Respiratory symptoms and chronic bronchitis in people with and without HIV infection.

OBJECTIVES: High rates of respiratory symptoms and chronic bronchitis (CB) are reported in people with HIV infection (PWH). We investigated the prevalence of respiratory symptoms and CB in PWH and HIV-negative people in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study. METHODS: Assessment of respiratory symptoms and CB was undertaken using the modified form of the St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease (COPD). Univariate (χ2 tests, Mann-Whitney U tests and Spearman's rank correlation) and multivariable (linear and logistic regression) analyses were performed to consider associations of respiratory symptoms with demographic, lifestyle and HIV-related parameters, and with depressive symptoms and quality of life. RESULTS: Among the 619 participants, respiratory Symptom scores were higher in older and younger PWH compared to older HIV-negative people, with median (interquartile range) scores of 17.7 (6.2, 39.5), 17.5 (0.9, 30.0) and 9.0 (0.9, 17.5), respectively (P = 0.0001); these differences remained significant after confounder adjustment. Sixty-three participants (10.2%) met the criteria for CB [44 (14.0%) older PWH, 14 (9.2%) younger PWH, and five (3.3%) older HIV-negative people; P = 0.002], with these differences also remaining after adjustment for confounding variables, particularly smoking status [older vs. younger PWH: odds ratio (OR) 4.48 (95% confidence interval (CI) 1.64, 12.30); P = 0.004; older PWH vs. HIV-negative people: OR 4.53 (95% CI 1.12, 18.28); P = 0.03]. Respiratory symptoms and CB were both associated with greater depressive symptom scores and poorer quality of life. No strong associations were reported between CB and immune function, HIV RNA or previous diagnosis of any AIDS event. CONCLUSIONS: Respiratory symptoms and CB are more common in PWH than in demographically and lifestyle-similar HIV-negative people and are associated with poorer mental health and quality of life.

The rate of bone loss slows after 1-2 years of initial antiretroviral therapy: final results of the Strategic Timing of Antiretroviral Therapy (START) bone mineral density substudy.

OBJECTIVES: Initial antiretroviral therapy (ART) causes loss of bone mineral density (BMD) over the first 1-2 years. Whether this loss continues with longer therapy is unclear. We determined changes in bone and spine BMD over 5 years in adults receiving immediate or deferred initial ART. METHODS: In the Strategic Timing of Antiretroviral Therapy (START) BMD substudy, ART-naïve adults with CD4 counts > 500 cells/µL were randomized to immediate or deferred ART. Deferred group participants not yet on ART were offered ART after May 2015. Mean per cent changes in total hip and lumbar spine BMD (measured annually by dual-energy X-ray absorptiometry) were compared between groups using longitudinal mixed models. Fracture rates were also compared between groups for all START participants. RESULTS: Substudy participants (immediate group, n = 201; deferred group, n = 210; median age 32 years; 80% non-white; 24% female) were followed for a mean 4.5 years until December 2016. In the immediate group, > 96% used ART throughout. In the deferred group, 16%, 58% and 94% used ART at years 1, 3 and 5, respectively. BMD decreased more in the immediate group initially; groups had converged by year 3 at the spine and year 4 at the hip by intent-to-treat (ITT). BMD changes after year 1 were similar in the immediate group and in those off ART in the deferred group [mean difference: spine, 0.03% per year; 95% confidence interval (CI) -0.4, 0.4; P = 0.88; hip, -0.2% per year; 95% CI -0.7, 0.3; P = 0.37]. Fracture incidence did not differ significantly between groups (immediate group, 0.86/100 person-years versus deferred group, 0.85/100 person-years; hazard ratio 1.01; 95% CI 0.76, 1.35; P = 0.98). CONCLUSIONS: Significant ART-induced bone loss slowed after the first year of ART and became similar to that in untreated HIV infection.

Factors associated with obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort: an observational cross-sectional analysis.

