Biomedical subjects

J M Gatell

Publications and source records attributed to J M Gatell.

At least 19 recordsLinked to original sources

PubMed2006

Intrathoracic fat in HIV-infected patients.

BACKGROUND: The impact of HIV infection or antiretroviral therapy on the intrathoracic fat compartment is unknown. METHODS: Consecutive clinically stable HIV-infected adult patients, irrespective of exposure to antiretroviral therapy, and non-HIV-infected healthy volunteers, both without clinical evidence of body fat changes consistent with lipodystrophy and adjusted for age, gender and body mass index, were recruited for this study. Thoracic and abdominal fat was assessed by computed tomography and compared between patients and controls. RESULTS: There were nine women (33%) and 18 men (67%) in each group. Nineteen patients (70%) had been taking antiretrovirals for a median of 8 months (interquartile range: 6-11). Among the HIV-infected patients, intrathoracic fat (median; interquartile range) did not differ significantly between treated (6.7 cm(2); 4.5-8.3 cm(2)) and untreated (6.9 cm(2); 5.7-10.9 cm(2)) individuals (P=0.288). However, intrathoracic fat content (median; interquartile range) was higher in HIV-infected patients (6.8 cm(2); 5.6-10.5 cm(2)) than in controls (5.6 cm(2); 3.9-6.7 cm(2)) (P=0.025). Intrathoracic fat was positively correlated with intra-abdominal fat both in patients (rho=0.6, P=0.002) and in controls (rho=0.7, P=0.004). CONCLUSION: In HIV-infected adults without clinical evidence of lipodystrophy, intrathoracic fat content was higher than in healthy persons and positively correlated with intra-abdominal fat content.

Abdomen↗

PubMed2005

Risk of selecting de novo drug-resistance mutations during structured treatment interruptions in patients with chronic HIV infection.

BACKGROUND: Structured treatment interruption (STI) may allow viral replication in the presence of decreased plasma drug levels, with risk of selection of resistance mutations. METHODS: For patients recruited for an STI study, genotypic resistance testing was performed at baseline (before receipt of any treatment), immediately before the STI, and 2 weeks after each interuption of therapy. RESULTS: During 20 (18%) of 112 STI cycles (95% CI, 11%-26%), resistance mutations were selected; 6% of the mutations were de novo (i.e., not detected before the start of STI), and 12% were archived mutations (i.e., mutations already detected before the STI). Overall, resistance mutations during STI were selected in 9 (26%) of 35 patients; 5 (14%) of the mutations were de novo, and 4 (12%) were archived mutations. Mutations conferring resistance to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) were selected in 3 (23%) of 13 patients receiving NNRTI-based regimens (all mutations were de novo). Mutations conferring resistance to lamivudine were selected in 9 (50%) of 18 patients receiving lamivudine-containing regimens (4 [22%] were de novo, and 5 [28%] were archived mutations). Mutations conferring resistance to nucleoside reverse-transcriptase inhibitors (NRTIs), excluding the M184V mutation, were selected in 2 (6%) of 35 recipients of NRTIs (1 [3%] of these mutations was de novo, and 1 [3%] was an archived mutation. Finally, mutations conferring resistance to protease inhibitors were selected in none of the 22 patients receiving protease inhibitors. In most cases, de novo and archived mutations were selected during the first STI cycle, and their number did not increase during successive cycles. Plasma viral load decreased to undetectable levels in all the patients when the earlier drug regimen was reintroduced. CONCLUSIONS: Genotypic mutations are selected during STI in a high proportion of patients (especially in patients receiving NNRTIs or lamivudine). Approximately one-half of selected mutations were archived mutations. Patients who had archived mutations did not have a higher risk of accumulating new mutations than did patients who were infected with wild-type virus before the STI.

Adult↗

PubMed2005

CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse.

