[Mechanisms of resistance to sexual transmission of HIV-1]. / Les mécanismes de résistance à la transmission sexuelle du VIH-1.

Sexual transmission is the most common pathway for HIV-1; nevertheless some individuals remain seronegative despite repeated high risk sexual exposure. These were grouped in cohorts of "highly exposed but persistently seronegative" individuals, mostly prostitutes and flailing couples. Three lines of defence were observed in these cohorts. The first one is the mucosal barrier, the determining factors of which are the type of epithelium (monolayer or multilayer), epithelial integrity, and the pre-existing microflora. The second one is linked to innate immunity directly related to the genetic and/or immune predispositions of the individual: mutations affecting the CCR5 chemokine receptor, secretion of protective soluble factors, and particular HLA alleles. The third one is acquired immunity via the mechanisms of humoral and/or specific cellular immunity. These studies suggest anti HIV-1 vaccinal strategies aiming at a local immunization combining the different types of responses observed in these individuals.

[Treatment interruption in HIV infected patients: clinical and biological evolution]. / Interruption thérapeutique chez des patients infectés par le virus de l'immunodéficience humaine: évolution clinique et biologique.

OBJECTIVE: The authors had for aim to evaluate the clinical and biological evolution in HIV-infected patients with viraemia lower than 30,000 copies/mL having decided to interrupt their treatment. PATIENTS AND METHODS: Patients with highly active antiretroviral therapy (HAART) for more than 3 months followed by treatment interruption longer than 1 month were included in a retrospective analysis. RESULTS: Forty-six patients having stopped treatment between November 1999 and July 2003 were included. The median duration of treatment interruption was 9.5 months. During the study, no clinical event occurred for 21 patients, and at least 1 clinical event occurred for the 25 others. The median CD4(+) cell counts (CD4) before and at the end of treatment interruption were 597/mm(3) and 437/mm(3), respectively (P<0.001). The median values of viral load before and at the end of treatment interruption were <50 and 23749 copies/mL, respectively (P<0.001). Among the 26 patients having started a new HAART, pre-treatment interruption and post-new HAART median CD4 (with a median delay after HAART of 9.7 months) were 548 and 432.5/mm(3) (P=0.02). Pre-treatment interruption and post-new HAART median viral load were 131.5 and 94.5 copies/mL (NS). CONCLUSIONS: Treatment interruption must be used with caution in spite of the absence of virological impact, because CD4 cell count after new HAART is lower than CD4 preceding treatment interruption. Treatment interruption is contraindicated for patients with AIDS. Physicians must carefully follow other patients who decide on a treatment interruption.

[Gonococcal conjunctivitis complicated by perforating corneal abscess in an adult]. / Conjonctivite à gonocoque compliquée d'abcès cornéen perforant chez un adulte.

We present a case of bilateral purulent conjunctivitis complicated by ocular perforation of the right eye secondary to fulminant corneal melt in a 29-year-old man. He developed urethritis after a sexual contact with a prostitute 3 weeks previously. Microbiological analyses of conjunctival and urinary cultures were positive for Neisseria gonorrhoeae resistant to penicillins, tetracyclines, and fluoroquinolones. Progression was favorable with a 15-day course of high doses of parenterally administered antibiotics associating imipenem and fosfomycin. Keratoplasty was done after 3 months. This observation is a good example of the problems raised by gonococcal conjunctivitis in adults. Extremely rare in developed countries, it remains widely unrecognized by ophthalmologists. It is a sexually transmitted disease usually resulting from autoinoculation from an infected genital site. The risk of marginal purulent corneal melt, which can lead to fulminant perforation, warrants prompt microbiological analysis and early parenteral antibiotic treatment.

[Can optic perineuritis be triggered by Mycobacterium tuberculosis?]. / La névrite péri-optique: complication méconnue de la tuberculose?

