Telomere length (TL) is a widely used biomarker of biological aging, and is shortened in people living with HIV (PWH) due to chronic inflammation and immune-activation. The DNA methylation-based estimator of TL (DNAmTL) has emerged as a promising alternative to classical TL measurements, but their comparative performance in PWH remains poorly characterized. We conducted a cross-sectional study comparing DNAmTL and monochrome multiplex quantitative PCR-based TL (qPCR-TL) in two cohorts of PWH: 160 ART-naïve individuals and 143 long-term treated individuals with sustained viral suppression. DNAmTL was derived from blood DNA methylation profiles generated using the Infinium MethylationEPIC arrays, while qPCR-TL was measured using a standardized assay. We evaluated the agreement between methods using correlation, Bland-Altman analysis and Cohen’s Kappa coefficient, and their associations with demographic, clinical and immunological factors were assessed using multivariable linear regression. DNAmTL and qPCR-TL were moderately correlated in both ART-naïve (r = 0.54, p < 0.001) and ART-treated participants (r = 0.46, p < 0.001), showing reasonable to fair agreement across continuous and categorical assessments. Both measures were inversely correlated with chronological age, although associations were stronger for DNAmTL. Compared to qPCR-TL, DNAmTL demonstrated more robust and independent associations with female sex and ethnicity, immunovirological markers of HIV disease severity such as plasma HIV-RNA viral load and the CD4:CD8 ratio, as well as with comorbidities including type 2 diabetes and hepatitis C virus coinfection. DNAmTL provides a more biologically informative measure of aging and disease burden in PWH. Further research is warranted to validate these results and to determine its predictive value for clinical outcomes.

BACKGROUND:The effect of archived lamivudine resistance mutations in the efficacy of dolutegravir plus lamivudine (DTG/3TC) remains unclear. We evaluated whether proviral-DNA M184V/I detection is associated with virological outcomes in the VOLVER-GESIDA 11820 study. METHODS:This open-label, single-arm, multicenter phase IIa trial (NCT04880785) enrolled virologically suppressed adults with documented or suspected historical lamivudine resistance if the M184V/I mutation was not detected in baseline proviral DNA population sequencing. Participants switched to DTG/3TC and were followed through week 96. Proviral-DNA M184V/I was assessed retrospectively by next-generation sequencing (NGS) of peripheral blood mononuclear cells at baseline and week 96. RESULTS:Of 121 participants, 94% had documented historical M184V/I. Proviral-DNA NGS detected M184V/I at ≥5% frequency in 37 (30.6%; 32 M184V, 5 M184I) at baseline and/or week 96: 12 only at baseline, 13 only at week 96, and 12 at both timepoints. Two virological failures occurred within the first 48 weeks; none were observed thereafter. No treatment-emergent resistance was detected. In the ITT-e population (Snapshot analysis), HIV-1 RNA <50 copies/mL at week 96 was maintained in 85.7% (72/84) with no detection of M184V/I, 66.7% (8/12) with detection only at baseline, and 100% with detection only at week 96 (13/13) or both time points (12/12). Among those with M184V/I at both time points, the proportion of proviral sequences carrying the mutation increased from 30% to 45% (P = .0037). CONCLUSIONS:Proviral-DNA M184V/I detection was not associated with virological outcomes in participants receiving DTG/3TC supporting its limited clinical value in this specific setting.

