autofluorescence from biological tissue and organs. When these probes are internalized into living cells or animals, time-gated photoluminescence imaging selectively collects long-lived signals for intensity analysis, while photoluminescence lifetime imaging reports the decay details of each pixel. Since the long-lived signals are differentiated from autofluorescence in the time domain, the imaging contrast and sensing sensitivity are remarkably improved. The future prospects and challenges in this rapidly growing field are addressed.

Rational Design of Phosphorescent Iridium(III) Complexes for Selective Glutathione Sensing and Amplified Photodynamic Therapy.

It is a huge challenge to avoid irreversible damage to normal tissues during irradiation in photodynamic therapy (PDT) for cancer. An effective strategy is to develop smart photosensitizers, which exhibit amplified generation of reactive oxygen species (ROS) through triggering specific reaction in the tumor microenvironment. In this work, we designed a class of glutathione (GSH)-activatable photosensitizers (Ir1 and Ir4) based on an effective strategy of GSH-induced nucleophilic substitution reaction. The addition of GSH, induced changes in both phosphorescence intensity and lifetime of photosensitizers with high sensitivity. Importantly, the amount of singlet oxygen generated was increased significantly by GSH-induced activation reaction. Hence, the photosensitizers can selectively distinguish cancer cells from normal cells through luminescence and lifetime imaging, and can amplify PDT effects in cancer cells, owing to the evidently higher level of GSH compared to normal cells. This work presents a novel paradigm for GSH-amplified PDT against cancer cells and provides a new avenue for smart-responsive theranostic systems that can avoid nonspecific damage to normal cells.

Dual-Phosphorescent Iridium(III) Complexes Extending Oxygen Sensing from Hypoxia to Hyperoxia.

Hypoxia and hyperoxia, referring to states of biological tissues in which oxygen supply is in sufficient and excessive, respectively, are often pathological conditions. Many luminescent oxygen probes have been developed for imaging intracellular and in vivo hypoxia, but their sensitivity toward hyperoxia becomes very low. Here we report a series of iridium(III) complexes in which limited internal conversion between two excited states results in dual phosphorescence from two different excited states upon excitation at a single wavelength. Structural manipulation of the complexes allows rational tuning of the dual-phosphorescence properties and the spectral profile response of the complexes toward oxygen. By manipulating the efficiency of internal conversion between the two emissive states, we obtained a complex exhibiting naked-eye distinguishable green, orange, and red emission in aqueous buffer solution under an atmosphere of N2, air, and O2, respectively. This complex is used for intracellular and in vivo oxygen sensing not only in the hypoxic region but also in normoxic and hyperoxic intervals. To the best of our knowledge, this is the first example of using a molecular probe for simultaneous bioimaging of hypoxia and hyperoxia.

A Mitochondria-Targeted Photosensitizer Showing Improved Photodynamic Therapy Effects Under Hypoxia.

Organelle-targeted photosensitizers have been reported to be effective photodynamic therapy (PDT) agents. In this work, we designed and synthesized two iridium(III) complexes that specifically stain the mitochondria and lysosomes of living cells, respectively. Both complexes exhibited long-lived phosphorescence, which is sensitive to oxygen quenching. The photocytotoxicity of the complexes was evaluated under normoxic and hypoxic conditions. The results showed that HeLa cells treated with the mitochondria-targeted complex maintained a slower respiration rate, leading to a higher intracellular oxygen level under hypoxia. As a result, this complex exhibited an improved PDT effect compared to the lysosome-targeted complex, especially under hypoxia conditions, suggestive of a higher practicable potential of mitochondria-targeted PDT agents in cancer therapy.

Bioorthogonal Labeling, Bioimaging, and Photocytotoxicity Studies of Phosphorescent Ruthenium(II) Polypyridine Dibenzocyclooctyne Complexes.

