Lipodystrophy syndromes are a group of disorders characterized by a loss of adipose tissue once other situations of nutritional deprivation or exacerbated catabolism have been ruled out. With the ...exception of the HIV-associated lipodystrophy, they have a very low prevalence, which together with their large phenotypic heterogeneity makes their identification difficult, even for endocrinologists and pediatricians. This leads to significant delays in diagnosis or even to misdiagnosis. Our group has developed an algorithm that identifies the more than 40 rare lipodystrophy subtypes described to date. This algorithm has been implemented in a free mobile application, LipoDDx®. Our aim was to establish the effectiveness of LipoDDx®. Forty clinical records of patients with a diagnosis of certainty of most lipodystrophy subtypes were analyzed, including subjects without lipodystrophy. The medical records, blinded for diagnosis, were evaluated by 13 physicians, 1 biochemist and 1 dentist. Each evaluator first gave his/her results based on his/her own criteria. Then, a second diagnosis was given using LipoDDx®. The results were analysed based on a score table according to the complexity of each case and the prevalence of the disease.
LipoDDx® provides a user-friendly environment, based on usually dichotomous questions or choice of clinical signs from drop-down menus. The final result provided by this app for a particular case can be a low/high probability of suffering a particular lipodystrophy subtype. Without using LipoDDx® the success rate was 17 ± 20%, while with LipoDDx® the success rate was 79 ± 20% (p < 0.01).
LipoDDx® is a free app that enables the identification of subtypes of rare lipodystrophies, which in this small cohort has around 80% effectiveness, which will be of help to doctors who are not experts in this field. However, it will be necessary to analyze more cases in order to obtain a more accurate efficiency value.
Background. Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is a known risk factor for hepatotoxicity in patients receiving highly active antiretroviral therapy ...(HAART). The aim of this study was to evaluate the role of HCV-related liver fibrosis in HAART-associated hepatotoxicity. Methods. In a prospective study involving 107 patients who underwent liver biopsy, fibrosis was graded according 5 stages, from F0 (no fibrosis) to F4 (cirrhosis). Hepatotoxicity was defined as an increase in levels of aspartate aminotransferase and alanine aminotransferase to >5 times the upper limit of normal, or a >3.5-fold increase if baseline levels were abnormal. The incidence of hepatotoxicity was compared with liver fibrosis stage and with time and composition of HAART. Results. Overall, 27 patients (25%) had hepatotoxic events (5.1 events/100 person-years of therapy). The incidence was greater for patients with stage F3 or F4 fibrosis (38%) than for those with stage F1 or F2 fibrosis (15%; 7.6 vs. 3 events/100 person-years; relative risk, 2.75; 95% confidence interval, 1.08–6.97; P = .013). Duration of HCV infection, duration of HAART, diagnosis of acquired immunodeficiency syndrome, HCV load, HCV genotype, and nadir CD4+ cell count did not affect the risk of hepatotoxicity. Of the 86 patients who received nonnucleoside reverse-transcriptase inhibitors (NNRTIs), 11 (13%) developed liver toxicity. In these patients, fibrosis stages F1 and F2 were associated with similar rates of toxicity (3 events/100 person-years for patients who received nevirapine, 3.3 events/100 person-years for those who received efavirenz, and 3.4 events/100 person-years for those who received non-NNRTIs). There was a greater incidence among patients with F3 or F4 fibrosis who received NNRTIs (11.7 events/100 person-years for patients who received nevirapine, and 8.6 events/100 person-years for those who received efavirenz), compared with those who received non-NNRTIs (4 events/100 person-years). Conclusions. HAART-associated hepatotoxicity correlates with liver histological stage in patients coinfected with HIV and HCV. There was no difference in hepatotoxicity risk for different antiretroviral therapies in patients with mild-to-moderate fibrosis.
The use of combination antiretroviral therapy has led to dramatic improvements in the life expectancy of HIV-infected persons. As result, the HIV population is aging and increasingly facing illnesses ...typically seen in the elderly, such as chronic kidney disease (CKD).
A retrospective longitudinal study was conducted using data from years 2010 and 2014 in all HIV-infected persons enrolled at the Spanish VACH cohort. We analyzed the prevalence and the predictive factors for developing CKD (estimated glomerular filtration rate, eGFR<60mL/min/1.73m2).
