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The evolution of HIV-1 sequences over time is the result of the selection of mutant variants that have escaped from host immune responses or the outgrowth of mutants with increased viral replication, or both. We investigated the contribution of both selection processes to the overall evolution of the Tat and Rev regulatory gene sequences from four individuals, ranging in time from just prior to seroconversion to stable asymptomatic infection. After sequencing at least 15 clones per sample per gene, we analyzed the sequence evolution of the MHC-I motifs that were predicted from the MHC-I haplotypes of these patients. For each identified Tat sequence, we tested the activity of the corresponding encoded protein in a transactivation assay in vitro. Our results suggest that the evolution of the Tat and Rev sequences from these individuals can be explained by mutational escape of the MHC-I epitopes and that no mutations that replaced the original sequences in the viral population are associated with either an increase or decrease in Tat activity. CTL-mediated selection appears to be an important determinant of HIV-1 regulatory gene sequence evolution during the early stages of infection.

Les tests de dépistage de l'infection à VIH sont de type ELISA. Ils détectent les anticorps sériquesanti-VIH-1 et 2, permettant ainsi d'assurer la sécurité transfusionnelle. Au cours des années, ces réactifs sont devenus non seulement plus spécifiques grâce à l'utilisation de protéines recombinantes ou de peptides synthétiques, mais aussi plus sensibles grâce à la détection des immunoglobulines totales. La très grande variabilité génétique des VIH, et plus particulièrement du groupe O de VIH-1, constitue une difficulté majeure de cette sérologie. Récemment, de nouveaux tests ELISA, très sensibles, ont été mis au point: ils permettent la détection des anticorps dans des échantillons de salive ou d'urine. Des tests simplifiés, unitaires et rapides, sont utilisés en complément des trousses ELISA. Cette simplification des formats des tests, associée à l'utilisation des prélèvements autres que le sang, présage une ère nouvelle: le test à domicile.

Teicoplanin was used in three hospitals over 6 years in 112 cases of bone or joint infection and the results were reviewed retrospectively. Teicoplanin was used at a dose of 400 mg/day, after a 3-day loading regimen, in combination with other agents, usually netilmicin at the beginning of the treatment. Most infections were chronic (mean duration = 20.9 months) and had failed previous antibiotic or surgical treatment. Gram-positive organisms were isolated in 120/137 identified strains (64 methicillin-resistant Staphylococcus aureus or coagulase négative Staphylococci) and all were susceptible to teicoplanin except one (intermediate for NCCLS norms). Median of follow-up was 17.3 months. The final outcome was clinical cure in 89/98 evaluable cases (91%). There were one improvement, four failures and four recurrences. Adverse events occurred in 11 patients (10%) but did not require any change in treatment. Despite the limitations of a retrospective study, teicoplanin appeared to be effective, well tolerated and easy to use with only one daily injection.

The incidence of severe falciparum malaria is increasing in the developed countries and mortality remains high despite progress in intensive care management and schizonticide treatment. Many authors emphasize the importance of exchange transfusion (EXT) in the most severe cases. We studied 21 cases (34±12 years, 6 females; SAPS: 8.4±3.7) of severe malaria (according to WHO criteria) consecutively admitted to ICU between 1985 and 1990: 3 patients underwent EXT. Twenty were febrile above 39°C, 10 had cerebral malaria, 14 hepatic impairment, 8 acute renal failure, 5 pulmonary oedema. Nine patients required mechanical ventilation, 1 haemodialysis, 1 intracranial pressure monitoring. Mean parasitemia was 13%, 16 patients had thrombocytopenia <50×109/l, 3 anemia <7 g/dl and 3 leucopenia <2.8×109/l. Nineteen received quinine i.v., 1 mefloquine, 1 chloroquine. Sixteen patients received blood products transfusion, 3 were treated by EXT in addition. Twenty were cured and discharged from hospital without sequelae (mean stay: 14 days); 4 had nosocomial infection, 1 a splenic infarction. One patient (17-years-old; SAPS: 17; parasitemia: 7.8%) died 12 h after admission from non-cardiogenic pulmonary oedema with multi-organ failure. The literature and this study lead us to propose EXT in patients with unfavourable evolution after conventional treatment rather than in all the patients with a parasitemia above 10% at admission. A randomized study to compare conventional treatment in ICU with or without EXT is necessary.

Objective:To identify the factors associated with a short period between the initial detection of HIV-1 antibodies and AIDS diagnosis among patients from Lyons, France.Design and method:Prospective hospital based cohort study of patients diagnosed with AIDS in Lyons University Hospitals from 1994 to 1997. Cox regression was used to identify the variables independently associated with a short period between the first positive HIV-1 detection test and AIDS.Results:466 patients were studied, the mean period between the detection of HIV-1 antibodies and AIDS was 48 months and did not change across calendar years. Age &lt;46 years (hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.58-1.00), HIV-1 transmission by heterosexual contact (HR 1.93, 95% CI 1.49-2.51), Pneumocystis carinii pneumonia (HR 1.67, 95% CI 1.28-2.17), or Kaposi's sarcoma (HR 1.42, 95% CI 1.06-1.90) as the first AIDS defining event, and CD4+ count &lt;100×10³/ml (HR 1.25, 95% CI 1.02-1.55) were associated with a short time interval between detection of HIV-1 antibodies and AIDS.Conclusion:Educational interventions focused on heterosexuals and those aged over 45 are needed to promote the early detection of HIV infection, in the hope of reducing transmission and improving individual prognosis.