A randomized study comparing triple versus double antiretroviral therapy or no treatment in HIV-1-infected patients in very early stage disease: the Spanish Earth-1 study

BACKGROUND: Most current guidelines state that antiretroviral therapy should be considered for HIV-infected patients with plasma HIV RNA > 5000-10000 copies/ml and CD4 cells > 500 x 10(6) cells/l. However, there is increasing concern about whether this is the optimal point to begin treatment or whether it is better to delay the initiation to more advanced stages. OBJECTIVE: To study the immunological and virological benefits of starting antiretroviral therapy at these early stages. METHODS: A total of 161 HIV-infected asymptomatic patients with CD4 cell count > 500 x 10(6) cells/l and viral load > 10000 copies/ml were randomly assigned to one of five treatment groups: no treatment, twice daily zidovudine and thrice daily zalcitabine (ZDV-ddC), twice daily zidovudine and didanosine (ZDV-ddI), twice daily stavudine and didanosine (D4T-ddI), or a twice daily three-drug regimen with stavudine and lamivudine and ritonavir. The endpoints were progression to < 350 x 10(6) cells/l CD4 cells, to < 500 x 10(6) cells/l with either two Centers for Disease Control class B symptoms or an increase of viral load > 0.5 log10 copies/ml above baseline, or to AIDS or death. In various substudies, the lymphoid tissue and cerebrospinal fluid viral load, development of genotypic resistance, proliferative responses to mitogens and cytomegalovirus, and HIV-1 specific antigens and other immunophenotypic markers were also analysed. RESULTS: Progression rates to study endpoints within 1 year were greater in the control group (31%) than in all groups receiving antiretroviral therapy pooled together (5%; estimated hazard ratio 7.41; 95% confidence interval 5.72-74.55; P < 0.001). The peak mean viral load decrease was greater in the three-drug group when compared with any of the three groups with a two-drug regimen (2.32, 1.65, 1.72 and 1.84, respectively; P < or = 0.001). At 1 year, viral load remained below 20 copies/ml in 30 out of 33 patients in the three-drug group (91%) and in only eight out of 94 patients (9%) in two-drug groups (P = 0.001). The peak mean increase in CD4 cells was also greater in the three-drug group than in the double treatment arms (259 versus 85, 144 and 145 x 10(6) cells/l, respectively; P = 0.001). By comparison, 36% of patients in the three-drug group regimen had to change the therapy as a result of adverse events. Substudies were performed in 60 patients recruited at two sites. Tonsillar tissue HIV RNA was measured in seven patients (two in the two-drug groups and five in the three-drug group) in whom plasma HIV RNA was < 20 copies/ml at 1 year. It was 15151 and 133333 copies/mg tissue in the two patients from the two-drug group, < 40 copies/mg tissue in four patients in the three-drug group, and 485 copies/mg in one patient in the three-drug group. At 1 year there was a mean increase of 4.21+/-2.94% in CD8+CD38+ cells in the control group and a decrease of 9.48+/-3.36% in the two-drug groups (P = 0.01), and 19.87+/-3.64 in the three-drug group (P = 0.001 and P = 0.05, for comparisons with control group and two-drug groups, respectively). Although proliferative responses to cytomegalovirus antigens were significantly greater in those receiving antiretroviral therapy, response to HIV-1 p24 antigen was not detected in any patient in either treatment group. CONCLUSIONS: This study supports the recommendation to start antiretroviral therapy with a three-drug combination during very early stages of HIV-1 disease, at least if viral load is above a cut-off point (10000 copies/ml in our study). The risk of progression was sevenfold higher in non-treated patients at 8 months of follow-up. Some immune system parameters improved toward normal values after 1 year of antiretroviral therapy, but the proliferative response of CD4 T lymphocytes against the p24 HIV-1 antigen was not recovered. Therapeutic approaches with more potent, better-tolerated and more convenient regimens will increasingly favour early intervention with antiretroviral t     

Weight-Related Quality of Life in Spanish Obese Subjects Suitable for Bariatric Surgery is Lower Than in Their North American Counterparts: a Case–Control Study

Background

Obesity impairs quality of life, but the perception of the impairment could be different from one country to another. The purpose was to compare weight-related quality of life (QOL) between cohorts from Spain and North America.

