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Biomedical subjects

J Castilla

Publications and source records attributed to J Castilla.

At least 73 records · Page 4Linked to original sources
PubMed1997

Short-term efficacy and safety of stavudine in pretreated HIV-infected patients.

Most of the information available on stavudine (d4T) comes from studies in patients with advanced human immunodeficiency virus (HIV) disease to whom stavudine was administered as monotherapy. Herein, we summarize the results of adding 40 mg stavudine twice daily to previous therapies in patients with mild to advanced immunological disease (mean CD4 T cell count 178 cells/mm3; range 6-480 cells/mm3). In an intention-to-treat, prospective, open trial, 64 patients (84.4% men; mean age 35.2 years) were analysed. Their average time on previous antiretroviral therapy was 19.8 months (range 6-52). Plasma HIV RNA load fell by a mean of 0.64 and 0.74 log at 1 and 3 months, respectively, after the start of stavudine therapy (P <0.001 Sign rank test). The CD4 cell count increased by a mean of 25.1 cells/mm3 in the third month (P = 0.002 Sign rank test). Antiviral activity was independent of the CD4 cell count at baseline, but more pronounced declines in viral load were seen in patients with shorter periods of previous antiretroviral therapy and in those in whom stavudine was combined with didanosine or lamivudine rather than zidovudine. Ten (15.6%) patients discontinued the drug during the first 6 months of treatment because of the development of toxicity (neuropathy in six cases, hepatitis in two, oedema in one and rash in another); all but one of them had CD4 counts < 200 cells/mm3. Another two patients stopped treatment voluntarily. The remaining 52 patients tolerated the drug well for the first 6 months and had a high level of compliance with treatment. In conclusion, stavudine is generally well tolerated and has significant antiretroviral activity when it is administered to patients with extensive previous treatment with multiple reverse transcriptase (RT) inhibitors. It should be expected that the short-term favourable effects of stavudine on laboratory markers will further translate into a reduced progression of disease and improved survival.

Adult↗
PubMed1997

Influence of time and storage conditions on plasma HIV viral load measurements.

Quantification of human immunodeficiency virus (HIV) RNA in plasma from HIV-infected patients is now widely used as a clinical indicator of disease prognosis and of response to antiretroviral therapy. However, controversy exists as to whether values obtained under different testing conditions could vary significantly, thus jeopardizing the appropriate interpretation of data. Herein, we demonstrate that results obtained after testing plasma versus whole blood, or immediate versus deferred processing, do not appear to influence viral load measurements significantly. Thirty blood samples from HIV-infected patients were analysed. The second generation branched-DNA assay was used for quantification of plasma viral load. HIV RNA remained stable for at least 24 h at room temperature, either in plasma or in whole blood, in 72.4% of the samples (< 0.2 log difference in viral load values) although lower levels of HIV RNA tend to be seen in samples after being stored as whole blood at room temperature. Only 3.4% of samples showed a decline > 0.5 log when they were left as whole blood at room temperature for 24 h in comparison with testing after immediate plasma separation. Although immediate separation and refrigeration of plasma samples may reduce the chance of significant falls in viral load measurements, this level of processing can be limited in regions where clinical blood samples cannot be processed rapidly. Our data provide confidence in the results obtained when testing specimens, either plasma or whole blood, 24 h after venepuncture and storage at room temperature, mimicking the conditions in the transport of blood samples to reference centres.

Blood Specimen Collection↗
PubMed1997

Influence of hepatitis C virus genotypes and HIV infection on histological severity of chronic hepatitis C. The Hepatitis/HIV Spanish Study Group.

OBJECTIVES: The factors influencing the histological severity of chronic hepatitis C (CHC) have not been well established. We therefore investigated the effect of hepatitis C virus (HCV) genotypes and human immunodeficiency virus (HIV) infection on histological liver damage in a cohort of intravenous drug users with CHC. METHODS: We analyzed the histological activity score and the HCV genotypes in 59 HCV-RNA-positive patients with biopsy-proven CHC. Forty-eight (81%) of them had concomitant HIV infection with a CD4+ cell count above 200 x 10(6) cells/L and an absence of AIDS-defining conditions. Multivariate analysis was performed to determine the features associated with the histological severity. RESULTS: Minimal/mild hepatitis was found in 16 patients (27%), moderate chronic hepatitis in 29 (49%), and severe chronic hepatitis in 14 (24%). Patients with HCV subtype 1b had a higher histological score than others (8.7 +/- 3.3 vs. 6.5 +/- 3.2, p = 0.012), either as single or mixed infections. In multivariate analysis, HIV-infected individuals had a higher score of piecemeal necrosis (OR = 21.7, p = 0.002) and a higher stage of fibrosis (OR = 17.9, p = 0.004) than patients without HIV infection. HIV infection and HCV genotype 1b were found to be independent factors of histological severity. CONCLUSIONS: Liver damage in patients with CHC seems to be directly influenced by HCV subtypes. Infection by HCV subtype 1b is closely associated with more severe forms of liver pathology. Furthermore, the presence of HIV infection is an independent factor associated with more aggressive histological damage. In these patients, higher degrees of piecemeal necrosis and fibrosis are commonly seen.

