Rui Marques

Fat Mass Ratio: An Objective Tool to Define Lipodystrophy in HIV-Infected Patients Under Antiretroviral Therapy

Human immunodeficiency virus (HIV) infection and its treatment with antiretroviral therapy (ART) have been associated with lipodystrophy. Different clinical methodologies have been used to define the syndrome. The aim of this study was to propose gender-specific reference values using objective measurements for defining lipodystrophy in HIV-infected patients. Using dual-energy X-ray absorptiometry (DXA), total body composition was analyzed in 221 HIV-infected patients under ART (146 men). We used fat mass ratio (FMR) as the ratio between the percent of the trunk fat mass and the percent of the lower-limb fat mass. One hundred forty patients (63.6%) presented clinically defined lipodystrophy. In men, the optimal cutoff value for the FMR was 1.961 (area under the receiver operating characteristic curve [AUC]: 0.74 [95% confidence interval (CI): 0.66-0.82], p<0.001), with a sensitivity 58.3%, a specificity 83.7%, a positive predictive value (PPV) of 89.6% and a negative predictive value (NPV) of 45.5%. In women, the optimal cutoff value for the FMR was 1.329 (AUC: 0.74 [95% CI: 0.63-0.86], p<0.001), with a sensitivity 51.4%, a specificity 94.6%, a PPV of 90.5%, and an NPV of 66.0%. The FMR evaluated by DXA with the gender-specific cutoffs defined here is an objective way to define HIV-related lipodystrophy.

Impact of Lipodystrophy on the prevalence and components of metabolic syndrome in HIV-infected patients.

BackgroundIn HIV-infected patients, combination antiretroviral therapy (cART) is associated with clinical lipodystrophy (CL) and metabolic abnormalities (MA). This study aimed to evaluate the prevalence of the metabolic syndrome (MS) and its components, and to determine whether patients with or without CL had a different prevalence of MA.MethodsWe evaluated 345 HIV-infected patients on cART using two different MS definitions (NCEP-ATPIII-2005 and IDF-2005) and the Framingham risk score.ResultsCL was present in 58.7% of the patients. The prevalence of the MS was 52.2% (ATPIII) and 43.2% (IDF), and it was not significantly different between patients with (W) or without (WT) CL, regardless of the definition used (ATPIII WCL 52.9% vs WT CL 51.1%; p = 0.738; IDF WCL 41.3% vs WTCL 46.0%; p = 0.379). Moderate concordance was observed between the 2 definitions (kappa = 0.484; p < 0.001) and after gender stratification there was good concordance in women (kappa = 0.759; p < 0.001). Patients with CL had lower waist circumference and HDL-C and higher triglycerides levels. In women, CL was significantly associated with MS, hypertriglyceridemia and low HDL cholesterol independently of age, cART and BMI. Patients with CL had a significantly higher risk of coronary heart disease at 10 years, measured by the Framingham risk score, than patients without CL. Those with CL and with MS had higher frequencies of moderate and high risk categories than those without MS.ConclusionsThe prevalence of the MS was high in these HIV-infected patients with an age average of 40 years and this finding could explain why HIV patients have an increased risk for cardiovascular disease (CVD).

Assessment of body fat composition disturbances by bioimpedance analysis in HIV-infected adults

HIV-lipodystrophy syndrome is characterized by different patterns of body fat distribution (BFD) which are identified by clinical and body composition (BC) assessment, including bioimpedance analysis (BIA). Our aim was to compare BC in HIV-infected patients on combination antiretroviral therapy (cART) according to 4 distinct phenotypes of BFD (G1-no lipodystrophy, G2-isolated central fat accumulation, G3-lipoatrophy, G4-mixed forms of lipodystrophy) and assessed factors associated with them. Anthropometry and BIA were performed in 344 HIV-1 patients. G2 and G4 phenotype patients had significantly higher fat mass (FM) but no differences were observed in fat-free mass (FFM) and total body water among the 4 phenotypes. Significant negative associations were found between the presence of lipoatrophy and female gender, body mass index (BMI), waist (WC), hip (HC) and thigh circumferences, and total body FM estimated by BIA. After adjustment for gender, cART duration and BMI, G3 had significant lower WC [odds ratio (OR)=0.84; 0.78–0.90] and HC (OR=0.88; 0.81–0.96) mean. Independently of gender, cART duration and BMI, G2 remained significantly associated with higher WC (OR=1.11; 1.05–1.18) and HC (OR=1.15; 1.07–1.23) mean, and with FM estimated by BIA [FM as %, OR=1.17 (1.09–1.26); and FM as kg, OR=1.15 (1.06–1.25)]. There was a significant positive association between G4 and female gender (OR=1.66; 1.01–2.75), BMI (OR=1.10; 1.04–1.17) and WC (OR=1.15; 1.09–1.21). The similar FFM along the BFD spectrum describes the actual BC of these patients without sarcopenia. In a clinical setting, BIA is an easy and useful tool to evaluate fat mass and FFM and gives us a picture of BC that was not possible with anthropometry.

Prevalence of obesity and its relationship to clinical lipodystrophy in HIV-infected adults on anti-retroviral therapy.

