Specific plasma microRNAs are associated with CD4 + T-cell recovery during suppressive antiretroviral therapy for HIV-1.

OBJECTIVE: This study investigated the association of plasma microRNAs before and during antiretroviral therapy (ART) with poor CD4 + T-cell recovery during the first year of ART. DESIGN: MicroRNAs were retrospectively measured in stored plasma samples from people with HIV (PWH) in sub-Saharan Africa who were enrolled in a longitudinal multicountry cohort and who had plasma viral-load less than 50 copies/ml after 12 months of ART. METHODS: First, the levels of 179 microRNAs were screened in a subset of participants from the lowest and highest tertiles of CD4 + T-cell recovery (ΔCD4) ( N  = 12 each). Next, 11 discordant microRNAs, were validated in 113 participants (lowest tertile ΔCD4: n  = 61, highest tertile ΔCD4: n  = 52). For discordant microRNAs in the validation, a pathway analysis was conducted. Lastly, we compared microRNA levels of PWH to HIV-negative controls. RESULTS: Poor CD4 + T-cell recovery was associated with higher levels of hsa-miR-199a-3p and hsa-miR-200c-3p before ART, and of hsa-miR-17-5p and hsa-miR-501-3p during ART. Signaling by VEGF and MET, and RNA polymerase II transcription pathways were identified as possible targets of hsa-miR-199a-3p, hsa-200c-3p, and hsa-miR-17-5p. Compared with HIV-negative controls, we observed lower hsa-miR-326, hsa-miR-497-5p, and hsa-miR-501-3p levels before and during ART in all PWH, and higher hsa-miR-199a-3p and hsa-miR-200c-3p levels before ART in all PWH, and during ART in PWH with poor CD4 + T-cell recovery only. CONCLUSION: These findings add to the understanding of pathways involved in persistent HIV-induced immune dysregulation during suppressive ART.

COVID-19 epidemiology and performance of the WHO clinical algorithm to diagnose COVID-19 in people with HIV from Ukraine.

BACKGROUND: The two main objectives were to evaluate the COVID-19 point prevalence and the test performance of the WHO case definition to diagnose COVID-19 clinically in people with HIV in West Ukraine. METHODS: Multicenter cross-sectional study in Lviv, Ukraine, from October 2020-November 2021. COVID-19 unvaccinated people with HIV were included regardless of COVID-19 symptoms at routine clinical visits and had standardized medical, quality of life (EQ(5D)) and SARS-CoV-2 serology assessments. Reported symptoms indicating potential COVID-19 events at inclusion or between March 2020 and inclusion were classified by the WHO case definition as suspected, probable or confirmed. A clinical COVID-19 case was defined as being SARS-CoV-2 seropositive with at least a suspected COVID-19 according to the WHO case definition. The primary endpoints were the clinical COVID-19 prevalence and the test characteristics of the WHO case definition with SARS-CoV-2 serology as reference. (Clinicaltrials.gov:NCT04711954). RESULTS: The 971 included people with HIV were median 40 years, 38.8% women, 44.8% had prior AIDS, and 55.6% had comorbidities. SARS-CoV-2 seroprevalence was 40.1% (95%CI:37.0-43.1) and 20.5% (95%CI:18.0-23.1) had clinical COVID-19 median 4 months (IQR:2-7) before inclusion. Clinical COVID-19 occurred less frequently in people with HIV with tuberculosis history, injecting drug use, CD4+ T-cells <200/mL and unemployment. The quality of life was not impacted after COVID-19. An at least probable COVID-19 classification by the WHO case definition had 44.1% sensitivity (95%CI:38.7-49.7), 85.2% specificity (95%CI:81.5-88.4), 66.6% positive predictive value (95%CI:59.8-73.0) and 69.5% negative predictive value (95%CI:65.5-73.3) to diagnose COVID-19. CONCLUSIONS: COVID-19 unvaccinated people with HIV from Ukraine had a significant COVID-19 rate and using the WHO case definition had insufficient diagnostic accuracy to diagnose these cases. The lower burden in vulnerable people with HIV was unexpected but might reflect a shielding effect.

Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies.

BACKGROUND: Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America. METHODS: In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period. FINDINGS: Among 189 301 people with HIV included in this study, 16 832 (8·9%) deaths were recorded during 1 519 200 person-years of follow-up. 13 180 (78·3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25·0%), non-AIDS non-hepatitis malignancy (2311; 13·7%), and cardiovascular or heart-related (1403; 8·3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16·8 deaths (95% CI 15·4-18·4) during 1996-99 to 7·9 deaths (7·6-8·2) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0·85 (95% CI 0·84-0·86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0·81; 0·79-0·83). There were also reductions in rates of cardiovascular-related (0·83, 0·79-0·87), liver-related (0·88, 0·84-0·93), non-AIDS infection-related (0·91, 0·86-0·96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0·94, 0·90-0·97), and suicide or accident-related mortality (0·89, 0·82-0·95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1·07, 1·00-1·14) and decreased slightly in men (0·96, 0·93-0·99). INTERPRETATION: Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population. FUNDING: US National Institute on Alcohol Abuse and Alcoholism.

Homogenizing out-of-plane cation composition in perovskite solar cells.

Perovskite solar cells with the formula FA1-xCsxPbI3, where FA is formamidinium, provide an attractive option for integrating high efficiency, durable stability and compatibility with scaled-up fabrication. Despite the incorporation of Cs cations, which could potentially enable a perfect perovskite lattice1,2, the compositional inhomogeneity caused by A-site cation segregation is likely to be detrimental to the photovoltaic performance of the solar cells3,4. Here we visualized the out-of-plane compositional inhomogeneity along the vertical direction across perovskite films and identified the underlying reasons for the inhomogeneity and its potential impact for devices. We devised a strategy using 1-(phenylsulfonyl)pyrrole to homogenize the distribution of cation composition in perovskite films. The resultant p-i-n devices yielded a certified steady-state photon-to-electron conversion efficiency of 25.2% and durable stability.

Integrase strand-transfer inhibitor use and cardiovascular events in adults with HIV: an emulation of target trials in the HIV-CAUSAL Collaboration and the Antiretroviral Therapy Cohort Collaboration.

BACKGROUND: A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events. METHODS: We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (≤50 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates. FINDINGS: The analysis in ART-naive individuals included 10 767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (-0·43 to 0·36). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373 965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference -0·068% (-0·60 to 0·52). INTERPRETATION: We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV. FUNDING: National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism.

Impaired gut microbiota-mediated short-chain fatty acid production precedes morbidity and mortality in people with HIV.

Antiretroviral therapy (ART) has dramatically lengthened lifespan among people with HIV (PWH), but this population experiences heightened rates of inflammation-related comorbidities. HIV-associated inflammation is linked with an altered microbiome; whether such alterations precede inflammation-related comorbidities or occur as their consequence remains unknown. We find that ART-treated PWH exhibit depletion of gut-resident bacteria that produce short-chain fatty acids (SCFAs)-crucial microbial metabolites with anti-inflammatory properties. Prior reports establish that fecal SCFA concentrations are not depleted in PWH. We find that gut-microbiota-mediated SCFA production capacity is better reflected in serum than in feces and that PWH exhibit reduced serum SCFA, which associates with inflammatory markers. Leveraging stool and serum samples collected prior to comorbidity onset, we find that HIV-specific microbiome alterations precede morbidity and mortality in ART-treated PWH. Among these microbiome alterations, reduced microbiome-mediated conversion of lactate to propionate precedes mortality in PWH. Thus, gut microbial fiber/lactate conversion to SCFAs may modulate HIV-associated comorbidity risk.

Perceptions of Rapid Antiretroviral Therapy Initiation Among Participants of The Netherlands Cohort Study on Acute HIV Infection.

