AIDS

Author: GARCÍA DE LA HERA MANUELA.
Year: 2003.
University: MIGUEL HERNÁNDEZ DE ELCHE.
Place of defense: MEDICINA.
Place of preparation: FACULTAD DE MEDICINA, DPTO. DE SALUD PÚBLICA.

Summary: REASONS AND PURPOSE Over the years, the number of women with AIDS has grown, taking a clear reflection of this in our country, where the consequences of drug use and injecting risk heterosexual relations within and outside the exercise on prostitution, are responsible for most cases of AIDS in women. Moreover, research shows increased vulnerability of women to HIV infection. The goal we considered in this dissertation is to determine gender differences in HIV disease, the risk of acquiring infection until his profresión to AIDS and death, and identify the factors that might explain these differences. METHOD For the four papers presented in this thesis has been used two methodologies: a cross design (in a job) and two prospective cohort studies (one of women working as prostitutes in Alicante and another injection drug users in the Community Valencia). In the cross-sectional study we used descriptive analysis and reagresión logistics, and the tracking perform logistic regression and survival analysis with the techniques as appropriate curves Kaplan Meire and Cox regression to see the factors associated with over time. RESULTS Women injected drug users (IDUs) in a cohort of UDI of the Valencia couple have a 71% versus 50% of men. Women tenína more prejas UDI when compared to men (OR = 7.86, 95% CI :5.66-10 .9), and HIV + couples compared to men (OR = 7.73, 95% CI :6.00-9 .96). We found no significant differences by gender in the use of health services among IDUs. Women have a lower risk UDI Aids in the multivariate analysis (HR 0.73 95% CI :0.52-1 .03). The risk of death was lowest among women compared with men (HR 0.67 95% CI :0.45-0 .99). Of the women who work in prostitution, the prevalence of condom use during the last visit was greater than in the first (84% versus 69%). CONCLUSIONS Women UDI in Alicante have not changed their patterns of sexual behavior in a comprehensive manner over the period 1986-1996 and that still more couples UDI and / or HIV infection than men. We found no gender differences in access and use of services among drug users HIV +. Among users injecting drugs, the progression to AIDS and death from serconversión HIV was lower in women compared to men. Women working in prostitution and who come more than once to the Center for Information and Prevention of AIDS (CIPS) of Alicante, have spoken favorable changes in condom use. These changes could be explained in part by the effectiveness of the council, training in the use and negotiating skills.

Author: JIMÉNEZ EXPÓSITO M. JESÚS.
Year: 2003.
University: ROVIRA I VIRGILI.
Place of defense: MEDICINA.
Place of preparation: UNIVERSIDAD ROVIRA I VIRGILI.

