PubMed Health⌕ Search

Biomedical subjects

W Rozenbaum

Publications and source records attributed to W Rozenbaum.

At least 37 records · Page 2Linked to original sources
PubMed2000

The VIRGO study: nevirapine, didanosine and stavudine combination therapy in antiretroviral-naive HIV-1-infected adults.

The virological and immunological efficacy of the triple regimen containing nevirapine (once or twice daily), didanosine (once daily) and stavudine, in antiretroviral-naive patients infected with HIV-1, was evaluated in an open-label, prospective, non-randomized, multi-centre, 52-week study. The first 60 patients (VIRGO I) received nevirapine as the standard dose, 200 mg twice daily; the subsequent 40 patients (VIRGO II) received nevirapine at a dose of 400 mg once daily. All patients received 400 mg of didanosine once daily and 40 mg of stavudine twice daily, adjusted for body weight. At baseline, the median CD4 cell count and plasma viral load (pVL) were 414 cells/mm3 and 4.59 log10 copies/ml in VIRGO I, and 412 cells/mm3 and 4.87 log10 copies/ml in VIRGO II. Using an intent-to-treat, 'non-completer equals failure', analysis, 78% (95% CI, 68-88%) of patients in VIRGO I and 68% (95% CI, 53-83%) of those in VIRGO II had a pVL <500 copies/ml at 24 weeks; the proportions achieving a pVL of <50 copies/ml were 62% (95% CI, 50-74%) and 50% (95% CI, 35-65%), respectively. The week 24 median CD4 cell count increase was 168 cells/mm3 (VIRGO I) and 139 cells/mm3 (VIRGO II). At week 52, 39/45 (87%) of VIRGO I patients had pVL <500 copies/ml and 30/45 (67%) <50 copies/ml. Of the 100 patients, 44 experienced grade 2 to 4 adverse events; 20 permanently discontinued study medication because of an adverse event. Combination therapy with the three reverse transcriptase (RT) inhibitors stavudine, once-daily didanosine and either once- or twice-daily nevirapine could be considered as an alternative option for first-line antiretroviral therapy.

Adult↗
PubMed1999

Diabetes, insulin resistance and dyslipidaemia in lipodystrophic HIV-infected patients on highly active antiretroviral therapy (HAART).

This study assessed glucose tolerance, insulin sensitivity and lipid parameters in HIV-infected patients presenting with lipodystrophy during HAART including protease inhibitors. Fourteen consecutive patients from Rothschild Hospital treated with HAART and presenting with marked facial lipoatrophy were evaluated. A 75 g oral glucose tolerance test (OGTT) with measurement of plasma glucose, insulin, proinsulin and free fatty acids at T0, 30, 60, 90 and 120 min was performed. Lipid parameters (triglycerides, cholesterol, apolipoproteins A1 and B) were studied as well as nutritional and inflammatory markers (albumin, prealbumin, transferrin, haptoglobin, orosomucoid, C-reactive protein), endocrine and cytokine parameters (thyrotropin, cortisol, leptin, interleukin-6), HIV viral load and CD4-lymphocyte count. These patients were compared with 20 non-lipodystrophic protease inhibitor-treated patients. The measurements performed during OGTT showed that among the 14 lipodystrophic patients, 11 (79%) presented with diabetes (5 patients) or normal glucose tolerance but with insulin resistance (6 patients). This frequency was strikingly different in the group of nonlipodystrophic patients, which included only 4 (20%) presenting with diabetes (1 patient), or impaired glucose tolerance (2 patients), or normal glucose tolerance but with insulin resistance (1 patient). Hypertriglyceridaemia was present in 11 lipodystrophic (79%) versus 7 nonlipodystrophic patients (35%). Nutritional and endocrine measurements were normal. An abnormal processing of proinsulin to insulin was excluded. Thus, lipodystrophy during HAART was associated with diabetes, insulin resistance and hypertriglyceridaemia. Diabetes, diagnosed by basal and/or 120 min-OGTT glycaemia, seems more frequent than previously described. The therapeutic consequences of these results deserve evaluation in clinical trials.