Starting antiretroviral therapy (ART) same-day, or as soon as possible after HIV diagnosis is advised in guidelines worldwide. Especially during acute HIV infection (AHI), rapid ART start may be more urgent because of a higher risk of transmission or symptoms of acute retroviral syndrome. During this phase, rapid ART start may have additional benefits for viral reservoir size and host immunity. We explored perceptions of rapid ART start among participants of The Netherlands Cohort Study on Acute HIV infection (NOVA study), who started ART rapidly after diagnosis of AHI. We conducted 20 in-depth qualitative interviews with NOVA study participants between October and December 2018. Data were analyzed thematically, using inductive and iterative coding techniques. Roughly half of the participants stated they felt well-informed about the importance of (rapid) ART. Starting ART rapidly was perceived positively by almost all participants, mostly because of the expected benefits on their health, and to prevent HIV transmission. Rapid ART start was seen as a way to cope with the diagnosis. However, a more negative perception was that rapid ART start confronted participants with their diagnosis, when they were still adjusting to a new situation. Our results show that among people diagnosed during AHI, rapid ART is well-accepted. These results should be encouraging to HIV care providers who encounter people with AHI in their clinical practice and to researchers who carry out cure-related studies, in which early ART is often included. The Clinical Trial Registration number is NCT05728996.

Gallium Sulfide Quantum Dots with Zinc Sulfide and Alumina Shells Showing Efficient Deep Blue Emission.

Solution-processed quantum dot (QD) based blue emitters are of paramount importance in the field of optoelectronics. Despite large research efforts, examples of efficient deep blue/near UV-emitting QDs remain rare due to lack of luminescent wide band gap materials and high defect densities in the existing ones. Here, we introduce a novel type of QDs based on heavy metal free gallium sulfide (Ga2 S3 ) and their core/shell heterostructures Ga2 S3 /ZnS as well as Ga2 S3 /ZnS/Al2 O3 . The photoluminescence (PL) properties of core Ga2 S3 QDs exhibit various decay pathways due to intrinsic defects, resulting in a broad overall PL spectrum. We show that the overgrowth of the Ga2 S3 core QDs with a ZnS shell results in the suppression of the intrinsic defect-mediated states leading to efficient deep-blue emission at 400 nm. Passivation of the core/shell structure with amorphous alumina yields a further enhancement of the PL quantum yield approaching 50 % and leads to an excellent optical and colloidal stability. Finally, we develop a strategy for the aqueous phase transfer of the obtained QDs retaining 80 % of the initial fluorescence intensity.

No association between use of tenofovir disoproxil fumarate, etravirine, or integrase-strand transfer inhibitors and acquisition or severe outcomes of SARS-CoV-2 infection in people with HIV in the Netherlands.

In two Dutch observational cohorts of people with HIV, the use of TDF, ETR, or INSTIs was not independently associated with either the risk of incident SARS-CoV-2 infection or severe COVID-19 outcomes, as was suggested by previous observational and molecular docking studies. Our findings do not support a strategy of modifying antiretroviral therapy to include these agents to protect against SARS-CoV-2 infection and severe COVID-19 outcomes.

Supple Formamidinium-Based Low-Dimension Perovskite Derivative for Sensitive and Ultrastable X-ray Detection.

Halide perovskite materials possess excellent optoelectronic properties and have shown great potential for direct X-ray detection. Perovskite wafers are particularly attractive among various detection structures due to their scalability and ease of preparation, making them the most promising candidates for X-ray detection and array imaging applications. However, device instability and current drift caused by ionic migration are persistent challenges for perovskite detectors, especially in polycrystalline wafers with numerous grain boundaries. In this study, we examined the potential of one-dimensional (1D) δ-phase (yellow phase) formamidinium lead iodide (δ-FAPbI3) as an X-ray detection material. This material possesses a suitable band gap of 2.43 eV, which makes it highly promising for X-ray detection and imaging using compact wafers. Moreover, we found that δ-FAPbI3 has low ionic migration, low Young's modulus, and excellent long-term stability, making it an ideal candidate for high-performance X-ray detection. Notably, the yellow phase perovskite derivative exhibits exceptional long-term atmospheric stability (RH of ≈70 ± 5%) over six months, as well as an extremely low dark current drift (3.43 × 10-4 pA cm-1 s-1 V-1), which is comparable to that of single-crystal devices. An X-ray imager with a large-size δ-FAPbI3 wafer integrated on a thin film transistor (TFT) backplane was further fabricated. Direct 2D multipixel radiographic imaging was successfully performed, demonstrating the feasibility of δ-FAPbI3 wafer detectors for sensitive and ultrastable imaging applications.