Background:Metformin is increasingly studied as a potential geroprotective agent in the general population. We aimed to test the efficacy and safety of metformin to improve epigenetic age in older, well-controlled, non-diabetic people living with HIV. Methods:METFORAGING was a single-centre, double-blind, randomised, parallel-group, placebo-controlled pilot trial. Non-diabetic participants living with HIV who were aged 50 years or older, virologically suppressed, on a stable antiretroviral regimen with undetectable viral load for at least 12 months, and had CD4+ T-cell counts >500 cells/μL were recruited from the HIV clinic at La Paz University Hospital (Madrid, Spain). Participants were randomly assigned (1:1) to receive 850 mg oral metformin or matching placebo twice a day for 96 weeks. Participants, investigators, and outcome assessors were masked to treatment allocation. Study visits were conducted at baseline and at weeks 4, 8, 24, 48, 72, and 96. Adherence was evaluated at each visit through pill count and self-report. At baseline and week 96, whole-blood samples were used to calculate biological age across 11 epigenetic biomarkers: first-generation epigenetic clocks (Horvath's clock and Hannum's clock), second-generation epigenetic clocks (PhenoAge and GrimAge V2), principal component-derived epigenetic clocks (PC-Horvath, PC-Hannum, PC-PhenoAge and PC-GrimAge), a third-generation clock (DunedinPACE), and the DNA methylation-based estimator of blood telomere length (DNAmTL). The primary outcome was the adjusted between-group difference in epigenetic age acceleration (EAA) change measured by the PhenoAge clock at week 96 in the per-protocol population. Analyses were stratified by age, sex, baseline CD4 count, smoking status, statin treatment, and route of HIV transmission. The trial was registered with EudraCT, 2021-003299-15. Findings:Between March 2, and Oct 2, 2022, 55 individuals were screened, and 40 were randomly assigned to metformin (n = 19) or placebo (n = 21). Enrolment was closed at 40 participants because of slow recruitment, below the pragmatic target of 60 outlined in the study protocol. Median age was 56.4 years (IQR 53.0-60.8), 12 (30%) were female, and 35 (87.5%) self-identified as White. Mean adherence by pill count was 97.5% in both groups. 35 (87.5%) of 40 participants continued treatment to 96 weeks (n = 17 in the metformin group and n = 18 in the placebo group; per-protocol population). At week 96, the adjusted between-group difference (metformin vs. placebo) for PhenoAge EAA was -1.02 years (95% confidence interval [CI] -5.30 to 3.26; p = 0.627). 48 adverse events occurred in 16 (84%) of 19 participants who received metformin and 48 adverse events occurred in 19 (90%) of 21 participants who received placebo. In the metformin group, no serious adverse events were attributed to the medication and no deaths or hospitalisation occurred. Interpretation:Although no significant difference was noted in the primary outcome between groups, these preliminary findings support the feasibility of geroscience-trials in this population and support further investigation of metformin in larger, adequately powered studies to determine whether metformin can modify biological ageing in people with HIV. Funding:Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, and the European Union.

BACKGROUND:Tuberculosis coinfection at HIV diagnosis drives early morbidity and mortality. We estimated tuberculosis prevalence at HIV diagnosis over two decades in a Spanish cohort and quantified its determinants and outcomes. METHODS:We analyzed 19,058 ART-naive adults in CoRIS (2004-2024). Prevalent tuberculosis was defined as a disease diagnosed from the date of HIV diagnosis up to 6 months after ART initiation. Predictors were identified using multivariable logistic regression; mortality was assessed using Kaplan-Meier and competing-risk methods. RESULTS:Prevalence was 2.2% (426/19,058), declining from 4.9% (2004-2008) to 0.8% (2019-2024), an 83% reduction (P < 0.001). Despite this decline, affected individuals presented with increasingly advanced immunosuppression. Strong independent predictors included geographical origin (Sub-Saharan Africa OR = 4.3; Latin America OR = 1.6), positive TB screening (OR = 7.5), viral load >1,000,000 copies/ml (OR = 2.9), injection drug use (OR = 2.9), and age ≥50 years (OR = 6.7), whereas university education (OR = 0.3) and CD4 ≥500 cells/µl (OR = 0.5) were protective. Model discrimination was good (AUC = 0.84). Mortality was higher with tuberculosis (15.0% vs 4.1%; RR = 3.6; 5-year survival 87% vs 97%). CONCLUSIONS:Although prevalence has declined substantially, tuberculosis at HIV diagnosis remains concentrated in high-risk groups and confers excess mortality. Targeted screening and prompt ART remain essential, particularly for migrants from high-burden regions.