Adult↗
PubMed1999

Adverse metabolic disorders during highly active antiretroviral treatments (HAART) of HIV disease.

Protease inhibitor treatment has dramatically improved rates of morbidity and mortality in HIV-infected patients. However, it has recently been shown that this medication is associated with long-term side effects characterized by metabolic, clinical and biological alterations. These modifications have been described in patients treated with highly active antiretroviral therapy (HAART), including nucleoside analogue reverse transcriptase inhibitors (NRTI) and generally (but not always) protease inhibitors (PI). Clinical alterations are characterised by a body fat redistribution syndrome or lipodystrophy, with peripheral lipoatrophy and/or central fat accumulation. They are often associated with biological alterations, i.e. insulin resistance, hyperglycaemia and dyslipidaemia, which can also be observed alone. The pathophysiology of these alterations is presently unknown. The deleterious effect of PI on adipose tissue could be direct or indirect, and is probably modulated by genetic or environmental factors. NRTI could also be involved because of their mitochondrial toxicity. The purpose of the treatment is to control metabolic disturbances in order to prevent immediate complications such as acute pancreatitis and limit possible cardiovascular and diabetic complications at longer term. Studies are in progress to evaluate the possibility of therapeutic alternatives to PI when major metabolic disturbances are present.

Anti-HIV Agents↗
PubMed1999

Stavudine, didanosine and nevirapine in antiretroviral-naive HIV-1-infected patients.

In an ongoing, open-label, non-comparative study, the safety and efficacy of nevirapine/stavudine/didanosine were evaluated in 100 antiretroviral-naive adults with CD4 cell counts > or = 200 cells/mm3 and plasma HIV-1 RNA (pVL) > or = 5000 copies/ml. Sixty patients received nevirapine twice daily (VIRGO I) and 40 received nevirapine once daily (VIRGO II); all patients received didanosine once a day. After median follow-ups of 44 weeks in VIRGO I and 30 weeks in VIRGO II, the following virological results were observed (ongoing study): an intent-to-treat, non-completer equals failure analysis at week 24 showed the proportions of patients with pVL <500 copies/ml were 78% in VIRGO I (60% <50 copies/ml) and 75% in VIRGO II. An on-treatment analysis at week 52 showed 80% of patients with a pVL <500 copies/ml and 59% with <50 copies/ml in VIRGO I. The mean CD4 cell count increase was +171 cells/mm3 at week 24 and +218 cells/mm3 at week 52 in VIRGO I and +158 cells/mm3 at week 24 in VIRGO II. Cutaneous rash (grades 1 to 3) occurred in 24% of patients leading to nevirapine discontinuation in eight of 24 patients. Five other patients discontinued therapy during the first 24 weeks because of hepatic cytolysis, peripheral neuropathy or biological pancreatitis. The nevirapine/stavudine/didanosine combination is a convenient and safe regimen, with rapid and potent immunological and antiviral effects sustained over 12 months.

Anti-HIV Agents↗
PubMed1998

Effect of indinavir on HIV-related wasting.