Adult↗
PubMed1997

[Quantification of viremia in patients infected with human immunodeficiency virus with different degrees of immunosuppression].

BACKGROUND: Many of the therapeutical decisions related to patients infected with human immunodeficiency virus (HIV) are taken considering the CD4+ lymphocyte count. The recent availability of procedures which quantitate the number of viral particles in peripheral blood has disclosed that viremia degree is the best predictor of HIV disease progression. Nevertheless, the proportion of subjects who despite a normal CD4+ lymphocyte count, have a high viremia and a high risk of short term progression to AIDS is not well known. PATIENTS AND METHODS: Plasma viremia was investigated in 120 adults subjects with a known time of HIV infection. Fifty-two patients had a CD4+ lymphocyte count > 500 x 10(6)/l (CDC group 1), 42 had a number of CD4+ lymphocytes ranging from 200 and 500 x 10(6)/l (CDC group 2), and 26 had a count < 200 x 10(6)/l (CDC group 3). None of the patients was receiving antiretroviral treatment or had intercurrent infections at the time of the study. RESULTS: Mean values of viremia showed an inverse significant relationship with the CD4+ lymphocyte count. In CDC group 1 subjects the distribution of viremia was as follows: low (< 3,000 copies of HIV RNA/ml) in 16 (30.8%), intermediate in 20 (38.4%), and high (> 30,000 copies of HIV RNA/ml) in 16 (30.8%). In eight subjects from CDC group 1, the duration of HIV infection was less than 5 years. In contrast, in patients from CDC group 3, viremia was high in 17 (65.4%), intermediate in 9 (34.6%), and none of them had a low degree viremia. In CDC group 2 patients, viremia was high in 14 (33.3%), intermediate in 20 (47.6%), and low in 8 (19.1%). CONCLUSION: There is an inverse correlation between the viremia degree and the CD4+ lymphocyte count among HIV-positive patients. Nevertheless, there can be a high viremia in absence of low CD4+ lymphocyte count, particularly among subjects with HIV infection for less than 5 years, in whom an early therapeutical intervention might be warranted.

Adult↗
PubMed1996

[Rapid and slow progression of the infection by the type 1 human immunodeficiency virus in a population of seropositive subjects in Madrid].

BACKGROUND: The rate of progression to AIDS in HIV-1 infected subjects is variable, and circumstances associated with more rapid or slow development of severe immunodeficiency might be grouped in three categories; environmental cofactors, host features, and particular virulence of the virus itself. Currently, it is not yet clear the the relative impact of each one. PATIENTS AND METHODS: A cross-sectional study was done in a cohort of 1,783 IV-1 infected persons from three centers located in Madrid, mainly devoted to attend persons at risks for HIV infection. Long-term nonprogressors (LTNP) were defined as those with more than 8 years of confirmed HIV seropositivity, and CD4+ T-cell count above 500 x 10(6)/I in the absence of antiretroviral therapy or symptoms suggesting immunodeficiency. Rapid progressors (RP) were those with less than 5 years from seroconversion and repeatedly current CD4+ T-cell count below 200 x 10(6)/I. An analysis of different epidemiological, immunological and virological features was performed comparing LTNP and RP. RESULTS: Among 1,783 HIV (+) subjects studied, 100 (5.6%) fulfilled criteria for LTNP and 12 (0.7%) for RP. Among LTNP, stabilized CD4 slope was seen in 16 (33%) out of 48 after more than 8 years of infection. Variables statistically associated with LTNP were: past history of intravenous drug addiction (80% of them), male gender (79% of them), high alcohol intake (48% of them), HIV-1 non-syncitium inducing viral phenotype, and very low or undetectable HIV-1 plasma viremia. In contrast, variables associated with RP were: infection by sexual contact (75% of cases), female gender (50% of them), syncitium-inducing viral plenotype, and high titers of plasma viremia. The CD4/CD8 ratio below 1 was seen in all RP and in 88% of LTNP. However, a preferent depletion of CD4+ cell occurred in the first group, instead of an enhancement of the CD8 T-cell count in LTNP. The prevalence of serological markers for hepatotropic viruses and other potential infectious cofactors was not higher in RP. CONCLUSIONS: Multiple factors seems to account for the different rate of disease progression observed in HIV-1 infected persons. The dynamic equilibrium between the immune system and the virulence of the virus seem to be influenced--but not determined--by environmental infectious or non infectious cofactors.

