Search PubMed⌕ Search

Biomedical subjects

C Katlama

Publications and source records attributed to C Katlama.

At least 127 records · Page 7Linked to original sources
PubMed1997

Reductions in HIV-1 disease progression for zidovudine/lamivudine relative to control treatments: a meta-analysis of controlled trials.

OBJECTIVES: Four randomized double-blind trials have demonstrated that zidovudine/lamivudine (ZDV/3TC) reduces HIV RNA and raises CD4 counts relative to control treatments (ZDV or ZDV/zalcitabine (ddC)]. A meta-analysis of the clinical events in these trails was conducted to determine whether treatment with ZDV/3TC was also associated with a clinical benefit. DESIGN: The four trials, ZDV/3TC versus ZDV (NUCA3001, NUCB3001, NUCB3002) or versus ZDV/ddC (NUCA3002), were run concurrently, using the same doses of ZDV and 3TC. SETTING: Investigational sites in Europe and North America. PATIENTS: The trials recruited 972 HIV-1-positive, male and female patients aged > or = 18 years, with CD4 counts of 100-500 cells x 10(6)I. Two trials were for ZDV-naive patients and two were for ZDV pre-treated patients. MAIN OUTCOME MEASURES: Progression to first new Centers for Disease Control and Prevention (CDC) B or C event was compared between all ZDV/3TC arms and all control (ZDV, ZDV/ddC) arms. RESULTS: A total of 118 patients progressed to a first new CDC B/C event during the four trials, while 28 progressed to a new CDC event. Meta-analysis of the trials showed a 49% reduction in progression to new CDC B/C events (relative risk, 0.509; 95% confidence interval, 0.365-0.710; P < 0.0001) and a 66% reduction in progression to new CDC C events (relative risk, 0.344; 95% confidence interval, 0.169-0.700; P = 0.003) for the ZDV/3TC patients relative to the control patients. Reductions in progression to CDC B/C disease were seen in subgroups of naive and pre-treated patients, those with high and low CD4 counts and symptomatic and asymptomatic patients. CONCLUSIONS: ZDV/3TC combination treatment delays the progression of CDC B/C disease compared with control treatments. In view of the low incidence of CDC C events, the results for progression to CDC C disease should be interpreted with caution.

Adolescent↗
PubMed1997

Survival of European patients with Kaposi's sarcoma as AIDS-defining condition during the first decade of AIDS. AIDS in Europe Study Group.

OBJECTIVES: To determine whether the survival of patients with Kaposi's sarcoma as first manifestation of AIDS has changed between 1979 and 1989; and to define whether prognosis factors could be identified. PATIENTS AND METHODS: This is a multicentric retrospective cohort study from 52 centers in 17 European countries involving adults AIDS patients diagnosed between 1979 and 1989. Variables such as age, sex, geographical regions, transmission groups, date of Kaposi's sarcoma diagnosis, zidovudine use, CD4+ cell count and concomitant opportunistic infections or AIDS-related malignancies were evaluated by using uni- and multivariable proportional hazard models. Log-rank tests were used to determine which variables were associated with survival. RESULTS: From the 6,546 AIDS patients recruited in the database of the AIDS in Europe Study Group, 1,394 were diagnosed with Kaposi's sarcoma at the time of AIDS diagnosis, from 1979 and 1989. A total of 1,047 Kaposi's sarcoma patients died during the follow-up period. By Kaplan-Meier analyses, the median and mean survival for these Kaposi's sarcoma patients were 17 and 25 months, respectively, with no change over time. However, age, sex (female), geographic region, low CD4+ cell count (< 150 x 10(6)/l) and some opportunistic infections and non-Hodgkin's lymphoma were associated with a poorer prognosis. Zidovudine use, year of diagnosis and risk factor for HIV-1 infection brought no additional information as predictor of mortality. CONCLUSIONS: This study suggests that the survival of patients with Kaposi's sarcoma as first manifestation of AIDS has remained poor during the last decade in contrast with the overall AIDS survival which had significantly improved from a median of 13-18 months during the same period of observation. There is a need for further prospective information to explain the worse prognosis in women and the geographical variations.

AIDS-Related Opportunistic Infections↗
PubMed1997

Cytomegalovirus retinitis in patients with AIDS in Europe. AIDS in Europe Study Group.