OBJECTIVE: To study the effect of the protease inhibitor indinavir on body weight and body composition of subjects with HIV-related wasting. DESIGN: Prospective measurement of body weight in patients who had wasting and were treated with indinavir. A subgroup of 16 representative patients also underwent a metabolic study that included measurements of body composition (skinfolds and bioelectrical impedance) and food intake. Seven from this subgroup who did not have chronic diarrhoea also underwent indirect calorimetry for measurement of resting energy expenditure; the nine patients with wasting and chronic diarrhoea had measurements of faecal losses and intestinal permeability using the lactulose-mannitol test. SETTING: A tertiary care university hospital. PATIENTS: Two hundred and fourteen HIV-infected patients with wasting (less than 95% of usual body weight) had their body weight measured at day 0; 186 patients had a second body weight measurement within the first 100 days of treatment, and 160 patients were weighed a third time, at a median of 176 days. RESULTS: Body weight increased significantly (P < 0.0001) during treatment, whatever the degree of weight loss at baseline. After a median of 176 days on treatment, body weight had increased in 119 out of the 160 patients followed (74.4%; mean weight gain, 6.3+/-SD 3.8 kg; range, 1-18 kg), had not changed in 13 (8.1%) and had fallen in 28 (17.5%; mean weight loss, 4.2+/-3.0 kg; range, 1-12 kg), relative to baseline. Overall, 119 out of the 214 patients (55.6%) from the initial population gained weight. Fat mass, fat-free mass and body cell mass increased significantly in the 16 patients who underwent metabolic studies, together with energy, protein and lipid intake. In the patients with chronic diarrhoea, intestinal permeability improved but there was no change in intestinal losses. In patients who had wasting but not chronic diarrhoea, resting energy expenditure did not change significantly. Body weight changes correlated with changes in the CD4+ cell count (r = 0.882; P = 0.00001) and, to a lesser extent, with changes in the viral load (r = -0.466; P = 0.047). CONCLUSION: Indinavir significantly improved the nutritional status of these patients with HIV-related wasting.

Adult↗
PubMed1998

Factors of weight loss in patients with HIV and chronic diarrhea.

Weight loss is significant in patients with HIV and chronic diarrhea. The aim of our study was to test for the links between weight loss, the level of food intake, and the severity of diarrhea and nutrient malabsorption. One hundred and sixteen patients with HIV and chronic diarrhea underwent a standardized gastrointestinal and nutritional evaluation, which included a questionnaire on diarrhea, a prospective estimation of food intake, a measurement of blood parameters and fecal lipid and nitrogen outputs, a stool examination for bacteria and parasites, and upper and lower digestive tract endoscopy. Diarrhea resulted from an infection by Cryptosporidia, Microsporida, or other pathogens in 22%, 20%, and 13% of the patients, respectively. Diarrhea appeared idiopathic in 45% of the patients. A significant negative correlation existed between the severity of weight loss and the levels of nutrient intake (p < .005), and a significant positive correlation between the severity of weight loss and stool frequency (p < .01). Multiple linear regression identified low caloric intake and high stool frequency as predictive of weight loss. No significant correlation was found between weight loss and the parameters of malabsorption, either by bivariate study or multiple regression. These results suggest that, in patients with HIV and chronic diarrhea, the degree of wasting is significantly related to the levels of dietary intake and the clinical severity of diarrhea, but not to the extent of nutrient malabsorption.

AIDS-Related Opportunistic Infections↗
PubMed1998

Production of HIV-1 by human B cells infected in vitro: characterization of an EBV genome-negative B cell line chronically synthetizing a low level of HIV-1 after infection.

Human immunodeficiency virus type 1 (HIV-1) has tropism for helper T lymphocytes and cells of the monocyte/ macrophage lineages. HIV-1 can also infect other cell types, including B cells. We show here that 10% of fresh circulating B cells from HIV-1-seronegative donors (i) express the CD4 receptor and CCR5 and CXCR4, two recently described coreceptors for HIV-1 and (ii) are permissive to HIV-1 with de novo proviral DNA integration following ex vivo infection by either SI (syncytium-inducing) or NSI (non-syncytium-inducing) isolates. To get further information on the interaction between HIV and B cells, the susceptibility of several EBV-positive or -negative B cell lines to infection by SI and NSI isolates was checked. Following infection of an EBV- CD4+ CXCR4+ CCR5- B cell line (DG75) by an SI HIV-1 isolate, we obtained a cell line which chronically produced low-level infectious HIV-1 for 2 years (HIV-DG75). Immunocytochemical data, combined with in situ PCR data, established that HIV-DG75 cells consist of at least three populations uninfected cells, infected virus-producing cells, and infected but nonproducing cells. Moreover, HIV-DG75 cells which express p24 antigen do not go into apoptosis, contrary to T lymphocytes. We infer from these results that B cells could constitute a reservoir of infectious virus in infected patients.

