The Current Mismatch Between COVID-19 Clinical Trial Design and the Evolving Profile of Hospitalized Patients: A Retrospective Cohort Analysis.

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.

Sex differences in the effectiveness and tolerability of dolutegravir plus rilpivirine as a switch strategy in people living with HIV.

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.

Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe Coronavirus Disease 2019: The PANCOVID Randomized Clinical Trial.

BACKGROUND: This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation. METHODS: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC. In the second randomization, patients with room air oxygen saturation <95% and at least 1 increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected. RESULTS: Of the 355 included participants, 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% confidence interval [CI], .52-5.91; P = .379); it was 0.42 (95% CI, .11-1.59; P = .201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI, .66-1.40; P = .774); it was 0.90 (95% CI, .61-1.33; P = .687) for those treated with baricitinib. CONCLUSIONS: Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials. CLINICAL TRIALS REGISTRATION: EudraCT: 2020-001156-18.

Remdesivir for 5 or 10 Days in Patients with Severe Covid-19.

BACKGROUND: Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). METHODS: We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. RESULTS: In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). CONCLUSIONS: In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.).

Change in metabolic parameters after switching from triple regimens with tenofovir alafenamide to dolutegravir-based dual therapy. Bi-lipid study.

INTRODUCTION: The use of tenofovir alafenamide (TAF) has been associated with increased cholesterol and body weight. Real-life data on the metabolic effects of switching from a TAF-based triple regimen to a dolutegravir (DTG)-based two-drug regimen (2-DR) are scarce. METHODS: A retrospective cohort study of patients who have switched from a triple TAF-based regimen to a 2-DR [DTG-lamivudine (DTG-3TC) or DTG- rilpivirine (DTG-RPV]) with at least 6 months of follow-up. The primary endpoint was the absolute change in lipid fractions at 6 months. Secondary outcomes were percentage changes in lipid fraction, effectiveness and safety at 6 and 12 months [intention to treat (ITT), missing = failures]. RESULTS: A total of 118 patients (87 on DTG-3TC, 31 on DTG-RPV) were included. Median age was 51 years (interquartile range: 43-59), 86% were male, CD4 T-cell count was 692 cells/µL, and 98% viral load (VL) < 50 copies/mL. At 6 months there was a decrease in total and low-density lipoprotein cholesterol of 10.7 mg/dL [95% confidence interval (CI): 2.2-19.1; p ≤ 0.001] and 8.3 mg/dL (95% CI: 0.74-15.9; p = 0.026), respectively. There was a reduction in cardiovascular risk from 4.5% at baseline to 4% at 12 months (p = 0.040). Virological effectiveness as determined by ITT analysis was 85.6% at 6 months and 66.1% at 12 months. Seven patients (5.9%) withdrew from the 2-DR and there was no virological failure. CONCLUSIONS: In real life, switching from a triple regimen with TAF to DTG-3TC or DTG-RPV dual therapy improves the lipid profile and is an effective and well-tolerated strategy.

Time from symptoms onset to remdesivir is associated with the risk of ICU admission: a multicentric analyses.

BACKGROUND: Shorter duration of symptoms before remdesivir has been associated with better outcomes. Our goal was to evaluate variables associated with the need of ICU admission in a cohort of hospitalized patients for COVID-19 under remdesivir including the period from symptoms onset to remdesivir. METHODS: We conducted a retrospective multicentric study analysing all patients admitted with COVID-19 in 9 Spanish hospitals who received treatment with remdesivir in October 2020. The main outcome was the need of ICU admission after 24 h of the first dose of remdesivir. RESULTS: In our cohort of 497 patients, the median of days from symptom onset to remdesivir was 5 days, and 70 of them (14.1%) were later admitted into ICU. The clinical outcomes associated with ICU admission were days from symptoms onset (5 vs. 6; p = 0.023), clinical signs of severe disease (respiratory rate, neutrophil count, ferritin levels and very-high mortality rate in SEIMC-Score) and the use of corticosteroids and anti-inflammatory drugs before ICU. The only variable significatively associated with risk reduction in the Cox-regression analyses was ≤ 5 days from symptoms onset to RDV (HR: 0.54, CI95%: 0.31-0.92; p = 0.024). CONCLUSION: For patients admitted to the hospital with COVID-19, the prescription of remdesivir within 5 days from symptoms onset diminishes the need of ICU admission.