The incidence of cytomegalovirus (CMV) retinitis and risk factors associated with the condition were studied in patients with the acquired immune deficiency syndrome (AIDS) in a multicenter retrospective cohort study of 6458 patients from 52 centers in 17 countries in Europe. Cytomegalovirus retinitis was diagnosed in 154 patients (2.4%) at the time of AIDS diagnosis, the probability of this diagnosis being significantly higher for those with CD4+ cell counts of < 100/mm3 (3.4%) than with counts of 100-200/mm3 (1.3%) or > 200/mm3 (0.8%). The rate of developing CMV retinitis after AIDS diagnosis was 9.4 per 100 patient years of follow-up. Multivariate analysis showed that risk behavior was significantly associated with the risk of developing CMV retinitis: lower for intravenous drug users [relative risk (RR) 0.47] and those engaged in "other risk behavior" (RR 0.58) than for homosexual men. The risk of developing CMV retinitis after AIDS diagnosis was significantly associated with CD4+ cell count at the time of AIDS diagnosis: for counts < 100/mm3 (RR 2.90) and from 100 to 200/mm3 (RR 2.13), there was a higher risk than for counts > 200/mm3. Patients with Pneumocystis carinii pneumonia, toxoplasmosis, or extraocular CMV infection at time of AIDS diagnosis exhibited an increased risk of developing CMV retinitis. Patients treated with zidovudine exhibited an increased rate of CMV retinitis: RR was 1.75 during and 2.87 after the second year of treatment as compared to those who had not received zidovudine. Median survival after CMV retinitis at time of AIDS diagnosis was eight months.

AIDS-Related Opportunistic Infections↗
PubMed1997

Tumor necrosis factor-alpha, microglia and astrocytes in AIDS dementia complex.

The pathogenesis of HIV-associated cognitive changes is poorly understood. Cytokines such as tumor necrosis factor-alpha (TNF-alpha) have been postulated to contribute to the mechanism of the neurological complications of HIV infection. One of the effects of TNF-alpha is to induce astrocyte proliferation in vitro. The purpose of this study was to look for a correlation between the expression of TNF-alpha, astrogliosis and the degree of cognitive impairment in 12 prospectively assessed AIDS cases without focal brain lesion, 8 of whom were demented. They were compared with 6 control patients without neurological disease. Neuropathological examination showed myelin pallor in 5 of the 8 demented patients. TNF-alpha expression was detected by immunohistochemistry in the midfrontal cortex, subcortical and deep white matter, and basal ganglia. Not only perivascular macrophages but also some microglial and endothelial cells were labeled. Most TNF-alpha-positive cells were in close contact with glial fibrillary acidic protein-positive astrocytes. They were more numerous than gp41-positive cells. Their density increased with increasing cognitive impairment and in parallel to the astrogliosis in the frontal cortex, basal ganglia and deep white matter. These findings further support the hypotheses that lesions of the deep white matter, driven by TNF-alpha, are associated with cognitive alteration, and that indirect effects of HIV infection in the brain participate in the development of HIV-associated dementia through a diffuse immune activation, mediated by cytokines.

AIDS Dementia Complex↗
PubMed1997

Survival of AIDS patients according to type of AIDS-defining event. The AIDS in Europe Study Group.

BACKGROUND: There are known to be wide differences in the prognosis of patients with a diagnosis of AIDS. In this study of 6578 patients with AIDS form 17 European centres, we develop a ranking of AIDS-defining illnesses, and determine how well this ranking holds after adjustment for potential confounding variables. METHODS: Survival from each AIDS-defining event was calculated and ranked using Kaplan-Meier estimation of median survival. Cox proportional hazards models with each disease modelled as a time dependant covariate were used to determine the risk of death after each diagnosis, before and after adjustment for potential confounders. RESULTS: Median survival after an initial AIDS-defining diagnosis of progressive multifocal leukoencephalopathy and malignant lymphoma was particularly poor (2 and 5 months respectively), while the longest median survival occurred after initial AIDS-defining illnesses of Kaposi's sarcoma and extrapulmonary tuberculosis (17 and 22 months respectively) Patients diagnosed with a primary brain lymphoma had shorter median survival times than patients with a peripheral lymphoma (median survival of 1 month and 4 months respectively P < 0.0001). In general, median survival in patients with cutaneous Kaposi's sarcoma (skin, oral) was between two and four times longer than patients with systemic involvement The ranking of diseases was found to be generally similar after adjustment for all potential confounders. CONCLUSIONS: AIDS-defining events can be grouped into three categories with median survival after diagnosis of < 6 months. 6-12 months and > 12 months. The assigned ranking of disease would not be altered by prognostic factors such as age or CD4 lymphocyte count. These results have important implications in the design of clinical trials and patient management.

