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Biomedical subjects

J Macías

Publications and source records attributed to J Macías.

At least 19 recordsLinked to original sources

Insulin resistance is not associated with liver fibrosis progression in HIV/hepatitis C virus-coinfected patients.

Insulin resistance (IR) is a common condition in chronic hepatitis C. Recent studies have reported that IR is associated with liver fibrosis progression in these patients. However, there is no information available on this issue in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. For these reasons, we investigate the relationship between IR and liver fibrosis in patients with HIV and HCV infections. This was a cross-sectional study where patients from an Infectious Diseases Unit with HIV/HCV coinfection who underwent a liver biopsy, with available frozen sera samples at the time of biopsy and a known or estimated date of infection were included. IR was determined by the homeostasis model assessment (HOMA-IR) method. The relationship between histological findings and several variables, including HOMA-IR values, was examined. Seventy-nine patients fulfilled the inclusion criteria. Age at HCV infection >21 years was the only variable independently associated with advanced liver fibrosis (stages F3 and F4) [adjusted odds ratio (AOR) 4.15; 95% confidence interval (CI) 1.5-11.3]. The variables associated with a fibrosis progression rate above the median were age at HCV infection >21 years (AOR 6.41; 95% CI 2.16-27.96) and previous exposure to nevirapine (AOR 8.9; 95% CI 2.01-39.36). There was no association between HOMA-IR values and the presence of advanced fibrosis or a faster fibrosis progression. Thus IR is not associated with liver damage or fibrosis progression in HIV/HCV-coinfected individuals.

Adult↗

Prediction of liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfected patients by simple non-invasive indexes.

BACKGROUND: Liver biopsy is an invasive technique with associated major complications. There is no information on the validity of five non-invasive indexes based on routinely available parameters, estimated and validated in hepatitis C virus (HCV) monoinfected patients, in human immunodeficiency virus (HIV)/HCV coinfected patients. AIM: To validate these predictive models of liver fibrosis in HIV/HCV coinfected patients. PATIENTS: A total of 357 (90%) of 398 patients from five hospitals were investigated, who underwent liver biopsy and who had complete data to validate all of the models considered. METHODS: The predictive accuracy of the indexes was tested by measuring areas under the receiver operating characteristic curves. Diagnostic accuracy was calculated by estimating sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. RESULTS: The models performed better when liver biopsies>or=15 mm were used as reference. In this setting, the Forns and Wai indexes, models aimed at discriminating significant fibrosis, showed PPV of 94% and 87%, respectively. Using these models, 27-34% of patients could benefit from exclusion of liver biopsy. If both models were applied sequentially, 41% of liver biopsies could be spared. The indexes aimed at predicting cirrhosis achieved NPV of up to 100%. However, they showed very low PPV. CONCLUSIONS: The diagnostic accuracy of these models was lower in HIV/HCV coinfected patients than in the validation studies performed in HCV monoinfected patients. However, simple fibrosis tests may render liver biopsy unnecessary in deciding anti-HCV treatment in over one third of patients with HIV infection and chronic hepatitis C.

Adult↗

[Prevalence of serum antibodies against Bartonella ssp. in a health population from the south area of the Seville province].

OBJECTIVE: To know the prevalence of serum antibodies against Bartonella spp. in a healthy population from south of Spain. PATIENTS AND METHODS: A clinical-epidemiological survey was conducted among 146 healthy individuals. An indirect immunofluorescence commercial technique was used in a sample of serum from each individual to detect the present of IgG type serum antibodies against Bartonella spp., considering a result equal to or greater than 1:128 as positive. RESULTS: Thirty six (24.7%) of all the subjects studied were asymptomatic carriers of antibodies against Bartonella spp. No crossed reactions against Chlamydia trachomatis, C. pneumoniae or Coxiella burnetti were observed. No significant association was found between the presence of seropositivity for Bartonella spp. and other factors. CONCLUSION: There is an elevated frequency of asymptomatic carriers of antibodies against Bartonella spp. among the healthy population of our area. This suggests that most of the infections by Bartonella are subclinical.

Adult↗

Relationship between osteopenia, free testosterone, and vitamin D metabolite levels in HIV-infected patients with and without highly active antiretroviral therapy.