Summary: INTRODUCTION The changes in nutritional status represent an important aspect of HIV / AIDS, which contributes to increased morbidity and mortality. The involuntary weight loss is a common complication in the course of the same, especially in advanced stages, and its etiology of multifactorial origin, the result of interactions between alterations in the apaorte caloric and energy metabolism, although neither the contribution of each these factors and their interrelationships are sufficiently established. Studies on energy expenditure in HIV-positive individuals offered contradictory results, discrepancies may relate to the presence of factors such as malabsorption, capable of changing the energy balance. On HIV / AIDS the presence of malabsorption is a common event, although their influence on energy balance, as well as their contribution to the nutritional disturbances and loss d epeso have not been sufficiently investigated. Nutritional status has been implicated in the progression of the disease. Several micronutrients are involved in maintaining a proper balance prooxidante-antioxidante, with a deficit of the same prevalent in HIV / AIDS, which affects an increase of oxidative stress involved in viral replication, immune deterioration and loss weight. MATERIALS AND METHODS We studied a total of 50 individuals with HIV / AIDS documented, classified into three groups: Group 1 (n = 17), asymptomatic HIV-positive, Group 2 (n = 16), AIDS without opportunistic infection; and Group 3 (n = 17), AIDS opportunistic infection. It established a control group (n = 19) in healthy volunteers. In all individuals were identified: 1-anthropometric measures. 2, body-composition through impedance bioeléctrica tetrapolar. 3 - resting energy expenditure, by indirect calorimetry in open circuit. 4-Test Absorption Absorption of fat through the breath test with trioleína checked, and carbohydrate absorption after oral D-xilosa overload. 5-plasma concentrations of vitamin E, copper and zinc, as well as various inflammatory parameters (markers and mediators of inflammation). RESULTS There was an affectation of nutritional status with alteration of anthropometric and biochemical parameters. The 86% (n = 43) of individuals with HIV / SIDa had lost weight compared to normal, generally rank leve-moderado (average 12.77%), while a 14% showed severe losses (increased 20%). Weight loss was more prevalent and severe in the presence of opportunistic infection (average weight loss of 17.06%), while a 76% of asymptomatic HIV-positive individuals had weight loss, with heavy losses in the 6 %. Analysis of body composition showed respect to the control group, significant reductions in the estate free tier in the three groups of patients (p less 0.01 Group 1, p less 0.05 Group 2, p less 0001 Group 3) and values lower fat mass in all three groups, although with significant differences only in individuals of the Group 1 and 3 (p less 0.05 and p less 0001, respectively). Of the total number of individuals infected with HIV / AIDS, 28% (n = 14) and 12% (n = 6) respectively, values presented below reference ranges for vitamins A and E. The prevalence of vitamin A deficit increased with the evolutionary stage of the disease (18% Group 1; 25% Group 2 and 41% in group 3), while the deficit of vitamin E was similar in all three groups (12% Group 1 ; 13% Group 2 and 12% Groups 3). Compared 8 with the G 19ae rupo control, the deficit Zn was more prevalent in patients [34% vs. 11%, p less 0.05], with the prevalence increases with disease progression [24% Group 1 ; 31% Group 2 and 47% Group 3]. Instead, the deficit of Cu was less prevalent in pacietnes than in controls [10% vs. 21%, NS], with a prevalence rate even lower in advanced stages. Regarding the control group, the plasma smedias vitamin concentrations were significantly lower in patients (p less 0001 for vitamins A, p less 0.05 for vitamin E), with no difference between groups, except for concentrations of vitamin E, whose values subject Group 2 were lower regard to the Group 3 (p less 0.05). Serum concentrations of Cu were higher in the three groups of patients (p less 0.05 for Group 1; NS for the Group 2; p lower 0001 for group 3), with concentrations significantly superores in individuals Group 3 respect to the subject Group 2 (p less 0.05). In all patients the vitamin A was negatively correlated with C-reactive protein (r = -0.31%, p less 0.05). Both the resting energy expenditure measured (determined by indirect calorimetry) and the estimate (calculated from the equation Harris), were significantly lower in patients with respect to controls (p less 0.01 and p less 00001 respectively). The resting energy expenditure measured fuer lower in the three groups of patients, with values significantly descended in individuals with AIDS opportunistic infection (5861.6 +-932.1 kJ / d compared with 6802.1 +-862.7 kJ / d , p less 0.01). With regard to the control group, in absolute terms, the resting energy expenditure measured showed declines of 8% in individuals of the Group 1 and 2, and 14% in Group 3, while expressing such parameters as a percentage of the estimate is no significant increases observed in the three group s (5%, 2% and 3% for group 1, 2 and 3 respectively), with no difference between them. The resting energy expenditure adjusted for fat-free mass (obtained after adjusting the values of resting energy expenditure by differences in body composition), compared with the control group was not significantly higher in the three groups of patients (increases 4%, 2% and 1% for group 1, 2 and 3 respectively). The resting energy expenditure adjusted showed no significant differences between groups, although like the measured values presented below in individuals Group 3 (declines of 3% compared with Group 1, and 1% from Group 2). The presence of malabsorption (alteration of one or both tests conducted absorption), was demonstrated in 34 (68%) individuals with HIV / AIDS: 9 (53%) of Group 1, 11 (69%) of Group 2, 14 (82%) of Group 3. Of the total number of individuals with malabasroción, 27 (54%) had malabsorption of carbohydrates and 21 (42%) malabasorción to fat, with a significant correlation between parameters of absorption and weight loss. In the presence of malabasorción, measured resting energy expenditure was significantly lower (6006.3 +-846.5 kJ / d compared with 985.5 kJ / d in patients without malabsorption, and 6802.1 +-862.7 kJ / day, individuals in the control group, p less 0.05), while the adjusted resting energy expenditure was less than that observed in individuals without malabsorption, and higher than shown in the control group, but no significant differences. CONCLUSIONS Individuals with HIV / AIDS show affectation nutritional status with impaired anthropometric and biochemical parameters, indicating the existence of a protein malnutrition severity of which increased with progression of the disease, especially in the presence of opportunistic infection. At the same time, demonstrate alterations of body composition since early stages of the disease, but with a different allocation of lean and fat compartments depending on the evolutionary, sex and the presence or absence of malabsorption. The shortage of micronutrients are prevalent in individuals with HIV / AIDS even in the early stages of the disease. Plasma concentrations of some micronutrients, as well as visceral proteins associated with the inflammatory response, so that they could respond more to the situation in which inflammation at the same nutritional status, limiting the usefulness of such parameters as markers of the same, especially in the presence of opportunistic infection. The hipermetabolismo is not a constant phenomenon in the course of infection by HIV / AIDS, with the metabolic status of the subjects variable regardless of evolutionary stage. Moreover, the moderate increase in the adjusted resting energy expenditure, next to the same decline seen in the presence of weight loss, and the lack of correlation between energy expenditure and weight loss suggest that the hypermetabolic response may not be sufficient to explain the the degree of weight loss and nutritional deterioration observed especialmetne in advanced stages of the disease, which suggests the influence of other factors, such as the presence of malabsorption. The presence of malabsorption conditions greater alteration of nutritional status, while exercising a modulatory effect on energy expenditure, and therefore, the factor that would explain the melnor degree of hipermetabolismo observed in our patients, especially in the presence of opportunistic infection. The decrease in resting energy expenditure observed in the presence of malabsorption indicates that individuals with HIV / AIDS show, in situations of energy deficit, a solution aimed at maintaining metabolic energy balance and preserve the body weight. However, this decline is probably insufficient, which would generate a stadium in hipermetabolismo relative and therefore a disbalance between calorie intake and energy intake, leading to a progressive loss of weight.

