HIV infection is associated with upregulated circulating levels of the inflammaging miR-21-5p.

BACKGROUND: HIV infection produces a chronic inflammation which leads to early aging of people living with HIV. Even though antiretroviral treatments (ART) have significantly increased HIV patient survival, an underlying chronic inflammation persists leading to HIV-related comorbidities. In this context, changes in microRNAs (miRNAs) expression may contribute to this inflammatory response. This study aims to detect differential expression of circulating miRNAs in treatment-naïve HIV-infected individuals compared to uninfected controls and evaluation of altered miRNAs after one year of ART. METHODS: Serum from patients and controls was collected at baseline and after 48-weeks on ART in HIV-treated patients. Circulating miRNAs were analysed using next generation sequencing. RESULTS: A total of 32 HIV patients and 10 controls were recruited. Of HIV+ individuals, 7 were long-term non-progressors (elite controllers), a group of HIV-infected individuals that spontaneously control the infection. Higher circulating levels of miR-21-5p, and lower levels of miR-6503-3p and miR-3135b were detected in HIV+ progressors. After one year of ART, these miRNAs remain altered. Moreover, miR-21-5p and miR-6503-3p were also altered in elite controllers compared to control group. In silico analyses showed that miR-21-5p target pathways are related to inflammation mechanisms and immune system. CONCLUSION: miR-21-5p circulating levels are involved in inflammation and oxidative stress mechanisms in HIV patients even after one year of ART or in elite controllers.

Switching to Dolutegravir/lamivudine or Bictegravir/Emtricitabine/Tenofovir alafenamide. A comparative real-world study.

BACKGROUND: This real-world study compared the safety and effectiveness of Dolutegravir/lamivudine (D/L) and Bictegravir/Emtricitabine/Tenefovir alafenamide (B/F/T) switch therapy regimens for people living with HIV (PLWH). METHODS: The retrospective study conducted from April 2019 to November 2022, included PLWH with < 50 copies/mL of HIV-RNA prior to recruitment who initiated either D/L or B/F/T switching therapy. The primary objective was to evaluate treatment discontinuation rates; safety and virologic outcomes were also evaluated. RESULTS: 690 PLWH were included, 358 in the D/L and 332 in the B/F/T, and a median follow-up of 728 and 1013 days, respectively. The discontinuation proportions were 8.7% (31 participants, incidence rate of 4.44 per 100 PYFU in the D/L group and 15.3% (51 participants, incidence rate of 6.25 per 100 PYFU) in the B/F/T group. The adjusted hazard ratio for B/F/T discontinuation compared to D/L was 1.20 (95% CI: 0.71;2.0; p = 0.494). Virologic failure (VL > 200 copies/mL in two consecutive measurements) occurred in 1.1% and 0.9% of patients in the D/L and B/F/T groups, respectively. Notably, one patient in D/L group with severe non-adherence and virologic failure developed resistance mutations. CONCLUSIONS: Switching to either B/T/F or D/L treatment for PLWH was effective and well tolerated in this real-world study. Treatment discontinuation rates did not significantly differ between the two regimens.

An Abnormal Inflammatory Pattern Associated with Long-Term Non-Progression of HIV Infection Impacts Negatively on Bone Quality.

Introduction. Long-term non-progressors (LTNPs) are HIV-infected individuals (HIV+) whose viral replication is controlled. However, these individuals experience complications associated with HIV, among them, bone remodeling impairment. This study aims to perform a comprehensive bone health assessment and its association with the inflammatory status of HIV+ LTNPs. A cross-sectional study was conducted comparing bone strength components (bone mineral density and bone tissue quality) between age-, sex-, and comorbidities-matched groups of HIV+ LTNPs, HIV+ progressors, and HIV-negative individuals. A panel of bone turnover and inflammatory biomarkers was measured in fasting plasma using ELISA. Bone tissue quality was assessed by bone microindentation, a technique that directly measures the bone resistance to fracture and yields a dimensionless quantifiable parameter called bone material strength (BMSi). Thirty patients were included: ten LTNPs, ten HIV+ progressors, and ten HIV-negative individuals. LTNPs showed an abnormal pattern of immune activation that was represented by significantly lower levels of anti-inflammatory cytokine IL-10 (p = 0.03), pro-inflammatory cytokine IL-8 (p = 0.01), and TNF-α (p < 0.001) with respect to the other groups. Regarding bone health, LTNPs presented lower BMSi, and thus, worse bone tissue quality than HIV-negative individuals (83 (78−85) vs. 90 (89−93), respectively; p = 0.003), and also lower BMSi than HIV+ progressors (83 (78−85) vs. 86 (85−89), respectively; p = 0.022). A trend was found of lower BMSi in HIV+ progressors with respect to the HIV-negative individuals (86 (85−89) vs. 90 (89−93), respectively; p = 0.083). No differences were detected in bone mineral density between groups. In conclusion, LTNPs showed a different inflammatory profile, along with worse bone tissue quality, when compared to HIV+ progressors and HIV-negative individuals. This may contribute to increasing evidence that HIV infection itself has a deleterious effect on bone tissue, likely through a persistent altered inflammation status.