Background:Weight gain is a major complication of contemporary antiretroviral treatment (ART). We evaluated the effects of metformin on weight trajectories and metabolic outcomes in non-diabetic, non-obese, older persons with HIV-1 (PWH). Methods:In this double-blind, randomized, placebo-controlled pilot trial (METFORAGING), PWH 50 years or older, virologically suppressed, without diabetes or insulin resistance, were randomly assigned (1:1) to metformin 850 mg or placebo twice daily for 96 weeks at La Paz University Hospital (Madrid, Spain). This prespecified secondary analysis evaluated changes in body weight, body mass index (BMI), glycemic indices, lipid parameters, and serum growth differentiation factor-15 (GDF-15) in the per-protocol population. Results:Forty participants were randomly assigned (metformin n = 19; placebo n = 21); 35 completed treatment through week 96 (per-protocol population). At week 96, mean weight change was -1.5 kg (95% CI -2.9 to -0.03) with metformin and +1.3 kg (-0.7 to 3.3) with placebo (between-group difference -2.8 kg [95% CI -5.2 to -0.4]; P = .025). After discontinuation, weight in the metformin group returned toward baseline (between-group difference from week 96 to 144: 2.2 kg [95% CI 0.05 to 4.5]; P = .045). At week 96, changes in body weight correlated inversely with changes in serum GDF-15 in the metformin group (r = -0.67; P = .003). No serious adverse events were attributed to metformin. Conclusions:Metformin attenuated weight gain in nondiabetic, nonobese PWH receiving contemporary ART, but the effect was not sustained after discontinuation. These findings support larger trials to confirm efficacy and define optimal treatment duration. Trial Registration:EudraCT 2021-003299-15 (https://www.clinicaltrialsregister.eu).

BACKGROUND:Epigenetic age acceleration (EAA) predicts morbidity and mortality in the general population, but its prognostic utility in people with human immunodeficiency virus (HIV) (PWH) on suppressive antiretroviral therapy remains unclear. METHODS:Longitudinal observational cohort of 216 PWH with sustained virological suppression (median 6.5 years) recruited from the DUAL-GESIDA trial and La Paz Aging Cohort (Spain). Baseline blood DNA methylation was assessed to evaluate 8 epigenetic clocks, their principal-component (PC) derivatives, and the telomere length estimator. Over 10 years, we recorded AIDS, serious non-AIDS (SNAEs), and aging-related events. Associations between EAA and outcomes were evaluated by multivariate Cox models. RESULTS:One hundred five participants experienced ≥ 1 event, 162 events recorded in total (1 AIDS event, 65 SNAEs, and 96 aging-related events). A positive EAA by Horvath's clock was associated with a 50% higher risk of aging-related events. Participants with positive EAA according to PC-GrimAge, GrimAge V1-V2, as well as Hannum´s clock experienced more than 2-fold increased risk of SNAEs. Positive EAA by PC-GrimAge and PhenoAge was associated with an increased risk of non-AIDS cancer. Additionally, positive EAA according to GrimAge V1-V2 was linked to a 4-fold increase in all-cause mortality risk. All individuals who died (n = 17) had a baseline DunedinPACE value >1. No associations were found for the composite endpoint or cardiovascular events. CONCLUSIONS:In this preliminary study, GrimAge and PC-GrimAge were associated with increased risk of adverse outcomes in people with well-controlled HIV infection. These findings suggest their potential as long-term health-risk biomarkers, warranting validation in larger cohorts.

Background We previously described the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) as a switch strategy in real life in people with HIV (PWH) at 48 weeks. We did not find that previous nucleoside reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs) had an impact on efficacy. Herein we report response rates after 3 years of follow-up. Methods This retrospective review comprised PWH who were treatment experienced and switched to B/F/TAF in a single-center cohort. HIV RNA <50 copies/mL was analyzed at 96 and 144 weeks in an intention-to-treat analysis (missing = failure) and per-protocol analysis; patients with missing data or changes for reasons other than virologic failure were excluded. Results An overall 506 PWH were included: 16.2% were women, the median age was 52.3 years, the median time of HIV infection was 18.9 years, and 13.6% had documented preexisting NRTI RAMs. At 96 weeks of follow-up in the intention-to-treat and per-protocol analyses, HIV RNA <50 copies/mL was seen in 73.1% and 95.4%, respectively. At 144 weeks, these figures were 68.2% and 94%. There were no statistically significant differences between patients with and without previous NRTI RAMs. A total of 140 patients were excluded for the per-protocol analysis at week 144: 46 were lost to follow-up, 32 discontinued treatment due to toxicity, 34 simplified to dual antiretroviral therapy, 7 switched for other reasons, and 20 patients died (no death was B/F/TAF related). Conclusions Through 3 years of follow-up, switching to B/F/TAF maintained high rates of virologic suppression in long-term PWH. These results were seen even in patients with preexisting NRTI RAMs.

