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C Katlama

Publications and source records attributed to C Katlama.

At least 145 records · Page 8Linked to original sources
PubMed1996

Dynamics of viral variants in HIV-1 Nef and specific cytotoxic T lymphocytes in vivo.

The vigorous CTL response directed against HIV is considered to be important in reducing HIV viral load, although it is unable to stop ongoing viral replication, which generates new antigenic variants. We analyzed the impact of sequential changes in five epitopes of HIV-1 Nef on CTL recognition in four stable patients. A high rate of variation was found, and in all these patients we could detect CTL specific for 32 out of 36 autologous viral variants occurring in 5 HLA-A2- or HLA-B7-restricted Nef epitopes at two time points. Two distinct patterns for dynamics of CTL responses to viral variation were observed: 1) temporary amplification of viral variants followed by expansion of variant-specific CTL, ultimately leading to the disappearance of 12 out of the 14 initial epitope variants within two years. A second set of viral variants that had replaced the initial ones could also stimulate specific CTL precursors in the context of the same or an alternative HLA molecule; and 2) persistence of 2 viral variants in relatively conserved epitopes despite specific CTL recognition. Therefore, a remarkable flexibility of the immune system allows constant adaptation of CTL to multiple HIV variants and thus elimination of HIV variant-producing cells in slow progressors.

Amino Acid Sequence↗
PubMed1996

Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group.

OBJECTIVE: To compare safety and efficacy of lamivudine-zidovudine combination therapy with zidovudine monotherapy in treating human immunodeficiency virus type 1 (HIV-1)-infected, antiretroviral therapy-naive patients. DESIGN: Double-blind, randomized, multicenter, comparative trial of 129 patients throughout 24 weeks followed by 24 weeks of open-label lamivudine in combination with zidovudine. SETTING: Outpatients from 14 hospitals in Belgium, France, Germany, Spain, and the United Kingdom were enrolled within 6 months. PATIENTS: HIV-1-positive, antiretroviral-naive ( < or = 4 weeks prior zidovudine use) patients aged atleast 18 years with CD4+ cell counts between 0.10 x 10(9)/L and 0.40 x 10(9)/L (100-400/microL). INTERVENTION: Patients received either 300 mg of lamivudine every 12 hours in combination with 200 mg of zidovudine every 8 hours for 24 weeks or zidovudine monotherapy for 24 weeks. All patients were then allowed to receive zidovudine in combination with open-label lamivudine (300 mg every 12 hours). MAIN OUTCOME MEASURES: Efficacy was assessed by changes in CD4+ cell counts beta 2-microglobulin, neopterin, HIV-1 immune-complex dissociated (ICD) p24 antigenemia, and HIV-1 viral load. Safety was assessed by incidence of adverse clinical events and defined laboratory-measured toxic effects. RESULTS: Combination therapy showed superior treatment effects compared with monotherapy during the first 24 weeks as documented by changes in CD4+ cell counts (increase of 0.08 x 10(9)/L vs 0.02 x 10(9)/L; P < .001), ICDp24 (-88% vs -49%; P = .04), cellular viremia (-1.27 vs -0.20 log10 median tissue-culture infected dose [TCID50] per 10(6) peripheral blood mononuclear cells; P = .001), and viral load measured by HIV-1 RNA polymerase chain reaction using a Roche method (-1.33 vs -0.57 log10 copies/mL; P = .001) or an immune-capture method (-0.6 vs -0.14log10 copies/mL; P = .008). Observed changes were sustained to 48 weeks for patients continuing to receive combination therapy. Patients switching to receive combination therapy at week 24 showed improvements in CD4+ cell count and viral load to week 48. Mutation results suggested that mutations associated with zidovudine resistance may have developed more slowly over the first 24 weeks in patients receiving combination therapy. In contrast, mutations associated with lamivudine resistance appeared to develop rapidly, despite sustained antiviral treatment effect. However, the number of patients evaluated for genotypic changes was small, and confirmation of these results is needed in larger studies. No statistically significant differences in incidence or severity of clinically manifested or laboratory-measured toxic effects were noted between treatment groups. CONCLUSIONS: The combination of lamivudine and zidovudine results in a potent and sustained antiviral effect in antiretroviral-naive patients that is superior to that observed with zidovudine monotherapy.

Adult↗
PubMed1996

Summary of the International Consensus Symposium on Advances in the Diagnosis, Treatment and Prophylaxis and Cytomegalovirus Infection.