Antigens, CD19↗
PubMed1998

Pericardial effusion and AIDS: benefits of surgical drainage.

OBJECTIVES: During the last few years, AIDS has been the main cause of large pericardial effusions in urban settings. We have therefore had to perform surgical pericardial drainage for diagnostic and/or therapeutic purposes in AIDS patients. This study was designed to establish the diagnostic and therapeutic yield of pericardial drainage for these patients. METHODS: We retrospectively reviewed the data of the 13 AIDS patients with a pericardial effusion, referred to our surgical department between December 1989 and December 1996 for surgical drainage and pericardial biopsy. RESULTS: Cytological studies and searches for bacteria, mycobacteria and parasites were all negative. The histology of the 13 pericardial biopsies disclosed three pericardial locations of a Kaposi's sarcoma (all three patients had a pre-existent extra-cardiac location of this sarcoma) and one pericardial location of an already known immature mediastinal teratoma. In the nine other cases, the lesions were aspecific. Four patients died of multivisceral failure within 30 days of surgery. For the survivors, surgical drainage afforded relief and there were no clinical signs of recurrent effusion. CONCLUSIONS: The cause of pericardial effusion in AIDS is still often unknown, even after pericardial biopsy. Here, aspecific pericarditis was the most common diagnosis. Although the prognosis of such effusion in these patients is known to be poor, surgical drainage provided relief for those who survived the post-operative period.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Tissue-type plasminogen activator activity in HIV-associated HUS.

BACKGROUND: In children, haemolytic uraemic syndrome (HUS) is associated with high plasma plasminogen activator inhibitor type 1 (PAI-1), which may contribute to the persistence of renal glomerular and arteriolar thrombi. HUS has been described in HIV-infected patients, but the pathophysiology of HUS in these patients is poorly understood. The aim of the study was to investigate plasma fibrinolytic activity in 18 patients with HIV-associated HUS. METHODS: We measured tissue type plasminogen activator (t-PA) and PAI-1 activities in the plasma of 18 HIV-infected patients with biopsy-proven HUS (HIV+/HUS+) and 48 HIV-infected patients without HUS (HIV+/HUS-). RESULTS: Patients with HUS had a significantly higher serum creatinine, a lower platelet count and an increased incidence of cytomegalovirus (CMV) infection (72% of patients HIV+/HUS+, vs 25% of patients HIV+/HUS-). Unexpectedly, plasma PAI-1 activity was similar in both groups. However, t-PA activity was significantly higher in HUS cases (11.5 vs 4.5 U/ml, P=0.001). Patients with CMV infection, with or without HUS, had significantly increased t-PA level (P=0.01). Multivariate analysis identified high t-PA (RR=9.21) and CMV infection (RR=3.36) as risk factors for HUS. CONCLUSION: This study provides evidence that HIV-infected patients with HUS have high plasma t-PA activity. PAI-1 plasma activity is not significantly increased, as opposed to non-HIV-associated HUS. Thus, in the setting of HIV infection, HUS cannot be attributed to decreased fibrinolytic activity.

Adult↗
PubMed1998

Stavudine plus didanosine and nevirapine in antiretroviral-naive HIV-infected adults: preliminary safety and efficacy results. VIRGO Study Team.