BACKGROUND:Although single-tablet, oral bictegravir, emtricitabine, and tenofovir alafenamide or dolutegravir and lamivudine are preferred regimens in several major guidelines and are widely used in many countries, they have not been compared in a fully powered trial. This study aimed to prospectively compare the 48-week results of dolutegravir and lamivudine versus bictegravir, emtricitabine, and tenofovir alafenamide as maintenance therapies for people with HIV. METHODS:PASO-DOBLE is a randomised, multicentre, open-label, non-inferiority trial done over 48 weeks at 30 sites in Spain. Adults (aged ≥18 years) with HIV-1, without previous viral failure, who had reached virological suppression on oral regimens containing at least one pill a day, cobicistat, efavirenz, or tenofovir disoproxil fumarate and no previous use of dolutegravir or bictegravir, and plasma HIV-1 RNA <50 copies per mL for at least 24 weeks were eligible. Participants were randomly assigned (1:1) to switch regimens to dolutegravir 50 mg and lamivudine 300 mg or bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily, using random block permutation, stratified by tenofovir alafenamide presence at baseline and sex assigned at birth. The primary endpoint was the proportion of participants with HIV RNA ≥50 copies per mL at week 48 in the intention-to-treat exposed population (ie, all participants who received at least one dose of study medication). The primary and safety analysis was done in the intention-to-treat exposed population. The non-inferiority margin was 4%. This trial is registered with ClinicalTrials.govNCT04884139 and is incomplete. FINDINGS:Between July 14, 2021, and March 24, 2023, 553 participants initiated dolutegravir and lamivudine (n=277) or bictegravir, emtricitabine, and tenofovir alafenamide (n=276). The difference in the proportion of participants with HIV RNA ≥50 copies per mL between the dolutegravir and lamivudine group (six [2%] of 277) and bictegravir, emtricitabine, and tenofovir alafenamide group (two [1%] of 276) was 1·4% (95% CI -0·5 to 3·4; p=0·16), showing non-inferiority. The most common adverse events occurring in at least 10% of participants in either group were infections, musculoskeletal, gastrointestinal, metabolic, and psychiatric events. Adverse events were usually mild or moderate and considered unrelated to the study drugs. More grade 3-4 adverse events occurred in the bictegravir group (ten [3%]) than in the dolutegravir group (three [1%]; p=0·049). Very few participants discontinued dolutegravir and lamivudine (n=1) or bictegravir, emtricitabine, and tenofovir alafenamide (n=2) due to adverse events. There were no deaths in either group. INTERPRETATION:These results provide further evidence that might be useful in shared decision-making between physicians and people living with HIV regarding switching oral antiretroviral therapy. FUNDING:ViiV Healthcare, CIBER de Enfermedades Infecciosas (CIBERINFEC), and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). TRANSLATION:For the Spanish translation of the abstract see Supplementary Materials section.