Author: MARTIN CARBONERO LUZ.
Year: 2004.
University: COMPLUTENSE DE MADRID.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: MEDICINA COMPLUTENSE.

Summary: Since 1996 has been introduced in HIV + patients Potent Antiretroviral Treatment (TAP). Ifsto has been a drastic reduction of morbidity and mortality in this. Population. In addition, diseases that appear frequently in HIV + patients, as the virus of hepatitisC (HCV) are taking a new prominence. This thesis consists of two parts that assess different aspects of coinfection VIH-VHC. The first part evaluated the impact of chronic liver disease (HC) as a cause of hospitalization and death in patients infected with HIV. It picked up all the reports of high HIV + patients admitted to the Hospital Carlos III from January 1996 to December 2000. We evaluated a total 1336 income fell to 875 patients. It was noted that the percentage of income by HC in these patients increased from 9.4% in 1996 to 16% in the year 2000. The percentage of deaths by HC rose even more, from 10% in 1996hasta45% in the year 2000.Desde 1997la primeracausade death in HIV + patients was the HC. Three quarters de-los income or cause deaths were due to liver HCV. The second part assesses factors that relate to a greater degree of liver injury in patients co-infected with HIV and HCV. It designed a retrospective multicenter European study, which included a total of 914 patients. All of them have had a liver biopsy done in the last 10 years. It was noted that 1 / 3 of patients had advanced liver fibrosis and cirrhosis in the biopsy, and this percentage increased with age (46% older than 40 years). Other factors associated with a greater degree of liver fibrosis were cop.sumode alcohol and immunosuppression (less than 500 CD4 lymphocytes at the time of liver biopsy).

Author: Hidalgo Estévez Alicia María.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: Centro de Biología Molecula "Severo Ochoa".
Place of preparation: Centro de Biología Molecular "Severo Ochoa".

Summary: The Tat protein of HIV-1 affects the expression of cellular genes by modulating the activity of transcription factors. We studied the role of Tat in the cooperation of transcription factors NFAT (Nuclear Factor T cells Activadas) and AP-1 (Protein Activadora 1). The Tat expression in T cells increased the dependent transcription of a elmento compound NFAT/AP-1 regardless of their ability to transactivar the viral promoter. Furthermore, the intracellular expression of the union of Tat rose complexes NFAT/AP-1 the promoter of interleukin 2. Tat interact with NFAT but not with AP-1, affect the cooperation of both transcription factors. The transient expression increased the activity of Tat domain transactivation amino-terminal of NFAT, mapeándose this functional interaction in the first 144 amino acids. Tat cooperates with the kinases Cot, PKC-zeta and NIK, with the phosphatase calcineurin and the coactivador CBP/p300 in this increase. In addition, cells expressing Tat presented less stable expression in surface receptor quimioquinas and correceptor HIV-1 CXCR4 in the presence of fetal bovine serum, but the transcript of this receiver. Tat umenta internalization of CXCR4 in the presence of ligand SDF-1, modulating its expression in T cells

Author: ARMAND-UGÓN RODRÍGUEZ MERCEDES.
Year: 2005.
University: AUTÓNOMA DE BARCELONA.
Place of defense: FACULTAT DE MEDICINA.
Place of preparation: FUNDACIÓ IRSICAIXA, HOSPITAL GERMANS TRIAS I PUJOL.