Trends in Cancer Incidence in Different Antiretroviral Treatment-Eras amongst People with HIV.

Despite cancer being a leading comorbidity amongst individuals with HIV, there are limited data assessing cancer trends across different antiretroviral therapy (ART)-eras. We calculated age-standardised cancer incidence rates (IRs) from 2006-2021 in two international cohort collaborations (D:A:D and RESPOND). Poisson regression was used to assess temporal trends, adjusted for potential confounders. Amongst 64,937 individuals (31% ART-naïve at baseline) and 490,376 total person-years of follow-up (PYFU), there were 3763 incident cancers (IR 7.7/1000 PYFU [95% CI 7.4, 7.9]): 950 AIDS-defining cancers (ADCs), 2813 non-ADCs, 1677 infection-related cancers, 1372 smoking-related cancers, and 719 BMI-related cancers (groups were not mutually exclusive). Age-standardised IRs for overall cancer remained fairly constant over time (8.22/1000 PYFU [7.52, 8.97] in 2006-2007, 7.54 [6.59, 8.59] in 2020-2021). The incidence of ADCs (3.23 [2.79, 3.72], 0.99 [0.67, 1.42]) and infection-related cancers (4.83 [4.2, 5.41], 2.43 [1.90, 3.05]) decreased over time, whilst the incidence of non-ADCs (4.99 [4.44, 5.58], 6.55 [5.67, 7.53]), smoking-related cancers (2.38 [2.01, 2.79], 3.25 [2.63-3.96]), and BMI-related cancers (1.07 [0.83, 1.37], 1.88 [1.42, 2.44]) increased. Trends were similar after adjusting for demographics, comorbidities, HIV-related factors, and ART use. These results highlight the need for better prevention strategies to reduce the incidence of NADCs, smoking-, and BMI-related cancers.

No evidence of rapid reversibility of tenofovir alafenamide and/or integrase strand transfer inhibitor-associated weight gain.

OBJECTIVE: We aimed to determine the reversibility of at least 7% weight gain within 12 months following tenofovir alafenamide (TAF) and/or integrase strand transfer inhibitor (INSTI) discontinuation in people with HIV (PWH) from the Dutch ATHENA cohort. DESIGN AND METHODS: PWH with at least 7% weight gain within 24 months after first switch to TAF and/or INSTI whilst being virally suppressed were selected, excluding those with comorbidities/co-medication known to be associated with weight gain. PWH who discontinued only TAF, only INSTI or TAF+INSTI, with available follow-up weight, were included. Mean weight change in the 24 months prior to and 12 months after discontinuation was modelled using mixed-effects linear regression. Factors associated with yearly weight change were assessed using linear regression. RESULTS: In 115 PWH, discontinuing only TAF ( n  = 39), only INSTI ( n  = 53) or TAF+INSTI ( n  = 23), the adjusted mean modelled weight change in the 24 months prior to discontinuation was +4.50 kg [95% confidence interval (CI) 3.04-6.10], +4.80 kg (95% CI 2.43-7.03) and +4.13 kg (95% CI 1.50-7.13), respectively, and -1.89 kg (95% CI -3.40 to -0.37), -1.93 kg (95% CI -3.92 to +0.07) and -2.55 kg (95% CI -5.80 to +0.02) in the 12 months postdiscontinuation. A greater number of years since HIV diagnosis was associated with greater reversibility of weight gain. No associations were found between weight change postdiscontinuation and changes in NRTI backbone or anchor agent at moment of discontinuation. CONCLUSION: There was no evidence of rapid reversibility of at least 7% TAF-associated and/or INSTI-associated weight gain after discontinuation of these agents. Studies of larger and more diverse populations of PWH are required to more fully understand the degree to which weight gain is reversible when discontinuing TAF and/or INSTI.