OBJECTIVES: The aims of the study were to describe the prevalence of obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort, to identify demographic, clinical and HIV-specific factors associated with obesity, and to characterize the association between obesity and sociodemographic, clinical and HIV-specific factors and quality of life (QoL). METHODS: A cross-sectional analysis was carried out of baseline data from the three groups ["older" people with HIV infection (PWH) aged ≥ 50 years, "younger" PWH aged < 50 years and HIV-negative controls aged ≥ 50 years] within the POPPY cohort. Obesity was defined as a body mass index (BMI) > 30 kg/m2 . RESULTS: A total of 1361 subjects were included in the study, of whom 335 (24.6%) were obese. The prevalence of obesity was higher in controls (22.3%) than in older (16.8%) and younger (14.2%) PWH, with no differences between the two groups of PWH. Factors associated with obesity were older age, female gender, black African ethnicity and alcohol consumption. Recreational drug use and a higher current CD4 T-cell count (in PWH) were associated with lower and higher odds of being obese, respectively. The presence of obesity was associated with worse physical health QoL scores, higher odds of having cardiovascular disease, type 2 diabetes and hypertension, but lower odds of having osteopenia/osteoporosis, irrespective of HIV status. CONCLUSIONS: Despite a lower prevalence of obesity in PWH, specific subgroups (women, people of black African origin and older people) were more likely to be obese, and negative health consequences of obesity were evident, regardless of HIV status. Whether targeted preventive strategies can reduce the burden of obesity and its complications in PWH remains to be determined.

Depression, lifestyle factors and cognitive function in people living with HIV and comparable HIV-negative controls.

OBJECTIVES: We investigated whether differences in cognitive performance between people living with HIV (PLWH) and comparable HIV-negative people were mediated or moderated by depressive symptoms and lifestyle factors. METHODS: A cross-sectional study of 637 'older' PLWH aged ≥ 50 years, 340 'younger' PLWH aged < 50 years and 276 demographically matched HIV-negative controls aged ≥ 50 years enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study was performed. Cognitive function was assessed using a computerized battery (CogState). Scores were standardized into Z-scores [mean = 0; standard deviation (SD) = 1] and averaged to obtain a global Z-score. Depressive symptoms were evaluated via the Patient Health Questionnaire (PHQ-9). Differences between the three groups and the effects of depression, sociodemographic factors and lifestyle factors on cognitive performance were evaluated using median regression. All analyses accounted for age, gender, ethnicity and level of education. RESULTS: After adjustment for sociodemographic factors, older and younger PLWH had poorer overall cognitive scores than older HIV-negative controls (P < 0.001 and P = 0.006, respectively). Moderate or severe depressive symptoms were more prevalent in both older (27%; P < 0.001) and younger (21%; P < 0.001) PLWH compared with controls (8%). Depressive symptoms (P < 0.001) and use of hashish (P = 0.01) were associated with lower cognitive function; alcohol consumption (P = 0.02) was associated with better cognitive scores. After further adjustment for these factors, the difference between older PLWH and HIV-negative controls was no longer significant (P = 0.08), while that between younger PLWH and older HIV-negative controls remained significant (P = 0.01). CONCLUSIONS: Poorer cognitive performances in PLWH compared with HIV-negative individuals were, in part, mediated by the greater prevalence of depressive symptoms and recreational drug use reported by PLWH.

High-risk behaviours, and their associations with mental health, adherence to antiretroviral therapy and HIV parameters, in HIV-positive men who have sex with men.

OBJECTIVES: To investigate the patterns and frequency of multiple risk behaviours (alcohol, drugs, smoking, higher risk sexual activity) among men who have sex with men (MSM) living with HIV. METHODS: Cross sectional study. RESULTS: 147 out of 819 HIV-positive MSM exhibited a high-risk phenotype (defined as >3 of smoking, excess alcohol, sexually transmitted infection and recent recreational drug use). This phenotype was associated with younger age, depressive symptoms and <90% adherence in multivariable logistic regression. CONCLUSION: In a cohort of MSM, a small, but significant proportion exhibited multiple concurrent risk behaviours.

The effect of initiation of antiretroviral therapy on monocyte, endothelial and platelet function in HIV-1 infection.