Longitudinal Changes in Epigenetic Age Acceleration in Aviremic Human Immunodeficiency Virus-Infected Recipients of Long-term Antiretroviral Treatment.

BACKGROUND: Human immunodeficiency virus (HIV) infection induces epigenetic age acceleration (EAA), but it remains unclear whether epigenetic aging continues to accelerate during successful antiretroviral therapy (ART) and prolonged virological suppression. METHODS: We longitudinally analyzed 63 long-term aviremic HIV-infected adults. Using blood DNA methylation patterns, we calculated EAA measures based on 3 epigenetic clocks (Horvath's clock, PhenoAge, and GrimAge). We recorded the emergence of serious AIDS-related and non-AIDS-related events throughout the study to assess its association with EAA. RESULTS: All participants were on stable ART and were virologically suppressed. After 4 years of follow-up, PhenoAge-EAA and GrimAge-EAA showed no differences, whereas Horvath-EAA slightly decreased (median difference, -0.53 years; P = .015). Longitudinal changes in EAA measures were independent of changes in CD4 cell counts, the ART regimen, or other HIV-related factors. Nineteen percent of participants experienced a serious clinical event during the study. Horvath-EAA was significantly higher at baseline in participants with clinical events (P = .027). After adjusting for confounders, we found a trend toward an association of higher levels of all EAA measures at baseline with serious clinical events. CONCLUSIONS: Epigenetic aging did not accelerate in long-term aviremic HIV-infected adults after 4 years of successful ART. EAA measures deserve further study as potential tools for predicting clinical events.

Effects of tenofovir on telomeres, telomerase and T cell maturational subset distribution in long-term aviraemic HIV-infected adults.

OBJECTIVES: To evaluate whether the negative impact of tenofovir on telomere length (TL) is due to immune reconstitution interference or inhibition of telomerase. METHODS: One hundred and twenty-eight long-term aviraemic HIV adults treated with tenofovir-containing (n = 79) or tenofovir-sparing regimens (n = 49) were recruited to compare the following: TL in whole blood, PBMCs, CD4+ T cells and CD8+ T cells by quantitative PCR (qPCR); telomerase activity in PBMCs, CD4+ cells and CD8+ T cells using the TRAPeze RT Telomerase Detection Kit; and T cell maturational subset distribution by flow cytometry. RESULTS: In an adjusted analysis, participants treated with tenofovir for at least 4 years had shorter TL in CD8+ T cells (P = 0.04) and lower telomerase activity in CD4+ (P = 0.012) and CD8+ T cells (P = 0.023). Tenofovir treatment was also associated with lower proportions of recent thymic emigrant (RTE) CD4+ cells (P = 0.031) and PD1 marker expression (P = 0.013). CONCLUSIONS: In long-term aviraemic HIV adults, the inhibition of telomerase by tenofovir could explain telomere shortening in CD8+ T cells. There is no telomere shortening in the CD4+ compartment and the decrease in telomerase activity could be explained both by the inhibition by tenofovir and by the lower proportion of RTE CD4+cells.

Detection of archived lamivudine-associated resistance mutations in virologically suppressed, lamivudine-experienced HIV-infected adults by different genotyping techniques (GEN-PRO study).

BACKGROUND: Previously selected lamivudine resistance-associated mutations (RAMs) may remain archived within the proviral HIV-DNA. OBJECTIVES: To evaluate the ability of proviral DNA genotyping to detect lamivudine RAMs in HIV-1 virologically suppressed participants; the correlation between Sanger and next generation sequencing (NGS); and predictive factors for detection of lamivudine RAMs in proviral DNA. METHODS: Cross-sectional study of participants on stable antiretroviral therapy and suppressed for ≥1 year. Analysis of proviral DNA was performed by Sanger sequencing in whole blood and by NGS in PBMCs. RESULTS: We analysed samples from 102 subjects (52 with and 50 without lamivudine RAMs in historical plasma RNA-genotypes). Among participants with previous lamivudine resistance, Sanger sequencing detected RAMs in 26.9%. Detection rates significantly increased using NGS: 47.9%, 64.6%, 75% and 87.5% with the 20%, 10%, 5% and 1% thresholds, respectively. As for participants without historical lamivudine resistance, Sanger detected the RAMs in 1/49 (2%), and NGS (5% threshold) in 8/45 (17.8%). Multivariate models fitted to the whole population revealed that having a history of lamivudine resistance was a risk factor for detection of lamivudine RAMs by NGS. Among participants with historical lamivudine resistance, multivariate analysis showed that a longer time since HIV diagnosis was associated with persistence of archived mutations by NGS at thresholds of >10% [OR 1.10 (95% CI: 1.00-1.24)] and >5% [OR 1.16 (95% CI: 1.02-1.32)]. CONCLUSIONS: Proviral DNA Sanger sequencing does not detect the majority of historical lamivudine RAMs. NGS increases the sensitivity of detection at lower thresholds, although the relevance of these minority populations with lamivudine RAMs needs further evaluation.