The synthesis, characterization, photophysics, lipophilicity, and cellular properties of new phosphorescent ruthenium(II) polypyridine complexes functionalized with a dibenzocyclooctyne (DIBO) or amine moiety [Ru(N^N)2 (L)](PF6 )2 are reported (L=4-(13-N-(3,4:7,8-dibenzocyclooctyne-5-oxycarbonyl) amino-4,7,10-trioxa-tridecanyl-aminocarbonyl-oxy-methyl)-4'-methyl-2,2'-bipyridine bpy-DIBO, N^N=2,2'-bipyridine bpy (1 a), 1,10-phenanthroline phen (2 a); L=4-(13-amino-4,7,10-trioxa-tridecanylaminocarbonyl-oxy-methyl)-4'-methyl-2,2'-bipyridine bpy-NH2 , N^N=bpy (1 b), phen (2 b)). The strain-promoted alkyne-azide cycloaddition (SPAAC) reaction of the DIBO complexes 1 a and 2 a with benzyl azide were studied. Also, the DIBO complexes 1 a and 2 a can selectively label N-azidoglycans located on the surface of CHO-K1 and A549 cells that were pretreated with 1,3,4,6-tetra-O-acetyl-N-azidoacetyl-D-mannosamine (Ac4 ManNAz). Additionally, the intracellular trafficking and localization of these biomolecules were monitored using laser-scanning confocal microscopy. Interestingly, the biolabeling and cellular uptake efficiency of the DIBO complexes 1 a and 2 a were cell-line dependent, as revealed by flow cytometry and ICP-MS. Furthermore, the complexes showed good biocompatibility toward the Ac4 ManNAz-pretreated cells in the dark, but exhibited photoinduced cytotoxicity due to the generation of singlet oxygen.

Dual-Emissive Cyclometalated Iridium(III) Polypyridine Complexes as Ratiometric Biological Probes and Organelle-Selective Bioimaging Reagents.

In this Article, we present a series of cyclometalated iridium(III) polypyridine complexes of the formula [Ir(N^C)2(N^N)](PF6) that showed dual emission under ambient conditions. The structures of the cyclometalating and diimine ligands were changed systematically to investigate the effects of the substituents on the dual-emission properties of the complexes. On the basis of the photophysical data, the high-energy (HE) and low-energy (LE) emission features of the complexes were assigned to triplet intraligand ((3)IL) and triplet charge-transfer ((3)CT) excited states, respectively. Time-dependent density functional theory (TD-DFT) calculations supported these assignments and indicated that the dual emission resulted from the interruption of the communication between the higher-lying (3)IL and the lower-lying (3)CT states by a triplet amine-to-ligand charge-transfer ((3)NLCT) state. Also, the avidin-binding properties of the biotin complexes were studied by emission titrations, and the results showed that the dual-emissive complexes can be utilized as ratiometric probes for avidin. Additionally, all the complexes exhibited efficient cellular uptake by live HeLa cells. The MTT and Annexin V assays confirmed that no cell death and early apoptosis occurred during the cell imaging experiments. Interestingly, laser-scanning confocal microscopy revealed that the complexes were selectively localized on the cell membrane, mitochondria, or both, depending on the nature of the substituents of the ligands. The results of this work will contribute to the future development of dual-emissive transition metal complexes as ratiometric probes and organelle-selective bioimaging reagents.

Selective Ag(I) binding, H2S sensing, and white-light emission from an easy-to-make porous conjugated polymer.

Separating silver (Ag(+)) from lead (Pb(2+)) is one of the many merits of the porous polymer framework reported here. The selective metal binding stems from the well-defined chelating unit of N-heterocycles, which consists of a triazine (C3N3) ring bonded to three 3,5-dimethylpyrazole moieties. Such a rigid and open triad also serves as the distinct building unit in the fully conjugated 3D polymer scaffold. Because of its strong fluorescence and porosity (e.g., BET surface area: 355 m(2)/g), and because of the various types of metal species that can be readily taken up, this versatile framework is especially fit for functionalization. For example, with AgNO3 loaded, the framework solid exhibits a brown color in response to water solutions of H2S, even at the dilution of 5.0 µM (0.17 ppm); whereas cysteine and other biologically relevant thiols do not cause notable change in color. In another example, tunable white-light emission was produced when an Ir(III) complex was doped (e.g., about 0.02% of the polymer weight) onto the framework. Mechanistically, the bound Ir(III) centers become highly emissive in the orange-red region, complementing the broad, bluish emission from the polymer host to result in the overall white-light quality: the color attributes of the emission are therefore easily tunable by the Ir(III) dopant concentration. With this exemplary study, we intend to highlight metal uptake as an effective approach to modify and enrich the properties of porous polymer frameworks and to stimulate interest in further examining metal-polymer interactions in the context of sensing, separation, catalyzes, and other applications.