Factors associated to neurocognitive impairment in older adults living with HIV.

OBJECTIVE: The HIV infection is a chronic disease that causes neurocognitive impairment (NI) and has been related with early development of frailty. We aimed to study the main risk factors for neurocognitive disorders and frailty in HIV older adults. MATERIALS AND METHODS: Cross-sectional study with 40 HIV individuals older than 65 years under antiretroviral therapy in Hospital del Mar (Barcelona) recruited between November 2019 and October 2020. Data has been obtained through clinical scores and a blood sample to evaluate NI and frailty and has been analyzed with non-parametric tests and a multivariate logistic regression model. RESULTS: Among the 40 patients admitted for the study, 14 (35%) had positive screening for NI. We found that HIV individuals with nadir CD4+ T-cell count lower than 350 cells/mm3 had 39.7 more risk for NI (95% CI 2.49-632.10; p = 0.009). Those with a lower education level had 22.78 more risk for neurocognitive disorders (95% CI 2.13-242.71; p = 0.01) and suffering any comorbidity with a punctuation ≥ 1 in the Charlson Comorbidity index had an increased risk of 18.26 of developing NI and frailty (95% CI 1.30-256.33; p = 0.031), among them diabetes was significantly more frequent in NI. CONCLUSION: We observed that the main risk factors for a positive NI screening in HIV older adults were low education level, a nadir CD4+ T-cell count < 350 cells/mm3 and the presence of any comorbidity, highlighting diabetes among them.

The use of secukinumab in an HIV-positive patient with axial spondyloarthritis: a case-based review.

Axial spondyloarthritis in HIV-positive patients raises specific treatment challenges as immunosuppressant and immunomodulating agents may adversely affect the course of the HIV infection and could increase the risk of opportunistic infections. The efficacy and safety of secukinumab in patients with HIV is unknown due to HIV patients were largely excluded from clinical trials and nowadays, the clinical evidence for the treatment with biological disease-modifying antirheumatic drugs (DMARDs) is provided from scarce case reports and case series. We hereby discuss a case of a male patient with concomitant axial spondyloarthritis and HIV infection successfully treated with secukinumab, achieving disease remission and without any associated complications. Nevertheless, the potential long-term effects in the use of monoclonal antibodies with a special emphasis on opportunistic infections, malignancies, and loss of HIV control clearly need to be determined more thoroughly, and continued research efforts are necessary before a clear recommendation can be made.

Bone density, microarchitecture and tissue quality after 1 year of treatment with dolutegravir/abacavir/lamivudine.

BACKGROUND: Bone mineral density (BMD) decreases with ART initiation with a tenofovir disoproxil fumarate-containing regimen, although bone tissue quality increases. The impact of dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC)-based ART initiation on bone health parameters is not clear. OBJECTIVES: To study the impact of DTG/ABC/3TC-based therapy on bone health parameters in ART-naive individuals with HIV after 48 weeks of treatment. METHODS: An observational, prospective and analytical study of treatment-naive patients with HIV undergoing a DTG/ABC/3TC-based regimen at 48 week follow-up. Changes in bone strength parameters (BMD, bone microarchitecture and bone tissue quality) were assessed with non-parametric methods. RESULTS: Sixteen HIV-infected ART-naive patients starting DTG/ABC/3TC were included. BMD in the lumbar spine showed a significant decrease of -2.25% (P = 0.007) and -4.1% in the femoral neck (P = 0.007). Bone microarchitecture, as measured by trabecular bone score, also decreased significantly by -2.5% (P = 0.03). In contrast, bone quality [bone material strength index (BMi)], as measured by microindentation, significantly increased with respect to baseline after 48 weeks of treatment, showing better bone properties of +6.53% (P < 0.001). No significant changes were found in bone turnover markers. In addition, a positive significant correlation between the CD4/CD8 cell count ratio at baseline and changes in BMSi after 48 weeks of treatment was observed (Spearman's rho = 0.4974; P = 0.04). CONCLUSIONS: After a 48 week treatment with DTG/ABC/3TC-based ART, BMD and trabecular bone score decreased while bone tissue quality, as measured by microindentation, improved significantly. The state of the immune system at ART initiation is related to bone quality recovery. An overarching approach to assess bone toxicity in ART-treated patients is needed.

Bone density, microarchitecture, and tissue quality after 1 year of treatment with tenofovir disoproxil fumarate.

