Objectives Fat mass ratio ( FMR ) has been suggested as an objective indicator of abnormal body fat distribution in HIV infection. Although it could provide more comprehensive information on body fat changes than limb fat mass, FMR has scarcely been used in clinical trials examining body fat distribution in HIV ‐infected patients. Methods A subanalysis of a controlled, randomized clinical trial in virologically suppressed HIV ‐1‐infected men switching from zidovudine ( ZDV )/lamivudine (3 TC ) to emtricitabine ( FTC )/tenofovir ( TDF ) versus continuing on ZDV /3 TC was carried out. FMR was assessed by dual X ‐ray absorptiometry ( DEXA ) for a period of 72 weeks. Lipoatrophy was defined as FMR ≥ 1.5. Multivariate linear regression models for the change in FMR from baseline were fitted. Results Sixty‐five men were randomized and treated (28 in the FTC / TDF arm and 37 in the ZDV / 3TC arm), and 57 completed the study (25 and 32 in each arm, respectively). In the FTC / TDF arm, adjusted mean FMR decreased by 0.52 at week 72 ( P = 0.014), and in the ZDV / 3TC arm it increased by 0.13 ( P = 0.491; P between arms = 0.023). Among subjects with lipoatrophy (baseline FMR ≥ 1.5), adjusted FMR decreased by 0.76 ( P = 0.003) in the FTC / TDF arm and increased by 0.21 ( P = 0.411; P between arms = 0.009) in the ZDV / 3TC arm. Baseline FMR and treatment group were significant predictors ( P < 0.05) of post‐baseline changes in FMR . Conclusions Switching from ZDV / 3TC to FTC / TDF led to an improvement in FMR , compared with progressive worsening of FMR in subjects receiving ZDV / 3TC , showing that fat mass not only increased but was also distributed in a healthier way after the switch.

Objectives Lipoatrophy is a long-term adverse effect of some antiretrovirals that affects quality of life, compromises adherence and may limit the clinical impact of HIV treatments. This paper explores the effect of tenofovir/emtricitabine (TDF/FTC) on the amount of limb fat in patients with virological suppression. Methods A randomized, prospective clinical trial was performed to compare continuation on a zidovudine/lamivudine (ZDV/3TC)-based regimen with switching to a TDF/FTC-based regimen in terms of the effect on limb fat mass as assessed by DEXA over a 72-week period. Results Eighty patients were included (39 in the TDF/FTC arm and 41 in the ZDV/3TC arm) and 73 completed the study (37 and 36, respectively). In the switch arm, limb fat increased by a median of 540g from baseline (P=0.022), while in the ZDV/3TC arm it decreased by a median of 379g (P=0.112; p between groups=0.007). Subjects with baseline limb fat 7200g, previous time on ZDV>5 years or a body mass index >25kg/m2 experienced higher limb fat gains than other subjects, and these differences were statistically significant. Haemoglobin increased by a median of 1.0g/dL in the TDF/FTC arm (P<0.001) and remained unchanged in the ZDV/3TC arm (p between groups=0.0002). There were no significant differences between groups in other secondary endpoints (body weight, total body and trunk fat content, total body bone mineral density, laboratory parameters, CD4 cell count and viral load). Conclusions Switching from a ZDV/3TC-based to a TDF/FTC-based regimen led to a statistically significant improvement in limb fat, in contrast to the progressive loss of limb fat in subjects continuing ZDV/3TC.

OBJECTIVE:The aim of the study was to investigate changes in plasma biomarkers of cardiovascular risk and lipids in a CD4-guided antiretroviral therapy interruption study. METHODS:This was a substudy of a prospective, randomized, multicentre treatment interruption study. At months 12, 24 and 36, monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), interleukin-8 (IL-8), soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin), and tissue plasminogen activator (t-PA) were measured using a multiplex cytometric bead-based assay. Total cholesterol (total-c), high-density lipoprotein cholesterol (HDL-c) and triglycerides (TG) were determined using standard methods. RESULTS:Fifty-four patients were included in the study [34 in the treatment continuation (TC) arm and 20 in the treatment interruption (TI) arm]. There were no differences at baseline between the groups, except in CD4 cell count, which was higher in the TI arm (P = 0.026), and MCP-1, which was higher in the TC arm (P = 0.039). MCP-1 and sVCAM-1 were increased relative to baseline at the three study time-points in the TI arm, with no changes in the TC arm. Soluble CD40L and sP-selectin were increased at month 36 in both arms, with a greater increase in the TI arm (P = 0.02). t-PA was increased in both arms at the three time-points. Total-c, HDL-c and low-density lipoprotein cholesterol (LDL-c) were decreased in the TI arm at the three time-points, with no changes in the total-c/HDL-c ratio. HIV viral load positively correlated with MCP-1 at months 12 and 24. Regression analysis showed a significant negative association of HDL-c with MCP-1 and sVCAM-1. CONCLUSIONS:A significant increase in cardiovascular risk biomarkers persisting over the prolonged study period was seen in the TI arm. This factor may contribute to the increased cardiovascular risk observed in previous studies.

