[Cowpox virus infection in a child]. / Infection à cowpox virus chez l'enfant.

UNLABELLED: Although human cowpox virus infection is rare nowadays, an animal reservoir of this virus still exists. The general course of cowpox virus infections is usually benign but the diagnosis is difficult and often late. CASE REPORT: An 11-year-old boy, owner of two cats, presented with an infected sacral wound lesion associated with fever and lymph nodes. The wound became necrotic and other cutaneous and mucous membrane lesions developed secondarily. Blood tests did not show hyperleukocytosis or a systemic inflammatory response. Concurrently one of the cats was examined by a veterinary because of multifocal cutaneous lesions. Evocative skin biopsy specimens from the animal and, secondarily from the patient, allowed the identification of orthopoxvirus. Evolution was slowly favourable under symptomatic treatment. CONCLUSION: Poxviruses are responsible for many animal and human diseases, the most famous of them being smallpox which today is considered eradicated. Vaccination against smallpox is no longer performed since 1977. Whether the arrest of vaccinations against smallpox may induce the apparition of other poxviruses infections or alter their clinical expression is an open question.

[Prophylactic antiretroviral therapy after sexual exposure to HIV: 93 cases]. / Traitement antirétroviral prophylactique après exposition sexuelle au VIH: 93 cas.

PATIENTS AND METHODS: We studied prospectively the feasibility of post exposure prophylaxis against HIV in 93 subjects consulting after sexual exposure at STD Center of Hopital Saint-Louis. Among the 93 subjects, 76 were men (45 homosexual) and 17 women. RESULTS: Delay to consultation was 38 h. Among sexual exposure 90 p. 100 were anal or vaginal intercourse and 10 p. 100 oral intercourse. Fifty percent were unprotected. Seventy-five percent of source subject HIV status was unknown, but controlled negative in 14 p. 100 of cases. Three subjects were infected initially. Seventy-two subjects were treated, with triple regimen, for 30 days without severe adverse event. Twenty-five percent were lost to follow up before the end of treatment, only 54 controlled their serology after the end of treatment (after 1 month: 70 p. 100, after 2 months: 51 p. 100 and after 4-6 months: 13 p. 100). DISCUSSION: This study underlines the difficulty in obtaining clinical and serological control after post exposure prophylaxis, even in a STD Department involved in prevention and counseling.

Comparison of genotypic and phenotypic resistance patterns of human immunodeficiency virus type 1 isolates from patients treated with stavudine and didanosine or zidovudine and lamivudine.

Sequencing of reverse-transcriptase genes and recombinant virus assays were performed on paired isolates from antiretroviral drug-naive patients randomized to stavudine and didanosine (group 1; n = 21) or zidovudine and lamivudine (group 2; n = 21) at baseline and after > or = 12 months of follow-up. The T215Y mutation emerged in 13 (61.9%) and 2 (9.5%) isolates in groups 1 and 2, respectively (P < .0001). Furthermore, in group 1, mutations associated with multidideoxynucleoside resistance were selected in 3 isolates. In group 2, all isolates carried the M184V mutation. The median fold changes in susceptibilities to zidovudine, stavudine, and lamivudine were 16.4 and 1, 2.2 and 0.6, and 4.5 and > 38 in groups 1 and 2, respectively (P < .0001, all comparisons). These results suggest that the combination of stavudine and didanosine is associated more frequently with the emergence of zidovudine resistance and a decrease in susceptibility to stavudine than the combination of zidovudine and lamivudine.

Once-daily combination therapy with emtricitabine, didanosine, and efavirenz in human immunodeficiency virus-infected patients.

The safety and efficacy of a once-daily regimen that combines emtricitabine, didanosine, and efavirenz was studied among 40 previously untreated human immunodeficiency virus (HIV)-infected patients. The median plasma HIV RNA level was 4.77 log(10) copies/mL at baseline and decreased by a median of 3.5 log(10) copies/mL at 24 weeks, with 98% and 93% of patients achieving plasma HIV RNA levels <400 and <50 copies/mL, respectively. The median CD4 cell count was 373 cells/microL at baseline and increased by a median of 159 cells/microL at week 24. The most common treatment-related adverse events were mild to moderate central nervous system symptoms (73% of patients), diarrhea (33%), rashes (10%), and biochemical abnormalities. Adverse reactions led to permanent drug discontinuation in only 1 patient. The once-daily combination therapy of emtricitabine, didanosine, and efavirenz was safe and demonstrated strong antiviral and immunologic effects that lasted for the 24-week period of the study.