CMV infection and CMV disease can be difficult to differentiate and the diagnosis is usually based on a compatible clinical picture and the results of a diagnostic test for CMV. The only exception to this rule is in HIV-infected patients where fundoscopy is sufficient to diagnose CMV retinitis. Of the current diagnostic tests, qualitative and quantitative PCR, branched DNA and Hybrid Capture, are the most promising. The pp65 antigenemia assay has the disadvantage of being more labor-intensive than the DNA based tests. Preliminary data show that a positive qualitative PCR in a HIV-infected patient has a predictive value for the development of CMV retinitis. However, of the patients positive by qualitative PCR, those with high viral loads in quantitative PCR were at the greatest risk of CMV disease. This might make it possible to identify with great certainty the patients who will go on to develop CMV retinitis, thereby decreasing the number of patients eligible for preemptive or prophylactic therapy and increasing the cost-benefit of this therapeutic measure. Quantitative test might also be useful in monitoring response to therapy, but randomized trials comparing the test are needed. Prophylactic antiviral agents should not be used in seronegative transplant recipients receiving organs from seronegative donors. In high-risk transplant recipients, ganciclovir should be used. CMV vaccines are useful for the protection of babies from CMV seronegative mothers against congenital CMV disease. It also may be useful in seronegative transplant recipients receiving a seropositive donor organ, although the benefit of chemo prophylaxis may surpass that of vaccine. HIV-infected patients with CMV retinitis who relapse under either ganciclovir or foscarnet benefit from subsequent combination therapy, rather than switching to the other drug. However, the cost is high in terms of quality of life. Intravitreal therapy for CMV retinitis is very efficacious, suggesting that drug delivery is a problem in systemic therapy. However, intravitreal therapy does not protect against the development of CMV retinitis in the contralateral eye or from CMV disease elsewhere. Therefore, systemic therapy should be added. CMV disease of the CNS should be diagnosed early and treated agressively, possible with combination therapy. A diagnosis of CMV disease should be based on a compatible clinical picture and the demonstration of CMV in CSF by DNA or antigen assays which are more sensitive than culture.

Animals↗
PubMed1996

Tuberculosis among European patients with the acquired immune deficiency syndrome. The AIDS in Europe Study Group.

OBJECTIVES: To describe the characteristics of acquired immune deficiency syndrome (AIDS) patients with tuberculosis in Europe; to assess the incidence and risk factors of tuberculosis after AIDS; to compare survival of AIDS patients with and without extra-pulmonary tuberculosis (EPTB) at the time of AIDS diagnosis. DESIGN: Multicentric retrospective cohort study of 6544 AIDS patients diagnosed in 52 clinical centres and 17 European countries. METHODS: Description of patient characteristics and comparisons of tuberculosis incidence and mortality after AIDS with multivariate Cox proportional hazard models. RESULTS: 14.6% of AIDS patients had tuberculosis and 78% of those with tuberculosis had EPTB. EPTB was the AIDS-defining condition in 8.7% of the patients. Tuberculosis incidence after AIDS was 3.1 per 100 person-years. Age, gender and HIV-transmission category were not significantly associated with an increased risk of tuberculosis and the strongest risk factor for both EPTB and pulmonary tuberculosis (PTB) was the region of origin. The adjusted hazard ratio of EPTB and PTB in Southern Europe compared to Northern Europe were 5.5 (95% confidence interval [CI]: 5.0-6.1) and 2.0 (CI: 1.4-2.7) respectively. The apparent survival advantage of AIDS patients with EPTB compared to patients diagnosed with other conditions (median survival time: 22 vs 16 months) was statistically not significant when confounding variables were adjusted for (Hazard ratio: 0.85; CI: 0.62-1.07). CONCLUSIONS: In Europe, there are large differences in the incidence of tuberculosis among AIDS patients in different countries. They do not seem to be due to differences in age or in the prevalence of injecting drug use and likely reflect differences in the prevalence of tuberculosis infection. The role of recent transmission should also be considered, and national tuberculosis control efforts and Europe-wide surveillance need to be reinforced accordingly.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Pyrimethamine-clindamycin vs. pyrimethamine-sulfadiazine as acute and long-term therapy for toxoplasmic encephalitis in patients with AIDS.