Biomarkers of central and peripheral inflammation mediate the association between HIV and depressive symptoms.

People living with HIV are at increased risk for depression, though the underlying mechanisms for this are unclear. In the general population, depression is associated with peripheral and central inflammation. Given this, and since HIV infection elicits inflammation, we hypothesised that peripheral and central inflammatory biomarkers would at least partly mediate the association between HIV and depressive symptoms. People living with HIV (n = 125) and without HIV (n = 79) from the COmorBidity in Relation to AIDS (COBRA) cohort were included in this study. Participants living with and without HIV had similar baseline characteristics. All participants living with HIV were on antiretroviral therapy and were virally suppressed. Plasma, CSF, and brain MR spectroscopy (MRS) biomarkers were measured. Using logistic regression models adjusted for sociodemographic factors, we found that participants with HIV were more likely to have Any Depressive Symptoms (Patient Health Questionnaire [PHQ-9] score >4) (odds ratio [95% confidence interval] 3.27 [1.46, 8.09]). We then sequentially adjusted the models for each biomarker separately to determine the mediating role of each biomarker, with a >10% reduction in OR considered as evidence of potential mediation. Of the biomarkers analysed, MIG (-15.0%) and TNF-α (-11.4%) in plasma and MIP1-α (-21.0%) and IL-6 (-18.0%) in CSF mediated the association between HIV and depressive symptoms in this sample. None of the other soluble or neuroimaging biomarkers substantially mediated this association. Our findings suggest that certain biomarkers of central and peripheral inflammation may at least partly mediate the relationship between HIV and depressive symptoms.

Contribution of alcohol use in HIV/hepatitis C virus co-infection to all-cause and cause-specific mortality: A collaboration of cohort studies.

Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART). Self-reported alcohol use data, collected in diverse ways between cohorts, were converted to grams/day. Eligible PWH started ART during 2001-2017 and were followed from ART initiation for mortality. Interactions between the associations of baseline alcohol use (0, 0.1-20.0, >20.0 g/day) and HCV status were assessed using multivariable Cox models. Of 58,769 PWH, 29,711 (51%), 23,974 (41%) and 5084 (9%) self-reported alcohol use of 0 g/day, 0.1-20.0 g/day, and > 20.0 g/day, respectively, and 4799 (8%) had HCV at baseline. There were 844 deaths in 37,729 person-years and 2755 deaths in 443,121 person-years among those with and without HCV, respectively. Among PWH without HCV, adjusted hazard ratios (aHRs) for mortality were 1.18 (95% CI: 1.08-1.29) for 0.0 g/day and 1.84 (1.62-2.09) for >20.0 g/day compared with 0.1-20.0 g/day. This J-shaped pattern was absent among those with HCV: aHRs were 1.00 (0.86-1.17) for 0.0 g/day and 1.64 (1.33-2.02) for >20.0 g/day compared with 0.1-20.0 g/day (interaction p < .001). Among PWH without HCV, mortality was higher in both non-drinkers and heavy drinkers compared with moderate alcohol drinkers. Among those with HCV, mortality was higher in heavy drinkers but not non-drinkers, potentially due to differing reasons for not drinking (e.g. illness) between those with and without HCV.

Robust Vaccine-Induced as Well as Hybrid B- and T-Cell Immunity across SARS-CoV-2 Vaccine Platforms in People with HIV.

