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Biomedical subjects

J M Gatell

Publications and source records attributed to J M Gatell.

At least 37 records · Page 2Linked to original sources
PubMed2001

Lymphoid tissue viral burden and duration of viral suppression in plasma.

OBJECTIVES: To assess virological response in lymphoid tissue and its impact on the durability of response in plasma in HIV-1-infected persons who achieved sustained suppression of plasma viraemia with different antiretroviral regimens. METHODS: Consecutive patients on first-line antiretroviral therapy were included if they had a plasma HIV-1 RNA viraemia < 20 copies/ml within the last 6 months and tonsillar tissue accessible for biopsy. First-line therapy contained two nucleoside analogues: alone (2NRTI group, n = 3); plus a HIV-1 protease inhibitor (PI group, n = 11) or plus nevirapine (NVP group; n = 16). Patients were followed until virus was detectable in plasma, they changed therapy or were lost to follow-up. RESULTS: Tonsillar HIV-1 RNA could be detected (> 100 copies/mg) in 10 patients: one in the PI group (9%), six (38%) in the NVP group and in all three patients in the 2NRTI group. Primary resistance mutations could be detected in only 2 of these 10 patients. After a median of 9 months after the biopsies, viral suppression in plasma had failed in 6 of these 10 patients whereas failure had only occurred in 1 out of 20 with initially undetectable viral load in lymphoid tissue (P = 0.01; log rank test). CONCLUSIONS: In patients with sustained viral suppression in plasma, triple therapy including a HIV-1 protease inhibitor was more potent than triple therapy containing nevirapine or dual therapy with nucleoside analogues to reduce viral burden in lymphoid tissue. A worse response in lymphoid tissue could not be explained by local selection of resistance and was associated with a less durable virological response in plasma.

Adult↗
PubMed2001

Preliminary data of a prospective study on neuropsychiatric side effects after initiation of efavirenz.

OBJECTIVE: To assess baseline variables able to predict neuropsychiatric side effects (NPSEs) associated with the initiation of an efavirenz (EFV)-containing regimen in HIV-1-infected patients. DESIGN: Open-label, prospective, observational study. METHODS: Consecutive HIV-1-infected outpatients in whom EFV was prescribed underwent a psychiatric interview. At baseline and at 2, 4, and 12 weeks, patients completed the Symptoms Check List-90-Revised (SCL-90-R), the Medical Outcome Study for HIV-positive patients (MOS-HIV), and a standardized questionnaire concerning potential NPSEs. RESULTS: Preliminary data showed that discontinuation of EFV because of NPSEs occurred in 4 of 31 patients (13%). Patients who completed the follow-up showed a decrease in SCL-90-R total score (p =.004) and in several subscales such as Interpersonal Sensitivity (p =.009), Depression (p =.001), and Anxiety (p =.040), whereas no changes in MOS-HIV were observed. Having fewer years of education (p =.006), having fewer baseline central nervous symptoms (p =.000), reporting better baseline physical status (p =.013), and having higher baseline scores in the Heath Transition subscale of the MOS-HIV (p =.000) and in the Somatization subscale of the SCL-90-R (p =.002) were associated with more NPSEs. CONCLUSION: Patients maintained on EFV showed a decrease in psychologic distress related to self-image, depression, and anxiety, without any effect on quality of life. Patients with a lower level of education, those who feel physically and psychologically better at baseline than in the past, and those who suffer from more distress as a result of physical complaints may be at greater risk of reporting more NPSEs after EFV initiation.

Adult↗
PubMed2001

Detection of unsuspected cases of nosocomial transmission of tuberculosis by use of a molecular typing method.

The aim of this study was to use restriction fragment length polymorphism to detect unsuspected cases of nosocomial transmission of tuberculosis (TB) among patients who had been admitted to a university hospital. One hundred fifty-one samples of Mycobacterium tuberculosis isolated from patients with pulmonary TB were studied. The isolates from 37 patients (24.5%) defined 11 clusters. None of the patients infected with these cluster isolates had hospital stays that coincided with one another, and for 5.4% of the patients, the epidemiological link was clearly outside the hospital. Previous incarceration was associated with infection with cluster isolates. In addition, 109 patients without TB (41 of whom were infected with human immunodeficiency virus) who shared a room with patients who had TB were followed for 18-60 months. Among the patients who survived, secondary cases of TB due to nosocomial transmission were not detected.