Background: Combination antiretroviral therapy (cART) is associated with lipodystrophy (lipoatrophy and lipoaccumulation) and several metabolic abnormalities that together can contribute to an increased cardiovascular risk. The aim of this study was to evaluate the prevalence of obesity in patients on cART according to the presence of clinical lipodystrophy (CL) and to analyze factors associated with obesity. Methods: We evaluated 368 HIV-infected adults on cART. Results: CL was present in 59.0%. Independently of gender, patients with CL were more frequently underweight [5.7% (21/368)] and of normal weight [47.3% (174/368)], and less frequently overweight [33.2% (122/368)] or obese [13.9% (51/368)]. Mean body mass index was higher in patients with abdominal prominence regardless of the presence of clinical lipoatrophy. Patients with CL had lower waist circumference, higher waist/hip and fat mass ratio and lower total and subcutaneous fat, without significant difference in visceral fat but with a higher visceral/subcutaneous fat ratio, as evaluated by CT at abdominal level. CL was significantly less frequent in overweight [odds ratio (OR)=0.21, 95% confidence interval (CI): 0.05–0.92] and obese (OR=0.05, 95%CI: 0.01–0.26) patients, when compared to underweight ones, independent of age, gender, duration of infection, cART regimen, virological suppression, and HIV-infection risk factor. Conclusions: Being overweight or obese is highly prevalent in HIV-infected patients on cART. Patients with CL were more frequently under- or normal weight, and less frequently overweight or obese. Obesity is a condition that should be considered in HIV patients on cART.

HIV-2 infection with a long asymptomatic period

We give details of a patient infected with HIV-2 which had what we believe to be the longest asymptomatic period so far reported. The infection was probably acquired though a blood transfusion in Africa 27 years ago. At present the patient remains asymptomatic and her cellular defence mechanisms, evaluated by CD+4 lymphocyte counts and hypersensitivity skin tests, are not severely compromised. HIV-2 has come distinct epidemiological, clinical and biological features which are different from the related HIV-1 and deserve investigation in order for its natural history to be better understood.

Population mobility and the changing epidemics of HIV-2 in Portugal

Portugal is the European country with the highest frequency of HIV‐2 infection, which is mainly concentrated in West Africa. The cumulative number of notified HIV‐2 infections in Portugal was 1813 by the end of December 2008. To better characterize the dynamics of HIV‐2 infection in the country and to obtain data that may be of use in the prevention of the spread of HIV‐2, we evaluated a large pooled sample of patients.

Reasons for treatment discontinuation in the first year after beginning antiretroviral therapy in a cohort of Portuguese HIV-infected patients

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

Factors associated with immune status in the diagnosis of HIV infection

Current guidelines recommend the start of antiretroviral therapy before advanced immunosuppression, which is not always possible. The purpose of this study is to evaluate factors associated with the degree of immunosuppression at the diagnosis of HIV infection.

Clinical and immunological presentation of new HIV-infected patients in an outpatient clinic

Results 311 new patients were observed (305 HIV-1 infected and 6 HIV-2 infected), with a mean age of 42 ± 13,7 years. 218 (70%) patients were men. Risk factor for HIV-infection was sexual in 271 (87%) patients (18% were homo-bisexual). At the time of diagnosis the mean CD4+ cell count was 333 ± 305 cells/mm3; 132 (42,4%) patients had CD4 cell count <200/mm. In 89 (28,6%) patients an AIDS-defining illness was diagnosed simultaneously with HIV-infection diagnosis; 43% of these were tuberculosis. After a mean follow-up of 15 ± 9,7 months 27 (8,6%) patients died, 24/27 (88,8%) with AIDS and the other 3 patients one each with eosophageal cancer, hepatic failure and MSSA sepsis,. In 22/27 (81,4%) of the deceased patients the CD4 cell count was <200 cells/mm at the time of the HIV diagnosis. Discussion In the last 3 years, 42% of the new diagnosed patients had a serious immunological deficit. In 28% of them HIV-infection was diagnosed simultaneously with a defining AIDS opportunistic infection. The fact that 81,4% of the deceased patients had a CD4 cell count <200/mm at diagnosis shows that HIV-infection diagnosis was done too late for ART to be of benefit.

Hospital admissions and associated diagnosis of HIV patients in the HAART era

of results 318 patients (approximately 20% of the patients followed at the clinic) were admitted, accounting for 521 admissions; 47.6% of them HIV-related. 227 (43.6%) admissions were due to AIDS opportunistic infections, 33 (6.4%) to AIDS-defining or non-AIDS-defining cancers, and 220 (42.2%) were due to non-opportunistic infections. 35 (6.7%) of the admissions were new HIV diagnoses (two acute HIV infections) and 25 (71.4%) of these were AIDS-defining conditions. Hepatic disase accounted for 33 (6.4%) of the total causes of admissions. Eight (1.5%) admissions were HAART-related (toxicity/tolerability). 221 (69.5%) of the admitted patients had been lost to follow-up at the outpatient clinic for >6 months and 239 (75.1%) had no/poor adherence to their HAART regimens. 85.1% of the patients who were under HAART >6 months (n = 47), were virologically suppressed. Mean CD4 cell count of admitted patients was 156 ± 178 cells/ mm3.