Few studies have comprehensively compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced and hybrid B- and T-cell responses in people with HIV (PWH) to those in comparable controls without HIV. We included 195 PWH and 246 comparable controls from the AGEhIV COVID-19 substudy. A positive nucleocapsid antibody (INgezim IgA/IgM/IgG) or self-reported PCR test defined prior SARS-CoV-2 infection. SARS-CoV-2 anti-spike (anti-S) IgG titers and anti-S IgG production by memory B cells were assessed. Neutralizing antibody titers were determined in a subset of participants. T-cell responses were assessed by gamma interferon (IFN-γ) release and activation-induced marker assay. We estimated mean differences in postvaccination immune responses (ß) between levels of determinants. Anti-S IgG titers and anti-S IgG production by memory B cells were not different between PWH and controls. Prior SARS-CoV-2 infection (ß = 0.77), receiving mRNA vaccine (ß = 0.56), female sex (ß = 0.24), fewer days between last vaccination and sampling (ß = 0.07), and a CD4/CD8 ratio of <1.0 (ß = -0.39) were independently associated with anti-S IgG titers, but HIV status was not. Neutralization titers against the ancestral and Delta and Omicron SARS-CoV-2 variants were not different between PWH and controls. IFN-γ release was higher in PWH. Prior SARS-CoV-2 infection (ß = 2.39), HIV-positive status (ß = 1.61), and fewer days between last vaccination and sampling (ß = 0.23) were independently associated with higher IFN-γ release. The percentages of SARS-CoV-2-reactive CD4+ and CD8+ T cells, however, were not different between PWH and controls. Individuals with well-controlled HIV generally mount robust vaccine-induced as well as hybrid B- and T-cell immunity across SARS-CoV-2 vaccine platforms similar to controls. Determinants of a reduced vaccine response were likewise largely similar in both groups and included a lower CD4/CD8 ratio. IMPORTANCE Some studies have suggested that people with HIV may respond less well to vaccines against SARS-CoV-2. We comprehensively compared B- and T-cell responses to different COVID-19 vaccines in middle-aged persons with well-treated HIV and individuals of the same age without HIV, who were also highly comparable in terms of demographics and lifestyle, including those with prior SARS-CoV-2 infection. Individuals with HIV generally mounted equally robust immunity to the different vaccines. Even stronger immunity was observed in both groups after prior SARS-CoV-2 infection. These findings are reassuring with respect to the efficacy of SARS-Cov-2 vaccines for the sizable and increasing global population of people with HIV with access and a good response to HIV treatment.

COVID-19 in people with HIV in the Netherlands.

OBJECTIVES: We investigated occurrence of and risk factors for severe COVID-19 outcomes in people with HIV (PWH) in the Netherlands. DESIGN: An ongoing prospective nationwide HIV cohort study. METHODS: COVID-19 diagnoses and outcomes with other relevant medical information were prospectively collected from electronic medical records in all HIV treatment centers in the Netherlands, from the start of the COVID-19 epidemic until December 31, 2021. Risk factors for COVID-19 related hospitalization and death were investigated using multivariable logistic regression, including demographics, HIV-related factors, and comorbidities. RESULTS: The cohort comprises 21 289 adult PWH, median age 51.2 years, 82% male, 70% were of Western origin, 12.0% were of sub-Saharan African and 12.6% Latin American/Caribbean origin, 96.8% had HIV-RNA less than 200 copies/ml, median CD4 + cell count 690 (IQR 510-908) cells/µl. Primary SARS-CoV-2 infections were registered in 2301 individuals, of whom 157 (6.8%) required hospitalization and 27 (1.2%) ICU admission. Mortality rates were 13 and 0.4% among hospitalized and nonhospitalized individuals, respectively. Independent risk factors for severe outcomes (COVID-19-related hospitalization and death) were higher age, having multiple comorbidities, a CD4 + cell count less than 200 cells/µl, uncontrolled HIV replication, and prior AIDS diagnosis. Migrants from sub-Saharan Africa, Latin America, and the Caribbean were at an increased risk of severe outcomes independently of other risk factors. CONCLUSION: In our national cohort of PWH, risk of severe COVID-19 outcomes was increased in individuals with uncontrolled HIV replication, low CD4 + cell count, and prior AIDS diagnosis, independently of general risk factors such as higher age, comorbidity burden and migrants originating from non-Western countries.