Adenosine deaminase (ADA), a protein whose deficit leads to severe combined immunodeficiency, binds to the cell surface by means of either CD26, A(1) adenosine receptors, or A(2B) adenosine receptors. The physiological role of these interactions is not well understood. Our results show that by a 3-fold reduction in the EC(50) for the antigen, ADA potentiated T cell proliferation in autologous cocultures with antigen-pulsed immature or mature dendritic cells. Costimulation was not due to the enzymatic activity but to the interaction of ADA-CD26 complexes in T cells with an ADA-anchoring protein in dendritic cells. From colocalization studies, it is deduced that ADA colocalizing with adenosine receptors on dendritic cells interact with CD26 expressed on lymphocytes. This costimulatory signal in the immunological synapse leads to a marked increase (3- to 34-fold) in the production of the T helper 1 and proimmflamatory cytokines IFN-gamma, TNF-alpha, and IL-6.

Adenosine Deaminase↗

PubMed2005

Mitochondrial DNA depletion in liver tissue of patients infected with hepatitis C virus: contributing effect of HIV infection?

OBJECTIVES: It has been suggested that chronic hepatitis C virus (HCV) infection depletes mitochondrial DNA (mtDNA) in the liver. Because decreased mtDNA levels were also found in humans infected with HIV, we investigated whether HIV may have aggravated hepatic mtDNA depletion in individuals with HCV infection. METHODS: In this cross-sectional study, liver biopsies were performed in a total of 40 individuals prior to any antiviral therapy. The individuals were recruited from the Hospital Clinic, Barcelona and the HIV Centre, Dusseldorf. Seventeen patients were negative for HIV and HCV and were biopsied for liver enzyme elevation of unknown cause (controls), 14 individuals had chronic HCV but no HIV infection, and nine subjects were coinfected with both viruses. mtDNA and liver histology were centrally assessed. RESULTS: The groups did not differ with respect to age, gender, liver function tests and HCV viral load, where applicable. mtDNA levels were decreased by 19% in the HCV-monoinfected group (P=0.03) and by 27% in the HIV/HCV-coinfected subjects (P=0.02) compared to controls. The mtDNA content, however, did not differ between individuals with HCV monoinfection and HCV/HIV coinfection (P=0.75). The degrees of liver fibrosis, inflammatory activity or steatosis did not correlate with mtDNA content. CONCLUSIONS: Liver mtDNA content is reduced in both HCV-monoinfected and HIV/HCV-coinfected patients. Under the limitations of our study, we could demonstrate only a slight trend towards more pronounced mtDNA depletion in HIV/HCV-coinfected subjects.

Adult↗

PubMed2005

Staphylococcus lugdunensis infective endocarditis: description of 10 cases and analysis of native valve, prosthetic valve, and pacemaker lead endocarditis clinical profiles.

OBJECTIVE: To evaluate the incidence and the clinical and echocardiographic features of infective endocarditis (IE) caused by Staphylococcus lugdunensis and to identify the prognostic factors of surgery and mortality in this disease. DESIGN: Prospective cohort study. SETTING: Study at two centres (a tertiary care centre and a community hospital). PATIENTS: 10 patients with IE caused by S lugdunensis in 912 consecutive patients with IE between 1990 and 2003. METHODS: Prospective study of consecutive patients carried out by the multidisciplinary team for diagnosis and treatment of IE from the study institutions. English, French, and Spanish literature was searched by computer under the terms "endocarditis" and "Staphylococcus lugdunensis" published between 1989 and December 2003. MAIN OUTCOME MEASURES: Patient characteristics, echocardiographic findings, required surgery, and prognostic factors of mortality in left sided cases of IE. RESULTS: 10 cases of IE caused by S lugdunensis were identified at our institutions, representing 0.8% (four of 467), 1.5% (two of 135), and 7.8% (four of 51) of cases of native valve, prosthetic valve, and pacemaker lead endocarditis in the non-drug misusers. Native valve IE was present in four patients (two aortic, one mitral, and one pulmonary), prosthetic valve aortic IE in two patients, and pacemaker lead IE in the other four patients. All patients with left sided IE had serious complications (heart failure, periannular abscess formation, or shock) requiring surgery in 60% (three of five patients) of cases with an overall mortality rate of 80% (four of five patients). All patients with pacemaker IE underwent combined medical treatment and surgery, and mortality was 25% (one patient). In total 59 cases of IE caused by S lugdunensis were identified in a review of the literature. The combined analysis of these 69 cases showed that native valve IE (53 patients, 77%) is characterised by mitral valve involvement and frequent complications such as heart failure, abscess formation, and embolism. Surgery was needed in 51% of cases and mortality was 42%. Prosthetic valve endocarditis (nine of 60, 13%) predominated in the aortic position and was associated with abscess formation, required surgery, and high mortality (78%). Pacemaker lead IE (seven of 69, 10%) is associated with a better prognosis when antibiotic treatment is combined with surgery. CONCLUSIONS: S lugdunensis IE is an uncommon cause of IE, involving mainly native left sided valves, and it is characterised by an aggressive clinical course. Mortality in left sided native valve IE is high but the prognosis has improved in recent years. Surgery has improved survival in left sided IE and, therefore, early surgery should always be considered. Prosthetic valve S lugdunensis IE carries an ominous prognosis.