Summary: The glycoproteins gp120 and gp41 of HIV-1 mediate entry of the virus into the cell to interact with target molecules that act of cellular receptors for the virus. Both are complex, being gp120 is the subunit of the same gp41 the surface transmembrane. At the start of the inning, gp120 is absorbed in the cells, facilitating their subsequent interaction with specific receptors. The adsorption of specific viral particles to the cell it has been found that molecules of heparan sulfate play a role attractive. The cellular molecules that followed the entry of HIV-1 are primarily receptor type immunoglobulin CD4 and two correceptores CCR5 and CXCR4, which are cell receptors for chemokines. Interfere with this step of viral cycle is an interesting attempt at extending therapy antirretrovial today. Prior to its development for the clinical application, it is necessary to know the mode of action of a compound. HIV-1 saves barriers to replication because of their great genetic variability selected viruses resistant or less sensitive to the selective pressure. This selective pressure can come in the form of a compound inhibiting replication, and the virus may have a selected replicative capacity or biological effectiveness different from the virus sensitive to the compound. Using different methods, has been carried out the study of the mechanism of action of three compounds. Two of them nature peptide (T-20 and C34) and a third in nature polianiónica (ADS-J1). All of them were designed to interfere with the function of the gp41 of VHI-1. T-20 is a peptide that has developed as a drug and is the first fusion inhibitor has been approved for clinical application. C34 and ADS-J1 seemed to have its antiviral activity depends on its ability to interact with a region of cavities in gp41 highly conserved in HIV-1. This region in gp41 is a very interesting pharmacological target because it has been described that certain mutations in this region originate with a capacity infectious virus defective. Much of the conclusions of this study are based on the study of drug-resistant virus we have selected in vitro, and we have seen that the mutations that confer resistance these inhibitors are located in gp120 and gp41. We deduced that the inhibitory potency of T-20 and C34 is conditioned by residues located in the same region of gp41. On the other hand, ADS-J1 shown to be active by inhibiting the entry interfering with the function of gp120 and not that of gp41. Our results indicate that ADS-J1 would inhibit the entry of both adsorption to the cell and at the level of interaction with the correceptor. We wonder what impact on the biological effectiveness of a virus may be the selection of resistance mutations compounds fusion inhibitors. AMD3100 is the prototype molecule receptor antagonist CXCR4 blocking the entrance viruses that use this correceptor to infect the target cell. Based on couples virus resistant wild and AMD-3100, it has become a comparative study of the replicative capacity of each virus. In the three couples studied virus, the virus resistant AMD3100 shown to have a lower replicative capacity that the wild virus. In summary, the study of mutations that confer resistance to one compound is a useful tool for determining the molecular target. Despite initial expectations, the conserved region of the cavities in gp41 is not essential for the inhibition by C34. Nor are the target of ADS-J1. The decline in the effectiveness of biological viruses resistant fusion inhibitors brings a positive perspective to the increased participation of such inhibitors in the clinic.

Author: Bosch Pagès Berta.
Year: 2006.
University: AUTÓNOMA DE BARCELONA.
Place of defense: Facultad de Medicina.
Place of preparation: Fundació irsiCaixa. Hospital Universitari Germans Trias i Pujol.

Summary: The transmission of HIV-1 between cells is one of the most efficient mechanisms of spread of the virus. The cell contacts between cells infected with HIV-1 and CD4 + T cells not infected can trigger the formation of sincitios, cell death by apoptosis target or transfer of viral antigens through the synapses virological. In this study, we have characterized the dynamics of the transfer of antigens of HIV-1 between T cells, we have identified cellular mechanisms involved in this process and the fate of viral antigens transferred. The mechanism of transfer of HIV-1 was completely dependent on the interaction of gp120 with the receptor CD4, expressed on the surface of effector T cells infected with HIV-1 and CD4 + T cells target, respectively. The absence of correceptor appropriate or blocking the process of merger or reverse transcription did not prevent the transfer of viral antigens, suggesting that the binding of gp120 with CD4 was the only stage of the replication cycle of HIV-1 strictly necessary for the antigen transfer of HIV-1 among cells T. The target cells were observed polarization receptor CD4 to the region where subcellular antigens of HIV-1 were transferred. In addition, a functional actin cytoskeleton of needed for the transfer of these antigens. The analysis by electron microscopy of lymphocytes tissues showed the presence of particles comprehensive HIV-1 in intracellular vesicles, revealing that a process endocítico could participate in the transfer of HIV-1 among cells T. In this aspect, was identified endocytosis dependent clatrina as the route endocítica involved in this process. Most of the antigens in HIV-1 internalized the target cells not colocalizaban with Lamp1, marker route lysosomal degradation, suggesting that the viral particles were not degraded internalized compartments Lamp1 positive. In fact, the antigens of HIV-1 captured were subsequently released as infectious viral particles. Using immature dendritic cells infected with HIV-1 as effector cells, it was also observed that the interaction gp120-CD4 was the only stage strictly necessary for the transfer of antigens of HIV-1.