Long-term efficacy of dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: Week 96 results of ART-PRO pilot study.

BACKGROUND: In the ART-PRO pilot trial there were no virological failures through 48 weeks of treatment with dolutegravir plus lamivudine in suppressed individuals with and without archived lamivudine resistance-associated mutations (RAMs) detected through next-generation sequencing (NGS) but without evidence of lamivudine RAMs in baseline proviral DNA population sequencing. OBJECTIVES: To present 96 week results from ART-PRO. METHODS: Open-label, single-arm pilot trial. At baseline, all participants switched to dolutegravir plus lamivudine. Participants were excluded if proviral DNA population genotyping detected lamivudine RAMs. To detect resistance minority variants, proviral DNA NGS was retrospectively performed from baseline samples. For this analysis the efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 96. Safety and tolerability outcomes were incidence of adverse events and treatment discontinuations. RESULTS: Forty-one participants were included, 21 with lamivudine RAMs in historical plasma RNA genotypes. Baseline proviral DNA NGS detected lamivudine RAMs (M184V/I and/or K65R/E/N) above a 5% threshold in 71.4% (15/21) and 15% (3/20) of participants with and without history of lamivudine resistance, respectively. At 96 weeks, 90.2% of participants achieved the efficacy endpoint. Between week 48 and 96 there was one discontinuation due to consent withdrawal and no discontinuations related to adverse events. Two participants had a transient viral rebound, both re-suppressed on dolutegravir plus lamivudine. Through week 96, there were no virological failures. CONCLUSIONS: In this pilot trial, dolutegravir plus lamivudine maintained virological suppression at 96 weeks despite historical lamivudine resistance and persisting archived minority lamivudine RAMs.

Alternative switching strategies based on regimens with a low genetic barrier: do clinicians have a choice nowadays?

Clinicians sometimes use switching strategies based on regimens such as RAL + ABC/3TC or RPV + ABC/3TC in order to resolve tolerability or safety issues associated with conventional recommended first-line strategies. Despite the low genetic barrier of these regimens, high safety and efficacy rates have been reported in retrospective studies.

Impact of Nucleos(t)ide Reverse Transcriptase Inhibitors on Blood Telomere Length Changes in a Prospective Cohort of Aviremic HIV-Infected Adults.

Background: Tenofovir is a potent inhibitor of human telomerase. The clinical relevance of this inhibition is unknown. Methods: A prospective cohort of human immunodeficiency virus (HIV)-infected participants with suppressed virological replication was recruited to compare whole-blood telomere length (measured by quantitative multiplex polymerase chain reaction analysis) in participants with current exposure to tenofovir disoproxil fumarate (TDF) to that in participants never exposed to TDF. Results: A total of 172 participants were included: 67 were in the TDF group, and 105 were in the non-TDF group (75 were receiving 2 nucleosides [of whom 69 were receiving abacavir], 25 were receiving a nucleos[t]ide reverse transcriptase inhibitor [N{t}RTI]-sparing regimen, and 5 were receiving lamivudine as the only nucleoside). After 2 years, the mean blood telomere length increased significantly in the whole cohort. The TDF group had significantly smaller gains in telomere length than the non-TDF group. In the analysis restricted to participants receiving N(t)RTIs, TDF exposure was not associated with an independent negative effect. In the non-TDF group, participants treated with 2 nucleosides also had significantly smaller gains in telomere length than those receiving N(t)RTI-sparing regimens or lamivudine as the only nucleoside. Discussion: In HIV-infected adults with prolonged virological suppression, treatment with TDF or abacavir was associated with smaller gains in blood telomere length after 2 years of follow-up.

Blood Telomere Length Changes After Ritonavir-Boosted Darunavir Combined With Raltegravir or Tenofovir-Emtricitabine in Antiretroviral-Naive Adults Infected With HIV-1.