Adoption is not associated with immunological and virological outcomes in children with perinatally acquired HIV infection in the Netherlands.

OBJECTIVES: To provide an overview of the demographics, treatment characteristics and long-term outcomes of children with perinatal HIV-1 infection (PHIV) living in the Netherlands (NL) and to specifically investigate whether outcomes differ by children's adoption status. DESIGN: A prospective population-based open cohort including children with PHIV in NL. METHODS: We included children with PHIV who had entered HIV care in NL since 2007, in view of a sharp increase in the number of adopted children with PHIV since that year. We compared the proportion with virologic suppression and CD4+T-cell count over time between the following groups of children with PHIV: adopted and born outside NL, non-adopted born in NL, and non-adopted born outside NL, using generalized estimating equations and linear mixed effects models, respectively. To account for the variation in cohort inclusion, we analyzed data of children exposed to at least one year of antiretroviral therapy (ART). RESULTS: We included 148 children (827.5 person-years of follow-up, 72% adopted, age at start care in NL 2.4 (0.5-5.3)). Under-18 mortality was zero. Over the years, a boosted PI-based regimen was most often prescribed. The use of integrase inhibitors increased since 2015. Non-adopted children born in NL were less likely to achieve virological suppression compared to adopted children (OR 0.66, 95%CI 0.51-0.86, p = 0.001), which disappeared after excluding one child with suspected treatment nonadherence (OR 0.85, 95%CI 0.57-1.25, p = 0.400). CD4+T-cell Z-score trajectories were not significantly different between groups. CONCLUSIONS: Despite considerable and increasing diversity of the population of children with PHIV in NL, geographical origin and adoption status do not seem to pose important challenges in achieving good immunological and virological outcomes.

Epigenetic ageing accelerates before antiretroviral therapy and decelerates after viral suppression in people with HIV in Switzerland: a longitudinal study over 17 years.

BACKGROUND: Accelerated epigenetic ageing can occur in untreated HIV infection and is partially reversible with effective antiretroviral therapy (ART). We aimed to make a long-term comparison of epigenetic ageing dynamics in people with HIV during untreated HIV infection and during suppressive ART. METHODS: In this longitudinal study, conducted over 17 years in HIV outpatient clinics in Switzerland, we applied 5 established epigenetic age estimators (epigenetic clocks) in peripheral blood mononuclear cells (PBMCs) in Swiss HIV Cohort Study participants before or during suppressive ART. All participants had a longitudinal set of PBMC samples available at four timepoints (T1-T4). T1 and T2 had to be 3 years or longer apart, as did T3 and T4. We assessed epigenetic age acceleration (EAA) and a novel rate of epigenetic ageing. FINDINGS: Between March 13, 1990, and Jan 18, 2018, we recruited 81 people with HIV from the Swiss HIV Cohort Study. We excluded one participant because a sample did not meet quality checks (transmission error). 52 (65%) of 80 patients were men, 76 (95%) were white, and the median patient age was 43 (IQR 37·5-47) years. Per year of untreated HIV infection (median observation 8·08 years, IQR 4·83-11·09), mean EAA was 0·47 years (95% CI 0·37 to 0·57) for Horvath's clock, 0·43 years (0·3 to 0·57) for Hannum's clock, 0·36 years (0·27 to 0·44) for SkinBlood clock, and 0·69 years (0·51 to 0·86) for PhenoAge. Per year of suppressive ART (median observation 9·8 years, IQR 7·2-11), mean EAA was -0·35 years (95% CI -0·44 to -0·27) for Horvath's clock, -0·39 years (-0·50 to -0·27) for Hannum's clock, -0·26 years (-0·33 to -0·18) for SkinBlood clock, and -0·49 years (-0·64 to -0·35) for PhenoAge. Our findings indicate that people with HIV epigenetically aged by a mean of 1·47 years for Horvath's clock, 1·43 years for Hannum's clock, 1·36 years for SkinBlood clock, and 1·69 years for PhenoAge per year of untreated HIV infection; and 0·65 years for Horvath's clock, 0·61 years for Hannum's clock, 0·74 years for SkinBlood clock, and 0·51 years for PhenoAge, per year of suppressive ART. GrimAge showed some change in the mean EAA during untreated HIV infection (0·10 years, 0·02 to 0·19) and suppressive ART (-0·05 years, -0·12 to 0·02). We obtained very similar results using the rate of epigenetic ageing. Contribution of multiple HIV-related, antiretroviral, and immunological variables, and of a DNA methylation-associated polygenic risk score to EAA was small. INTERPRETATION: In a longitudinal study over more than 17 years, epigenetic ageing accelerated during untreated HIV infection and decelerated during suppressive ART, highlighting the importance of limiting the duration of untreated HIV infection. FUNDING: Swiss HIV Cohort Study, Swiss National Science Foundation, and Gilead Sciences.