Adult↗

PubMed2004

Native valve endocarditis due to Candida glabrata treated without valvular replacement: a potential role for caspofungin in the induction and maintenance treatment.

Conventional antifungal therapy for fungal endocarditis has been associated with a poor cure rate. Therefore, combined medical and surgical therapy has been recommended. However, new potent antifungal agents, such as echinocandins, could increase the medical options and, in some cases, avoid the need for surgery. We report a case of Candida endocarditis treated successfully without valve replacement with intravenous liposomal amphotericin B (total dose, 4 g) and intravenous caspofungin (a 100-mg loading dose followed by 50 mg per day for 8 weeks) as induction therapy and intravenous caspofungin (100 mg 3 times per week for 12 weeks) as maintenance therapy.

Aged, 80 and over↗

PubMed2004

Therapeutic immunization with an inactivated HIV-1 Immunogen plus antiretrovirals versus antiretroviral therapy alone in asymptomatic HIV-infected subjects.

To determine whether the addition of an inactivated-gp120-depleted HIV-1 Immunogen to antiretrovirals (ARTs) conferred a beneficial effect on delaying time to virologic failure relative to that obtained by ARTs alone, a phase II clinical trial was performed in 243 asymptomatic, ART naïve, HIV-1 seropositive adults. The Cox model showed that HIV-1 Immunogen treatment was associated with a 34% decrease in the risk of virologic failure (P = 0.056). When the analysis incorporated baseline HIV-RNA stratification the risk of virologic failure in the HIV-1 Immunogen Arm was significantly reduced a 37% compared to the IFA placebo Arm (P = 0.034). The data suggest that therapeutic immunization plus ARTs could influence virologic control.

AIDS Vaccines↗

PubMed2004

Immunosuppressive drugs as an adjuvant to HIV treatment.

Although highly active antiretroviral therapy (HAART) has dramatically changed the epidemiological impact of HIV infection, many problems with currently used antiretroviral therapy have underscored the urgent need for additional therapeutic approaches. Structured treatment interruption trials, which can be considered an immune-based therapy with an autologous virus, have failed to control viral replication in most chronically HIV-1-infected patients. Alternative approaches could be the use of immunosuppressive drugs to enhance the control of viral replication mediated by their immune and antiviral properties. The use of immunosuppressive drugs may reduce the number of activated CD4 cells that support massive virus production and may prevent sequestration of CD4 T cells into lymphoid tissue, which is the place of antigen presentation and productive HIV infection. The strategy of using drugs that interfere with the HIV life-cycle, acting on the target cells of HIV rather than on viral enzymes, offers the advantage of avoiding the development of antiretroviral drug-resistant HIV mutants. However, it is not known if these approaches will clinically benefit long-term infection, by establishing a new immunological set-point that may affect the rate of disease progression. Caution is required when using HAART in combination with cytostatic drugs in HIV-1 infection until their impact and long-term safety have been investigated further in larger clinical trials.