Acquired Immunodeficiency Syndrome↗
PubMed1996

[Changes in the spectrum of AIDS-defining diseases in Spain].

BACKGROUND: Since the late 1980s the use of prophylaxis against several AIDS-diagnostic diseases has been recommended. In order to detect the impact of these measures we analyzed the shifts in the spectrum of AIDS-diagnostic diseases in Spain. PATIENTS AND METHODS: AIDS cases (CDC-1987) among patients over 12 years of age diagnosed in Spain during the period 1988-1993 were studied. Number and percentage of annual AIDS cases corresponding to each reported AIDS-diagnostic disease were analyzed. Annual percentage trends were assessed by means of chi 2 trend test and logistic regression adjusting for possible changes in distribution by transmission category, sex, and age-group. RESULTS: Annual incidence in most of AIDS-defining diseases rose over the period 1988-1993, although the proportion of cases in which the respective conditions appeared as AIDS-diagnostic diseases exhibited declining trends (p < 0.05) in: invasive candidiasis, Herpes simplex virus infection, isosporidiasis, Pneumocystis carinii pneumonia, extrapulmonary tuberculosis, Salmonella (non-typhoid) septicemia, HIV encephalopathy and wasting syndrome. Increases were observed in the proportion of Mycobacterium avium complex disease and progressive multifocal leukoencephalopathy (p < 0.05). CONCLUSIONS: Some shifts in the spectrum of diseases are noted, which could be due to primary prophylaxis. Efforts should be targeted to improve coverage and compliance, and to develop guidelines of prophylaxis against the remaining diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1996

[The treatment of chronic hepatitis C with interferon in patients infected with the human immunodeficiency virus. The Spanish Group for the Study of Viral Hepatitis in HIV+ Patients].

BACKGROUND: Alfa-interferon (aIFN) is widely recommended for the treatment of chronic hepatitis C (CHC). Hepatitis C virus (HCV) infection is very common in injecting drug users (IDUs), which in Spain represent the large number of HIV-infected persons. Interaction between human immunodeficiency virus (HIV) and HCV in coinfected patients might accelerate the clinical course of HCV-associated liver disease. The efficacy and safety of aIFN therapy in HIV-infected patients with CHC is not well known. PATIENTS AND METHODS: In a multicenter, prospective, open, non randomized and partially controlled study, we compared the efficacy and safety of aIFN therapy in 119 patients with CHC, of whom 90 were HIV-positive and 29 HIV-negative. Interferon was started at 5 mega U tiw for 3 months, followed in responders by 3 megaU tiw for additional 9 months. RESULTS: One hundred seven patients completed the study. A normalization of the aminotransferase values at the end of treatment (complete response, CR) was observed in 26/80 (32.5%) HIV-positive and 10/27 (37.0%) HIV-negative individuals (p = 0.666). Relapses at 12 months of stopping aIFN were seen in 30.8% of HIV-positive subjects and 12.5% of HIV-negatives (p = 0.403). Side effects were uncommon and did not have severity; only one patient required to stop the medication. However, 3 HIV-positive subjects treated with aIFN (3.5% of them) showed an irreversible fall of CD4+ T-cells below half the baseline values. CONCLUSION: HIV-infected patients with CHC seems to respond to aIFN with a similar rate than HIV-negatives. Moreover, the drug is similarly well tolerated in both groups of patients, although a fall of CD4+ T-cells is an unusual side effect of particular relevance observed in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1996

[The pattern of AIDS-indicative diseases in adults and adolescents in Spain, 1988-1993].

