Resolution of HIV retinitis with zidovudine therapy.
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Biomedical subjects
Publications and source records attributed to F Ferchal.
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In order to select and standardize a reliable assay for the analysis of sensitivity of HIV isolates to AZT, we have compared two culture methods. The first assay (Cell-Associated Isolate Sensitivity Assay: CAISA) quantified AZT-resistant HIV isolates by end-point dilution cultures of peripheral blood mononuclear cells (PBMCs) in the presence of various concentrations of AZT. In the second assay (Cell-Free Isolate Sensitivity Assay: CFISA), following a conventional isolation of HIV, dilutions of infected cell-free supernatants were cultivated with fresh normal donor PBMCs in the presence of increasing concentrations of AZT. Samples from 64 untreated and AZT-treated patients were studied by CAISA (41), CFISA (43) or both assays (20). The CFISA, which allows the determination of titration parameters with respect to various kinetics patterns of viral replication was selected, and some of the CFISA phenotypically characterized isolates were further studied by nucleotide sequence analysis of the reverse transcriptase gene. CFISA showed that isolates from untreated patients were susceptible to AZT while the frequency of resistance increased with the duration of therapy. Genotypic analysis of CFISA-resistant isolates exhibited mutations at crucial positions, particularly at residue 215. We consider CFISA as a consensus culture technique for longitudinal studies of isolates from patients receiving AZT or other analogs of nucleosides.
OBJECTIVE: To compare two published methods for determining plasma viraemia in HIV-seropositive patients, with reference to a cellular viraemia assay. PATIENTS, PARTICIPANTS: Three patient groups were defined according to CD4 cell count: group I, less than 200 x 10(6)/l (23 patients); group II, 200-500 x 10(6)/l (18 patients); and group III, greater than 500 x 10(6)/l (13 patients). METHODS: The two reported methodologies were applied to all fresh samples, simultaneously and on the same day. RESULTS: The two techniques did not differ significantly in the detection of plasma viraemia: 82.3% of group I patients and 55% of group II patients were positive, while all group III patients were negative. Cellular viraemia was positive for 96% of the overall population. CONCLUSIONS: These results, obtained in a network of seven French laboratories involved in clinical trials, confirm that both plasma viraemia and cellular viraemia are useful virological markers.
OBJECTIVE: The routine screening of organ donors for HIV-1 since 1985 has markedly reduced the risk of acquiring infection in organ recipients. However, commercial HIV-1 p24-antigen assays reveal false-positive reactivity in certain recipients. This observation will be discussed here. METHODS: Post-transplantation sera collected sequentially from different organ recipients were tested for HIV antigen: 79 samples were from 14 kidney recipients, 57 from seven bone-marrow allografts and 18 from two heart recipients. Neutralization assays to determine specificity were performed on reactive samples. Immunoblots prepared from sera containing high levels of antigens were tested by Western blot using polyclonal anti-HIV sera. RESULTS: Abbott HIV-1-EIA kits detected non-neutralizable antigens in early post-transplantation sera from 12 kidney, five bone-marrow and two heart recipients. Using in-house immunoblots prepared from positive non-neutralizing antigen sera, a 25-30 kD protein was detected and shown to be the cause of the false HIV antigen cross-reactivity. CONCLUSION: False-positive HIV antigens related to the emergence of a 25-30 kD protein in early post-transplantation sera are detectable in transplant recipients.
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We studied the seroconversion to human T-cell leukemia virus type-1 (HTLV-I) in two immunocompromised patients after transfusions of cellular blood components. One patient produced IgM antibodies against the viral p19 protein 149 days post-transfusion (a serum on day 43 was negative). Both patients showed indeterminate Western-blots (IgG anti-p19 and anti-gp46 but no anti-p24). Using the polymerase chain reaction (PCR) with two primer pairs (SK43/44 and SK54/56), we demonstrated HTLV-I infection prior to seroconversion. This infection was confirmed by Southern blot.