Background Epigenetic age acceleration (EAA) predicts morbidity and mortality in the general population, but its prognostic utility in people with human immunodeficiency virus (HIV) (PWH) on suppressive antiretroviral therapy remains unclear.Methods Longitudinal observational cohort of 216 PWH with sustained virological suppression (median 6.5 years) recruited from the DUAL-GESIDA trial and La Paz Aging Cohort (Spain). Baseline blood DNA methylation was assessed to evaluate 8 epigenetic clocks, their principal-component (PC) derivatives, and the telomere length estimator. Over 10 years, we recorded AIDS, serious non-AIDS (SNAEs), and aging-related events. Associations between EAA and outcomes were evaluated by multivariate Cox models.Results One hundred five participants experienced >= 1 event, 162 events recorded in total (1 AIDS event, 65 SNAEs, and 96 aging-related events). A positive EAA by Horvath's clock was associated with a 50% higher risk of aging-related events. Participants with positive EAA according to PC-GrimAge, GrimAge V1-V2, as well as Hannums clock experienced more than 2-fold increased risk of SNAEs. Positive EAA by PC-GrimAge and PhenoAge was associated with an increased risk of non-AIDS cancer. Additionally, positive EAA according to GrimAge V1-V2 was linked to a 4-fold increase in all-cause mortality risk. All individuals who died (n = 17) had a baseline DunedinPACE value >1. No associations were found for the composite endpoint or cardiovascular events.Conclusions In this preliminary study, GrimAge and PC-GrimAge were associated with increased risk of adverse outcomes in people with well-controlled HIV infection. These findings suggest their potential as long-term health-risk biomarkers, warranting validation in larger cohorts.

Person-reported outcomes (PROs) are valuable in clinical practice but can be time-consuming. Our goal was to understand how people living with HIV (PLHIV) and healthcare professionals (HCPs) perceive and interact with a mHealth app, “Prepara Tu Consulta” (PTC), designed to provide essential information, requiring less effort than completing multiple validated PROs, and to evaluate its performance compared with these PROs. Data from 393 PLHIV on antiretroviral treatment for ≥ 1 year were collected (June 2022–June 2023). Participants completed PTC, EuroQoL-5D-5L (generalized), and specific PROs, including WHOQOL-HIV BREF, HADS, HIV Symptoms Index (HSI), EACS depression scale, and SMAQ. PLHIV and HCPs rated PTC positively for usability, satisfaction, and usefulness (77

BACKGROUND:We investigated the efficacy of dolutegravir/lamivudine for maintenance treatment for people with human immunodeficiency virus (HIV, PWH) and previous lamivudine resistance. METHODS:Open-label, single arm, multicentric clinical trial including virologically suppressed PWH with historical lamivudine resistance (confirmed by genotypic testing or suspected based on clinical history), no integrase resistance and CD4+ >200 cells/mm3 whose antiretroviral therapy (ART) was changed to dolutegravir/lamivudine if the M184V/I mutation was not detected in baseline proviral DNA population sequencing. Proviral DNA next-generation sequencing (NGS) was retrospectively performed in baseline samples. Primary endpoint was proportion of participants with huma immunodeficiency virus type 1 (HIV-1) RNA viral load (VL) ≥50 copies/mL at 48 weeks in the intention-to-treat-exposed (ITT-e) population using the Food and Drug Administration snapshot algorithm. RESULTS:In total, 121 participants enrolled, 114 with a prior genotype with M184V/I, mean virological suppression of 9 years. And 24 (19.8%) had the M184V/I in baseline proviral DNA NGS (>5% threshold). At 48 weeks, 4 participants had a VL ≥50 copies/mL (3.3%, 95% confidence interval [CI]: ·.9%-8.2%, FDA-Snapshot ITT-e): 1 confirmed virologic withdrawal, 1 precautionary virologic withdrawal, and 2 discontinued from study treatment for other reasons with last VL ≥50 copies/mL; none had M184V/I in baseline proviral DNA NGS, and there was no emergent integrase resistance. Also, 90.1% participants (109/121) had a VL <50 copies/mL (95% CI: 83.3%-94.8%), and there were no data for 6.6% (8/121 participants) at 48 weeks. CONCLUSIONS:After excluding lamivudine mutations in proviral DNA by population sequencing, dolutegravir/lamivudine effectively maintained virological suppression in PWH with CD4+ >200 cells/mm3 and history of lamivudine resistance. Notably, no treatment-emergent resistance was observed.