Adult↗
PubMed2001

Hepatotoxicity in HIV-1-infected patients receiving nevirapine-containing antiretroviral therapy.

OBJECTIVES: To assess the incidence and risk factors for hepatotoxicity associated with nevirapine. DESIGN: A prospective cohort study in a teaching and referral hospital involving all consecutive patients who were prescribed a nevirapine-containing antiretroviral regimen between September 1997 and May 2000. METHOD: Cutaneous and hepatic adverse reactions and clinical hepatitis were assessed. Blood analysis including plasma HIV-1 RNA CD4 cell counts, liver chemistry tests, and serology for hepatitis B and C viruses. Hepatotoxicity was defined as an increase of at least threefold in serum alanine aminotransferase or aspartate aminotransferase levels compared with baseline values. RESULTS: Of a total of 610 patients, 82 (13.4%) were antiretroviral naive when commencing nevirapine, and 46.2 and 8.9% were coinfected with hepatitis C and B viruses, respectively. Median duration of exposure to nevirapine was 8.7 months (interquartile range 3.4--14.3). Hepatotoxicity developed in 76 (12.5%), an incidence of 13.1/100 person-years. Kaplan--Meier estimated incidence of hepatotoxicity at 3, 6 and 12 months was 3.7, 9.7 and 20.1%, respectively. In seven (1.1%) patients, hepatotoxicity was associated with clinical hepatitis, which was reversible upon discontinuation of therapy. Multivariate analysis identified the duration of prior exposure to antiretroviral drugs, hepatitis C virus, and higher baseline levels of alanine aminotransferase as independent risk factors for hepatotoxicity. CONCLUSIONS: Hepatotoxicity but not clinical hepatitis was common in HIV-1-infected patients receiving nevirapine-containing regimens and the incidence steadily increased over time. Prolonged exposure to any antiretroviral therapy, coinfection with hepatitis C virus and abnormal baseline levels of alanine aminotransferase identified patients at a higher risk.

Adult↗
PubMed2001

Simultaneous determination of the HIV-protease inhibitors indinavir, amprenavir, ritonavir, saquinavir and nelfinavir in human plasma by reversed-phase high-performance liquid chromatography.

A rapid, simple and sensitive high-performance liquid chromatographic (HPLC) assay has been developed for the simultaneous quantification of the HIV-protease inhibitors indinavir, amprenavir, ritonavir, saquinavir and nelfinavir in human plasma. The method involved the solid-phase extraction of the five drugs and the internal standard (I.S., verapamil) from 400 microl of human plasma. The HPLC analysis used a reversed-phase C18 analytical column and a mobile phase consisting of a gradient with 15 mM phosphate buffer (pH 5.75)-acetonitrile and UV monitoring. The method was linear over the therapeutic concentration range for the five HIV-protease inhibitors. The accuracy of the method ranged from 98.2 to 106.7% and the precision values ranged from 1.4 to 8.1% for intra-day precision and from 3.1 to 6.4% for the inter-day values.

Carbamates↗
PubMed2001

The virological and immunological consequences of structured treatment interruptions in chronic HIV-1 infection.