Treml4, an Ig superfamily member, mediates presentation of several antigens to T cells in vivo, including protective immunity to HER2 protein.

Members of the triggering expressed on myeloid cells (Trem) receptor family fine-tune inflammatory responses. We previously identified one of these receptors, called Treml4, expressed mainly in the spleen, as well as at high levels by CD8α(+) dendritic cells and macrophages. Like other Trem family members, Treml4 has an Ig-like extracellular domain and a short cytoplasmic tail that associates with the adaptor DAP12. To follow up on our initial results that Treml4-Fc fusion proteins bind necrotic cells, we generated a knockout mouse to assess the role of Treml4 in the uptake and presentation of dying cells in vivo. Loss of Treml4 expression did not impair uptake of dying cells by CD8α(+) dendritic cells or cross-presentation of cell-associated Ag to CD8(+) T cells, suggesting overlapping function between Treml4 and other receptors in vivo. To further investigate Treml4 function, we took advantage of a newly generated mAb against Treml4 and engineered its H chain to express three different Ags (i.e., OVA, HIV GAGp24, and the extracellular domain of the breast cancer protein HER2). OVA directed to Treml4 was efficiently presented to CD8(+) and CD4(+) T cells in vivo. Anti-Treml4-GAGp24 mAbs, given along with a maturation stimulus, induced Th1 Ag-specific responses that were not observed in Treml4 knockout mice. Also, HER2 targeting using anti-Treml4 mAbs elicited combined CD4(+) and CD8(+) T cell immunity, and both T cells participated in resistance to a transplantable tumor. Therefore, Treml4 participates in Ag presentation in vivo, and targeting Ags with anti-Treml4 Abs enhances immunization of otherwise naive mice.

Cyclometalated Iridium(III) Complexes Containing Viologen-Modified Phenylpyridine Ligands as Electroluminochromic Active Molecules for Information Display.

Electroluminochromic (ELC) materials have garnered significant research interest because of their potential applications in lighting, displaying, and sensing. These materials exhibit reversible modulation of photoluminescence under low-voltage stimuli. Here five phosphorescent iridium(III) complexes are reported featuring viologen-substituted 2-phenylpyridine (Vppy) ligands acting as electroactive components. Four of the complexes are bis-cyclometalated and coordinated with either neutral bipyridine derivatives or negatively charged 2-picolinate. The remaining complex is heteroleptic tris-cyclometalated, containing one Vppy and two 2-phenylquinoline ligands. Upon photoexcitation, the bis-cyclometalated complexes exhibit orange to red phosphorescence originating from mixed triplet metal-to-ligand charge transfer (3MLCT) and intraligand (3IL) dπ(Ir)/π(Vppy) → π*(Vppy) state, whereas the tris-cyclometalated complex is non-emissive due to a low Ir(IV/III) oxidation potential favoring oxidative quenching by the viologen pendants. When the cationic viologens are electrochemically reduced to their neutral form, the bis-cyclometalated complexes show a remarkable blue-shift in their phosphorescence maxima due to increased energy levels of the Vppy molecular orbitals. In the case of the tris-cyclometalated complex, reduction of the viologen groups interrupts the quenching process, leading to a luminescence turn-on. These complexes are used to develop ELC devices, which exhibit reversible luminescence response in terms of color or on-off switching under a low voltage of 2 V.

Spin crossover of a Fe(II) mononuclear complex induced by intermolecular factors involving chloride and solvent ordering.