BACKGROUND: The pattern of AIDS-defining diseases in adults and adolescents in Spain from 1988-1993 has been described. METHODS: Twenty-two thousand two hundred thirty-nine cases (CDC, 1987) diagnosed in patients over the age of 12 years from 1988 to 1993 were taken from the National AIDS Registry. The percentage of cases which each of the indicative diseases on registry was evaluated and the differences based on the category of HIV transmission, sex and age were identified. RESULTS: The most frequent AIDS indicative diseases were extrapulmonary tuberculosis (29.7%), Pneumocystis carinii (28.2%) and invasive candidiasis (24.8%). The percentage of cases with extrapulmonary tuberculosis was higher among the intravenous drug users and Kaposi's sarcoma, non Hodgkin's lymphoma (NHL) and cytomegalovirus disease (CMV) among the homosexual males. The disease pattern has demonstrated some differences between sexes on adjustment by transmission category and age. Herpes simplex disease, retinitis by CMV and cerebral toxoplasmosis appeared were more frequent in women and extrapulmonary tuberculosis and NHL in males. On adjustment by transmission category and sex, extrapulmonary tuberculosis was observed with a higher frequency in patients under the age of 30 years while wasting syndrome and progressive multifocal leukoencephalopathy were more often observed in those over the age of 30 years. CONCLUSIONS: The category of HIV transmission plays and important role in the pattern of AIDS-defining diseases. Sex and age also play a role although to in a lesser degree.

AIDS-Related Opportunistic Infections↗
PubMed1996

Injecting drug use as risk factor for visceral leishmaniasis in AIDS patients.

In Madrid Region 6652 AIDS cases were diagnosed between 1982 and 1993. Visceral leishmaniasis (VL) was present in 166 (2.49%). VL frequency among injecting drug users proved higher than that for the other transmission categories (relative risk 2.57; 95% confidence interval 1.64-4.01). This could point to an alternative Leishmania transmission route via needle sharing.

AIDS-Related Opportunistic Infections↗
PubMed1996

Interferon alpha for the treatment of chronic hepatitis C in patients infected with human immunodeficiency virus. Hepatitis-HIV Spanish Study Group.

Liver disease secondary to hepatitis C virus (HCV) infection is a rising cause of morbidity and mortality among individuals who have been infected parenterally with human immunodeficiency virus (HIV) such as injection drug users, hemophiliacs, and transfused patients. We analyzed both the efficacy of interferon (IFN) alpha therapy in these patients and the predictors of response to this agent. A total of 119 patients with chronic hepatitis C (90 of whom were infected with HIV and 29 of whom were not) were included in a multicenter, prospective, open, nonrandomized observational study. IFN-alpha was given subcutaneously in a dosage of 5 million units three times a week during a 3-month period; those patients who responded received a dose of 3 million units given subcutaneously three times a week for an additional 9 months. One hundred seven patients completed the study; the level of aminotransferases returned to normal and sera became negative (complete response) for HCV RNA in 26 (32.5%) of 80 HIV-infected patients and 10 (37.0%) of 27 non-HIV-infected patients (P = .666) after completion of the treatment. Two variables were independently associated with a response in HIV-infected patients: a CD4+ T lymphocyte count of > 500 x 10(6)/L and a baseline HCV viremia level of < 10(7) copies/mL. In the 12 months following treatment, relapses occurred in 30.8% of the HIV-infected patients and 12.5% of non-HIV-infected patients (P = .403).

Adult↗
PubMed1995

The AIDS epidemic among Spanish women.

BACKGROUND: The number of female cases of AIDS in Spain continues to rise. This paper describes the epidemiological pattern involved and identifies differences compared to heterosexual males. METHODS: An analysis based on data gathered via the Spanish AIDS surveillance system was carried out on cases among females aged > 12, broken down by reporting year, age, transmission category and area of residence. A comparison was run against cases among heterosexual males. RESULTS: By December 1993, 22,114 cases of AIDS among patients aged > 12 had been reported, 3812 (17.2%) involving females. Although a rise was to be observed in the number and percentage of female cases reported each year, climbing to 1039 cases in 1993 and accounting for 18.5% of all cases in adults, the heterosexual male-to-female ratio remained relatively constant at around 3.8:1. Average age at diagnosis was higher among heterosexual males than among females (31.1 versus 29.8; P < 0.0001). Intravenous drug users (IVDU) accounted for 71.7% and heterosexual contact for 19.4% of women with AIDS, against 81.7% and 5.8% respectively in males. Until 1993 the cumulative rate for AIDS stood at 221 cases per million adult females. CONCLUSIONS: Intravenous drugs, whether through direct use or heterosexual relations with IVDU partners, are the principal cause of female AIDS in Spain. In females, the epidemic exhibits different characteristics compared to that in males.

Acquired Immunodeficiency Syndrome↗