Background:People with HIV-1 (PWH) age differently than the general population. Blood telomere length (BTL) attrition is a surrogate biomarker of immunosenescence and aging in PWH. BTL is reduced immediately after HIV-1 infection and recovers in PWH with long-term virologic suppression, but the extent of this recovery is unknown. Methods:This prospective 6-year observational study assessed the evolution of BTL in PWH who were virologically suppressed. A cross-sectional analysis additionally compared BTL with age- and sex-matched blood donors and sex-matched persons older than 60 years from a general population cohort. DNA from whole blood was isolated, and relative BTL was determined by monochrome quantitative multiplex polymerase chain reaction assay and expressed as the ratio of telomere to single-copy gene (T/S). Results:A total of 128 PWH were included in the prospective 6-year observational study. These same 128 PWH (median age, 55 years; 27.3% women) were compared cross-sectionally at 6-year follow-up with 128 age- and gender-matched blood donors (median age, 55 years) and 128 gender-matched individuals older than 60 years from a general population cohort (median age, 70 years). An inverse correlation between age and BTL was observed. The median BTL of PWH was shorter than their matched blood donors (T/S, 1.07 [IQR, 0.95-1.17] vs 1.28 [IQR, 1.12-1.48]; P < .001) but longer than the elderly population (T/S, 0.89 [IQR, 0.77-0.98], P < .001). PWH experienced a BTL increase at 6 years of 2.9% (T/S, 1.04 vs 1.07; P = .002). In PWH, age was associated with a shorter BTL (coefficient, -0.007 45, SE = 0.002 04, P = .002) and baseline lower CD4 count with a gain in BTL (coefficient, -0.000 06, SE = 0.000 02, P = .004). Shorter baseline BTL (odds ratio, 0.91 [95% CI, .87-.94]; P < .001) and higher glucose levels (odds ratio, 1.04 [95% CI, 1.02-1.07]; P = .003) were associated with a greater similarity of BTL to the elderly population. Conclusions:PWH with long-term virologic suppression experience a trend toward an increased BTL after 6 years of follow-up. Middle-aged people with long-term controlled HIV-1 have a shorter BTL than expected for their chronologic age but longer than that of people 15 years older in the general population.

Evaluating 100 adult coronavirus disease 2019 (COVID-19) patients at a Madrid hospital, we identified a mismatch between current clinical trial designs and the evolving profile of hospitalized patients. Most patients were ineligible due to design constraints, suggesting a need to rethink trial criteria for a more accurate representation of the hospitalized COVID-19 cohort.

INTRODUCTION:Dolutegravir + rilpivirine (DTG + RPV) is an effective antiretroviral therapy regimen approved in clinical guidelines as a switch therapy for virologically suppressed people with HIV. Our study aimed to compare the effectiveness and tolerability of DTG + RPV in women and men in real-world clinical practice. METHODS:This was a retrospective analysis of treatment-experienced people with HIV from a large HIV unit who switched to DTG + RPV. We analysed treatment effectiveness, rates of adverse events and discontinuation, and metabolic changes after 48 weeks of treatment. HIV-RNA levels <50 copies/mL were analysed at 48 weeks using both intention-to treat analysis (where missing data were interpreted as failures) and per-protocol analysis (excluding those with missing data or changes due to reasons other than virological failure). Outcomes were compared between women and men based on sex at birth. RESULTS:A total of 307 patients were selected (71 women and 236 men). No transgender people were included. At baseline, women had lived with HIV infection and received antiretroviral therapy for longer than men (23.2 vs 17.4 years and 18.9 vs 14.2 years, respectively). In the intention-to-treat analysis, 74.6% (95% confidence interval [CI] 63.4-83.3%) of women and 83.5% (95% CI 78.2-87.7) of men had HIV-RNA <50 copies/mL. In the per-protocol analysis, 96.4% (95% CI 87.7-99) of women and 99% (95% CI 98.9-99.7) of men had HIV-RNA levels <50 copies/mL. Two women and two men had HIV-RNA >50 copies/mL at 48 weeks. Discontinuation due to adverse events was more frequent in women than in men: 12.7% vs 7.2% (p < 0.02). Neuropsychiatric and gastrointestinal events were the most frequently reported. A median (interquartile range) weight gain of 1.9 kg (0-4.2) in women and 1.2 kg (-1-3.1) in men was reported (median of differences between baseline visit and week 48); the remaining changes in metabolic parameters were neutral. CONCLUSIONS:DTG + RPV exhibited good and similar virological effectiveness in women and men in real-world settings. However, poorer tolerability and more treatment interruptions were observed in women.