AIDS-Related Opportunistic Infections↗
PubMed1997

Maternal virus load during pregnancy and mother-to-child transmission of human immunodeficiency virus type 1: the French perinatal cohort studies. SEROGEST Cohort Group.

Virus load in pregnancy and its relation to mother-to-child human immunodeficiency virus (HIV) transmission were studied prospectively. From 1989 to 1994, 320 HIV-infected women from 18 centers had plasma samples stored. Among women not receiving antiretroviral therapy, the polymerase chain reaction RNA level was 3.6 log at delivery, and 15% of women had levels below the detection limit. There was no variation during pregnancy. Women born in sub-Saharan Africa had lower RNA levels, although their CD4 cell distribution did not differ from that in other women. Among 236 evaluable children, 19% +/- 5% were infected. Transmission occurred in 12% of cases (confidence interval, 5%-22%) with <1000 copies/mL versus 29% +/- 10% of those with >10,000 copies/mL (P < .02). Maternal virus load appears strongly related to HIV transmission to the child.

Africa South of the Sahara↗
PubMed1997

Potential efficacy of fumagillin in intestinal microsporidiosis due to Enterocytozoon bieneusi in patients with HIV infection: results of a drug screening study. The French Microsporidiosis Study Group.

OBJECTIVE: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a frequent cause of chronic diarrhoea in patients with HIV infection for which there is no available therapy. This study was designed to search for a drug with activity against this organism. DESIGN: Prospective open-labelled Phase II multicentre study. SETTING: University hospitals. PATIENTS: Sixty HIV-infected men with intestinal E. bieneusi infection. INTERVENTIONS: Ten drug regimens were consecutively tested orally for 3 weeks: albendazole plus metronidazole, sulphadiazine plus pyrimethamine, atovaquone, doxycycline plus nifuroxazide, itraconazole, flubendazole, chloroquine, paromomycin, sparfloxacin and fumagillin. Nine evaluable patients per regimen were required, but each patient could be enrolled up to three times in the study. OUTCOME MEASURE: Efficacy was assessed primarily by the clearance of E. bieneusi from stools and intestinal biopsies. The safety of each regimen was also assessed. RESULTS: Only purified fumagillin was able to clear E. bieneusi from stools as well as intestinal biopsies, whereas all other regimens failed to show antiparasitic efficacy. However, only four patients received fumagillin because of drug-induced thrombocytopenia. The four patients who received fumagillin remained free of E. bieneusi infection after a mean follow-up of 10 months. CONCLUSION: Eradication of E. bieneusi from the intestinal tract of patients with HIV infection and persistent immunosuppression is an achievable goal. Our study allowed the identification of oral fumagillin as a potential treatment for intestinal microsporidiosis due to E. bieneusi.

AIDS-Related Opportunistic Infections↗
PubMed1997

Human immunodeficiency virus type 1 DNA and RNA load in brains of demented and nondemented patients with acquired immunodeficiency syndrome.

The relationship between dementia and human immunodeficiency virus type 1 (HIV-1) cerebral load is not clearly understood. We used immunohistochemistry and competitive polymerase chain reaction to evaluate the density ofgp 41 immunostained cells and the amount of HIV-1 DNA and RNA in the midfrontal gyrus of 21 HIV-1 infected patients, nine of whom were demented. The amounts of HIV-1 DNA and RNA, and the density of gp 41-positive cells were significantly linked. In this small series of cases, (1) although as a mean, there was a larger viral load in demented patients than in nondemented, this did not reach the significance level (2) discrepancies appeared in the population under study, some demented patients having low viral loads.

AIDS Dementia Complex↗
PubMed1997

Reductions in viral load and increases in T lymphocyte numbers in treatment-naive patients with advanced HIV-1 infection treated with ritonavir, zidovudine and zalcitabine triple therapy.