OBJECIVE: Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is used to assess bone health in HIV patients. DXA measures the amount of mineral, but not other key aspects of bone strength such as bone microarchitecture or bone quality. Trabecular bone score (TBS) and in-vivo microindentation directly measure trabecular microarchitecture and bone tissue quality, respectively. The aim of this study is to measure bone strength properties using these techniques. RESULTS: Forty naive HIV patients who were going to start antiretroviral therapy (ART), a single pill treatment with elvitegravir/cobicistat, tenofovir disoproxil fumarate (TDF), emtricitavine (FTC) were included. A significant reduction in BMD at spine (-3.25%, P < 0.001) and in femoral neck (-3.82%, P = 0.016) between baseline and 48 weeks of treatment were found. Bone microarchitecture score at the spine, as measured by TBS, also significantly decreased from 1.357 (0.09) to 1.322 (0.09) (-2.5%, P = 0.011) between baseline to 48 weeks of treatment. Microindentation (BMSi) values were significantly higher than at baseline [89.04 (4.2) versus 86.07 (6.1); 3.49%, P < 0.001] after 48 weeks of TDF-based ART treatment, indicating improved bone material properties CONCLUSION:: A significant decrease in BMD and TBS were observed after 1 year of TDF therapy. However, tissue quality significantly improved after 1 year of treatment, suggesting a recovery of bone material properties following the control of the infection despite the significant reduction of BMD. These techniques provide additional and necessary information to DXA about bone health in treated HIV patients, and because of its convenience and feasibility they could be routinely apply to assess bone in clinical practice.

Bone Density, Microarchitecture, and Tissue Quality After Long-Term Treatment With Tenofovir/Emtricitabine or Abacavir/Lamivudine.

OBJECTIVES: HIV infection has been associated with reduced bone mineral density (BMD). Antiretroviral therapy (ART) has a deleterious effect on BMD, but its effect on bone fragility is not clear. The objective of this study is to analyze the BMD, microarchitecture, and tissue quality of bone in patients receiving long-term tenofovir- or abacavir-based ART. DESIGN: We conducted a cross-sectional study in patients with HIV undergoing tenofovir or abacavir ART for more than 5 years. METHODS: We measured BMD using dual X-ray absorptiometry ,bone michroarchitecture using trabecular bone score (TBS), and bone tissue quality using microindentation. TBS is a dual X-ray absorptiometry-based software that is more highly correlated with bone fragility than BMD. Microindentation (BMSi) directly assesses bone quality at the tissue level. RESULTS: A total of 63 patients were included in this study, with 36 belonging to the TDF-FTC group and 27 to the ABC-3TC group. Patients receiving TDF-FTC treatment showed lower BMD values than those in the ABC-3TC group. We found no differences in TBS or microindentation between the 2 groups. However, after adjusting for sex, age, body mass index, and 25[OH]vitD we found lower BMSi and thus poorer bone properties in the TDF-FTC group than in the ABC-3TC group [beta coefficient -3.594 (confidence interval: 95% -0.12 to -7.61); P = 0.043]. CONCLUSIONS: Long-term treatment with TDF-FTC leads to impaired bone health, not only in terms of BMD but also in terms of bone quality, another determinant of overall bone strength. To complement BMD-based predictions, these other techniques may also be used to identify patients with excess fracture risk.

Validation Protocol of Vitamin D Supplementation in Patients with HIV-Infection.

Hypovitaminosis D and secondary hyperparathyroidism are frequent among HIV-infected patients. As there are no data about the best supplementation therapy both in treatment and in maintenance, we conducted an observational study of 300 HIV-infected patients for whom vitamin D and parathormone (PTH) had been measured in order to validate a protocol of vitamin D supplementation in patients with HIV-infection. Patients with vitamin D deficiency (defined as 25(OH)D < 10 ng/mL), insufficiency (defined as 25(OH)D < 20 ng/mL), or hyperparathyroidism (PTH > 65 pg/mL) were supplemented with cholecalciferol 16.000IU (0.266 mg) weekly (if deficiency) or fortnightly (if insufficiency or high PTH levels). Rates of normalization of 25(OH)D (levels above 20 ng/mL) and PTH levels (<65 pg/mL) were analyzed. Multivariate analysis of factors related to normalization was carried out. With a median follow-up of 2 years, 82.1% of patients with deficiency and 83.9% of cases with insufficiency reached levels above 20 ng/mL. However, only 67.2% of individuals with hyperparathyroidism at baseline reached target levels (<65 pg/mL). Independent factors for not achieving PTH objective were tenofovir (TDF) and protease inhibitors use. In HIV-infected patients with hypovitaminosis, the protocol of cholecalciferol supplementation normalized vitamin D levels regardless of antiretroviral regimen in a high proportion of patients but it was less effective to correct hyperparathyroidism.

Brief Report: HIV Infection Is Associated With Worse Bone Material Properties, Independently of Bone Mineral Density.

Low bone mineral density (BMD) in HIV-infected individuals has been documented in an increasing number of studies. However, it is not clear whether it is the infection itself or the treatment that causes bone impairment. Microindentation measures bone material strength (Bone Material Strength index) directly. We recruited 85 patients, 50 infected with HIV and 35 controls. Median Bone Material Strength index was 84.5 (interquartile range 83-87) in HIV-infected patients and 90 (88.5-93) in controls (P < 0.001). No significant differences in BMD between cases and controls at any of the sites examined (total hip, femoral neck, and lumbar spine). HIV infection is associated with bone damage, independently of BMD.

Insuficiencia renal aguda asociada al uso de tenofovir combinado con atazanavir en pacientes con infección por el VIH / Acute renal failure associated with the use of tenofovir combined with atazanavir in patients with HIV infection

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