Determinants of blood telomere length in antiretroviral treatment-naïve HIV-positive participants enrolled in the NEAT 001/ANRS 143 clinical trial.

OBJECTIVES: Our aim was to investigate factors associated with baseline blood telomere length in participants enrolled in NEAT 001/ANRS 143, a randomized, open-label trial comparing ritonavir-boosted darunavir (DRV/r) plus raltegravir (RAL) with DRV/r plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in antiretroviral therapy (ART)-naïve HIV-positive adults. METHODS: A cross-sectional study of 201 randomly selected participants who had stored samples available was carried out. We measured telomere length (i.e. the relative telomere length, calculated as the telomere to single copy gene ratio) at baseline with monochrome quantitative multiplex polymerase chain reaction (PCR). We used multivariable predictive linear regression to calculate mean differences and 95% confidence intervals (CIs) for the association between baseline telomere length and baseline characteristics. RESULTS: The baseline characteristics of the 201 participants did not differ from those of the 805 participants in the parent trial population: 89% were male, the mean age was 39 years, 83.6% were Caucasian, 93% acquired HIV infection via sexual transmission, the mean estimated time since HIV diagnosis was 2.1 years, the mean HIV-1 RNA load was 4.7 log10 HIV-1 RNA copies/mL, the mean nadir and baseline CD4 counts were 301 and 324 cells/µL, respectively, and the mean CD4:CD8 ratio was 0.4. In the univariate analysis, shorter telomere length was associated with older age (per 10 years) (P < 0.001), HIV-1 RNA ≥ 100 000 copies/mL (P = 0.001), CD4 count < 200 cells/µL (P = 0.037), lower CD4:CD8 ratio (P = 0.018), statin treatment (P = 0.004), and current alcohol consumption (P = 0.035). In the multivariable analysis, older age (P < 0.001) and HIV RNA ≥ 100 000 copies/mL (P = 0.054) were independently associated with shorter telomere length. CONCLUSIONS: Both age and HIV RNA viral load correlated with shorter blood telomere length in untreated persons living with HIV. These results suggest that HIV infection and age have synergistic and independent impacts upon immunosenescence.

Hepatitis C treatment outcome in former or current intravenous drug users coinfected with HIV, with or without directly observed therapy.

BACKGROUND: Intravenous drug users (IDUs) with hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfection are recognised as a high-risk, vulnerable group. METHODS: Between February 2015 and April 2018, a single-centre, non-interventional cohort study was conducted in an outpatient setting, to evaluate the sustained virologic response (SVR12) and assess treatment uptake models. The study included 385 former or recent IDUs divided into two groups: A-without use of opioid substitution treatment (OST) and B-patients taking opioid substitution; patients in group B received OST and self-administered therapy (B1) or OST and therapy under DOT (B2). Patients were characterised by demographic and clinical features and compared for treatment response. Correlations between SVR12 and independent variables were determined by logistic regression. RESULTS: Patients were mostly males (88.3%) with a mean age of 46 ± 5 years and HCV genotype 1a (63.7%). Approximately 28% were treatment-experienced and 84.9% received sofosbuvir/ledipasvir. The mean CD4+T count was 649 cells/mm3, and most individuals were on antiretroviral therapy with undetectable viral loads (97.4%). SVR12 was achieved in 94.8%, and only eight patients relapsed. No significant differences were found in treatment effect between individuals taking opioid substitutes under different treatment models. Correlations were found between HCV viral response and both HIV suppression and albumin levels. CONCLUSIONS: IDU with HCV/HIV coinfection, including individuals on self-administration of HCV therapy and opioid substitution treatments or in DOT programmes, are no longer considered a difficult-to-treat group, as they achieve high rates of SVR12.

Glycaemic profile changes by highly active antiretroviral therapy in human immunodeficiency virus-infected patients.

To study dysglycaemia in human immunodeficiency virus (HIV)-infected patients we conducted a retrospective cohort study of the glucose profile in HIV-infected patients. The fasting blood glucose was analysed taking into consideration conventional risk factors as well as HIV infection and highly active antiretroviral therapy (HAART). One hundred seventy-three cases were selected for this study. Five risk factors had significant effects (p < 0.05) on glucose levels: age, body mass index (BMI), hepatitis C virus/hepatitis B virus (HCV/HBV) co-infection, viral load (VL), and CD4(+) T-lymphocyte count. Fasting blood glucose levels increased with age (0.59 mg/dL/year), decreased with the VL (-4.1 × 10(-6 )mg/dL/number of viral RNA copies) and the CD4(+) T-lymphocyte count (-0.016 mg/dL/cell count). Furthermore, obese patients and those co-infected with HCV/HBV were more prone to develop dysglycaemia having, on average, 15.4 mg/dL and 13.8 mg/dL higher levels, respectively, of fasting blood glucose. Despite an increase of 1.0% and 8.4% in the glucose levels noticed among HIV patients treated with non-nucleotide inhibitors of reverse transcriptase and protease inhibitors, respectively, HAART did not prove to be a significant predictor of fasting glucose levels as well as lipodystrophy and male gender. Age, BMI, HCV/HBV co-infection and HIV-related (VL and CD4(+) T-lymphocyte count) factors seem to be the most influential on fasting blood glucose levels in HIV-infected individuals.

Lipid profile changes by high activity anti-retroviral therapy.

OBJECTIVE: Study of the lipid profile in patients infected with HIV treated with different combinations of high activity anti-retroviral therapy (HAART). DESIGN AND METHODS: A retrospective cohort study of the lipid profile in patients undergoing HAART. The study analyzes the evolution of concentrations of triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDLc) and HDL-cholesterol (HDLc) in a period of at least 3 years of treatment. From a total of 750 clinical cases analyzed in Hospital Joaquim Urbano (Oporto, Portugal) 124 patients were selected for this study. RESULTS: After 3 years of treatment, we observed the development of dyslipidaemia by increases in TG (17%), TC (29%) and LDLc (9%), particularly in patients treated with a combination of drugs which included protease inhibitors (PI). Moreover, the non-nucleoside reverse transcriptase inhibitors (NNRTI) were associated with better lipid profile. The increase of 46% in HDLc was the most surprising finding. CONCLUSIONS: The results indicate that patients with HAART have a more atherogenic lipidic profile with increased TC, LDLc and TG levels. Since the effectiveness of NNRTI is similar to that of PI, but with a smaller atherogenic profile, it should be the first choice drug to be selected in the HIV treatment.