In order to test the hypothesis that a combination of protease inhibitors with nucleoside analogues-agents known to inhibit different steps of the human immunodeficiency virus (HIV) life cycle--is likely to prove more effective in reducing viral loads than either of those modalities alone, we performed a 60 week, open-label trial in 32 HIV-positive patients with depressed CD4 T lymphocyte cell counts but no active AIDS-defining illnesses. For the first 2 weeks, patients received 600 mg twice daily of liquid ritonavir, a protease inhibitor; then zidovudine 200 mg three times daily and zalcitabine 0.75 mg three times daily were added to the treatment regimen. Mononuclear blood cell fractions were analysed for infected cell levels, using a co-culture system. HIV-1 RNA in plasma was measured both by reverse transcriptase-polymerase chain reaction (RT-PCR) and reverse transcriptase quantitative PCR (QcRT-PCR); lymphocyte counts were determined by standard laboratory methods. In the 2 weeks of ritonavir therapy, both the mean count of infectious blood cells and plasma HIV RNA levels decreased dramatically. Mean CD4 cell counts increased from 173 cells/mm3 at baseline to 286 cells/mm3; CD8 cell counts rose from 951 cells/mm3 to 1,141 cells/mm3. With the introduction of the nucleoside analogues, infectious cell counts and plasma virus dropped another log unit to a nadir at 8 weeks, while CD4 T lymphocyte counts continued to rise slowly. By week 28, 12 patients had withdrawn due to adverse events, none of which were life-threatening. At week 36, infectious material could not be detected in the cells of 10 of the 17 remaining patients; by week 60, four of the seven patients with residual viraemia at week 24 had undergone viral relapse. After the introduction of a more palatable capsule formulation of ritonavir at week 52, infectious cells and plasma virus were undetectable in 50-60% of patients. The combination of protease inhibitors and nucleoside analogues significantly reduces HIV load, and in some patients may suppress viral activity for sustained periods.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Additional mutations detected in sequential HIV-1 isolates from ZDV-treated patients.

Sequential isolates from four patients under zidovudine (ZDV) therapy were obtained using PBMC coculture in the absence or in the presence of 0.25 microM ZDV. PBMC-based HIV susceptibility assay demonstrated the emergence of ZDV-resistance in the sequential isolates from the four patients. Except in one case, the isolates obtained in the presence of ZDV did not exhibit a greater resistance pattern than their counterparts obtained in the absence of the drug. In parallel, partial reverse transcriptase gene sequence was determined directly on amplified products from proviral DNA. In addition to the mutations previously described at the critical codons 41, 67, 70, 215, and 219, numerous additional mutations were found in either ZDV-sensitive or ZDV-resistant isolates. The mutation Thr215Tyr was not observed in a case of highly resistant virus (ZDV IC50 > 6.25 microM), while the mutation Lys70Arg was found in either resistant or sensitive ones. The analysis of additional mutations did not reveal any clear pattern for ZDV resistance but pointed out the existence of highly variable regions neighbouring the five critical codons. Neither nucleotide sequence nor PBMC-based susceptibility assay provided unambiguous data about pretherapy isolates or early on-therapy isolates which could predict the emergence of ZDV resistance in further samples.

Anti-HIV Agents↗
PubMed1997

Efficacy and safety of desensitization with sulfamethoxazole and trimethoprim in 48 previously hypersensitive patients infected with human immunodeficiency virus.

OBJECTIVE: To study the safety and efficacy of desensitization with the use of a combination product of sulfamethoxazole and trimethoprim in previously hypersensitive patients infected with the human immunodeficiency virus. DESIGN: Prospective survey, with a median follow-up of 16 months (range, 5-24 months). SETTING: Day-care hospital in a referral center. PATIENTS: All human immunodeficiency virus-infected patients who had a history of allergic reactions (eg, rash) to sulfamethoxazole-trimethoprim and who required sulfamethoxazole-trimethoprim prophylaxis. INTERVENTION: The desensitization procedure took 2 days. The full dose (sulfamethoxazole-trimethoprim, 400-80 mg) was reached on the third day according to the following schedule: day 1--4-0.8 mg at 9 AM, 8-1.6 mg at 11 AM, 20-4 mg at 1 PM, and 40-8 mg at 5 PM; day 2--80-16 mg at 9 AM, 160-32 mg at 3 PM, and 200-40 mg at 9 PM; and day 3--400-80 mg at 9 AM. MAIN OUTCOME MEASURE: The onset of cutaneous adverse effects attributable to sulfamethoxazole-trimethoprim therapy within 3 months after desensitization. RESULTS: Of the 48 evaluable patients, 37 (77%) tolerated sulfamethoxazole-trimethoprim desensitization without toxic effects and continued to take sulfamethoxazole-trimethoprim daily. Desensitization failed in 11 cases (5 on day 1, 3 on day 2, and 1 each on days 9, 11, and 90). Acute hypotension and a nonfatal myocardial infarction developed in 1 of these patients. The factors that were predictive of failure were a relatively high CD4+ cell percentage (11% vs 8%; P = .008) and a relatively high CD4+/CD8+ ratio (0.27 vs 0.12; P = .02). CONCLUSIONS: The efficacy of desensitization with sulfamethoxazole-trimethoprim was confirmed; this desensitization procedure was more often successful in patients with lower CD4+ cell percentages and CD4+/CD8+ ratios. However, sulfamethoxazole-trimethoprim therapy should be reintroduced carefully.