Photocatalytic CO2 reduction using La-Ni bimetallic sites within a covalent organic framework.

The precise construction of photocatalysts with diatomic sites that simultaneously foster light absorption and catalytic activity is a formidable challenge, as both processes follow distinct pathways. Herein, an electrostatically driven self-assembly approach is used, where phenanthroline is used to synthesize bifunctional LaNi sites within covalent organic framework. The La and Ni site acts as optically and catalytically active center for photocarriers generation and highly selective CO2-to-CO reduction, respectively. Theory calculations and in-situ characterization reveal the directional charge transfer between La-Ni double-atomic sites, leading to decreased reaction energy barriers of *COOH intermediate and enhanced CO2-to-CO conversion. As a result, without any additional photosensitizers, a 15.2 times enhancement of the CO2 reduction rate (605.8 µmol·g-1·h-1) over that of a benchmark covalent organic framework colloid (39.9 µmol·g-1·h-1) and improved CO selectivity (98.2%) are achieved. This work presents a potential strategy for integrating optically and catalytically active centers to enhance photocatalytic CO2 reduction.

Narrow Near-Infrared Emission from InP QDs Synthesized with Indium(I) Halides and Aminophosphine.

Nonpyrophoric aminophosphines reacted with indium(III) halides in the presence of zinc chloride have emerged as promising phosphorus precursors in the synthesis of colloidal indium phosphide (InP) quantum dots (QDs). Nonetheless, due to the required P/In ratio of 4:1, it remains challenging to prepare large-sized (>5 nm), near-infrared absorbing/emitting InP QDs using this synthetic scheme. Furthermore, the addition of zinc chloride leads to structural disorder and the formation of shallow trap states inducing spectral broadening. To overcome these limitations, we introduce a synthetic approach relying on the use of indium(I) halide, which acts as both the indium source and reducing agent for aminophosphine. The developed zinc-free, single-injection method gives access to tetrahedral InP QDs with an edge length > 10 nm and narrow size distribution. The first excitonic peak is tunable from 450 to 700 nm by changing the indium halide (InI, InBr, InCl). Kinetic studies using phosphorus NMR reveal the coexistence of two reaction pathways, the reduction of transaminated aminophosphine by In(I) and via redox disproportionation. Etching the surface of the obtained InP QDs at room temperature with in situ-generated hydrofluoric acid (HF) leads to strong photoluminescence (PL) emission with a quantum yield approaching 80%. Alternatively, surface passivation of the InP core QDs was achieved by low-temperature (140 °C) ZnS shelling using the monomolecular precursor zinc diethyldithiocarbamate. The obtained InP/ZnS core/shell QDs that emit in a range of 507-728 nm exhibit a small Stokes shift (110-120 meV) and a narrow PL line width (112 meV at 728 nm).