The prevalence of osteopenia in HIV-infected patients is high. However, the mechanisms implicated in bone mass loss in HIV infection are unclear. Because of this, we analyzed serum free testosterone and vitamin D3 hydroxylated metabolites in HIV-infected patients, with and without antiretroviral treatment, and the relation between them and osteopenia. Seventy-four HIV-infected patients were selected because they had frozen sera available at a date close to a DEXA evaluation. Free testosterone, 25(OH)D3, and 1,25(OH)2D3 were determined in frozen serum. There were no differences in free testosterone, 25(OH)D3, and 1,25(OH)2D3 levels between patients with and without osteopenia. 25(OH)D3 levels in naive and HAART-treated patients were 26.2 (10.3-32.8) and 33.1 (20.6-46.8) ng/ml, respectively (p = 0.04). 1,25(OH)2D3 levels in naive and HAART treated patients were 60.3 (49.2-80.8) and 85.5 (68-111.6) pmol/liter (p = 0.01). Free testosterone levels in 9 naive men and in 50 HAART-treated men were 42.6 (24.1-67.3) and 69.2 (47.5-112.1) pmol/liter, respectively (p = 0.04). In conclusion, HIV-infected patients with and without osteopenia showed similar levels of vitamin D metabolites and free testosterone. However, antiretroviral drug-naive patients showed lower serum levels of vitamin D metabolites and free testosterone than HAART-treated patients.

Adult↗

Impaired recovery of CD4+ cell counts following highly active antiretroviral therapy in drug-naïve patients coinfected with human immunodeficiency virus and hepatitis C virus.

Coinfection with the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) is highly prevalent in southern Europe. However, there are few and contradictory data about the effect of HCV carriage on the response to highly active antiretroviral therapy (HAART). In this study, the recovery of CD4+ T cells following HAART among antiretroviral-naïve patients seropositive for HIV with and without HCV coinfection was investigated. Two hundred one HIV-infected patients without previous exposure to antiretroviral drugs were included in the study. HCV coinfection was detected in 123 (61%) patients. The time to recover 200 CD4+ cells/ microl was longer in the HCV-positive group ( P<0.001). In a Cox model, HCV infection and lack of persistent HIV viremia (defined as <200 copies/ml) were associated with the time to recover 200 CD4+ cells/ microl. The mean increase in CD4+ cell counts was lower in the HCV-positive group during the first year of therapy. HIV/HCV-coinfected patients naïve for antiretroviral therapy show a delayed recovery of CD4+ cell counts after starting HAART.

Adult↗

Influence of hepatitis C virus coinfection on failure of HIV-infected patients receiving highly active antiretroviral therapy to achieve normal serum beta2microglobulin levels.

The influence of hepatitis C virus (HCV) coinfection on the kinetics of serum beta2microglobulin levels in HIV-infected patients undergoing highly active antiretroviral therapy was analyzed. After 96 weeks of therapy, beta2microglobulin levels declined significantly both in 24 HCV seronegative and 16 HCV-infected individuals. Throughout the follow-up period, HCV-infected patients showed higher beta2microglobulin values than non-HCV-infected patients. These results show that HCV infection precludes immune deactivation in HIV-infected patients undergoing highly active antiretroviral therapy.

Antiretroviral Therapy, Highly Active↗

Mortality due to liver failure and impact on survival of hepatitis virus infections in HIV-infected patients receiving potent antiretroviral therapy.

The aim of the present study was to examine the causes of death, the mortality attributable to liver failure, and the impact of hepatitis virus infections on the survival of a cohort of HIV-infected patients before and after the extensive use of highly active antiretroviral therapy (HAART). Liver disease associated with hepatitis C virus (HCV) seems to be accelerated in patients infected with the human immunodeficiency virus (HIV). On the other hand, the effect of HCV on HIV progression was controversial before the introduction of HAART. However, the last study to report changes in mortality due to liver failure was published in 1997, and the impact of HCV carriage on the survival of HIV-infected patients receiving HAART needs to be clarified. In this investigation, 492 patients who were prescribed antiretroviral drugs between April 1989 and September 2000 were included in the study cohort. The median duration of follow-up of the cohort was 1,392 days. HCV infection was present in 323 (68%). Mortality attributable to AIDS decreased from 4.5 to 1.8 per 100 persons per year. Mortality due to liver failure increased from 0.3 to 0.5 per 100 persons per year ( P<0.01). The survival of patients with and without HCV infection was similar ( P=0.8). Although liver failure is an increasing cause of death among HIV-infected patients receiving HAART, HCV infection has still no impact on the survival of HIV-infected patients.

AIDS-Related Opportunistic Infections↗

The high sensitivity of a PCR-ELISA in the diagnosis of cutaneous and visceral leishmaniasis caused by Leishmania infantum.