Two new salts of a mononuclear tripodal Fe(II) complex were prepared, using ClO4- and Cl-. The ClO4- sample (1) remained HS at low temperatures, similar to the previously reported BF4- analogue. Crystallising with the Cl- anion (2) led to a markedly different crystal packing arrangement, and engendered SCO activity. This has been correlated to the lower crystal packing density in 2 and the coordination complex conformational differences arising due to the packing motifs of 1 and 2. Further, solvent ordering effects have been proposed to facilitate spin transition behaviour in 2.

Luminescent iridium(III) porphyrin complexes as near-infrared-emissive biological probes.

We report herein the design, synthesis and characterisation of a series of luminescent iridium(III) porphyrin complexes [Ir(ttp)(CH2CH2OH)] (H2ttp = 5,10,15,20-tetra-4-tolylporphyrin) (1), [Ir(tpp-Ph-NO2)(CO)Cl] (H2tpp-Ph-NO2 = 5-(4-((4-nitrophenoxy)carbonyloxymethyl)phenyl)-10,15,20-triphenylporphyrin) (2), [Ir(tpp-COOMe)(Py)2](Cl) (H2tpp-COOMe = 5-(4-methoxycarbonylphenyl)-10,15,20-triphenylporphyrin; Py = pyridine) (3) and [Ir(tpp-COOH)(Py)2](Cl) (H2tpp-COOH = 5-(4-carboxylphenyl)-10,15,20-triphenylporphyrin) (4). All the complexes displayed long-lived near-infrared (NIR) emission attributed to an excited state of mixed triplet intraligand (3IL) (π → π*) (porphyrin) and triplet metal-to-ligand charge transfer (3MLCT) (dπ(Ir) → π*(porphyrin)) character. The cytotoxicity of the complexes toward HeLa cells was examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cationic complexes 3 and 4 exhibited higher cytotoxic activity toward HeLa cells than their neutral counterparts 1 and 2. Cellular uptake studies by inductively coupled plasma-mass spectrometry (ICP-MS) and laser-scanning confocal microscopy (LSCM) indicated that complexes 3 and 4 showed higher cellular uptake efficiencies than complexes 1 and 2 due to their cationic charge, and they were enriched in the perinuclear region of the cells with negligible nuclear uptake. Additionally, the carboxyl complex 4 was used to label a model protein bovine serum albumin (BSA) via an amidation reaction. The resultant luminescent protein conjugate 4-BSA displayed similar photophysical properties and intracellular localisation behaviour to its parent complex. The results of this work will contribute to the development of luminescent iridium(III) porphyrin complexes and related bioconjugates as NIR-emissive probes for bioimaging applications.

Bioorthogonal dissociative rhenium(i) photosensitisers for controlled immunogenic cell death induction.

Photosensitisers for photoimmunotherapy with high spatiotemporal controllability are rare. In this work, we designed rhenium(i) polypyridine complexes modified with a tetrazine unit via a bioorthogonally activatable carbamate linker as bioorthogonally dissociative photosensitisers for the controlled induction of immunogenic cell death (ICD). The complexes displayed increased emission intensities and singlet oxygen (1O2) generation efficiencies upon reaction with trans-cyclooct-4-enol (TCO-OH) due to the separation of the quenching tetrazine unit from the rhenium(i) polypyridine core. One of the complexes containing a poly(ethylene glycol) (PEG) group exhibited negligible dark cytotoxicity but showed greatly enhanced (photo)cytotoxic activity towards TCO-OH-pretreated cells upon light irradiation. The reason is that TCO-OH allowed the synergistic release of the more cytotoxic rhenium(i) aminomethylpyridine complex and increased 1O2 generation. Importantly, the treatment induced a cascade of events, including lysosomal dysfunction, autophagy suppression and ICD. To the best of our knowledge, this is the very first example of using bioorthogonal dissociation reactions as a trigger to realise photoinduced ICD, opening up new avenues for the development of innovative photoimmunotherapeutic agents.