Adult↗
PubMed1997

Astrocytic adhesion molecules are increased in HIV-1-associated cognitive/motor complex.

Half of AIDS dementia cases are associated with HIV-encephalitis or myelin pallor. Another half die with no HIV-related neuropathological changes. Previous observations suggest that cerebral dysfunction may result from more subtle cellular interactions. and that some of them may be mediated by cell adhesion molecules. In the present study the expression by astrocytes and endothelial cells of intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) was analysed as a function of the neuropathological diagnosis, the density of astrogliosis and of HIV-1 positive cells, and of the mental status. Twelve AIDS cases, without focal brain lesion, eight of whom were demented, were selected from a prospective study. They were compared with six control cases with multiple sclerosis, and with six control patients without neurological disease. ICAM-1 and VCAM-1 expression was localized by immunofluorescence and confocal microscopy. HIV protein gp41 was detected by immunohistochemistry on adjacent sections. Endothelial expression of ICAM-1 and VCAM-1 was significantly up-regulated in all AIDS patients. VCAM-1 only was related to myelin pallor. The density of VCAM-1 or ICAM-1 positive astrocytes increased in demented AIDS patients, independently of the neuropathological findings or the density of gp41 positive cells. Expression of cell adhesion molecules, together with other secondary mechanisms such as secretion of cytokines may play a role in the pathogenesis of white matter lesions leading to HIV-1-associated cognitive changes.

AIDS Dementia Complex↗
PubMed1996

Effects of lamivudine on replication of hepatitis B virus in HIV-infected men.

BACKGROUND: Therapy for hepatitis B virus (HBV) infection is still unsatisfactory, particularly in patients who are co-infected with the human immunodeficiency virus (HIV). Lamivudine, a retroviral inhibitor, has been shown to have activity against HBV replication in vitro, in animal models, and in studies of immunocompetent persons. OBJECTIVE: To assess the efficacy of lamivudine in inhibiting HBV replication during a 12-month period in patients with both HBV and HIV infection. DESIGN: Prospective, open study. SETTING: University hospital. PATIENTS: 40 consecutive patients (39 men and 1 woman) infected with both HIV and HBV. All had progressive HIV disease; were refractory to or unable to tolerate therapies other than lamivudine; and received lamlvudine, 600 mg/d or 600 mg/d followed by 300 mg/d, as therapy for HIV disease. MEASUREMENTS: Serum concentrations of HBV DNA were assessed every 2 months by using molecular hybridization. Polymerase chain reaction (PCR) for HBV DNA was done at baseline and was done at months 2, 6, and 12 only if the HBV DNA concentration was less than 5 pg/mL. RESULTS: Two groups were retrospectively identified at baseline: patients with high HBV replication (serum HBV DNA concentrations > 5 pg/mL) (n = 30) and patients with low HBV replication (serum HBV DNA concentrations < 5 pg/mL) (n = 10). After 12 months of treatment, 26 of 27 patients (96.3% [95% Cl, 81% to 99.9%]) who had had high HBV replication at baseline had serum HBV DNA concentrations less than 5 pg/mL. However, PCR could still detect HBV DNA in serum in 11.5% (Cl, 2% to 30%) of these patients. Among patients who had had low HBV replication at baseline, the results of PCR for serum HBV DNA became negative in the 6 patients who had had a positive result on PCR at baseline. No serious adverse events occurred during treatment. CONCLUSION: Although this study was not a randomized, blinded trial, it suggests that lamivudine is active against.

AIDS-Related Opportunistic Infections↗