In general, the conventional techniques available for the diagnosis of leishmaniasis have relatively low sensitivity. This means that parasite-rich samples (which can usually only be collected by very invasive methods, such as bone-marrow aspiration) must be employed. This problem has not yet been solved even by use of the PCR-based techniques currently available. However, a new PCR-ELISA has been developed for the diagnosis of cutaneous (CL) and visceral leishmaniasis (VL) caused by Leishmania infantum. This assay appears to have sufficient sensitivity to be effective in the diagnosis of VL not only when bone-marrow aspirates are investigated but also when the samples are of peripheral blood. Overall, the ability of the PCR-ELISA to detect Leishmania, in 76 samples (22 of peripheral blood, 36 bone-marrow aspirates and 18 skin samples) from 72 patients living in a endemic region, was better than that of culture or the examination of Giemsa-stained smears. For example, L. infantum kDNA was detected by PCR-ELISA in 15 (83%) of the 18 skin samples from suspected cases of CL, whereas the combined use of several classical techniques only confirmed the presence of amastigotes in five (28%) of these samples. Similarly, only 21 individuals were diagnosed as having VL by conventional techniques whereas 30 were found Leishmania-positive in the PCR-ELISA. The new PCR-ELISA also appears to be a suitable technique for detecting leishmanial kDNA in samples of peripheral blood from cases of L. infantum-HIV co-infection. The assay is more sensitive than the combined use of several conventional techniques in the diagnosis of subclinical VL, probably because those with subclinical infection have relatively low parasitic loads that are generally undetectable using the other techniques.

Animals↗

Structural normalization of the lymphoid tissue in asymptomatic HIV-infected patients after 48 weeks of potent antiretroviral therapy.

BACKGROUND: The hallmark of HIV infection is the involution and destruction of lymphoid tissue. However, very little information exists on the effect of highly active antiretroviral therapy (HAART) on lymphoid tissue structure. OBJECTIVE: To evaluate the effect of a HAART regimen after 48 weeks on the architecture and cell regeneration of tonsil lymphoid tissue in HIV-infected patients with CD4 T cell counts > or = 500/microl. METHODS: From June 1997 to February 1998 all asymptomatic HIV-infected patients with CD4 T cell counts > or = 500/microl seen at our unit were offered quadruple antiretroviral therapy. Tonsil biopsies were obtained at baseline and at 48 weeks. Tonsil tissue sections were examined to evaluate structural and immunohistochemical changes by two blinded and independent pathologists. Cell numbers were counted for selected markers in T-dependent zones. RESULTS: Eleven patients were evaluable, six were excluded because of insufficient or inadequate sampling in at least one of the biopsies. Cellular depletion, plasma cell accumulation and prominent vessels were observed in all cases; three excluded patients with evaluable baseline biopsies showed similar tissue lesions. Follow-up biopsies demonstrated some degree of improvement in all patients. Germinal centres appeared in seven cases that were not seen at baseline. CD4 cell counts increased and CD8 cell counts decreased significantly in lymphoid tissue. An increase in CD45RA+ cells was observed; however, the proportion of CD45+Ki67+ cells did not differ between baseline and 48 weeks. CONCLUSION: This study shows an unexpected range of moderate to severe lymphoid tissue lesions in mildly immunosuppressed HIV-infected patients, which was partly restored after 48 weeks of HAART.

Adult↗

Influence of highly active antiretroviral therapy on the outcome of subclinical visceral leishmaniasis in human immunodeficiency virus-infected patients.

Seventeen human immunodeficiency virus-infected patients who were harboring untreated subclinical visceral leishmaniasis (VL) were prospectively followed up. None of the 11 patients who received highly active antiretroviral therapy (HAART) presented with symptomatic VL during follow-up, whereas 2 out of 6 patients who received therapy other than HAART had an episode of overt kala-azar. These findings suggest that HAART does not induce the evolution of latent VL into symptomatic disease.

AIDS-Related Opportunistic Infections↗

Evidence of increased risk for leishmania infantum infection among HIV-seronegative intravenous drug users from southern Spain.