Methods

A cross-sectional case–control study was performed between two populations. Four hundred Spanish and 400 North American obese subjects suitable for bariatric surgery closely matched for race, gender, age, and body mass index (BMI) were included. Two non-obese control groups matched for gender, age, and BMI from each population were also evaluated (n?=?400 in each group). The participants completed the Impact of Weight on Quality of Life—Lite (IWQOL—Lite) questionnaire, a measure of weight-related QOL.

Results

Spanish morbidly obese patients showed poorer QOL than their North American counterparts in physical function, sexual life, work, and total score. By contrast, Spanish non-obese control subjects reported better QOL in all domains than their North American counterparts. Women, both in Spain and North America, reported reduced QOL compared to men on the domain of self-esteem. In addition, North American women reported reduced QOL on the sexual life domain compared to men. BMI correlated negatively with all domains of QOL except for self-esteem in both national groups.

Conclusions

Spanish obese subjects suitable for bariatric surgery report poorer weight-related quality of life than their North American counterparts, and obese women, regardless of nationality, perceive a reduced quality of life compared to men.     

Gender inequalities in the medical profession: are there still barriers to women physicians in the 21st century?

Aim

To analyze women's advancement compared with that of men and to determine whether advancement in hierarchical status differs from advancement in the professional recognition achieved by women from 1996 to 2008.

Methods

A retrospective study was carried in Hospital Clínic in Barcelona. We analyzed data on temporary and permanent positions, hierarchy, promotions, specialty, age, and sex among the participants.

Results

The female-to male ratio among trainee medical specialists was higher than 1 throughout the study period. After completion of specialist training, the proportion of women with temporary contracts more than doubled that of men. Less than 50% of women achieved permanent positions compared with 70% of men. For permanent non-hierarchical and hierarchical positions, the female-to-male ratio gradually decreased from 0.5 to below 0.2. Although more than 50% of trainee specialists were women, the number of female consultants remained 25% lower than that of men. In 2008, the final year of the study, the percentage of women who had achieved the grade of senior consultant was one-third that of men (29.5% of men vs 10.9% of women; p < 0.0001).

Conclusions

The significant differences in medical positions held by men and women illustrate the ‘leaky pipeline phenomenon’, consisting of a disproportionately low number of women achieving leading medical positions. The full potential of the increasing number of women physicians will not be reached without continuing efforts to improve the hospital medicine environment.     

Focal segmental glomerular sclerosis in two patients with Addison's disease: any more than fortuitous development of glomerular disease?

Adjustment of the mineralocorticoid activity under substitution therapy is of primary importance in Addison's disease. We report the clinical and biological conditions of 2 patients with Addison's disease who developed nephrotic proteinuria during their deficient mineralocorticoid state. Renal biopsy was performed and the specimens processed using conventional histochemistry, Congo red staining, and indirect immunofluorescence. The renal biopsy specimens showed focal segmental glomerular sclerosis and nodular deposits of IgM and C3. Negative for Congo red staining. Serum complement, circulating immune complexes, and anti-DNA and hepatitis B and C and human immunodeficiency virus antibodies were all normal or negative. Absence of vesicoureteral reflux was assessed by X-ray studies. Our observations suggest that deficiency in mineralocorticoid substitution therapy inducing a status of hyperreninemia could play a role in the development of focal segmental glomerulosclerosis in patients with Addison's disease.     

Sample conservation prior to total EDTA and Fe(III)EDTA measurements

Ethylenediamine tetraacetic acid (EDTA) is a potent chelating agent and has the potential to affect the environmental mobility of heavy metals. A reliable quantification of EDTA and its speciation is required in order to accurately estimate the actual impact of this compound on the aquatic environment. This study aimed to determine the optimal conservation conditions for samples in order to accurately measure EDTA speciation and total EDTA concentration. The results obtained by studying the effects of time elapsed between sampling, conditioning [i.e., addition of reagents to complex EDTA with Fe (III)], and analysis show that the determination of EDTA speciation needs to be carried out immediately after sampling. The measurement of total EDTA may be performed within 2 mo, as long as the sample is filtered and conditioned on the day of sampling.