In individuals receiving antiretroviral therapy (ART), persistent low-level viraemia not attributed to suboptimal ART adherence, detrimental pharmacological interactions, or drug resistance is referred to as non-suppressible viraemia (NSV). This Review presents recent findings in the virological characterisation of NSV, revealing that it consists of one or a few identical populations of plasma viruses without signs of evolution. This finding suggests that NSV originates from virus production by expanded HIV-infected cell clones, reflecting the persistence of the HIV reservoir despite ART. We discuss knowledge gaps regarding the management and the clinical consequences of NSV. The prevalence of NSV remains to be precisely determined and there is very little understanding of its effects on virological failure, HIV transmission, secondary inflammation, morbidity, and mortality. This issue, along with the absence of specific recommendations for the management of NSV in HIV clinical guidelines, underscores the complexities involved in treating individuals with NSV.

BACKGROUND:Studies on switching to tenofovir alafenamide (TAF)-based regimens raise concerns about a worse metabolic profile in people with HIV, even though most received tenofovir disoproxil fumarate (TDF) in their previous regimen. This study aims to evaluate changes in lipid fractions, glucose, and serum markers for hepatic steatosis (HS) after switching from a TDF- or TAF-sparing regimen to bictegravir/emtricitabine/TAF (B/F/TAF). METHODS:We performed a retrospective cohort study of people with HIV who switched to B/F/TAF from TDF- or TAF-sparing regimens between January 2019 and May 2022 with at least 6 months of follow-up. The primary endpoint was the absolute change in lipid fractions at 6 months. Secondary outcomes were changes in lipid fractions at 12 months and changes in other metabolic parameters (glucose, creatinine, and HS based on the triglyceride-to-glucose [TyG] ratio at 6 and 12 months). Changes were analysed using mixed linear regression models with random intercept and time as a fixed effect. RESULTS:The study included 259 people with HIV (median age 55 [interquartile range (IQR) 47-60] years; 80% male; 88% Caucasian; CD4+ T-cell count 675 [IQR 450-880] cells/mm3; 84.3% HIV-RNA <50 copies/mL). In total, 63 patients (30%) had hypertension, 93 (44%) dyslipidaemia, 30 (14%) diabetes, and 45% obesity/overweight. Most (60%) switched from integrase inhibitor-based regimens, and 21% switched from a boosted regimen. At 6 months, significant reductions were observed in total cholesterol (-7.64 mg/dL [95% confidence interval (CI) -13.52 to -1.76; p = 0.002]), triglycerides (-23.4 [95% CI -42.07 to -4.65]; p = 0.003), and TyG ratio (-0.14 [95% CI -0.23 to -0.05]; p < 0.001). CONCLUSION:In our real-life cohort, the effect of switching TDF-/TAF-sparing regimens to triple therapy with B/F/TAF improved total cholesterol, triglycerides, and serum markers of HS at 6 months and was neutral for the remaining metabolic parameters at 12 months.

COVID-19 has proven to be particularly aggressive in patients with chronic kidney disease (CKD). The lower immune response rate and the greater susceptibility to progress to severe forms of the disease have contributed to this phenomenon, which has persisted in the post-vaccination era of the pandemic. Paradoxically, CKD has been excluded from most clinical trials of the main therapeutic tools developed against SARS-CoV-2. However, experience in the use of these drugs has been accumulating in different stages of CKD, supporting their use with guarantees of efficacy and safety.The objective of this review is to gather all treatment indications for COVID-19 in the different phases of the disease, tailored to CKD in its various stages, including renal replacement therapy.