A 38-year-old woman presented with a swollen left optic disc while being treated for miliary tuberculosis. The diagnosis of optic perineuritis was made, antibiotics were adapted, and the patient slowly recovered. We discuss the elements required to confirm optic perineuritis and the differential diagnosis in cases of papilledema with no visual impairment, as well as the hypotheses on the possible etiologies: dysimmune neuropathy as opposed to infection or toxicity.

Possibly linezolid-induced peripheral and central neurotoxicity: report of four cases.

BACKGROUND: Linezolid is the first member of the new synthetic class of antibacterial agents that prevent the formation of the 70S ribosomal subunit. It represents an attractive choice in the therapeutic arsenal because it is effective against methicillin-resistant strains of Staphylococcus spp. Adverse hematological events have been reported. They are rapidly reversible after discontinuation of treatment and usually occur during treatment courses of more than 2 weeks. The advised duration of linezolid use is 28 days and the consequences of prolonged use are unknown. In addition, this drug has some dopaminergic properties that can induce the serotonin syndrome if a monoamine oxidase inhibitor is used simultaneously. PATIENTS AND METHODS: Since linezolid became available for use in 2002, four cases of probable central and peripheral linezolid-induced neurotoxicity have been recorded in our unit. RESULTS: Two de novo peripheral neuropathies and one worsening of a preexisting toxic neuropathy have been observed. In each case, linezolid therapy was used during a prolonged duration of 8, 23, and 24 weeks, respectively. First neurological signs appeared in one case during the 2nd week of treatment and beyond the 1st month in the other cases. To date, all cases of peripheral neuropathy resulted in persistent neurological damage after discontinuation of linezolid. Assessments did not reveal any other explanation for these neurological impairments. Another case concerned a patient who developed transient encephalopathy attributed to linezolid during a coadministration with hydroxyzine. CONCLUSION: Linezolid may induce persistent peripheral neuropathy after prolonged use and may cause a transient central neurotoxicity in combination with an anticholinergic agent, such as an antihistamine. Close neurological monitoring should be recommended in prolonged linezolid therapy and coadministration of a serotonin reuptake inhibitor or antihistamine should be avoided to limit neurological adverse events.

Disseminated cryptococcosis and histoplasmosis co-infection in a HIV-infected woman in France.

We report the first case in Europe of co-infection with disseminated cryptococcosis and histoplasmosis. The diagnosis of invasive histoplasmosis was confirmed by microscopic examination of the anatomic right colon specimen (hemicolectomy). Histoplasma antigen detection is not yet available in France but it could have a key role in the early diagnosis of disseminated histoplasmosis co-existing with a cryptococcal infection, especially in HIV-infected African people.

Long-term safety and antiretroviral activity of hydroxyurea and didanosine in HIV-infected patients.

Long-term safety, immunologic effects, and antiretroviral activity of hydroxyurea and didanosine were evaluated in this retrospective study. Some 65 HIV-1-infected patients (39 of whom were antiretroviral naive) were studied (mean baseline CD4 count, 362 cells/mm3; mean plasma HIV-1 RNA viral load, 4.8 log10 copies/ml). The mean treatment duration was 20 months. Overall tolerance was good: 15 patients interrupted treatment because of clinical or biologic side effects. Four patients experienced a category B event. Patients had a mean increase of 27 CD4 cell counts after 12 months, of 112 after 24 months and of 59 after 36 months. They had a mean 1. 03 log10 fall in HIV-1 RNA after 12 months, 1.59 log10 after 24 months, and 1.27 log10 after 36 months. After 12 months, 35% developed an HIV-1 RNA viral load <200 copies/ml, 53% after 24 months, and 36% after 36 months. Those whose viral load became undetectable after 12 months have significantly lower baseline RNA values (p =.03). Fourteen patients had a viral load <3.4 log10 copies/ml after 24 months of the double therapy. A prolonged viral load suppression can be achieved using a simple combination of two drugs that are inexpensive and well tolerated.