The objective of this open-label trial is to evaluate the virological and immunological effects of triple therapy with stavudine (40 mg twice daily if > or = 60 kg, 30 mg twice daily if < 60 kg)/didanosine (400 mg once daily if > or = 60 kg, 300 mg once daily if < 60 kg)/nevirapine (200 mg daily from day 1 to 14, then 200 mg twice daily) in 60 antiretroviral-naive HIV-infected adults with CD4 cell counts > or = 200 cells/mm3 and plasma HIV RNA > or = 5000 copies/ml. At present, 59 patients have begun receiving the trial regimen. Characteristics of patients at baseline were as follows: 46 men/13 women, CDC stage A, 75%; mean CD4 cell count, 429 cells/mm3; mean HIV RNA, 4.6 log10 copies/ml). Mean decrease of viral load was -1.9 log10 at week 4 (n = 39), -1.9 log10 at week 16 (n = 20), with HIV RNA below the detectable level (< 500 copies/ml) in 62% of patients at week 4 and 85% at week 16. Mean CD4 cell count increase was +118 cells/mm3 at week 4. Cutaneous intolerance occurred within the first 4 weeks in 11/59 (19%) patients after a mean of 14 days (range, 3-24 days) and led to nevirapine discontinuation in 3/11 patients. Preliminary results of this ongoing trial show that combination therapy with stavudine/didanosine/nevirapine is a convenient (seven pills in two daily intakes) triple-therapy regimen with rapid immunological and antiviral effects. Rash, frequent in the first weeks of therapy, usually can be managed without stopping nevirapine. Long-term suppression of plasma HIV RNA with this combination needs to be confirmed but may support use of nevirapine as a component of first-line anti-HIV therapy along with two nucleosides.

Adult↗
PubMed1997

Intravenous methotrexate for primary central nervous system non-Hodgkin's lymphoma in AIDS.

OBJECTIVE: To evaluate high-dose intravenous methotrexate in primary central nervous system (CNS) lymphoma in HIV-infected patients. DESIGN: An uncontrolled pilot trial. SETTING: An infectious diseases department in Paris, France. PATIENTS: All consecutive AIDS patients with primary CNS lymphoma attending the same unit from August 1994 to March 1996. INTERVENTIONS: Methotrexate was intravenously administered at a dose of 3 g/m2 every 14 days with leucovorin rescue. A maximum of six cycles was planned. Steroids were given to all patients and haematological growth factors were administered as required. MAIN OUTCOME MEASURES: Rate of response, time to response and survival. RESULTS: Fifteen patients (10 with histological documentation) were recruited. The median time since clinical onset was 27 days (range, 7-69 days), median Karnofsky score was 51 (range, 30-70), and mean CD4+ cell count was 30 +/- 19 x 10(6)/l (range, 7-69 x 10(6)/l). Complete responses, defined as clinical improvement and disappearance of contrast-enhancing brain abnormalities on computed tomography or magnetic resonance imaging, were obtained in seven out of 15 patients (three out of 10 patients with histological diagnosis and four out of five patients without histological confirmation). The Karnofsky score of these seven patients improved to 80 +/- 10 (range, 70-100). The mean time taken to respond was 62 +/- 20 days (range, 45-90 days). One patient relapsed at 6 months. Six patients failed to respond, and two died of severe sepsis on days 15 and 45. The median survival time was 290 days (range, 11-570 days): 73 days (range, 11-570 days) in the 10 patients with histological diagnosis, and 347 days (range, 286-409 days) in the five patients without histological confirmation. Side-effects occurred in 10 patients, with gastrointestinal disorders in five, mucositis and skin rash in two, and fever in three patients; however, these events were mild and did not require cycle postponement or dose changes. No cognitive dysfunction occurred. CONCLUSION: Methotrexate appears to be an attractive alternative to radiation therapy for primary CNS lymphoma and is associated with a far greater improvement in quality of life relative to historical series of radiation therapy.

Adult↗
PubMed1997

Interferon beta transduction of peripheral blood lymphocytes from HIV-infected donors increases Th1-type cytokine production and improves the proliferative response to recall antigens.

