Metabolic effects of switching to Biktarvy (B/F/TAF) in patients with HIV-1 treated with antiretroviral regimens that do not include tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF): The Metabic study.

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.

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.

Prevalence and Temporal Trends of Autoimmune Diseases in People Living with HIV.

Since the introduction of modern antiretroviral treatment for HIV and hepatitis C virus (HCV), the pattern of autoimmune diseases (ADs) in people living with HIV (PWH) might have changed. This is a retrospective study in a cohort of 5,665 PWH at the HIV Clinic of Hospital Universitario La Paz (Spain) to estimate the prevalence of ADs from January 1990 to June 2020. We divided the timeline into four periods: <1996, 1996-2006, 2006-2015, and 2015-2020. In total 369 participants were diagnosed with at least one AD, with a prevalence of 5.3% (95% confidence interval 4.7-5.9). In total, 302 (81%) participants were diagnosed simultaneously or after HIV diagnosis. Most prevalent diseases were immune thrombopenia (IT) (n = 90), cutaneous psoriasis (n = 52), autoimmune thyroid disorders (n = 36), spondylarthritis (n = 24), and inflammatory bowel disease (IBD) (n = 21). There was a significant trend for more ADs in recent periods (p = .037). In recent years, participants with ADs were older, had a long time since HIV diagnosis, and had higher CD4+ T cell count and higher CD4+ T cell nadir (temporal linear trend p < .001). There was a change in the pattern of ADs over time with a decrease in IT and an increase in spondylarthritis, arthritis, IBD, and thyroid disorders. One hundred thirty-nine participants (46%) were coinfected with HCV, with a steady decline throughout the study period. Only cryoglobulinemia was statistically associated with HCV infection. AD increases over time in PWH with reasonable immune virological control. We observed a higher frequency of spondylarthritis, arthritis, autoimmune thyroid disorders, and IBD in recent years.

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.

Psoriasis and Liver Damage in HIV-Infected Patients.

Background/objectives: Psoriasis is the most frequent skin disease in HIV-infected patients. Nonalcohol fatty liver disease (NAFLD) is more prevalent in patients with psoriasis. We report the prevalence of psoriasis and NAFLD and investigate risk factors of liver damage in HIV-infected patients with psoriasis. Methods: We performed a retrospective observational study. Steatosis was defined as indicative abdominal ultrasound findings, CAP (controlled attenuated parameter by transient elastography) > 238 dB/m, and/or triglyceride and glucose index (TyG) > 8.38. Significant (fibrosis ≥ 2) and advanced liver fibrosis (fibrosis ≤ F3) were studied by transient elastography (TE) and/or FIB-4 using standard cutoff points. FIB-4 (Fibrosis 4 score) results were adjusted for hepatitis C (HCV)-coinfected patients. Results: We identified 80 patients with psoriasis (prevalence, 1.5%; 95% CI, 1.1-1.8). Psoriasis was severe (PASI > 10 and/or psoriatic arthritis) in 27.5% of cases. The prevalence of steatosis was 72.5% (95% CI, 65-85). Severe psoriasis was an independent risk factor for steatosis (OR, 12; 95% CI, 1.2-120; p = 0.03). Significant liver fibrosis (p < 0.05) was associated with HCV coinfection (OR 3.4; 95% CI, 1.1-10.6), total CD4 (OR 0.99; 95% CI, 0.99-1), and time of efavirenz exposure (OR 1.2; 95% CI, 1.0-1.3). Conclusions: The prevalence of psoriasis in HIV-infected patients was similar to that of the general population. Steatosis is highly prevalent, and severe psoriasis is an independent risk factor for steatosis in HIV-infected patients.