Background: Tenofovir is a potent inhibitor of human telomerase. The clinical relevance of this inhibition is unknown. Methods: NEAT001/ANRS143 is a randomized trial that showed noninferiority over 96 weeks of ritonavir-boosted darunavir plus raltegravir versus tenofovir disoproxil fumarate/emtricitabine in 805 antiretroviral antiretrovrial-naive HIV-infected adults. We compared changes in whole-blood telomere length measured with quantitative polymerase chain reaction in 201 randomly selected participants (104 raltegravir and 97 tenofovir disoproxil fumarate/emtricitabine). We performed multivariable estimative and predictive linear regression. Results: At week 96, participants receiving tenofovir disoproxil fumarate/emtricitabine had a statistically significant higher gain in telomere length than participants receiving raltegravir. Difference in mean telomere length change between groups (tenofovir disoproxil fumarate/emtricitabine minus raltegravir) from baseline to week 96 adjusted by baseline telomere length was 0.031 (P = .009). This difference was not significantly confounded by age, gender, known duration of HIV infection, CD4 (baseline/nadir), CD8 cells, CD4/CD8 ratio, HIV viral load (baseline/week 96), tobacco and alcohol consumption, statins, or hepatitis C. Conclusion: Antiretroviral-naive HIV-infected adults receiving ritonavir-boosted darunavir and tenofovir disoproxil fumarate/emtricitabine had a significant higher gain in blood telomere length than those receiving ritonavir-boosted darunavir and raltegravir, suggesting a better initial recovery from HIV-associated immunosenescence.

New Strategies of ARV: the Road to Simplification.

PURPOSE OF REVIEW: Simplification of antiretroviral therapy is a strategy aiming to reduce pill burden, drug interactions, and toxicity. This review focuses on the most recent and important studies evaluating a reduction on the number of drugs for HIV treatment, both in naive and virologically suppressed patients. RECENT FINDINGS: Interesting studies have been performed in the past years testing dual therapy and monotherapy, with variable rates of virological control. Novel therapeutics like immunotherapy or long-acting antiretrovirals can also be considered for simplification. Reducing the number of drugs for HIV treatment can be an option for selected patients. Current available evidence favors dual therapy over monotherapy. Future research should seek to identify the best candidates for simplification.

In vitro activity of isavuconazole against fluconazole-resistant isolates of Histoplasma capsulatum.

No clinical trials for histoplasmosis have been performed with the newer azoles, leaving itraconazole as the azole of choice. In vitro studies suggest that Histoplasma capsulatum from patients that relapse on fluconazole has higher minimum inhibitory concentrations (MICs) to fluconazole and voriconazole but not itraconazole and posaconazole. The newest azole, isavuconazole, shares structural similarity to voriconazole, but to date nobody has explored emergence of resistance. In vitro susceptibilities to isavucoanzole and fluconazole were performed on previously obtained isolates from the patients who relapsed on fluconazole therapy. Susceptibilities were determined by NCCLS method M27A developed for yeasts, as modified for H. capsulatum. The change in the MIC from the primary to the relapse isolate was tested using Wilcoxon Rank-Sum for paired data. Among the primary isolates, the median MICs were 1.0 (range 0.25 to 4.0) µg/ml for fluconazole and ≤0.007 (range ≤0.007 to 0.015) µg/ml for isavuconazole. In the group of relapsed isolates, the median MICs rose to 8.0 (range 0.25 to 64.0) µg/ml for fluconazole and remained unchanged at ≤0.007 (range ≤0.007 to 0.015) µg/ml for isavuconazole (P < .001). Only one isolate exhibited a nonsignificant increase in MIC to isavuconazole. Histoplasma isolates from patients who relapsed on fluconazole did not have an elevation in MICs to isavuconazole. This differs from the results previously seen with voriconazole and suggests that despite a closer structural similarity to voriconazole than itraconazole and posaconazole, isavuconazole has a higher barrier to resistance and may be effective as therapy for histoplasmosis.

Non-suppressible viraemia during HIV-1 therapy: a challenge for clinicians.

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.

Strategies for prevention and treatment of SARS-COV-2 infection in patients with chronic kidney disease: Literature review.

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.

Partial Recovery of Telomere Length After Long-term Virologic Suppression in Persons With HIV-1.

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.