We are developing a gene therapy method of HIV infection based on the constitutive low production of interferon (IFN) beta. Peripheral blood lymphocytes (PBL) from HIV-infected patients at different clinical stages of infection were efficiently transduced with the HMB-HbHuIFNbeta retroviral vector. The constitutive low production of IFN-beta in cultured PBL from HIV-infected patients resulted in a decreased viral production and an enhanced survival of CD4+ cells, and this protective effect was observed only in the PBL derived from donors having a CD4+ cell count above 200 per mm3. In IFN-beta-transduced PBL from healthy and from HIV-infected donors, the production of the Th1-type cytokines IFN-gamma and interleukin (IL)-12 was enhanced. In IFN-beta-transduced PBL from HIV-infected donors, the production of IL-4, IL-6, IL-10, and tumor necrosis factor alpha was maintained at normal levels, contrary to the increased levels produced by the untransduced PBL. The proliferative response to recall antigens was partially restored in IFN-beta-transduced PBL from donors with an impaired antigen response. Thus, in addition to inhibiting HIV replication, IFN-beta transduction of PBL from HIV-infected donors improves several parameters of immune function.

CD4 Lymphocyte Count↗
PubMed1997

Definition and diagnosis of cytomegalovirus colitis in patients infected by human immunodeficiency virus.

The definition and routine diagnosis of cytomegalovirus (CMV) colitis in patients infected by human immunodeficiency virus (HIV) are controversial. In 100 consecutive HIV-infected patients who underwent colonoscopy for the investigation of diarrhea, we compared the yields of routine diagnostic tools for CMV infection and assessed the risk of further CMV organ disease in subgroups of patients with the following features: full evidence of CMV colitis (group 1), colonic CMV infection but no endoscopic lesions (group 2), and no evidence of colonic CMV infection (group 3). All biopsies taken during colonoscopy were examined immediately by routine hematoxylin and eosin (H&E) staining and viral culture and then pooled for second-line H&E staining and immunohistology. Among the 15 diagnoses of CMV colitis (group 1), two were missed during initial H&E examination, and both patients developed further CMV organ disease during follow-up. Of the 12 group 2 patients 11 were not receiving anti-CMV drugs at the time of initial colonoscopy. CMV organ disease was not significantly more common in these patients than in group 3 during follow-up. We conclude that routine H&E staining of colonic biopsy specimens for CMV inclusions is not 100% sensitive for CMV colitis. The favorable outcome of colonic CMV infection without endoscopic lesions suggests that only patients with full evidence of CMV colitis warrant specific antiviral therapy.

Adult↗
PubMed1997

Two cases of cytomegalovirus infection revealed by hearing loss in HIV-infected patients.

Neurological complications are particularly common during HIV infection. Among various opportunistic diseases, cytomegalovirus (CMV) is one of the most frequent causes of central and peripheral neurological manifestations. Previously, there have been several reports of cranial nerve infection by CMV, but to our knowledge, no cases of auditory nerve involvement have been described. We report two cases in which CMV infection was revealed by involvement of the VIIIth cranial nerves. Cytomegalovirus (CMV) infection is frequent in severely immunodeficient patients infected by human immunodeficiency virus (HIV). The main targets of CMV are the retina, gastrointestinal tract and central nervous system. We describe two cases in which neurologic CMV infection was revealed by hearing loss.

AIDS-Related Opportunistic Infections↗
PubMed1997

[Development of an anti-HIV gene therapy based on the antiviral properties of beta interferon].

The aim of our work is to explore the use of IFN-beta for gene therapy in the HIV-infection. Transduction of various HIV target cells with a retroviral vector that carries the Hu-IFN-beta coding sequence under constitutive low expression control, confers resistance to HIV without affecting cell replication or function. After transduction, lymphocytes from HIV-infected patients develop resistance to the endogenous virus, provided the cells are derived from individuals with a CD4 cell count higher than 200 per mm3.

Anti-HIV Agents↗