This European multicenter study compares the efficacy and tolerance of the combination of pyrimethamine-clindamycin (Pyr-Cm) with the standard therapy pyrimethamine-sulfadiazine (Pyr-Sdz) for the treatment of toxoplasmic encephalitis (TE) in patients with AIDS. Two hundred ninety-nine human immunodeficiency virus-infected patients with TE were randomly assigned to receive 50 mg of pyrimethamine daily combined with either 2,400 mg of clindamycin or 4 g of sulfadiazine for 6 weeks followed by maintenance therapy with 25 mg of pyrimethamine daily with either 1,200 mg of clindamycin or 2 g of sulfadiazine. An intent-to-treat analysis showed that Pyr-Cm was less effective than Pyr-Sdz; the overall risk of progression of TE was 1.84 times higher for patients receiving Pyr-Cm therapy. There was no statistically significant difference in efficacy during acute therapy, although the rate of crossover motivated by a lack of response was higher among Pyr-Cm recipients. The difference in efficacy was evidenced during the maintenance phase of treatment; the relapse rate was twice as high among patients in the Pyr-Cm group (P = .02). The rate of side effects due to both regimens was similar, although the toxic effects of Pyr-Cm led to fewer discontinuations of therapy than did those of Pyr-Sdz (11% vs. 30%, respectively; P = .001). Pyr-Sdz appears to be the most effective treatment of TE. Pyr-Cm is a valuable alternative but is less effective for long-term prevention of relapses.

AIDS-Related Opportunistic Infections↗
PubMed1996

Epidemiology of cryptosporidiosis among European AIDS patients.

OBJECTIVE: To study epidemiology and possible risk factors associated with the development of cryptosporidiosis among European patients with AIDS. METHODS: An inception cohort of 6548 patients with AIDS, consecutively diagnosed from 1979 to 1989, from 52 centres in 17 European countries was studied. Data on all AIDS defining events were collected retrospectively from patients' clinical records. Kaplan-Meier estimates, log rank tests and Cox proportional hazard models were used to examine for possible risk factors associated with cryptosporidiosis. RESULTS: Cryptosporidiosis was diagnosed in 432 (6.6%) patients, 216 at time of the AIDS diagnosis and 216 during follow-up. The probability of being diagnosed with cryptosporidiosis at AIDS diagnosis was significantly lower for intravenous drug users (1.3%) than for homosexual men (4.1%) and for patients belonging to other transmission categories (4.0%) (p < 0.001). The probability was also higher for patients from Central Europe compared with patients from South Europe (4.1% versus 2.5%, p = 0.005). The rate of developing cryptosporidiosis after the diagnosis of AIDS was 3 per 100 patient years of follow-up. The rate was significantly lower for intravenous drug users than for homosexual men (relative risk 0.34, 95% confidence limits 0.22-0.54) and for women compared with men (RR 0.43 (0.21-0.87)). The risk was higher in North Europe than in South and Central Europe. In a multivariate analysis only transmission category remained a significant predictor for the development of cryptosporidiosis. CONCLUSION: The development of cryptosporidiosis in AIDS patients may be associated with sexual risk behaviour.

AIDS-Related Opportunistic Infections↗
PubMed1996

Epidemiology of AIDS-related Kaposi's sarcoma in Europe over 10 years. AIDS in Europe Study Group.

OBJECTIVES: To determine the incidence and risk factors associated with Kaposi's sarcoma (KS) occurrence as an AIDS-defining condition or after the diagnosis of AIDS. DESIGN: Multicentre retrospective cohort study of AIDS in Europe database from 52 clinical centres in 17 European countries. METHODS: Patients' charts (n = 6546) were reviewed and collected in the database of the AIDS in Europe Study Group from 1979 to 1989. At the time of AIDS diagnosis 1394 patients had KS, whereas an additional 525 others developed KS after AIDS diagnosis. Univariate analysis and development of multivariate models determined factors associated with KS occurrence. RESULTS: Frequency of KS as an AIDS-defining condition significantly declined over time (P < 0.0001). In our cohort of patients, homo-/bisexual men from central Europe with CD4 cell counts > 150 x 10(6)/l were statistically more likely to develop KS at the time of AIDS diagnosis (P < 0.0001). For patients with an AIDS diagnosis other than KS, the probability of developing KS during the follow-up was 10 and 24% after 12 and 36 months, respectively. Variables significantly associated with a further KS development were transmission group, central European residence, previous herpes simplex infection other than ulcers, and low CD4 cells (< 150 x 10(6)/l). Previous zidovudine therapy had no influence on KS appearance. For patients who developed KS subsequent to AIDS diagnosis, there was no significant decline of the incidence over the 10-year time period. CONCLUSIONS: This large cohort study clearly shows that demographic data such as sex, transmission group and region of Europe have a major influence on KS development. It also suggests that KS as an AIDS-defining disease occurs earlier in the course of the chronic HIV infection than other opportunistic diseases. Reasons for geographical variations and its declining frequency as an initial AIDS diagnosis remain undetermined.