Astrovirus enteritis in a chronic lymphocytic leukemia patient treated with fludarabine monophosphate.

We report on a case of severe astrovirus gastroenteritis in a chronic lymphocytic leukemia (CLL) patient treated with fludarabine monophosphate (FAMP). Astrovirus was detected in stools using both an immunoenzymatic assay and an electronic microscopy analysis. Treatment consisted in symptomatic care and the outcome was favorable. Astrovirus infection might constitute a common etiology of gastroenteritis in patients with hematologic malignancies that have been severely immunocompromised with FAMP or other purine analogues, and therefore should be more systematically investigated.

The ALBI trial: a randomized controlled trial comparing stavudine plus didanosine with zidovudine plus lamivudine and a regimen alternating both combinations in previously untreated patients infected with human immunodeficiency virus.

A total of 151 previously untreated patients infected with human immunodeficiency virus type 1 (HIV-1) with CD4 cell counts >/=200/microL and plasma HIV-1 RNA levels of 10,000-100,000 copies/mL were randomly assigned to 24 weeks of open-labeled stavudine plus didanosine (group 1), zidovudine plus lamivudine (group 2), or stavudine plus didanosine followed by zidovudine plus lamivudine (group 3). The mean decrease in HIV-1 RNA level was greater in group 1 (2.26 log10 copies/mL) than in groups 2 (1.26 log10 copies/mL) or 3 (1.58 log10 copies/mL; P<.0001). The mean increase in CD4 cell counts was greater in groups 1 (124 cells/microL) and 3 (118 cells/microL) than in group 2 (62 cells/microL; P=.02). All regimens were generally well tolerated. The combination of stavudine plus didanosine reduced plasma HIV-1 RNA concentrations and increased CD4 cell counts more effectively than did the combination of zidovudine plus lamivudine or the regimen alternating both combinations.

Stavudine resistance: an update on susceptibility following prolonged therapy.

The current report summarizes the available published and unpublished data from several investigators on resistance in clinical isolates following prolonged stavudine therapy. Results suggest that stavudine resistance is both modest in degree and infrequent in appearance. Phenotypic evaluation of 61 patients on stavudine therapy showed only modest changes in drug sensitivity following up to 29 months of treatment. The post-treatment isolates from 15 patients exhibited an increase in EC50 value > fourfold (level above variability of assay) when compared with the corresponding pretreatment isolates. However, the vast majority (11) of these pretreatment isolates either had unexpectedly low EC50 levels and/or had post-treatment isolates that lacked any amino acid changes within their reverse transcriptase (RT) gene to account for the observed change in sensitivity. Of the four remaining isolates, two appeared to have a multi-resistant phenotype to several nucleoside analogues and two had no detectable RT amino acid changes to account for the observed change in stavudine sensitivity. To date, clinical HIV-1 isolates displaying stavudine-specific resistance have yet to be reported. Furthermore, full or partial RT sequence analysis of 194 post-treatment isolates failed to identify any consistent amino acid changes. The strain-specific V75T mutation reported to confer stavudine resistance to the HXB2 HIV-1 strain in vitro, was found in only six isolates and did not correlate with stavudine resistance. This low incidence of stavudine resistance is in striking contrast to that observed with other nucleoside analogues and further supports the use of stavudine in first-line combination therapy for HIV patients.

Zidovudine resensitization and dual HIV-1 resistance to zidovudine and lamivudine in the delta lamivudine roll-over study.