Human immunodeficiency virus (HIV) infection is, to a great extent, a sexually transmitted disease (STD). Its diffusion among the heterosexual population is still limited. STD treatment centres are particularly well organized to watch this diffusion. At the STD centre of the Saint-Louis hospital, Paris, we conducted a 6-week prospective study concerning the systematic detection of HIV-1 infection in 240 consecutive female out-patients in 1988, and in 504 male out-patients in 1989. The results obtained were as follow: 5/240 women (2.1 percent) and 19/504 men (3.8 percent) were seropositive for HIV-1. Out of these 24 subjects, 15 did not know they were seropositive. Predictive factors for seropositivity were male homosexuality, addiction to heroin and, in women, drug addicts as sex partners. Altogether, 23 of the 24 seropositive subjects had the classical risk factors for HIV-1 infection. None of the 744 subjects in this study were HIV-2 seropositive, and only 1 out of 504 men was HTLV-1 seropositive. We conclude that the prevalence of HIV-1 infection was high in our centre, and this prompts us to suggest that the serological test should be proposed to all out-patients and that patient's education and preventive measures should be organized by STD centres, even though the infection is still limited to patients at a particularly high risk (drug addicts, homosexuals, country of origin).
Between November 1986 and June 1987, the microbial aetiology of genital ulcers was assessed in 75 male patients attending the Sexually Transmitted Disease (STD) clinic in Hôpital Saint-Louis, Paris. Evidence of Haemophilus ducreyi was found in 18 patients (24%), Herpes simplex virus in 19 (25.3%). Syphilis was diagnosed on the basis of dark field microscopy and/or positive serology test in 19 patients (25.3%). Lymphogranuloma venereum was not diagnosed in any patient. Primary pathogens were not identified from the remaining 19 (25.3%) men. Neisseria gonorrhoea was isolated in five patients, from the ulcer in three cases, from the urethra in two. Asymptomatic urethral carriage of Chlamydia trachomatis was culture proven in seven cases. The presence of IgM antibodies to C. trachomatis at a titre greater than 40 found in 17 patients was a indication of a current chlamydial infection. Three patients (4%) were discovered to be HIV-1 positive.
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STUDY OBJECTIVE: To determine whether zidovudine is effective in increasing the platelet count in patients with thrombocytopenic purpura related to human immunodeficiency virus (HIV) infection. DESIGN: Nonrandomized controlled trial with two consecutive regimens. SETTING: Immunopathology and hematology clinics at two general hospitals. PATIENTS: Consecutive sample of 34 patients infected with HIV who had thrombocytopenic purpura (platelets less than 50 x 10(9)/L) without visceral bleeding. Twenty-nine patients completed the study; one patient was removed because of drug toxicity. INTERVENTIONS: Zidovudine for 12 weeks, 250 mg every 6 hours orally in 10 patients; and 500 mg every 8 hours orally in 24 patients. MEASUREMENTS AND MAIN RESULTS: Three of ten patients receiving 250 mg every 6 hours and 12 of 24 patients receiving 500 mg every 8 hours had a persistent increase in their platelet counts. In both groups the mean value of the platelet count increased significantly by week 12; from 28 x 10(9)/L +/- 12 (SD) to 57 x 10(9)/L +/- 36 in the first group and from 20 x 10(9)/L +/- 13 to 77 x 10(9)/L +/- 42 in the second group (P less than 0.05 and P less than 0.01, respectively). CONCLUSIONS: Zidovudine is effective on platelet counts in some patients with HIV-related thrombocytopenia. These results suggest that HIV itself may play a direct or indirect role in the pathogenesis of this disorder.
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We report a case of acute adult T-cell leukemia associated with HTLV1 infection in a young African woman. The leukemic proliferation consisted of CD4-, CD25-positive lymphoid cells with typically convoluted nuclei and monoclonal integration of the HTLV1-proviral DNA. The clinical course was characterized by a rapid progression of the leukemia with development of hypercalcemia, resistance to chemotherapy, and the presence of multiple opportunistic infections. The additional finding of a seropositivity for HIV2 raises the problem of the respective contribution of the two retroviruses in this patient's disease.
Cytomegaloviruses are characterized by the long duration of their reproducible cycle, their narrow host range, their latency of infection properties of the subfamily beta-herpesviridae. The cell infection leads either to the production of infectious viruses, as in the human fibroblast which is the only permissive cell in vitro, or to a latent infection possibly reactivated in cases of cellular immunodepression. Although these viruses shave some of the properties of the oncogenic viruses, there is no definitive evidence that they cause human tumors. They should be considered as cocarcinogens.
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