摘要:

Eleven subjects who presented with a clinical illness characteristic of primary HIV-1 infection were treated with 1 g zidovudine daily for a median period of 56 days (range, 28–111 days). Primary HIV-1 infection was confirmed in each subject by seroconversion and virus isolation. The acute phase of the illness resolved a median of 4 days (range, 3–14 days) from commencement of zidovudine. Six subjects reported symptoms that may have been side-effects of zidovudine, the most common being nausea in four subjects and headache in two. Treatment was discontinued in one subject who had persistent headache and nausea. Haemoglobin, haematocrit and erythrocyte counts decreased and mean corpuscular volume increased significantly during the treatment. None of the subjects developed anaemia and none required dose modification or blood transfusion as a result of haematological side-effects. There were no significant differences in the granulocyte count or the lymphocyte count during any week of treatment when compared with baseline levels. There were no significant differences in T-cell subset numbers of the subjects during treatment compared with a group of historical controls. HIV-1 was isolated from several subjects during and after termination of zidovudine treatment. The results of this investigation indicate that zidovudine is a safe drug to administer to people with primary HIV-1 infection. There was no clear evidence, however, of any clinical benefit in terms of resolution of the acute illness and no indication that the treatment would prevent development of persistent infection. Nevertheless, the results urge the establishment of a placebo-controlled trial to further evaluate this treatment and its effect on long-term outcome in people with primary HIV-1 infection.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

A new mechanism is proposed for the apparent breakthrough of HIV that occurs approximately 6 months after the commencement of therapy with zidovudine (AZT). Using a simple mathematical model of the interacting population dynamics of HIV and its major host cell in the circulation (the CD4+ lymphocyte), predicted patterns of HIV plasma viraemia in the weeks following treatment with zidovudine are generated. These are in close agreement with observed patterns despite the fact that the model contains no mechanisms for the development of drug-resistant strains of virus. It is suggested that the patterns of viral abundance observed during the first 6 months after treatment may be the result of non-linearities in the interactions between HIV and CD4+ cells, and that it is only after the first post-treatment burst of viral production that drug resistance plays an important role.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Zidovudine therapy of AIDS patients has been shown to cause only transient improvements in the numbers of circulating CD4+ cells and thein vitrofunctional activities of cultured lymphocytes. The present studies were undertaken to determine whether prolonged zidovudine therapy enhanced reactivity in two sensitive assays of T-cell function: the ability of phytohemagglutinin (PHA)-stimulated cells to form T-cell colonies and their capacity to express receptors for the growth factor interleukin-2 (IL-2). Treated patients, studied over periods of 20–60 weeks, showed no improvement in colony formation at any time interval, even in plates supplemented with exogenous IL-2. However, mitogen-stimulated T lymphocytes showed a significant increase in the capacity to express IL-2 receptors (CD25). This enhanced expression resulted primarily from activation of the CD8+ cell subset.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

HIV-1 proviral DNA contains two binding sites for the transcription factor NF-xB. HIV-1-infected individuals have, on average, abnormally high levels of tumour necrosis factor α (TNFα) and abnormally low plasma cysteine levels. We therefore investigated the effects of cysteine and related thiols on HIV-1 replication and NF-xB expression. The experiments in this report show that cysteine orN-acetylcysteine (NAC) raise the intracellular glutathione (GSH) level and inhibit HIV-1 replication in persistently infected Molt-4 and U937 cells. However, inhibition of HIV-1 replication appears not to be directly correlated with CSH levels. Cysteine and NAC also inhibit NF-xB activity as determined by electrophoretic mobility shift assays and chloramphenicol acetyl-transferase (CAT) gene expression under control of NF-xB binding sites in uninfected cells. This suggests that the cysteine deficiency in HIV-1-infected individuals may cause an over-expression of NF-xB-dependent genes and enhance HIV-1 replication. NAC may be considered for the treatment of HIV-1-infected individuals.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Four assays for serum levels of cellular products of immune activation were examined as prognostic markers for AIDS in a prospective study of asymptomatic HIV-seropositive homosexual men. Baseline serum values of β2-microglobulin (β2M), neopterin, soluble CD8 (sCD8), and soluble interleukin-2 receptor (sIL-2R) for 185 men were examined univariately and multivariately as predictors of AIDS during 36 months of follow-up. Thirty-three cases of AIDS (18%) were diagnosed during the follow-up period. All four assays correlated highly with each other (r = 0.48–0.63), and all four were good univariate predictors of AIDS and comparable to CD4 lymphocyte count. β2M, neopterin, and sCD8 predicted AIDS independently of both CD4 count and HIV p24 antigen or p24 antibody in multivariate analysis. Within the range of CD4 count 200–499 × 106cells/I, an immune activation marker used in combination with an assay for p24 antigen identifies those at 3–6% risk of AIDS over 36 months (low risk on both assays) and those at 63–86% risk (high risk on both assays). These results can be used to guide physicians and patients making decisions about treating asymptomatic HIV infection with zidovudine in individuals with CD4 lymphocyte count of 200–499 × 106cells/l.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Neutralizing and complement-mediated infection-enhancing antibodies to HIV-1 were measured in sera or plasma from 54 HIV-1-positive individuals at various stages of disease, and from an additional 36 HIV-1-positive individuals for whom no clinical data were available. Antibodies were measured in microtiter infection assays utilizing MT-2 cells and the IIIB strain of HIV-1. The frequency of detection of both types of antibodies was identical, being 77 out of 90 cases (86%). Neutralizing and infection-enhancing antibodies were not always found together, and in four cases both were undetectable. No correlation was found between liters of either type of antibody and stage of disease. Furthermore, liters of infection-enhancing antibodies at early stages of disease did not predict rate of disease progression.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