OBJECTIVE: To study zidovudine resensitization and dual resistance to zidovudine/lamivudine in HIV-1 isolates from nucleoside reverse transcriptase (RT) inhibitor-experienced patients during selective pressure exerted by zidovudine/lamivudine combination therapy. DESIGN AND METHODS: HIV-1 isolates from 29 patients receiving zidovudine/lamivudine combination therapy in the Delta roll-over study were analysed at entry and during a 1 year follow-up period for phenotypic susceptibility to zidovudine and lamivudine in the ANRS PBMC assay. The RT gene from codon 20 to 230 and at codon 333 was analysed by nucleotide sequencing of the corresponding isolates. RESULTS: HIV-1 isolates from 23 of the 29 patients were phenotypically resistant to zidovudine at baseline; 61% of these patients showed significant zidovudine resensitization during follow-up. The zidovudine IC50 value correlated positively with log10 plasma HIV-1 RNA (P = 0.02) and negatively with the CD4 cell count (P = 0.004). Zidovudine resensitization (related to acquisition of the M184V mutation) was transient, with evolution towards dual resistance to zidovudine and lamivudine in 20 of the 29 patients. The phenotype of certain dually resistant isolates coincided with the emergence of multiple mutations in the 5' part of the RT gene. CONCLUSIONS: M184V-mediated zidovudine resensitization of HIV-1 is transient in most patients who are given zidovudine/lamivudine combination therapy when zidovudine resistance has already emerged. The subsequent evolution towards dual phenotypic resistance to zidovudine/lamivudine corresponds to complex genotypic profiles.

Results of the ALBI trial: a randomized comparison of stavudine/didanosine, zidovudine/lamivudine and alternating treatment in antiretroviral-naive patients.

In the ALBI trial, 151 antiretroviral-naive patients with plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 10,000 to 100,000 copies/ml and CD4 cell counts > or = 200 cells/mm3 received 24 weeks of treatment with stavudine/didanosine (n=51), zidovudine/lamivudine (n=51) or stavudine/didanosine for 12 weeks followed by zidovudine/lamivudine (n=49). Baseline plasma HIV-1 RNA and CD4 cell counts were comparable in the treatment groups. The mean decrease in plasma HIV-1 RNA at 24 weeks in the stavudine/didanosine group (2.26 log10) was significantly greater than that in either the zidovudine/lamivudine group (1.26 log10) or the alternating treatment group (1.58 log10) (P<0.0001 for both). Proportions of patients with plasma HIV-1 RNA level <500 copies/ml (91% vs 42% and 60%) and <50 copies/ml (47% versus 4% and 9%) were significantly greater in the stavudine/didanosine group (P<0.001 for pairwise comparisons). Stavudine/didanosine was associated with a mean increase in CD4 cell count (124 cells/mm3) significantly greater than that in the zidovudine/lamivudine group (62 cells/mm3, P<0.01) and comparable to that in the alternating group (118 cells/mm3). All study regimens were well tolerated. These findings, indicating superiority of stavudine/didanosine over zidovudine/lamivudine in virological and immunological response over 24 weeks, suggest that the combination should be considered as a basis for highly active antiretroviral therapy.

Inhibition of human immunodeficiency type 1 virus replication in monocytic U-937 cells by superinfection with Chlamydia trachomatis.

The aim of this study was to investigate the effects of infection of monocytic cells with both the human immunodeficiency type 1 virus (HIV-1) and Chlamydia trachomatis on the replication of each pathogen. U-937 cells, chronically infected with HIV-1 (strain LaVLai), either induced to differentiate into immature macrophage-like cells by 32 pM 12-O-tetradecanol phorbol-13-acetate or uninduced, were superinfected with C. trachomatis serovar L2. Both HIV-1 infection and differentiation rendered the U-937 cells highly susceptible to C. trachomatis lytic infection. Differentiation and superinfection of HIV-1-infected cells with C. trachomatis both affected cell viability and reduced viral production in vitro. RT activity was one tenth the original value after differentiation of HIV-1-infected cells, one twentieth the original value after superinfection with C. trachomatis, and one hundredth the original value after differentiation and superinfection with C. trachomatis.

The rhesus macaque CCR3 chemokine receptor is a cell entry cofactor for HIV-2, but not for HIV-1.