A review on the biological, epidemiological, and statistical relevance of COVID-19 paired with air pollution.

This narrative review paper is aimed to critically evaluate recent studies of the associations between air pollution and the outcomes in the COVID-19 pandemic. The main air pollutants we have considered are carbon monoxide (CO), nitrogen dioxide (NO2), ground-level ozone (O3), particulate matter (PM2.5 and PM10), and sulfur dioxide (SO2). We, specifically, evaluated the influences of these pollutants, both individually and collaboratively, across various geographic areas and exposure windows. We further reviewed the proposed biological mechanisms underlying the association between air pollution and COVID-19. Ultimately, we aim to inform policy and public health practice regarding the implications of COVID-19 and air pollution.

Cellular imaging properties of phosphorescent iridium(III) complexes substituted with ester or amide groups.

Phosphorescent iridium(III) complexes have been extensively investigated as cellular imaging reagents and sensors. The intracellular localization of the complexes is known to be closely related to their formal charge, molecular size, lipophilicity, and bioactive pendants. Herein, we reported four phosphorescent iridium(III) complexes with the diimine ligands being modified with ester or amide groups as imaging reagents for living cells. The complexes have the same positive charge and very similar molecular size and weight. The lipophilicity of the complexes is similar ranging from 1.45 to 2.14. Upon internalization into living HeLa cells, while complexes 2-4, like most other iridium(III) complexes, were localized in the cytoplasm, complex 1 unexpectedly stained the whole cells including nuclei. The nuclear uptake of complex 1 was not observed when the cells were pretreated with chlorpromazine or nocodazole, suggesting that clathrin and microtubules mediated the nuclear uptake of complex 1. Additionally, the nuclear uptake efficiency is related to the cell division cycle. The complex was mainly concentrated in the nucleus when the cells were in mitosis, and distributed in whole cells when the cells were in the interphases. Furthermore, complex 1 exhibited a longer luminescence lifetime in the nucleus than in the cytoplasm as revealed by photoluminescence lifetime imaging microscopy (PLIM). Incubation of the cells in the hypoxia environment elongated the lifetime of the cytoplasmic complex, but hardly affected the luminescence properties of the intranuclear complex.

Evidence synthesis evaluating body weight gain among people treating HIV with antiretroviral therapy - a systematic literature review and network meta-analysis.

Background: This systematic review aimed to compare body weight gain associated outcomes over time between dolutegravir (DTG)-based antiretroviral (ART) regimens to other ART regimens, to compare tenofovir alafenamide (TAF)-based regimens, and to evaluate the associated prognostic factors. Methods: Systematic searches of MEDLINE, Embase, and CENTRAL for RCTs and observational studies comparing ART regimens were conducted on 13 September 2021. Outcomes of interest included: change in body weight, body mass index (BMI), waist circumference; and risk of hyperglycaemia and diabetes. Network meta-analyses were conducted at 12, 24, 48, 96 and 144 weeks using two networks differentiated by 3rd agents and backbone agents. Findings: The review identified 113 publications reporting on 73 studies. DTG-based regimens led to statistically higher weight gains than efavirenz-based regimens at all time points (mean difference: 1·99 kg at 96 weeks; 95% credible interval: 0·85-3·09) and was higher over time than low-dose efavirenz-, elvitegravir-, and rilpivirine-based regimens. They were comparable to raltegravir-, bictegravir- and atazanavir-based regimens. For backbones, TAF led to higher weight gain relative to tenofovir disoproxil fumarate (TDF), abacavir, and zidovudine. Prognostic factor analysis showed both low CD4 cell count and high HIV RNA viral load at baseline were consistently associated with higher weight gain, while sex was an effect modifier to African origins. Interpretation: DTG-based regimens lead to larger average weight gains than some other ART regimens and TAF leads to larger average weight gains than all other backbone antiretrovirals. Further research is needed to better understand long-term outcomes and their relationship to other metabolic outcomes. Funding: The WHO Global HIV, Hepatitis and Sexually Transmitted Infections Programmes.