The CKD prevalence at baseline was 456/8968, 5.1% 4.6–5.6%. Of 8512 HIV-positive individuals examined without CKD at baseline (73.7% male, median age 44 years-old), 2.15% developed CKD (eGFR<60mL/min/1.73m2). The odds ratios 95%CI for the independent predictive factors identified were gender (male) 0.54 0.39–0.75, age (per year) 1.08 1.07–1.10, AIDS diagnosis 1.40 1.03–1.91, protease inhibitor-based regimens 1.49 1.10–2.02, hypertension 1.37 0.94–1.99, diabetes 1.84 1.33–2.55 and history of cardiovascular events 1.66 0.96–2.86.
The prevalence and risk factors for CKD and its progression are high in the VACH cohort. Thus, preventive measures such as control of hypertension, diabetes and obesity, as well as efforts for avoiding exposure to nephrotoxic drugs, including some antiretrovirals, are warranted in this aging HIV population.
El uso de tratamiento antirretroviral combinado ha dado lugar a mejoras sustanciales en la esperanza de vida de las personas infectadas por el virus de la inmunodeficiencia humana (VIH). Como resultado, la población con VIH está envejeciendo y haciendo frente cada vez más a enfermedades normalmente observadas en las personas de edad avanzada, como la nefropatía crónica (NC).
Se ha realizado un estudio longitudinal retrospectivo usando datos de los años 2010 y 2014 en todas las personas infectadas por el VIH incluidas en la cohorte VACH española. Se ha analizado la prevalencia y los factores predisponentes para el desarrollo de NC (filtración glomerular estimada FGe:<60ml/min/1,73m2).
La prevalencia de NC al inicio fue de 456/8.968; 5,1% (4,6-5,6%). De las 8.512 personas infectadas por el VIH evaluadas sin NC al inicio (73,7 varones, mediana de edad: 44 años), el 2,15% desarrolló NC (FGe<60ml/min/1,73m2). Los cocientes de posibilidades (IC del 95%) de los factores predictivos independientes identificados fueron 0,54 (0,39-0,75) para el sexo (varón); 1,08 (1,07-1,10) para la edad (por año); 1,40 (1,03-1,91) para el diagnóstico de sida; 1,49 (1,10-2,02) para los tratamientos basados en inhibidores de la proteasa; 1,37 (0,94-1,99) para la hipertensión; 1,84 (1,33-2,55) para la diabetes y 1,66 (0,96-2,86) para los antecedentes de acontecimientos cardiovasculares.
La prevalencia y los factores de riesgo para la NC y su progresión son elevados en la cohorte VACH. Por lo tanto, está justificada la aplicación de medidas preventivas (como el control de la hipertensión, la diabetes y la obesidad), así como la aplicación de esfuerzos para evitar la exposición a fármacos nefrotóxicos (incluidos algunos antirretrovirales) en esta población con VIH que envejece.
To evaluate the frequency and predictive factors of discordant immune response, we performed a prospective cohort study of 288 antiretroviral-naive human immunodeficiency virus (HIV)–infected ...patients who initiated highly active antiretroviral therapy (HAART) and maintained complete virus suppression for ⩾24 months. The median CD4+ cell count was 186 × 106 cells/L, and the median HIV RNA level was 5 log10 copies/mL. After 24 months of therapy, 42 (16.5%) of 255 patients had a median CD4+ cell count increase of < 100 × 106 cells/L. By logistic regression analysis, previous injection drug use was associated with a CD4+ cell count increase of < 100 × 106 cells/L (risk ratio RR, 2.326; 95% confidence interval CI, 1.077–5.023; P = .032); inclusion of a protease inhibitor (PI) in the HAART regimen reduced the risk of poor immunologic recovery (RR, 0.160; 95% CI, 0.061–0.417; P < .001). Failure of the CD4+ cell count to increase was relatively common among antiretroviral-naive patients in the year after the initiation of HAART and the achievement of complete virus suppression. PI-containing regimens provided better immunologic response.
Objective: To validate a questionnaire to identify psychosocial repercussions of the lipodystrophy syndrome (LD) in HIV-infected patients. Methods: A questionnaire containing 35 items in 6 subscales ...body image, anxiety, depression, social support, social distress, quality of life (QoL) was consecutively administered to 128 patients with LD, 25 naïve patients or on therapy without LD, and to 15 HIV negative patients from January to July '04. Reliability was assessed using Cronbach's alpha and the intraclass correlation coefficient (ICC). The area under the curve (AUC) was used for discrimination between patients and control groups, and the scores were compared according to the severity of the LD. Results: In all the subscales, the relationship between higher scores and LD severity was statistically significant (0.37-0.64, p<0.01), whereas the control groups had significantly lower scores. The internal consistency showed Cronbach's alpha coefficients ranging from 0.64 to 0.93. Test-retest reliability after 15 days in 30 patients showed ICC values of 0.8-0.94. AUC values for the different subscales were higher than 0.7 with the exception of QoL score, and construct validity showed a significant correlation with the Beck Depression Inventory and the MOS-HIV scores (0.49 and 0.51, respectively, p<0.01). Conclusions: Our questionnaire shows satisfactory psychometric properties for identifying psychosocial repercussions of the LD in HIV-infected patients.