To assess the prevalence of markers of Leishmania infection, 93 intravenous drug users and 77 nonusers of intravenous drugs underwent a Leishmania skin test and a serum Leishmania antibody search. All participants were human immunodeficiency virus seronegative. The Leishmania skin test was positive in 24 intravenous drug users and in 10 non-users of intravenous drugs (P=0.038). Leishmania seropositivity was detected in 3 of 11 active intravenous drug users and in 3 of 82 former drug injectors (P=0.02). Positivity in the Leishmania skin test was associated with intravenous drug use (adjusted odds ratio, 2.33; 95% confidence interval, 1.03-5.24). The prevalence of Leishmania infection markers among intravenous drug users is higher than that among controls. This suggests that this parasite spreads through the sharing of needles.

Adult↗

HIV-1 plasma viremia not increased in patients receiving highly active antiretroviral therapy after influenza vaccination.

The effect of vaccinating patients with sustained undetectable HIV-1 viremia (VL) achieved with highly active antiretroviral therapy was prospectively investigated. During the 1998 influenza immunization period, 39 HIV-1-infected patients who showed a VL<20 copies/ml for at least 6 months before the study entry date were vaccinated for influenza. Twenty-two vaccinees were immunized at entry. Seventeen controls were followed for 4 weeks after entry, crossing over then to the vaccination group. The proportion of patients with undetectable VL was not significantly different between the vaccination and control groups 2 and 4 weeks after entry. Therefore, influenza immunization of patients with undetectable viremia achieved with highly active antiretroviral therapy does not seem to affect VL.

Adult↗

Usefulness of route of transmission, absolute CD8+ T-cell counts, and levels of serum tumor necrosis factor alpha as predictors of survival of HIV-1-infected patients with very low CD4 + T-cell counts.

Potential cofactors of survival in HIV-1-infected patients with CD4+ T-cell counts of < or = 100 cells/microl were investigated. All 132 patients with CD4+ T-cell counts of < or = 100 cells/microl were selected from 416 patients included in an antiretroviral therapy cohort (1989-1999). Fifty of 54 deaths were due to AIDS. There were significant associations (P<0.05) between survival and CD8+ T-cell counts, clinical AIDS stage, risk group, and antiretroviral drug regimen after baseline, but only the use of protease inhibitors had an independent effect on survival (hazard ratio [HR], 0.096; 95% confidence interval [95%CI], 0.094-0.097). A substudy restricted to the cohort of 108 patients never exposed to PIs detected independent associations between survival and CD8+ T-cell counts (P=0.0016), experience with antiretroviral therapy before baseline (HR, 2.52; 95%CI, 1.31-4.82), sexual risk group for HIV infection (HR, 3.7; 95%CI, 1.92-7.12), and levels of serum tumor necrosis factor alpha (P=0.02). This study confirms that the use of PI-containing antiretroviral regimens strongly predicts survival of HIV-1-infected patients with very low CD4+ T-cell counts. When the study was restricted to patients never exposed to PIs, the parenteral route of disease transmission, high absolute CD8 + T-cell counts, and low serum levels of tumor necrosis factor alpha were independent predictors of survival in extremely advanced HIV-1 disease.

Acquired Immunodeficiency Syndrome↗

Minimal liver injury in chronic hepatitis C virus infection is associated with low levels of soluble TNF-alpha/Fas receptors and acquisition in childhood.

BACKGROUND/AIMS: The rate of progression to cirrhosis of chronic hepatitis C might be related to an upregulation of TNF-alpha/Fas pathways. METHODS: The serum levels of soluble TNF-alpha type II receptor (sTNFr-II) and soluble Fas antigen (sFas) were analyzed in patients with different histological outcomes of chronic parenterally acquired HCV infection of similar duration. RESULTS: One hundred and forty-five HCV-infected patients had a known duration of infection. Twelve (8.3%) patients had minimal changes and were assigned to the case group. The control group was selected from the 24 (17%) patients with cirrhosis and the 54 (37%) with chronic active hepatitis (CAH). Two controls, one with CAH and one with cirrhosis, were paired with the cases following these criteria: duration of infection, transmission route and sex. The proportions of genotype 1b and HCV RNA serum levels were similar among the groups. The median serum levels of sTNFr-II and sFas were significantly lower in the case group than in the control groups. The cases were significantly younger when they became infected than the control groups. Indeed, most cases were infected within the first 10 years of life. sTNFr-II and age at infection were independently associated with the minimal injury case group. When sTNFr-II was excluded from the logistic regression model, sFas and age at infection were independently associated with the case group. CONCLUSION: The rate of progression of parenterally acquired chronic hepatitis C to end-stage liver disease might be related to an upregulation of the TNF-alpha/Fas pathways and an age-dependent host response.

Adolescent↗