To establish the prevalence of HIV-related oral lesions, we performed oral examinations of members of three San Francisco epidemiological cohorts of homosexual and bisexual men over a 3-year period. Hairy leukoplakia, pseudomembranous and erythematous candidiasis, angular cheilitis, Kaposi's sarcoma, and oral ulcers were more common in HIV-infected subjects than in HIV-negative subjects. Among HIV-infected individuals, hairy leukoplakia was the most common lesion [20.4%, 95% confidence interval (CD 17.5–23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% Cl 4.1–7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposi's sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P< 0.05). The prevalence of erythematous candidiasis and Kaposi's sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Bronchoalveolar lavage (BAD cell differentials and T-lymphocyte subpopulations were analysed in 95 HIV-infected patients with pulmonary symptoms to determine whether the type of cellular inflammatory response could be useful in diagnosis or as a prognostic marker. Patients withPneumocystis cariniipneumonia (PCP) had more BAL fluid lymphocytes, mainly comprising CD8+ cells, and patients with bacterial infection had more neutrophils than other patients. Neither of these changes were mirrored in peripheral blood. Seven patients who died after their acute episode of PCP had significantly higher BAL fluid neutrophils than 53 patients with PGP who survived (P= 0.002). There seems to be correlation between BAL fluid neutrophilia, PCP and concomitant bacterial infection since four out of seven patients with a fatal outcome had coinfection with bacteria, whereas only one patient with PCP and bacterial coinfection survived (P= 0.0007).

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

HIV establishes a chronic infection in the central nervous system (CNS) of AIDS patients. The immunopathogenesis of this chronic encephalitis is unknown. Because of the importance of major histocompatibility (MHO class I and class II antigens in modulating the immune response, we examined the tissue expression of MHC molecules in relation to CNS damage and expression of viral antigens. By immunocytochemical staining we found that β2-microglobulin (β2M) expression is elevated in all cases with signs of viral encephalitis. β2M was expressed at high levels on endothelial cells, macrophages and possible oligodendroglia within regions of histopathology. In histologically normal regions elevated expression of β2M was noted only on endothelial cells. MHC class II expression was elevated only in the HIV encephalitis cases, and was restricted to macrophages/microglia and occasional endothelial cells. When compared with other viral encephalitides these findings suggest that the intra-CNS immune response to HIV is appropriate for viral presentation; however, the absence of responsive systemic T cells may lead to chronic viral infection.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

In order to determine the prevalence of risk behaviour for, and antibodies to HIV and hepatitis B in clients of a needle-exchange scheme in central London we employed an anonymous, self-administered questionnaire along with salivary antibody testing by immunoglobulin (Ig) G antibody capture immunoassay. Two hundred and thirty-two subjects (193 men, 39 women; median age 32) participated; a response rate of 89%. Clients were long-term, frequent injectors. Lending used equipment at any time was reported by 55%, and borrowing by 52%. Of those who had shared needles and syringes during the last year, the majority had lent to, or borrowed from, one person only (53 and 55%, respectively). Younger clients (<29 years of age) reported more recent sharing than older clients (>30 years of age). Five out of 211 (2.4%) samples tested for anti-HIV were positive. One hundred and eleven out of 199 (56%) samples were positive for anti-hepatitis B core (HBc). In this population of needle-exchange attenders there is no evidence of further spread of HIV, and a low prevalence of HIV infection appears to have been sustained. However, the high prevalence of anti-HBc provides evidence of previous risk behaviour and so constant vigilance is necessary if further viral spread is to be avoided. This study has established an acceptable method for the anonymous surveillance of current risk behaviour and salivary antibodies to HIV and hepatitis B virus (HBV) in a drug-using population.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID