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Biomedical subjects

C Katlama

Publications and source records attributed to C Katlama.

At least 109 records · Page 6Linked to original sources
PubMed1998

Survival in 2367 zidovudine-treated patients according to use of other nucleoside analogue drugs. The EuroSIDA Study Group.

To evaluate survival according to use of different nucleoside drugs in a routine clinical setting, we studied a large group of zidovudine-treated patients seen in clinics across Europe. A total of 3128 subjects was recruited to the observational, prospective EuroSIDA study in May 1994. These were consecutive patients (up to a predefined limit) seen at outpatient clinics in 37 centers from 16 European countries and followed at 6-month intervals by use of standardized forms completed by clinicians at the respective centers. This report concerns 2367 subjects who began antiretroviral therapy with a regime that included zidovudine either before study entry or during the course of follow-up. Cox proportional hazards models were fitted, with use of other antiretroviral drugs, CD4 count, and date of development of AIDS fitted as time-dependent covariates. Survival times from start of therapy were left truncated at study entry to avoid survival bias. In addition to zidovudine, antiretroviral drugs used included didanosine (ddI) (n = 1119; median 1.6 years after starting zidovudine), dideoxycytidine (ddC) (n = 592; median 1.9 years after starting zidovudine), stavudine (d4T) (n = 241; median 2.9 years after starting zidovudine) and lamivudine (3TC) (n = 33 ; median 2.7 years after starting zidovudine). Of the 2367 patients, 613 died during follow-up. Overall, risk of death was reduced in those zidovudine-treated patients who began at least one other nucleoside analogue drug with or after taking zidovudine (relative hazard [RH], 0.61; 95% confidence interval [CI], 0.51-0.72, adjusting for CD4 count, development of AIDS, and age). Fitting each drug separately, there was a larger association with reduced mortality for starting 3TC (RH, 0.41; 95% CI, 0.28-0.62) than for starting ddl (RH, 0.79; 95% CI, 0.67-0.93), ddC (RH, 0.74; 95% CI, 0.59-0.92) or d4T (RH, 0.67; 95% CI, 0.49-0.91). These results suggest that the beneficial effect of nucleoside combination therapy identified in controlled trials can be seen in routine clinical practice.

Adult↗
PubMed1998

[Epidemiologic characteristics of cerebral toxoplasmosis in 399 HIV-infected patients followed between 1983 and 1994].

OBJECTIVE: To describe the epidemiological characteristics of toxoplasmic encephalitis in HIV-infected patients with a more than 12-year follow-up. METHODS: From a data base of 1,628 AIDS subjects hospitalized from 1983 to 1994, we studied the epidemiological characteristics of 399 patients with toxoplasmic encephalitis. Diagnosis of toxoplasmic encephalitis was based on the association of central neurological disorders, typical lesions on CT scan or MRI, and favorable outcome under appropriate toxoplasmosis therapy. RESULTS: Four hundred sixty-four cases of toxoplasmic encephalitis were reported in 399 patients (24.5% of the patients with AIDS). The overall incidence was 20.5 per 100 patients-year. Toxoplasmic encephalitis was the first AIDS defining event in 51% of the cases and revealed HIV infection in 13% of the cases. In the remaining 49%, the mean delay from AIDS diagnosis to toxoplasmic encephalitis was 13 months (range: 1-71 months). At the time of diagnosis, mean CD4 count was 44/mm3 (range: 0-408/mm3). Antibodies to Toxoplasma gondii were found in 97% of the cases. Before the first episode of toxoplasmic encephalitis, 58% of the patients were given antiretroviral therapy (mean: 17.8 months; range: 1-64 months). Of the 399 patients with toxoplasmic encephalitis, 366 (92%) did not receive any primary toxoplasmosis prophylaxis. Among them, 205 (56%) did not receive any drug prophylaxis, and 161 (44%) had Pneumocystis carinii pneumonia prophylaxis alone (aerosolized pentamidine). Thirty-three failures were observed (8%) with cotrimoxazole: 14 cases (3%) were considered to have irregular compliance. Sixty-five relapses were observed in 52 patients. At the end of the study 334 patients had died (84%). The median survival was 11.4 months (95% confidence interval, range: 10.4-12.4 months). CONCLUSIONS: Toxoplasmic encephalitis incidence has decreased since the introduction of appropriate drug prophylaxis.

AIDS-Related Opportunistic Infections↗
PubMed1998

Perturbation of CD4+ and CD8+ T-cell repertoires during progression to AIDS and regulation of the CD4+ repertoire during antiviral therapy.

The T-cell antigen receptor (TCR) repertoire was studied longitudinally by analyzing the varying lengths of the beta chain CDR3 hypervariable region during the course of HIV-1 infection and following combination antiretroviral therapy. Drastic restrictions in CD8+ T-cell repertoire usage were found at all stages of natural progression and persisted during the first six months of treatment. In contrast, significant CD4+ T-cell repertoire perturbations were not found in early stages of infection but correlated with progression to AIDS. Out of ten patients presenting with pretreatment perturbations, normalization of the CD4+ repertoire was observed in eight good responders, but not in two cases of unsuccessful therapy. These results indicate that, besides CD4+ cell count rise, an efficient control of HIV replication may allow qualitative modifications of the CD4+ repertoire balance.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Identification of crystals in kidneys of AIDS patients treated with foscarnet.

Three acquired immune deficiency syndrome patients given foscarnet to treat cytomegalovirus retinitis developed renal failure with crystal deposits within the renal glomeruli. We identified these crystals as a mixture of sodium salt, calcium salt, and a mixed salt containing both sodium and calcium ions. This composition has not been previously reported. Foscarnet can complex available ionized calcium and secondarily precipitate in glomeruli. The percentage of complexing depends on calcium concentration in serum and the poor calcium salt solubility.

AIDS-Related Opportunistic Infections↗
PubMed1998

Pyogenic bacterial pneumonia in human immunodeficiency virus-infected inpatients: a clinical, radiological, microbiological, and epidemiological study.

We prospectively studied features of pyogenic bacterial pneumonia in 263 consecutive human immunodeficiency virus-infected inpatients over a 6-month study period. Risk factors for bacterial pneumonia were examined by a case-control study that included 33 cases who presented with at least one episode of bacterial pneumonia and 80 controls without bacterial pneumonia. The estimated cumulative incidence of bacterial pneumonia per year was 12.5 cases per 100 inpatients (95% confidence interval [CI], 8.8-17.2). The 38 episodes of bacterial pneumonia that occurred in the 33 inpatients were mainly unilateral, but 32 episodes were patchy lobar or diffuse infiltrates. Microbiological etiologies were obtained in 33 of the 38 episodes of bacterial pneumonia. Thirty-seven pathogens were identified, including Streptococcus pneumoniae (16, of which 12 had a decreased susceptibility to penicillin), Haemophilus influenzae (6), and Pseudomonas aeruginosa (6). The risk factors for bacterial pneumonia that were identified after logistic regression included prior sinusitis within 1 month before admission (odds ratio [OR], 3.2; 95% CI, 1.1-9.1) and prior bacterial infection of the lower respiratory tract within 6 months before admission (OR, 3.1; 95% CI, 1.1-8.3).

AIDS-Related Opportunistic Infections↗
PubMed1998

Acyclovir-resistant herpes zoster in human immunodeficiency virus-infected patients: results of foscarnet therapy.

We retrospectively studied 18 consecutive cases of acyclovir-resistant zoster. All the patients had chronic skin lesions that failed to heal despite treatment with intravenous acyclovir (30 mg/[kg.d]) in 15 cases and oral acyclovir (4 g/d) in three cases for > 10 days. The mean CD4+ cell count was 20 x 10(6)/L. The mean number of previous zoster episodes was 1.53. Fifteen of the 16 patients evaluable for previous acyclovir treatment had received the drug. Thirteen patients were treated with intravenous foscarnet (200 mg/[kg.d]) for a mean of 17.8 days. Complete healing was observed in 10 (77%) of the 13 treated patients. Zoster relapsed after cessation of foscarnet therapy in five of the 10 responding patients. The median time to relapse was 110 days. Four patients died of varicella-zoster virus-associated visceral complications. These results show that acyclovir-resistant zoster has a poor prognosis but responds well to foscarnet therapy.