AIDS-Related Opportunistic Infections↗
PubMed1996

Atovaquone as long-term suppressive therapy for toxoplasmic encephalitis in patients with AIDS and multiple drug intolerance. Atovaquone Expanded Access Group.

OBJECTIVE: To evaluate the efficacy and tolerance of atovaquone used as long-term maintenance therapy in patients with toxoplasmic encephalitis and intolerant of conventional anti-Toxoplasma therapies. DESIGN: Uncontrolled open-label study of atovaquone given through an expanded access programme; statistical analysis was performed on an intent-to-treat basis. PATIENTS: Sixty-five patients intolerant of conventional toxoplasmic encephalitis therapies-pyrimethamine, sulphadiazine or clindamycin-received atovaquone as maintenance therapy after resolution of an acute episode of toxoplasmic encephalitis. Patients were clinically and neurologically evaluated monthly. Toxoplasmic encephalitis relapse was defined as the occurrence of neurological abnormalities, except in the case of a proven alternative diagnosis. RESULTS: Sixty-five patients were treated with atovaquone 750 mg four times daily and followed up for a mean period of 1 year. Mean CD4 lymphocytes count was 29 x 10(6)/l. Prior to starting atovaquone, patients had experienced a total of 129 episodes of intolerance to conventional anti-Toxoplasma drugs. Atovaquone was used as a single anti-toxoplasmic agent in 75% of the cases. Seventeen patients (26%) experienced a toxoplasmic encephalitis relapse. Sixty-three patients (97%) were able to tolerate and continued taking atovaquone. Two patients had to discontinue therapy because of side-effects. In a multivariate analysis, only the duration of pyrimethamine-sulphadiazine therapy during the acute therapy phase of toxoplasmic encephalitis was significantly associated with a decreased risk of toxoplasmic encephalitis relapse during maintenance therapy [relative risk, 0.64 for each week of pyrimethamine-sulphadiazine; 95% confidence interval (CI), 0.42-0.96; P = 0.03]. The survival probability was 70% at 1 year after the episode of toxoplasmic encephalitis (95% CI, 57-83). CONCLUSION: These results suggest that atovaquone is a well-tolerated alternative anti-Toxoplasma treatment for maintenance therapy in patients who are intolerant to conventional anti-Toxoplasma drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Consequences for the management of cytomegalovirus.

BACKGROUND: Recent advances in the field of antiretroviral therapy have led to a new era where it is possible to effectively prolong the survival of HIV-infected patients. However, a corollary is the increasing prevalence of opportunistic infections, such as cytomegalovirus (CMV). CMV disease is associated with substantial morbidity, mortality, moral prejudice, impaired quality of life and cost. THE NATURAL HISTORY OF CMV INFECTION: The natural history of CMV infection consists of three phases: there is latent CMV infection with a low CMV viral load where, ideally, prophylactic treatment is indicated; then at the opposite end of the spectrum there is CMV visceral localization, associated with clinical symptoms and tissue injuries, where acute therapy is required. In between these two stages, there is reactivation of CMV, in the absence of clinical symptoms, characterized by a medium or high viral load. Early pre-emptive therapy is indicated at this stage. It is clearly very important to distinguish between these stages in order that the patient receives optimum therapy. PROPHYLAXIS AND PRE-EMPTIVE THERAPY: A recent large, placebo-controlled study has revealed the prophylactic efficacy of oral ganciclovir, with a significant reduction in the incidence of CMV disease after both 12 and 18 months. The fact that patients in this study who had reactivation of CMV virus experienced more limited benefits than those who did not have reactivation leads directly to the idea of pre-emptive therapy in those patients who are at high risk of developing the disease. Drugs used for pre-emptive therapy include foscarnet, ganciclovir and cidofovir; oral adefovir and lobucavir are also currently in development. CONCLUSIONS: The understanding of CMV infection and disease is entering a new phase. However, new drugs and new therapeutic regimens need to be evaluated and there is an urgent need for techniques to evaluate virological markers of infection and the efficacy of treatment.

AIDS-Related Opportunistic Infections↗
PubMed1995

Changes in survival over time after a first episode of Pneumocystis carinii pneumonia for European patients with acquired immunodeficiency syndrome. Multicentre Study Group on AIDS in Europe.