: Switching from boosted protease inhibitors (PI/r) to raltegravir (RAL) results in a better plasma lipid profile than continuing PI/r. Whether this strategy affects plasma biomarkers associated with ...atherosclerosis is unknown.
: We assessed 48-week changes in fasting lipids and several biomarkers including serum high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein 1 (MCP-1), osteoprotegerin, interleukin (IL) 6, IL-10, tumor necrosis factor alpha (TNF-α), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin and P-selectin, adiponectin, insulin, and D-dimer in otherwise healthy, virologically suppressed HIV-infected patients treated with PI/r who randomly switched from PI/r to RAL or continued with PI/r in the SPIRAL trial. Biomarkers and lipids at baseline and 48-week changes between both study arms were compared. Correlations between changes in biomarkers and changes in lipids were also evaluated.
: Of 273 patients initiating study drugs in the SPIRAL trial, 233 (119 RAL, 114 PI/r) remained on allocated therapy for 48 weeks and had sera available for the purpose of this substudy. Triglycerides (-28%, P < 0.0001), total (-14%, P < 0.0001), low-density lipoprotein (-9%, P = 0.0069), and high-density lipoprotein (-10%, P = 0.0017) cholesterol decreased in RAL relative to the PI/r group. Among biomarkers, hsCRP (-40%, P < 0.0001), MCP-1 (-20%, P = 0.0003), osteoprotegerin (-13%, P = 0.0024), IL-6 (-46%,P < 0.0001), TNF-α (-27%, P = 0.0011), insulin (-26%, P < 0.0001), and D-dimer (-8%, P = 0.0187) decreased in RAL relative to PI/r group, whereas IL-10 (+1%, P = 0.7773), ICAM-1 (-6%, P = 0.1255), VCAM-1(0%, P = 0.8671), E-selectin (-9%, P = 0.2174), P-selectin (-6%, P = 0.3865), and adiponectin (+8%, P = 0.2028) remained unchanged. Biomarkers and lipids changes at 48 weeks were weakly correlated.
: Switching from PI/r to RAL induced significant changes in several cardiovascular biomarkers that were not completely explained by lipid changes.
Switching to raltegravir in selected patients treated with ritonavir-boosted protease inhibitors may result in similar efficacy and lower plasma lipids.
SPIRAL is a 48-week multicentre, open-label ...trial in which HIV-infected adults with less than 50 copies/ml of plasma HIV RNA for at least the previous 6 months on ritonavir-boosted protease inhibitor-based therapy were randomized (1: 1) to switch from the ritonavir-boosted protease inhibitor to raltegravir or to continue on ritonavir-boosted protease inhibitor-based therapy. Primary endpoint was the proportion of patients free of treatment failure (noncompleter = failure) at 48 weeks. SPIRAL study was powered to show noninferior efficacy of raltegravir-based therapy with a margin of -12.5%.
Two hundred and seventy-three patients assigned to switch to raltegravir (n = 139) or to continue ritonavir-boosted protease inhibitor (n = 134) were included in the efficacy analysis. At 48 weeks, 89.2% (raltegravir-based therapy) and 86.6% (ritonavir-boosted protease inhibitor-based therapy) of the patients remained free of treatment failure difference 2.6%; 95% confidence interval (CI) -5.2 to 10.6. A total of 96.9% (raltegravir-based therapy) and 95.1% (ritonavir-boosted protease inhibitor-based therapy) of the patients remained free of virological failure (difference 1.8%; 95% CI -3.5 to 7.5). Switching to raltegravir was associated with significant decreases in plasma lipids and total-to-HDL cholesterol ratio relative to continuing ritonavir-boosted protease inhibitor. Severe adverse events and study drug discontinuations due to any adverse event occurred in 4 and 2% of the patients in each group.
In patients with sustained virological suppression on ritonavir-boosted protease inhibitor-based therapy, switching from ritonavir-boosted protease inhibitor to raltegravir demonstrated noninferior efficacy and resulted in a better lipid profile at 48 weeks than continuing ritonavir-boosted protease inhibitor.
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