Background Although HIV-infected patients are at greater risk of presenting with ischaemic necrosis of the femoral head, there have been concerns about whether total hip arthroplasty (THA) may have worse outcomes than expected. Methods From the Orthopedic and Trauma Surgery database we identified all patients who had undergone THA because of ischaemic necrosis of the femoral head from January 2001 until March 2010. Patient's diagnosis of HIV infection was confirmed at the time of arthroplasty by cross-matching with the HIV unit database. For every THA in HIV-infected patients, two THAs in patients not known to be HIV-infected, with the same diagnosis of ischaemic necrosis of the femoral head and having undergone surgery over the same period, were randomly selected. THAs were compared in HIV- and non-HIV-infected patients for surgical procedure, in-patient stay and long-term prognosis. Results There were 18 THAs in 13 HIV-infected patients and 36 THAs in 27 non-HIV-infected patients. No significant differences were observed in the mean time spent in surgery (106 vs. 109 minutes, respectively; P?=?0.66), the need for red cell transfusion (1 vs. 4, respectively; P?=?0.48) or the mean duration of hospitalization (7.8 vs. 9.4 days, respectively; P?=?0.48). The two groups showed similar postoperative functional results, which were maintained until the end of the follow-up period (median 3.3 years in the HIV-positive group and 5.8 years in the HIV-negative group). Conclusion Our study suggests that the outcome of THA in HIV-positive patients is not worse than that of HIV-negative patients, although future research on larger numbers of patients is required to confirm this.

ObjectivesHIV-infected adults are considered to be at higher risk for influenza A H1N1 complications but data supporting this belief are lacking. We aimed to compare epidemiological data, clinical characteristics, and outcomes of influenza A H1N1 infection between HIV-infected and -uninfected adults.MethodsFrom 26 April to 6 December 2009, each adult presenting with acute respiratory illness at the emergency department of our institution was considered for an influenza A H1N1 diagnosis by specific multiplex real-time polymerase chain reaction. For every HIV-infected adult diagnosed, three consecutive adults not known to be HIV-infected diagnosed in the same calendar week were randomly chosen as controls.ResultsAmong 2106 adults tested, 623 (30%) had influenza A H1N1 infection confirmed. Fifty-six (9%) were HIV-positive and were compared with 168 HIV-negative controls. Relative to HIV-negative controls, HIV-positive patients were older, more frequently male, and more frequently smokers (P < 0.02). In the HIV-positive group, prior or current AIDS-defining events were reported for 30% of patients, 9% and 30% had CD4 counts of < 200 and 200-500 cells/mu L, respectively, and 95% had HIV-1 RNA < 50 copies/mL. Pneumonia (9% vs. 25%, respectively, in the HIV-positive and HIV-negative groups; P=0.01) and respiratory failure (9% vs. 21%, respectively; P=0.04) were less common in the HIV-positive group. Oseltamivir (95% vs. 71% in the HIV-positive and HIV-negative groups, respectively; P=0.003) was administered more often in HIV-positive patients. Three patients (all HIV-negative) died. In the HIV-positive group, CD4 cell count and plasma HIV-1 RNA did not differ before and 4-6 weeks after influenza A H1N1 diagnosis (P > 0.05).ConclusionsHIV infection did not increase the severity of influenza A H1N1 infection, and influenza A H1N1 infection did not have a major effect on HIV infection.

Armario, P.; Castellanos, P.; Larrousse, M.; Hernandez-Del-Rey, R.; Vázquez, S.; Sans, L.; Oliveras, A.; De La Sierra, A.; Martin-Baranera, M. Author Information

Con la introducción del tratamiento antirretroviral de alta eficacia, las enfermedades arterioscleróticas han ganado importancia como causa de morbilidad y mortalidad en personas infectadas por el virus de la inmunodeficiencia humana (VIH). A continuación, se examinará el riesgo de enfermedades cardiovasculares en personas infectadas por el VIH y se comparará con la población no infectada. Se expondrán las contribuciones relativas al huésped, a la infección por el VIH, y la terapia antirretroviral a la luz de los conocimientos actuales.

Resistant (or refractory) hypertension (RH) is a clinical diagnosis based on blood pressure (BP) office measurements. About one third of subjects with suspected RH have indeed pseudo-resistant hypertension and 24-h ambulatory-blood pressure-monitoring aids to precisely identify them. Our aim was to determine those clinical, laboratory or echocardiographic variables that may be associated with subjects with sustained hypertension (namely true RH). We carried out a cross-sectional analysis of 143 patients consecutively enrolled with the clinical diagnosis of RH. All patients underwent clinical-demographic, laboratory evaluation, 2D-echocardiography and 24-h ambulatory-blood pressure-monitoring. Pseudo-resistant hypertension or white-coat RH was defined if office BP was ⩾140 and/or 90 mm Hg and 24-h BP <130/80 mm Hg. One-hundred and three (72%) patients had true RH and 40 (28%) patients had white-coat RH. True RH patients had significantly higher diabetes prevalence and higher office-systolic blood pressure (SBP) levels. Regarding target organ damage, left ventricular mass index (LVMI) and 24-h urinary albumin excretion (UAE) were also higher in true RH after adjustment for possible confounders (P=0.031 and P=0.012, respectively). In a logistic regression analysis, only office-SBP (multivariate OR (95%CI): 1.030 (1.003–1.057), P=0.030) and UAE (multivariate OR (95% CI): 2.376 (1.225–4.608), P=0.010) were independently associated with true RH. We conclude that true resistant hypertension is associated with silent target organ damage, especially UAE. In patients with suspected RH, assessment of 24 h ambulatory BP is the most accurate way to detect a population with high risk for target-organ damage.