Anti-HIV Agents↗

PubMed2004

Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendations.

Chronic hepatitis B and C represent a leading cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients worldwide. New treatment options against both hepatitis B (HBV) and C (HCV) viruses have prompted us to update previous recommendations for the management of coinfected individuals. Fifteen topics (nine related to HCV, five to HBV and one to both viruses) were selected for this purpose. A panel of Spanish experts in the field was invited to review these areas and propose specific recommendations, which were scored according to the Infectious Disease Society of America (IDSA) grading system. These guidelines represent a comprehensive and updated overview on the management of hepatitis B and C in HIV-infected patients.

Anti-HIV Agents↗

PubMed2004

Changes in hospital admissions across Europe: 1995-2003. Results from the EuroSIDA study.

OBJECTIVES: To describe changes in the proportions of patients admitted to hospital and the duration of admission during the month of March between 1995 and 2003 and to describe the factors related to admission for 9802 patients from EuroSIDA, a pan-European, observational cohort study. METHODS: Generalized estimating equations were used to determine changes over time in the proportion of patients admitted and the median duration of admission. Logistic regression was used to determine factors related to admission in March 1995, March 1998 and March 2001. RESULTS: The proportion of patients admitted during March declined from 7.4% in 1995 to 2.6% in 2003. After adjustment, the estimated reduction in the proportion of patients admitted was 5.5% per year [95% confidence interval (CI) 2.5-8.5%; P=0.0004], a 26% reduction. The median duration of hospital admission declined by 58% from 12 days in 1995 [interquartile range (IQR) 5-19 days] to 5 days in 2003 (IQR 3-12 days), a significant decline of 0.7 days per year after adjustment (95% CI 0.5-0.9 days; P=0.031). Patients with a lower CD4 lymphocyte count, and with an AIDS diagnosis made within the 3 months prior to March, all had increased odds of admission during March 1995, 1998 or 2001. In March 2001, patients whose treatment regimen was changed as a consequence of toxicities had increased odds of admission [odds ratio (OR) 2.34; 95% CI 1.26-4.37; P=0.0074]. In addition, patients who were hepatitis C virus-positive during March 2001 (OR 1.66; 95% CI 1.02-2.68; P=0.041) had increased odds of admission. CONCLUSIONS: There has been a considerable decline in both the proportion of patients admitted to hospital and the median duration of the stay. Patients with hepatitis C had increased odds of admission, but there was little evidence of an increase in admissions among patients taking highly active antiretroviral therapy (HAART) associated with serious adverse events, although longer follow up is required.

Antiretroviral Therapy, Highly Active↗

PubMed2003

[Cytokines value as a sepsis and mortality predictor in elderly patients with fever].

BACKGROUND AND OBJECTIVE: Proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha) are excellent predictive factors of tissue damage, inflammation and infection. However, there is not sufficient data about their usefulness in elderly patients with acute septic pathology. Our objective was to identify the cytokines related to bacteremia and those that predicted a bad prognosis in elderly patients. PATIENTS AND METHOD: Prospective study carried out during 1999. Patients aged >= 60 years with temperature >= 38 C admitted to the emergency ward. We determined IL-1beta, IL-6, TNF-alpha and C-reactive protein (CRP); cultures were done according to the infectious source. On the 4th day, cytokines and CRP were recorded again. The follow-up was completed until cure or death. RESULTS: 50 patients were included (29 males). Median age was 75.6 (SD: 8.98). The etiology was infectious in 44 (88%): respiratory in 29 (66%), urinary in 8 (18%) and other sources in 7. Thirteen patients had bacteremia (32%): Escherichia coli (4), Streptococcus pneumoniae (5) and others (4). Ten patients died (20%). Median values on admission were CRP : 6.67 mg/dl (NV 0.8), TNF-alpha: 29 pg/ml (NV 0-20), IL-1beta: 7 pg/ml (NV 15) and IL-6: 121 pg/ml (NV 5). 4th day values were: 4.23 mg/dl, 22 pg/ml, 1 pg/ml and 41 pg/ml, respectively. The levels of IL-1b in the 2nd determination were significantly lower in females (p = 0.019). Initial TNF-alpha (p = 0.033), IL-1beta (p = 0.013) and IL-6 (p = 0.031) values were significantly higher in bacteremia patients. IL-6 values on the 4th day were higher in patients who died (p = 0.06). In patients who died, IL-6 levels were higher in the 2nd determination (p = 0.09). CONCLUSIONS: Median values of all cytokines were higher in the bacteremia population. Patients who died showed higher levels of IL-6 on the 4th day.