OBJECTIVES: Monocyte activation, endothelial dysfunction and platelet activation all potentially contribute to the increased risk of cardiovascular disease (CVD) reported in those with HIV-1 infection. To date, no study has examined how initiation of antiretroviral therapy (ART) affects markers of all three processes. We aimed to compare markers of monocyte, endothelial and platelet function between untreated HIV-positive subjects and HIV-negative controls and to examine the early effects of ART initiation on these markers. METHODS: We measured monocyte [soluble CD14 (sCD14) and sCD163], endothelial [von Willebrand factor (vWF), intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1)] and platelet [soluble P-selectin (sP-selectin), soluble CD40 ligand (sCD40L) and soluble glycoprotein VI (sGPVI)] biomarkers before and at weeks 4 and 12 post ART initiation in HIV-positive and well-matched HIV-negative controls. RESULTS: We examined 40 subjects, 25 HIV-positive subjects and 15 controls, with a median age of 34 years [interquartile range (IQR) 31, 40 years], of whom 60% were male and 47.5% Caucasian. Pre-ART, all biomarkers (monocyte, endothelial and platelet) were significantly higher in HIV-positive patients versus controls (all P < 0.05) and decreased with ART initiation, except for sCD14, which remained unchanged [median 1680 (IQR 1489, 1946) ng/mL at week 12 versus 1570 (IQR 1287, 2102) ng/mL at week 0; P = 0.7]. Although platelet activation markers reduced to levels comparable to those in controls, endothelial dysfunction markers remained elevated, as did sCD163 [at week 12, median 1005 (IQR 791, 1577) ng/mL in HIV-positive patients versus 621 (IQR 406, 700) ng/mL in controls; P < 0.0001]. CONCLUSIONS: ART initiation resulted in reductions in levels of CVD-associated biomarkers; however, although they improved, markers of endothelial dysfunction and monocyte activation remained elevated. How these persistent abnormalities affect CVD risk in HIV infection remains to be determined.

Effectiveness of interferon-free therapy for the treatment of HCV-patients with compensated cirrhosis treated through the Irish early access program.

BACKGROUND: We investigated the real-world effectiveness of interferon-free regimens for the treatment of patients with compensated cirrhosis infected with hepatitis C virus (HCV). METHOD: Using the Irish national HCV treatment registry, the effectiveness and safety of interferon-free regimens for HCV-infected patients treated between April 2015 and August 2016, was determined. RESULTS: A SVR12 was achieved in 86% of subjects treated with sofosbuvir/ledipasvir ± ribavirin (SOF/LDV±RBV), 93% treated with paritaprevir, ombitasvir and ritonavir combined with dasabuvir ± ribavirin (3D±RBV) and 89% treated with sofosbuvir/daclatasvir ± ribavirin (SOF/DCV±RBV). The discontinuation rate was 5% and the on-treatment mortality rate was 1%. CONCLUSION: The availability of interferon-free regimens represents a significant breakthrough for the treatment of HCV infection. Treatments options, with high SVR12 rates, are now available for patients with compensated cirrhosis who were unsuitable for treatment with interferon-based regimens. Data obtained from studies conducted in real world practice provide robust information fundamental for input into future economic evaluations for agents used for the treatment of HCV infection.

Minor changes in calculated creatinine clearance and anion-gap are associated with tenofovir disoproxil fumarate-containing highly active antiretroviral therapy.

BACKGROUND: Tenofovir disoproxil fumarate (Tenofovir DF, TDF), the first nucleotide reverse transcriptase inhibitor approved for the treatment of HIV disease, has been associated with renal dysfunction in isolated cases. The aim of this study was to assess changes in renal parameters in individuals receiving TDF- and non-TDF-containing highly active antiretroviral therapy (HAART). METHODS: All individuals on HAART attending our clinic were included in the analysis. Time-weighted changes in serum creatinine, calculated creatinine clearance (CCrCl) and anion-gap were assessed for individuals on TDF- and non-TDF HAART. RESULTS: Of 948 individuals on HAART, 290 (31%) and 618 (65%) were on TDF- and non-TDF HAART, with 40 (4%) having ceased TDF HAART. Baseline values for serum creatinine, CCrCl and anion-gap were similar for those on TDF- and non-TDF HAART. In a multivariate analysis, statistically significant differences were observed in time-weighted change from baseline in anion-gap and CCrCl between individuals on TDF- and non-TDF HAART [mean difference in change between groups: anion-gap 0.78 mmol/L (standard error, 0.19) and CCrCl-6.80 (standard error 2.2); P = 0.005 and P = 0.032, respectively] after adjusting for baseline anion-gap and CCrCl, respectively. Two cases of TDF-associated renal failure were observed. CONCLUSION: Overt renal failure with TDF HAART is rare. However, subtle but statistically significant changes in anion-gap and CCrCl were observed which were associated with TDF HAART. These parameters may be of use in monitoring individuals on HAART.