The eotaxin receptor (CCR3) is a CD4-associated coreceptor for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). By comparison with other chemokine receptors, such as CCR5 and CXCR4, the primary sequences of human CCR3 and its rhesus macaque homolog were markedly different in their extracellular domains. Human CD4+ cells expressing CCR3 from either human or macaque origin could be infected by HIV-2, with apparently similar efficiency, but only cells expressing human CCR3 could be infected by HIV-1. It suggests that HIV-1 and HIV-2 envelope proteins interact differently with the CCR3 coreceptor HIV-1 could infect cells expressing chimeric human/macaque CCR3 bearing either the first and second, or the third and fourth extracellular domains of human CCR3. As previously observed for CCR5, there seems to be a certain functional redundancy between domains supporting the coreceptor activity of CCR3. In spite of their close genetic relationship to HIV-2, two macaque simian immunodeficiency virus strains were apparently unable to use the CCR3 coreceptor from either human or simian origin.

Usage of the coreceptors CCR-5, CCR-3, and CXCR-4 by primary and cell line-adapted human immunodeficiency virus type 2.

The chemokine receptors CCR-5 and CXCR-4, and possibly CCR-3, are the principal human immunodeficiency virus type 1 (HIV-1) coreceptors, apparently interacting with HIV-1 envelope, in association with CD4. Cell lines coexpressing CD4 and these chemokine receptors were infected with a panel of seven primary HIV-2 isolates passaged in peripheral blood mononuclear cells (PBMC) and three laboratory HIV-2 strains passaged in T-cell lines. The CCR-5, CCR-3, and CXCR-4 coreceptors could all be used by HIV-2. The ability to use CXCR-4 represents a major difference between HIV-2 and the closely related simian immunodeficiency viruses. Most HIV-2 strains using CCR-5 could also use CCR-3, sometimes with similar efficiencies. As observed for HIV-1, the usage of CCR-5 or CCR-3 was observed principally for HIV-2 strains derived from asymptomatic individuals, while HIV-2 strains derived from AIDS patients used CXCR-4. However, there were several exceptions, and the patterns of coreceptor usage seemed more complex for HIV-2 than for HIV-1. The two T-tropic HIV-2 strains tested used CXCR-4 and not CCR-5, while T-tropic HIV-1 can generally use both. Moreover, among five primary HIV-2 strains all unable to use CXCR-4, three could replicate in CCR-5-negative PBMC, which has not been reported for HIV-1. These observations suggest that the CCR-5 coreceptor is less important for HIV-2 than for HIV-1 and indicate that HIV-2 can use other cell entry pathways and probably other coreceptors. One HIV-2 isolate replicating in normal or CCR-5-negative PBMC failed to infect CXCR-4+ cells or the U87MG-CD4 and sMAGI cell lines, which are permissive to infection by HIV-2 but not by HIV-1. This suggests the existence of several HIV-2-specific coreceptors, which are differentially expressed in cell lines and PBMC.

Lymphocytic alveolitis after primary HIV infection with CMV coinfection.

Herein is a report of an adult case of primary HIV infection with cytomegalovirus coinfection causing cough, fever, and lymphocytic alveolitis. Primary HIV infection has not been previously reported as a cause of lymphocytic alveolitis.

Chlamydia trachomatis growth stimulates interleukin 8 production by human monocytic U-937 cells.

Growth of Chlamydia trachomatis serotypes L2 and L3 in a human monocytic cell line, U-937, increased the rate of interleukin 8 (IL-8) release 100-fold. Heat-killed chlamydiae induced a 10-fold-lower level of production of IL-8. IL-8 may play an important role in the inflammatory reaction to chlamydial infection.

Long-term follow-up of non-HIV Kaposi's sarcoma treated with low-dose recombinant interferon alfa-2b.

BACKGROUND AND DESIGN: We reviewed the follow-up of 16 patients with Kaposi's sarcoma not related to human immunodeficiency virus (13 with classic Kaposi's sarcoma and three with endemic Kaposi's sarcoma; median age, 58 years) treated by low-dose recombinant interferon alfa-2b (5 million U three times weekly for at least 6 months). RESULTS: One patient had a complete response, nine had a major response, three had stable disease, and one had a minor response. Visceral disease stabilized and symptoms improved in three patients. Limited relapse was noted in four patients after withdrawal of interferon. CONCLUSION: Our results confirm the efficacy and safety of low-dose recombinant interferon alfa-2b in the long-term treatment of both cutaneous and visceral lesions of Kaposi's sarcoma not related to human immunodeficiency virus.

Fulminant adenovirus hepatitis after allogeneic bone marrow transplantation.