AIDS-Related Opportunistic Infections↗
PubMed1998

The level of human immunodeficiency virus (HIV) type 1 RNA in cerebrospinal fluid as a marker of HIV encephalitis.

We prospectively evaluated the level of human immunodeficiency virus (HIV) type 1 RNA in cerebrospinal fluid (CSF) as a marker of HIV encephalitis. Fifty-two HIV-1-infected patients (41 males and 11 females; mean age, 39 years) were tested for the presence of HIV-1 RNA in plasma and CSF. Samples of CSF were obtained by lumbar puncture to evaluate cognitive deficits, seizures, or fever among these patients. HIV encephalitis was diagnosed in 11 patients (21%), other CNS diseases were diagnosed in 12 (23%), and fever without CNS disease was diagnosed in 29 (56%). HIV-1 RNA was detectable in 92% of the plasma specimens and 75% of the CSF specimens. No significant difference was observed in CSF levels of HIV-1 RNA between patients with or without HIV encephalitis. CSF levels of HIV-1 RNA correlated with plasma levels of HIV-1 RNA (Spearman's rank correlation, +0.31; P = .02) and CSF white blood cell counts (Spearman's rank correlation, +0.4; P < .01). The absence of any significant difference between patients with or without HIV encephalitis suggests that the CSF HIV-1 RNA level is not a good marker for the diagnosis of HIV encephalitis.

AIDS Dementia Complex↗
PubMed1998

Mycobacterium avium complex common-source or cross-infection in AIDS patients attending the same day-care facility.

To delineate the epidemiology of Mycobacterium avium complex (MAC) infection in acquired immunodeficiency syndrome patients, we studied 32 case patients with disseminated MAC infection who attended the same daycare facility during a period of 13 months. Pulsed-field gel electrophoresis analysis showed very low similarity between MAC strains, suggesting that, despite close contacts between the patients, nosocomial cross-transmission or exposure to a common source of MAC did not occur.

AIDS-Related Opportunistic Infections↗
PubMed1998

CD8hi+CD57+ T lymphocytes are enriched in antigen-specific T cells capable of down-modulating cytotoxic activity.

Major expansions of CD8hi+CD57+ T lymphocytes frequently occur during human immunodeficiency virus (HIV) infection and after transplantation. To investigate mechanisms of such cell expansion, we compared the activation and functional status of CD8hi+CD57+ and CD57-peripheral blood lymphocytes (PBL) from normal, bone marrow transplantation (BMT) and HIV+ donors. The CD8hi+CD57+ PBL from BMT and HIV+ donors preferentially displayed CD38 and HLA-DR activation markers without correlation between CD8hi+CD57+ percentages and HIV load, the CD45RA+ isoform in all ex vivo conditions but acquired CD45RO after in vitro expansion, CD11b and CD11c in BMT and HIV+ donors but decreased expression of CD62-L, VLA-2 and VLA-6. The CD8hi+CD57+ cells were positive for perforin and granzyme B and spontaneously mediated cytolytic activity in a CD3-redirected assay. In contrast the inhibitor of cytolytic functions (ICF) produced by CD8hi+CD57+ cells down-modulated the CD3-redirected cytolytic activity but only at low levels of CD3 cross-linking. While CD3-triggering induced a low, if any, short-term proliferation of CD8+CD57+ cells, this subset could be amplified after long-term stimulation either with mitogens or with HIV antigens, thereby enriched in HIV-specific T cells producing tumor necrosis factor-alpha. Altogether these data suggest that CD8hi+CD57+ cells represent a terminal differentiation state of activated effector cytotoxic T lymphocytes which are enriched in antigen-specific T cells and down-modulate their own cytolytic potential, thus participating in a negative control of effector cell functions during persistent viral infections or transplantations.

CD57 Antigens↗
PubMed1998

Line probe assay for detection of human immunodeficiency virus type 1 mutations conferring resistance to nucleoside inhibitors of reverse transcriptase: comparison with sequence analysis.

We compared the line probe assay (LiPA) to sequence analysis for the detection of mutations conferring resistance to nucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Plasma samples from 40 patients who had received zidovudine, dideoxyinosine, and dideoxycytosine, alone or in combination, and who were enrolled in the ALTIS 2 clinical trial (lamivudine [3TC] plus stavudine) were tested at enrollment and at week 24. RT PCR products from plasma were used for LiPA, and DNA was used for sequence analysis. LiPA gave uninterpretable results for 8.5% of the analyzed codons corresponding to 63 samples, mainly for codons 41, 69, and 70. Several minor discrepancies between the two methods occurred, mainly due to the ability of LiPA to detect mixed populations while sequence analyses detect a single homogeneous population. LiPA is suitable for detecting mixed populations and easy to implement in clinical laboratories and might be useful for epidemiological surveys of primary HIV-1 resistance.

Anti-HIV Agents↗
PubMed1998

[Clinical importance of the quantification of HIV-1 RNA in cerebrospinal fluid for the diagnosis of HIV encephalitis].

We evaluated prospectively the HIV-1 RNA level in CSF as a marker of HIV encephalitis diagnosis. 110 HIV-1 infected patients (mean age: 39 years; sex-ratio M/F: 94/16) were tested for HIV-1 RNA in plasma and CSF. Lumbar punctures were performed to explore cognitive deficit, seizure or fever. HIV encephalitis was diagnosed in 15 patients (14%), other CNS disease in 34 (31%), and fever without CNS disease in 61 (55%). HIV-1 RNA was detectable in 93% of the plasma and in 62% of the CSF. No significant difference was observed in CSF HIV-1 RNA between patients with or without HIV encephalitis. CSF HIV-1 RNA was correlated with plasma HIV-1 RNA (p < 0.01), CSF protein (p < 0.01) and CSF white cell counts (p < 0.01). The absence of any significant difference between patients with or without HIV encephalitis, suggests that the CSF HIV-1 RNA level is not a good marker for its diagnosis.

AIDS Dementia Complex↗
PubMed1997

Regional differences in use of antiretroviral agents and primary prophylaxis in 3122 European HIV-infected patients. EuroSIDA Study Group.

Little is known about how widely HIV-related drugs are used outside controlled clinical trials. We therefore assessed factors associated with use of antiretroviral (ARV) therapy and primary prophylactic regimens to prevent HIV-associated opportunistic infections. Baseline data from a prospective study from May to August 1994, on 3122 consecutive HIV infected patients with a CD4 count <500 cells/microl, followed in 37 centers from 16 European countries, were analyzed. Two thousand and twenty patients (65%) were receiving at least 1 ARV drug at the time of the study. ARV therapy was more frequently used among patients from southern and central Europe as compared with patients from northern Europe, especially among patients with CD4 counts >200 cells/microl (73%, 57%, and 42%, respectively, p < 0.0001). Of patients on ARV therapy, 34% received open-label combination therapy. This proportion was higher in central Europe compared with other regions (27%, 50%, and 31% for southern, central, and northern Europe, respectively, p < 0.0001). Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) was used by 85% of patients with a CD4 count <200 cells/microl, without marked regional differences. In patients without esophageal candidiasis or other invasive fungal infections, antifungal drugs were far less frequently used in patients from southern and central Europe compared with patients from northern Europe (10%, 10%, and 25%, respectively, p < 0.0001). Only 5% of patients with a CD4 count <100 cells/microl received rifabutine as primary prophylaxis against nontuberculous mycobacterioses. ARV and antifungal therapies are used differently in different parts of Europe, whereas primary PCP prophylaxis is uniformly administered to most at-risk patients. U.S. recommendations on the use of antimycobacterial prophylaxis have not been implemented in Europe.

AIDS-Related Opportunistic Infections↗
PubMed1997

Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease.

Highly active antiretroviral therapy (HAART) increases CD4(+) cell numbers, but its ability to correct the human immunodeficiency virus (HIV)-induced immune deficiency remains unknown. A three-phase T cell reconstitution was demonstrated after HAART, with: (i) an early rise of memory CD4(+) cells, (ii) a reduction in T cell activation correlated to the decreasing retroviral activity together with an improved CD4(+) T cell reactivity to recall antigens, and (iii) a late rise of "naïve" CD4(+) lymphocytes while CD8(+) T cells declined, however, without complete normalization of these parameters. Thus, decreasing the HIV load can reverse HIV-driven activation and CD4(+) T cell defects in advanced HIV-infected patients.

Adult↗