BACKGROUND: Factors associated with improved survival over time for patients with the acquired immunodeficiency syndrome (AIDS) who have Pneumocystis carinii pneumonia at diagnosis are not clearly defined. METHODS: An inception cohort of 2533 patients with AIDS, diagnosed from 1979 to 1989, from 52 centers in 17 European countries was studied. Survival 3 months and 3 years after diagnosis was estimated by Kaplan-Meier life tables. Independent predictors of survival were analyzed by construction of Cox proportional hazards models. RESULTS: Patients in whom AIDS and P carinii pneumonia had been diagnosed before 1988 had a poorer 3-month (ie, short-term) survival, whereas the survival 1 and 2 years after P carinii pneumonia was lower only for patients whose disease was diagnosed before 1987 compared with those with more recent diagnoses. Other variables associated with poorer outcome were greater age, infection via blood transfusion, diagnosis made in south Europe, and coexisting illnesses. After controlling for these prognostic markers in multivariate analysis, improvement in survival over time was still evident. For patients who survived the P carinii pneumonia episode, both zidovudine and secondary prophylaxis for P carinii pneumonia initiated around the time of diagnosis were associated with improved survival, and, after controlling for these treatment variables, no statistically significant improvement in survival over time was observed. CONCLUSIONS: Survival after an episode of P carinii pneumonia has improved within recent years. Increased awareness of early symptoms of P carinii pneumonia and better treatment of the pneumonia may have led to improvement in short-term survival over time, whereas the introduction of zidovudine and increased use of secondary P carinii pneumonia prophylaxis may have resulted in the recent increase in survival 1 and 2 years after the diagnosis. However, 3-year survival remained unchanged over time, implying that the underlying human immunodeficiency virus infection and other complications are not effectively controlled.

AIDS-Related Opportunistic Infections↗
PubMed1995

Adverse cutaneous reactions to pyrimethamine/sulfadiazine and pyrimethamine/clindamycin in patients with AIDS and toxoplasmic encephalitis.

We assessed the value of clinical and laboratory parameters for predicting the occurrence of skin reactions induced by pyrimethamine/sulfadiazine and pyrimethamine/clindamycin and the effects of continued therapy for patients with these reactions. We retrospectively studied all episodes of toxoplasmic encephalitis in patients with AIDS who were treated with pyrimethamine/sulfadiazine or pyrimethamine/clindamycin. Eighteen (75%) of 24 patients treated with pyrimethamine/sulfadiazine had cutaneous reactions after a mean of 11 days, whereas 15 (58%) of 26 patients treated with pyrimethamine/clindamycin had cutaneous reactions after a mean of 13 days (P = .56). Nine (50%) of the 18 patients continued to be treated with pyrimethamine/sulfadiazine throughout the duration of hypersensitivity, compared with all 15 patients who were treated with pyrimethamine/clindamycin (P = .002). Nine patients had to stop therapy with pyrimethamine/sulfadiazine (two had Stevens-Johnson syndrome and one had Lyell's syndrome). Thus, treatment throughout the duration of hypersensitivity is more likely to succeed for patients receiving pyrimethamine/clindamycin, whereas therapy with pyrimethamine/sulfadiazine is associated with a high risk of Lyell's syndrome and Stevens-Johnson syndrome.

AIDS-Related Opportunistic Infections↗
PubMed1995

Evaluation of safety and efficacy of 3TC (lamivudine) in patients with asymptomatic or mildly symptomatic human immunodeficiency virus infection: a phase I/II study.

In a phase I/II study, 7 levels of 3TC therapy (from 0.5 to 20.0 mg/kg/day) were studied in 104 asymptomatic and mildly symptomatic human immunodeficiency virus-infected patients with CD4 cell counts < or = 400 x 10(6)/L. Mild and transient episodes of diarrhea, headache, fatigue, nausea, and abdominal pain were the most frequent events reported. No dose-limiting toxicities were observed. Small and transient increases in CD4 cell counts were detected during the first 4 weeks of treatment. These were followed by progressive declines during prolonged therapy. Sustained decreases in beta 2-microglobulin, neopterin, and p24 antigen levels were seen over the 52-week study. There was no consistent dose-response correlation for any surrogate marker. Penetration of 3TC into cerebrospinal fluid (CSF) was in the same range as reported for ddC and ddI; the mean CSF-to-serum ratio was 0.06. These findings indicate that 3TC exhibits an excellent safety profile and has antiretroviral activity at the dosages studied.

Adult↗