BACKGROUND: Some individuals with chronic HIV-1 infection have discontinued their drug therapy with consequent plasma virus rebound. In a small number of patients, a delayed or absent rebound in plasma virus load has been noted after drug cessation, apparently associated with prior drug interruptions and autologous boosting of HIV-1 specific immune responses. We hypothesized that cyclic structured treatment interruptions structured treatment interruptions (STI) could augment HIV-1 specific immune responses in chronic HIV-1 infection, which might help to control HIV-1 replication off therapy. METHODS: We initiated an STI pilot study in 10 antiretroviral treatment-naive HIV-1 chronically infected subjects with baseline CD4 T-cell counts > 500 x 10(6) cells/l and plasma viral load > 5000 copies/ml who received highly active antiretroviral therapy (HAART) for 1 year with good response (plasma viral load < 20 copies/ml for at least 32 weeks). Three cycles of HAART interruption were performed. RESULTS: In all of the patients viral load rebounded, but doubling times increased significantly between the first and third stops (P = 0.008), and by the third stop, six out of nine subjects had a virological set-point after a median 12 months off therapy that was lower than baseline before starting HAART (ranging from 0.6 log(10) to 1.3 log(10) lower than baseline) and in four it remained stable below 5000 copies/ml. Those subjects who controlled viral replication developed significantly stronger HIV-1 specific cellular immune responses than subjects lacking spontaneous decline (P < 0.05). During viral rebounds no genotypic or phenotypic changes conferring resistance to reverse trancriptase inhibitors or protease inhibitors was detected, but mean absolute CD4 T-cell counts declined significantly, although never below 450 x 10(6)/l and the mean value at 12 months off therapy was significantly higher than the pre-treatment level (P = 0.004). CONCLUSIONS: Our findings suggest that STI in chronic HIV-1 infection might augment HIV-1-specific cellular immune responses associated with a spontaneous and sustained drop in plasma viral load in some subjects but at the potential cost of lower CD4 T-cell counts.

Adult↗
PubMed2001

Pulmonary infiltrates in HIV-infected patients in the highly active antiretroviral therapy era in Spain.

OBJECTIVE: To study the incidence, etiology, and outcome of pulmonary infiltrates (PIs) in HIV-infected patients and to evaluate the yield of diagnostic procedures. DESIGN: Prospective observational study of consecutive hospital admissions. SETTING: Tertiary hospital. PATIENTS: HIV-infected patients with new-onset radiologic PIs from April 1998 to March 1999. METHODS: The study protocol included chest radiography, blood and sputum cultures, serologic testing for "atypical" causes of pneumonia, testing for Legionella urinary antigen, testing for cytomegalovirus antigenemia, and bronchoscopy in case of diffuse or progressive PIs. RESULTS: One hundred two episodes in 92 patients were recorded. The incidence of PIs was 18 episodes per 100 hospital admission-years (95% confidence interval [CI]: 15-21). An etiologic diagnosis was achieved in 62 cases (61%). Bacterial pneumonia (BP), Pneumocystis carinii pneumonia (PCP), and mycobacteriosis were the main diagnoses. The incidences of BP and mycobacteriosis were not statistically different in highly active antiretroviral therapy (HAART) versus non-HAART patients. The incidence of PCP was lower in those receiving HAART (p =.011), however. Nine patients died (10%). Independent factors associated with higher mortality were mechanical ventilation (odds ratio [OR] = 83; CI: 4.2-1,682), age >50 years (OR = 23; CI: 2-283), and not having an etiologic diagnosis (OR = 22; CI: 1.6-293). CONCLUSIONS: Pulmonary infiltrates are still a frequent cause of hospital admission in the HAART era, and BP is the main etiology. There was no difference in the rate of BP and mycobacteriosis in HAART and non-HAART patients. Not having an etiologic diagnosis is an independent factor associated with mortality.

Adult↗
PubMed2001

Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study.