To assess the correlation between endothelial dysfunction and the serum levels of biomarkers of inflammation, remodelling and oxidative stress in essential hypertension, 78 treatment-naïve essential hypertensives (mean age 43 years) underwent measurement of endothelial dysfunction, using the maximal acetylcholine-induced forearm vasodilation and serum levels of adhesion molecules, selectins, chemokines, metalloproteinases, copper, zinc, selenium, vitamins, homocysteine, malondialdehyde, erythrocyte glutathione peroxidase and erythrocyte superoxide dismutase. Mean (±s.e.m.) maximal acetylcholine-induced vasodilation was 367±20%. Patients with a more impaired acetylcholine-dependent vasodilation (first tertile) had increased levels of e-selectin (P=0.009), p-selectin (P<0.001), monocyte chemotactic protein type 1 (MCP-1; P=0.012) and the tissue inhibitor of metalloproteinases type 1 (TIMP-1; P=0.044), which in turn showed significant inverse correlations with maximal endothelium-dependent vasodilation. Serum levels of selenium (P=0.012), vitamin C (P=0.038), erythrocyte glutathione peroxidase (P<0.001) and superoxide dismutase (P=0.022) activities were reduced in patients with a more impaired endothelium-dependent vasodilation. Recently diagnosed treatment-naïve essential hypertensives showed a relationship between the endothelial dysfunction, serum markers of inflammation and remodelling and levels of antioxidant substances. These could be potentially helpful markers of high risk in hypertensive patients.

The relationship between the subjective diagnosis of lipoatrophy and the objective amount of limb fat loss in HIV-infected adults is unclear.Using Medline, we identified published articles reporting the amount of arm, leg or limb fat measured by dual X-ray absorptiometry in HIV-infected patients with moderate-severe lipoatrophy and in healthy non-HIV-infected adults. We calculated the relative content of fat in the limbs, arms and legs of lipoatrophic patients with regard to the weighted arithmetic means of those fat values in healthy controls.We found 799 patients from 10 articles, and 73 healthy controls from two articles. Limb fat ranged from 2.6 to 4.4 kg in patients, and from 7.1 to 7.2 kg in controls. Both patients and controls were almost exclusively men, of white race, and in their forties. Weighted arithmetic means of arm, leg and limb fat in HIV-infected patients with clinically evident lipoatrophy were 1.0, 2.1 and 3.1 kg, respectively (48, 41 and 43% relative to healthy non-HIV-infected males, respectively).The diagnosis of lipoatrophy was highly correlated with the amount of limb fat, irrespective of the investigators. HIV-infected men with clinically evident lipoatrophy had a limb fat loss of > 50% compared with non-HIV-infected healthy males.

Aims: The aim of this study was to evaluate the hemodynamic pattern, vascular compliance, as well as the levels of vasoregulatory hormones and markers of inflammation and oxidative stress in a group of chronic hypotensive (CH) patients undergoing hemodialysis (HD) and to compare them with a group of normotensive HD patients. Material and methods: 14 normotensive and 10 CH hemodialysis patients were included in the study. Hemodynamic characteristics were evaluated by means of the pulse waveform analysis. Plasma levels of nitrites, interleukin-6 (IL-6), malondialdehyde (MDA), PTH-related peptide (PTHrp), catecholamines, angiotensin II and endothelin were measured. Results: Blood pressure (BP) and peripheral vascular resistances (PVR) were lower in the hypotensive group (p < 0.001 and p = 0.005, respectively), whereas cardiac output was similar in both groups. Large (C1) (p = 0.001) and small (C2) (p = 0.022) artery elasticity indices were higher in hypotensive patients. In the whole group, C1 and C2 inversely correlated with mean BP (MBP). Plasma levels of nitrites (p = 0.011) were higher in hypotensive patients and inversely correlated with MBP (r = -0.516, p = 0.012). Time on HD correlated with plasma nitrites (r = 0.478, p = 0.024) and inversely with MBP (r = -0.598, p = 0.003). Conclusions: CH in HD patients is characterized by decreased PVR, a preserved cardiac output and greater vascular compliance. CH is associated with longer time on HD and higher plasma levels of nitrites/nitrates, suggesting that an enhanced production of nitric oxide induced by long-term HD, could be involved in CH. These findings suggest that functional vascular changes, likely related to an enhanced production of vasodilator agents, are responsible for CH in HD patients.