Adenoviruses may cause severe infections in bone marrow transplant recipients. We report the case of a patient who developed fulminant hepatitis 5 months after bone marrow transplantation. Adenovirus type 2 was cultured from stool and blood samples. The patient died from liver failure. Histologic examination of post-mortem liver samples showed extensive necrosis with nuclear inclusions. Adenovirus was identified in liver cells by electron microscopy and immunohistochemical staining using a monoclonal anti-adenovirus antibody. No other pathogen was identified.

Profound and possibly primary "idiopathic CD4+ T lymphocytopenia" in a patient with fungal infections.

A profound and long-lasting reduction in circulating CD4+ T lymphocytes (< 80/microliters) was found in a 37-year-old man (without known risk factors for HIV infection) presenting with recurrent oral candidiasis who subsequently developed cryptococcal meningitis. Infection with HIV was ruled out by serological and virological studies. In vitro and in vivo cell-mediated immunity was severely impaired. Abnormal phenotypic patterns of both CD4+ and CD8+ cells were consistently observed. A systematic family survey revealed in some of his asymptomatic relatives several immunological abnormalities which may point to a genetically based primary immunodeficiency disorder.

Human immunodeficiency virus (HIV) nef-specific cytotoxic T lymphocytes in noninfected heterosexual contact of HIV-infected patients.

We report on the detection of HIV-specific cytotoxic T lymphocytes (CTL) among 23 regular partners of HIV-infected individuals. 15 of the 46 individuals enrolled in the study were positive for HLA-A2.1 typing. Among the 23 contacts studied, 7 were seropositive and 16 were seronegative on repeated tests. None of the 16 seronegative contacts were positive for p24 antigenemia nor were they positive by the lymphocytes coculture assay, although, in two instances HIV-1 DNA could be detected by PCR (in one case using a gag SK 38/39 primer, and in the other using a primer for the pol P3/P4 primer). These two individuals remained seronegative for 18 and 36 mo, respectively. HIV-specific cytotoxicity was performed in the 15 HLA-A2.1 subjects (7 indexes, 2 seropositive contacts, and 6 seronegative contacts) and in 4 HLA-matched HIV negative donors. CTL specific for env, gag, or nef proteins could not be detected in unstimulated bulk cultures of peripheral blood lymphocytes in any of the six seronegative contacts. However, using a limiting dilution assay we found an usually high frequency of HIV nef-specific CTL precursors (CTLp) for HIV env and gag was very similar to that observed in seronegative HLA-matched healthy donors. Because no presence of HIV could be demonstrated in these individuals, these findings argue against the possibility of a silent HIV infection and suggest that a CTL response against nef may be involved in a rapid and effective clearance of the virus after sexual exposure.

Simultaneous progressive multifocal leukoencephalopathy, Epstein-Barr virus (EBV) latent infection and cerebral parenchymal infiltration during chronic lymphocytic leukemia.

We report a non-HIV patient who had B chronic lymphocytic leukemia (CLL) with progressive multifocal leukoencephalopathy (PML) and diffuse cerebral leukemic parenchymal infiltration in the presence of JC virus and Epstein-Barr virus (EBV) cerebral co-infection. Multiple subcortical hypodensities lining the cortico-subcortical junction were present within the white matter on computerized tomography (CT) scan, with large areas of high signal intensity on T2-weighted sequences on magnetic resonance imaging (MRI). JCV DNA was identified in peripheral blood nuclear cells and cerebrospinal fluid polymerase chain reaction (PCR) DNA/DNA hybridization plus Southern blot analysis. Frontal stereotactic biopsy confirmed the diagnosis of PML by immunocytochemistry, in situ hybridization (ISH) with JC Enzo probe and electron microscopy. Leukemic B cells with the same phenotype as leukemic blood cells were disseminated in the demyelinated areas. They were labeled by anti-latent membrane protein and by BamHl W EBV probe after ISH. Adhesion and activation molecules were positive for CD23. Autopsy showed diffuse visceral leukemic infiltration without acutization. EBV-transformed B lymphocytes would favour JCV penetration and/or intracerebral reactivation of previously latent JCV infection with further development of simultaneous PML and cerebral CLL infiltration in an immunosuppressed patient.