BACKGROUND: Risk factors for lipodystrophy in patients infected with HIV-1 treated with highly active antiretroviral therapy (HAART) containing HIV-1 protease inhibitors are poorly understood. We aimed to identify the risk factors for lipodystrophy in antiretroviral-naive HIV-1-infected adults on HAART. METHODS: Moderate or severe body-fat changes were clinically assessed and categorised as subcutaneous lipoatrophy, central obesity, or both, in all consecutive antiretroviral-naïve HIV-1-infected adults who began HAART with two nucleoside reverse transcriptase inhibitors plus at least one protease inhibitor from October, 1996, to September, 1999. A person-years analysis was used to calculate the incidence of types of lipodystrophy, and Cox proportional hazards models were used to describe the univariate and multivariate factors associated with progression to any lipodystrophy. FINDINGS: After a median follow-up of 18 months, 85 (17%) of the 494 patients developed some type of lipodystrophy. The incidences of any lipodystrophy, lipodystrophy with subcutaneous lipoatrophy, and lipodystrophy with central obesity were 11.7 (95% CI 9.2-14.2), 9.2 (7.0-11.4), and 7.7 (5.7-9.7) per 100 patient-years. An increased risk for any lipodystrophy was found among women as compared with men (relative hazard 1.87 [1.07-3.28]), heterosexuals (2.86 [1.50-5.48]), and homosexuals (2.17 [1.07-4.42]) as compared with intravenous drug users, with increasing age (1.33 per 10 years older [1.08-1.62]), and with the duration of exposure to antiretroviral therapy (1.57 per 6 months extra [1.30-1.88]) but not with any individual antiretroviral agent. The factors associated with an increased risk for lipodystrophy with subcutaneous lipoatrophy or lipodystrophy with central obesity were very similar to those associated with any lipodystrophy. The duration of indinavir use may represent an additional contribution for the development of lipodystrophy with central obesity (1.26 per 6 months extra [0.99-1.60]); p=0.064). INTERPRETATION: Risk factors associated with development of any lipodystrophy, lipodystrophy with subcutaneous lipoatrophy, and tipodystrophy with central obesity in patients infected with HIV-1 who were receiving HAART containing protease inhibitors are multifactorial and overlapping, and cannot be exclusively ascribed to the duration of exposure to an particular antiretroviral agent.

Adult↗
PubMed2001

Reappraisal of the aetiology and prognostic factors of severe acute respiratory failure in HIV patients.

The introduction of highly active antiretroviral therapy with protease inhibitors in 1996 has changed the morbidity and mortality of acquired immune deficiency syndrome patients. Therefore, the aetiologies and prognostic factors of human immunodeficiency virus (HIV)-infected patients with life-threatening respiratory failure requiring intensive care unit (ICU) admission need to be reassessed. From 1993 to 1998, we prospectively evaluated 57 HIV patients (mean+/-SEM age 36.5+/-1.3 yrs) admitted to the ICU showing pulmonary infiltrates and acute respiratory failure. A total of 21 and 30 patients were diagnosed as having Pneumocystis carinii and bacterial pneumonia, respectively, of whom 13 and eight died during their ICU stay (p=0.01). Both groups of patients had similar age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and severity in respiratory failure. The number of cases with bacterial pneumonia admitted to ICU decreased after 1996 (p=0.05). Logistic regression analysis showed that (APACHE) II score >17, serum albumin level <25 g.(-1), and diagnosis of P. carinii pneumonia were the only factors at entry associated with ICU mortality (p=0.02). Patients with bacterial pneumonia are less frequently admitted to the intensive care unit after the introduction of highly active antiretroviral therapy with protease inhibitors in 1996. Compared to the previous series, it was observed that the few Pneumocystis carinii pneumonia patients that need intensive care still have a bad prognosis.

AIDS-Related Opportunistic Infections↗
PubMed2001

Lipodystrophy syndrome in patients with HIV infection: quality of life issues.

Current antiretroviral therapy has lead to longer survival in patients infected with HIV, but it is also associated with new and important problems. Body fat redistribution and metabolic abnormalities, the so-called lipodystrophy syndrome, are among the most prevalent and worrisome ones. While an increasing number of patients infected with HIV are becoming affected by this syndrome, the pathogenesis of this syndrome and how to prevent and treat the problem all remain largely unknown. Body fat changes stigmatise the bodies of patients infected with HIV giving them a similar look to that seen in patients some years ago when the wasting syndrome was more prevalent and HIV infection was ultimately fatal. The psychological impact of body fat changes may be severe enough to affect a patients' desire to continue with antiretroviral therapy. Metabolic abnormalities, probably with the exception of symptomatic diabetes mellitus and hypertriglyceridaemia-induced pancreatitis, do not have an immediate impact on the quality of the lives of patients with HIV. However, their potential long term cardiovascular and bone consequences may increase the morbidity and the mortality of patients infected with HIV through noninfectious diseases. The impact of lipodystrophy on patients infected with HIV is not readily captured with the classic instruments used to measure quality of life and hence it is necessary to modify them urgently. Though treating lipodystrophy seems fully justified, there is no proven treatment for this problem, although a number of treatments have been used with varying success. Despite the recognition that lipodystrophy may have important psychological repercussions, the best psychological approach for this problem is not known at present. Although lipodystrophy has its own peculiarities, existing knowledge about how to psychologically help other patients with deforming body changes might be of help for patients infected with HIV, or at least may act as a starting point.