Age Factors↗

PubMed2003

Infective endocarditis not related to intravenous drug abuse in HIV-1-infected patients: report of eight cases and review of the literature.

OBJECTIVES: To add to the limited information on infective endocarditis (IE) not related to intravenous drug abuse (IVDA) in HIV-1-infected patients. METHODS: We have reviewed the characteristics of eight cases of IE in non-IVDA HIV-1 infected patients diagnosed in our institution between 1979 and 1999 as well as cases in the literature. RESULTS: All our patients were male, and the mean age was 44 years (range 29-64). HIV-1 risk factors were: homosexuality in five, heterosexuality in two, and the use of blood products in one. HIV stage C was found in six cases, and the median (range) CD4 cell count was 22/microL (4-274 cells/microL). IE was caused by Enterococcus faecalis in three cases, staphylococci in two cases, and Salmonella enteritidis, viridans group streptococci and Coxiella burnetii in one case each. Three patients acquired IE while in the hospital. All IE cases involved a native valve, and underlying valve disease was found in three patients. The aortic valve was the most frequently affected (five cases). Two patients underwent surgery, with a good outcome, and one patient died. Fourteen cases of IE not related to IVDA in HIV-1-infected patients were found in the literature review. The most common causative agents were Salmonella spp. and fungi (four cases each). Two patients had prosthetic valve IE, and the mitral valve was the most frequently affected (10 cases). The remaining clinical characteristics and the outcome were similar to those in the present series. CONCLUSIONS: IE not related to IVDA is rare in HIV-1-infected patients. In more than half of the cases, IE develops in patients with advanced HIV-1 disease. A wide etiologic range is found, reflecting different clinical and environmental conditions. None of the patients who underwent surgery died, and the overall mortality rate was not higher than in non-HIV-1-infected patients with IE.

AIDS-Related Opportunistic Infections↗

PubMed2003

Bacteraemia in adults due to glucose non-fermentative Gram-negative bacilli other than P. aeruginosa.

BACKGROUND: Glucose non-fermentative Gram-negative bacilli other than P. aeruginosa (NF) are emerging pathogens. AIM: To evaluate the epidemiology, clinical characteristics, predictors of acquisition, and outcome of bacteraemia due to NF. DESIGN: Retrospective analysis of prospectively recorded data. METHODS: We reviewed episodes of NF bacteraemia in patients older than 14 years, recorded through a blood culture surveillance program. Patients were identified at the time of their bacteraemia and prospectively followed. RESULTS: Between January 1991 and December 2000, 296 episodes of NF bacteraemia were detected: 87% were due to Acinetobacter sp., Pseudomonas sp. other than P. aeruginosa, or Stenotrophomonas maltophilia. The global incidence (0.87 cases per 1000 discharges) remained stable during the study period. Patients were of all ages and both sexes, and 282/296 (95.3%) had some predisposing underlying disease or condition, the most common being haematological malignancies without transplantation (85/296, 28.7%), treatment with steroids (78/296, 26.3%), and transplantation (bone marrow or solid organ) (70/296, 23.6%). Fifty (16.9%) were neutropenic. The most common sources of bacteraemia were central venous catheter infection (117/296, 39.5%) and unknown primary site (97/296, 32.8%). Sixty-one episodes (20.6%) were community-acquired and 235 (79.4%) were nosocomial. Forty-three patients (14.5%) died. Pneumonia (RR 1.5, 95%CI 1.1-14.2), age<65 (RR 3.1, 95%CI 1.4-10.3), hospitalization in the intensive care unit (ICU) (RR 3.2, 95%CI 1.3-9.8), rapidly fatal disease (RR 4.9, 95%CI 3.1-12.6), and severe sepsis (RR 9.8, 95%CI 1.6-19.7) were independent predictors of death. Factors predicting the probability that an episode of nosocomial bacteraemia was due to NF included: rapidly fatal disease (RR 1.23, 95%CI 1.02-4.1), age<65 (RR 2.05, 95%CI 1.4-3), hospitalization in the ICU (RR 2.06, 95%CI 1.4-3, and pneumonia (RR 2.1, 95%CI 1.05-4.8). DISCUSSION: NF bacteraemia mainly affects patients with malignant haematological disease, with and without transplantation, and patients in the ICU. The most common known source is a central venous catheter, though many sources are unknown. Mortality is relatively low, and depends on the severity of the underlying disease.

Adolescent↗

PubMed2003

A nosocomial outbreak of influenza during a period without influenza epidemic activity.

The objective of this study was to describe a nosocomial outbreak of influenza during a period without influenza epidemic activity in the community. Outbreak investigation was carried out in an infectious diseases ward of a tertiary hospital. Presence of two or more of the following symptoms were used to define influenza: cough, sore throat, myalgia and fever. Epidemiological survey, direct immunofluorescence, viral culture, polymerase chain reaction, haemagglutination-inhibition test in throat swabs and serology for respiratory viruses were performed. Twenty-nine of 57 healthcare workers (HCW) (51%) and eight of 23 hospitalised patients (34%) fulfilled the case definition. Sixteen HCW (55%) and three inpatients (37%) had a definitive diagnosis of influenza A virus infection (subtype H1N1). Among the symptomatic HCW, 93% had not been vaccinated against influenza that season. Affected inpatients were isolated and admissions in the ward were cancelled for 2 weeks. Symptomatic HCW were sent home for 1 week. On the seventeenth day of the outbreak the last case was declared. The incidence of cases in this outbreak of influenza, which occurred during a period without influenza epidemic activity in the community, was notably high. Epidemiological data suggest transmission from healthcare workers to inpatients. Most healthcare workers were not vaccinated against influenza. Vaccination programmes should be reinforced among healthcare workers.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Streptococcus agalactiae infective endocarditis: analysis of 30 cases and review of the literature, 1962-1998.

We describe 30 cases (1.7%) of community-acquired penicillin-susceptible Streptococcus agalactiae endocarditis among 1771 episodes of endocarditis diagnosed in 4 Spanish hospitals from 1975 through 1998. Endocarditis affected a native valve (most often the mitral valve) in 25 cases (83%). Surgical valve replacement was performed for 12 patients (40%). Fourteen patients (47%) died. Mortality rates for patients with native and prosthetic valve endocarditis were 36% and 100%, respectively (P=.01). The mortality rate for native valve endocarditis decreased during the last 6 years of the study (from 61% in 1975-1992 to 8% in 1993-1998; P<.05). Additionally, 115 cases in the literature from 1962-1998 were reviewed. During 1980-1998, the percentage of patients who underwent cardiac surgery increased from 24% (in the previous period, 1962-1979) to 43% (P=.05) and the mortality rate decreased from 45% to 34% (P=NS). S. agalactiae is an uncommon cause of endocarditis with a high mortality rate, although the prognosis of native valve endocarditis has improved in recent years, probably because of an increased use of cardiac surgery.

Adult↗

PubMed2002

Influence of highly active anti-retroviral therapy (HAART) on the natural history of extra-pulmonary tuberculosis in HIV patients.