Antiretroviral Therapy, Highly Active↗
PubMed2000

Comparison of T-cell subsets' reconstitution after 12 months of highly active antiretroviral therapy initiated during early versus advanced states of HIV disease.

UNLABELLED: This research comprised a pilot open prospective clinical study comparing T-cell subset reconstitution in antiretroviral-naive patients, after 12 months of HAART when treatment was initiated in early stages (ES; n = 18) of infection versus advanced stages (AS; n = 20). CONTROL GROUP: 10 healthy HIV-negative individuals. Immunophenotypic markers were evaluated before and after 6-and 12-months' therapy. Functional assays were performed in one subset. RESULTS: Viral load (VL) was < 200 copies/ml in all patients. Median percentages of CD4+ pretherapy were 33% and 6%, respectively, in the ES and AS groups, increment after 12 months of therapy was +15% and +13% respectively. Only the ES group achieved normal values. Declines of CD8+ percentage were significantly higher in the ES (-18%) than in the AS group (-2%). CD4+ memory and naive cells in the ES group were similar to those of controls before treatment and did not change after therapy. In contrast, CD4+ memory and naive cells in the AS group did not reach normal levels despite treatment. In the ES group, there was a significant increment in CD8+ naive cells (+8%) and a decrement in CD8+CD38+ cells (-17%), both populations reached values close to normal, whereas these subsets remained far from normal in the AS group. Improvement of lymphoproliferative response after therapy was observed in both groups. One patient in the ES group showed positive LPR against p24 after treatment. After 12 months' highly active antiretroviral therapy, only those who began such therapy in ES disease reached values within the range of healthy controls. To achieve a more complete immunologic reconstitution, early initiation of potent antiretroviral therapy should be recommended.

Adult↗
PubMed2000

Comparison of twice-daily stavudine plus once- or twice-daily didanosine and nevirapine in early stages of HIV infection: the scan study.

OBJECTIVES: To evaluate the safety and effectiveness of once-daily didanosine and nevirapine plus twice-daily stavudine versus twice-daily administration of all three drugs. METHODS: This open-label, randomized, multicentre study enrolled 94 antiretroviral-naive patients with chronic HIV infection, CD4+ cell counts > 500 x 10(6) cells/l, and viral loads > 5000 copies/ml. Patients were treated with either 40 mg stavudine (twice daily) plus 400 mg didanosine (once daily) and 400 mg nevirapine (once daily) or 40 mg stavudine (twice daily) plus 200 mg didanosine (twice daily) and 200 mg nevirapine (twice daily). RESULTS: After 12 months, 68% of patients who received twice-daily didanosine and nevirapine had viral loads < 200 copies/ml in the intention-to-treat and 79% in the on-treatment analysis, respectively. The corresponding values for patients treated with didanosine and nevirapine, taken once-daily, were 73 and 85%. The percentages of patients in each group with viral loads < 5 copies/ml at 12 months were 40% (once daily ) and 45% (twice daily) for the intention-to-treat analysis. Five of 11 patients (45%) with plasma viral loads < 5 copies/ml at 12 months had detectable virus in tonsillar tissue. Genotypic resistance to nevirapine was noted in seven of the 14 patients with detectable viral load at month 12. Mean changes in CD4+ cell counts for patients treated with stavudine plus once- or twice-daily didanosine and nevirapine were 154 and 132 x 10(6) cells/l, respectively. Treatment was interrupted due to adverse events in seven patients (8%) (four who received once-daily didanosine and nevirapine and three treated with twice-daily doses). CONCLUSIONS: The combination of twice-daily stavudine plus once-daily didanosine and nevirapine was as safe and well tolerated as twice-daily administration of all three agents. Both regimens were equally effective in reducing viral loads and in increasing CD4+ cell counts.

Anti-HIV Agents↗