OBJECTIVE: To determine factors related to survival in acquired immune-deficiency syndrome (AIDS) patients with extra-pulmonary tuberculosis (EPTB), when this condition is the first AIDS-defining disease. DESIGN: A retrospective cohort-study of 549 AIDS patients with EPTB as the first AIDS-defining disease. Potential candidates to predict survival were sex, human immunodeficiency virus (HIV) exposure, the coexistence of pulmonary and EPTB at diagnosis, tuberculin skin test, directly observed therapy for tuberculosis (DOT), and highly active anti-retroviral therapy (HAART). The Kaplan-Meier method and Cox regression models were used to assess factors associated with survival. RESULTS: Estimated 3-year survival was 47.0% for those diagnosed before 1993, 72.6% for patients with first AIDS diagnosis during 1995-1996 and 84.6% for those diagnosed after 1996. A negative tuberculin test (hazard ratio [HR] = 1.6, 95% CI 1.1-2.3), not being on DOT (HR 2.2; 95% CI 1.3-3.7) and having pulmonary tuberculosis involvement also (HR 1.3; 95% CI 1.1-1.7) were independently associated with poorer survival. The survival of patients significantly improved after the introduction of HAART (HR 0.4; 95% CI 0.2-0.6). CONCLUSION: The survival of HIV patients with EPTB as their first AIDS-defining disease has substantially improved during the last decade. A negative tuberculin skin test and not receiving DOT are associated with poorer survival among HIV-infected patients whose first AIDS-defining disease is EPTB.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Non-Hodgkin lymphoma in HIV-infected patients in the era of highly active antiretroviral therapy.

This study was designed to assess the influence of highly active antiretroviral therapy (HAART) on non-Hodgkin lymphoma (NHL) among patients infected with human immunodeficiency virus (HIV). Within EuroSIDA, a multicenter observational cohort of more than 8500 patients from across Europe, the incidences of NHL and subtypes (Burkitt, immunoblastic, primary brain lymphoma [PBL], and other/unknown histology) were determined according to calendar time of follow-up, and for those who initiated HAART (> or =3 drugs) also time on HAART. Potential predictive factors of NHL were evaluated in Cox proportional hazard models. Over 26 764 person-years of prospective follow-up (PYF) from May 1994 to December 2000, the incidence of NHL decreased from 1.99 (95% confidence interval, 1.51-2.47) before September 1995 to 0.30 (0.19-0.42) cases/100 (PYF) after March 1999 (P <.001). The incidence of all subtypes of NHL decreased significantly and most pronouncedly for PBL. Among patients who started HAART, the incidence of NHL decreased from 0.88 (0.60-1.16) within the first 12 months after starting HAART to 0.45 (0.31-0.60) cases/100 PYF after more than 24 months (P =.004). In an adjusted Cox model for patients on HAART, the latest CD4 cell count and plasma viral load were both significantly associated with diagnosis of NHL; the relative hazard was 1.39 (range, 1.14-1.69) per 50% lower CD4 cell count, and 1.51 (range, 1.21-1.88) per 1 log higher plasma viral load. In conclusion, the incidence of NHL among HIV-infected patients has decreased significantly after the introduction of HAART, and the decline was most pronounced for PBL. After starting HAART, patients with insufficient immunologic and virologic responses were at highest risk of NHL.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Determination of efavirenz in human plasma by high-performance liquid chromatography with ultraviolet detection.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor for the treatment of the HIV infection. A simple, high-performance liquid chromatographic method has been developed and validated for the quantitative determination of efavirenz in human plasma. The method involved solid-phase extraction of the drug and the internal standard (L-737,354) from 300 microl of human plasma. The analysis was via UV detection at 250 nm using a reversed-phase C8 analytical column and a isocratic mobile phase consisting of phosphate buffer (pH 5.75)-acetonitrile that resolved the drug and internal standard from endogenous matrix components and potential coadministered drugs. Within- and between-day precisions were less than 8.6% for all quality control samples. The lower limit of quantification was 0.1 microg/ml. Recovery of efavirenz from human plasma was greater than 83%. This validated assay is being used in pharmacokinetic studies with efavirenz.

Alkynes↗