摘要:

The T-cell line Jurkat E6–1 was rendered resistant to zidovudine (AZT) in vitro by exposure to low but gradually increased concentrations of the drug. Biochemical pharmacology studies of [3H]AZT in the AZT-resistant T-cell lines showed a significant reduction of AZT phosphorylation to the mono-, di-, and triphosphate anabolites. Peripheral blood mononuclear cells (PBMCs) from pediatric patients with human immunodeficiency virus type 1 (HIV-1) infection showed a similar pattern of decreased AZT anabolism. Enzymatic studies with purified thymidine kinase (TK) preparations from these cell lines showed a gradual decline inVmaxrelated to their level of resistance to AZT. The Jurkat/AZT-20 and Jurkat/AZT-100 cells were studied in greater detail with reverse transcriptase/polymerase chain reaction (RT/PCR) cloned probes to determine possible molecular mechanisms of resistance to AZT. TK mRNA was significantly decreased (∼5− to 10-fold) in the AZT-resistant T-cell lines. Southern blot analyses indicated that there were no major rearrangements or deletions of theTKgene, but the 5‘ end of the gene in the AZT-resistant cells is highly methylated when compared to wild-type cells. No apparent differences were seen in thymidylate kinase (dTMPk) mRNA levels in the same T-cell lines. Thus the decreased expression of TK mRNA and resultant TK enzymatic activity is responsible for the observed reduction in the AZT anabolism in the resistant T-cell lines. Decreased T-cell TK activity could allow wild-type, AZT-sensitive HIV-1 to replicate in the presence of subinhibitory AZT triphosphate (AZT-TP) cellular concentrations enabling a genetic variant with drug resistance to emerge and outgrow the AZT-sensitive, wild-type virus.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The human immunodeficiency virus type 1 (HIV-1)-encodedvpuproduct is a small class 1 integral membrane protein that is phosphorylated by the ubiquitous casein kinase II (CKII) in HIV-1-infected cells. The Vpu protein facilitates the release of budding virions from the surface of infected cells and delays the rate of syncytium formation. In this study, we investigated the role of phosphorylation in the biological activity of Vpu. Our results show that phosphorylation of Vpu occurs on serine residues at positions 52 and 56 located in a highly conserved dodecapeptide sequence. Mutation of either Ser 56, or both Ser 52 and Ser 56 impaired the ability of Vpu to delay the rate of syncytium formation while retaining virion release activity at levels comparable tovpu+proviruses. Flow cytometry analysis indicates that the relative amounts of envelope glycoprotein gp120 expressed at the surface of cells transfected with thesevpumutant proviruses was two- to threefold greater than that observed on cells transfected with avpu+provirus. This increased expression of gp120 at the cell surface may explain the more rapid onset of syncytium formation observed in cell transfected withvpumutant proviruses. These results suggest that Vpu-facilitated virion release and delayed cytopathic effect are the consequence of two distinct functional activities of the protein.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Neurologic complications associated with human immunodeficiency virus type 1 (HIV-1) infection vary geographically. To understand the pattern of HIV-associated neurologic complications in Mexico, 120 AIDS patients from Mexico City, Mexico, and 500 AIDS patients from Houston, Texas, were studied cross-sectionally and retrospectively. Neurologic, laboratory, imaging, and pathologic examinations identified 40 Mexican patients and 130 U.S. patients with neurologic complications. Whereas AIDS dementia complex was the most common neurologic manifestation in both groups, intracranial tuberculoma was present only in the Mexican population (10%). Primary brain lymphoma was more prevalent in the U.S. population (8.4%). The different findings in the Mexican population likely reflect afflictions common to developing countries—a high prevalence of tuberculosis and a high mortality rate. These conditions preclude complications such as lymphoma, which develop later in the natural course of HIV infection.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

It is widely acknowledged that the course of HIV infection is accelerated in infants and children compared with adults. Whereas ≥80% of untreated perinatally infected children will have symptoms of HIV infection by 18–24 months of age, the average duration of clinical latency in adults is 8–10 years (Table 1). Different patterns of disease expression have been found in HIV-infected children. Some have an accelerated disease course, developing manifestations of AIDS within the first year of life and dying earlier than other children. Others develop AIDS-related symptoms at a somewhat slower pace during the first several years of life, and a small number become symptomatic during their early teens. Understanding the factors that contribute to these different patterns of disease expression could have important implications for understanding the immunopathogenesis of HIV infection in infants and children and for defining guidelines for optimal monitoring and intervention.In recent years, investigators have attempted to delineate the clinical and laboratory features that serve as prognostic indicators of disease progression in HIV-infected infants and children. Disease progression changes over time, as therapeutic or prophylactic interventions are improved or made available earlier in the course of a patient's illness. Furthermore, investigators around the world have used different criteria to define the symptoms or disease manifestations associated with “symptomatic HIV infection” or disease progression. It is important, therefore, to reanalyze the validity of prognostic factors over time. For example, the clinical prognostic markers may be consequences of direct HIV infection or indirect complications resulting from HIV-induced immunosuppression. These prognostic markers should be defined as independent or dependent and must be assessed in univariate and multifactorial analyses of disease progression.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Our objective was to examine the efficacy and toxicity of continuous, low-dose interferon-α therapy for human immunodeficiency virus-related immune thrombocytopenic purpura (HIV-ITP) in a Phase II clinical trial overseen by a community-based consortium of physicians conducting clinical trials in HIV-related diseases. Sixteen patients with HIV-ITP defined by prospective clinical criteria were enrolled; the majority had failed other therapies for HIV-ITP. Baseline and serial measurements were made of platelet counts, complete blood counts, serum chemistries, platelet-associated immunoglobulin, and CD4+T-lymphocyte counts; subjective symptoms and bleeding were recorded. Three million units of interferon-α 2b were self-administered by subcutaneous injection every Monday, Wednesday, and Friday for 16 weeks. Thirteen participants were evaluable for response. One obtained a complete response, eight had partial responses, and four had no response to interferon-α therapy. The mean absolute platelet count of the group rose from 15.5 × 109/L at baseline to 47.3 × 109/L at 2 weeks and remained in this range for the duration of the study. CD4+T-lymphocyte counts and serum chemistries did not change significantly during therapy. Ability to detect platelet-associated immunoglobulin did not change in a predictable manner in relation to platelet count response. Hematologic toxicity was limited to one episode of granulocytopenia, which resolved after a lowering of zidovudine dosage. Subjective toxicities were mild and tolerable, and minor bleeding problems improved in all participants so affected. Low-dose, continuous therapy with interferon-α resulted in meaningful increases in the platelet counts of the majority of study participants with HIV-ITP. Interferon-α was safe and tolerable for most participants with HIV-ITP at the dosage and schedule employed in this study. Interferon-α should be considered as a therapeutic option for patients with HIV-ITP who require therapy for clinically significant thrombocytopenia and who have failed to respond to zidovudine.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We reviewed all episodes of nonmycobacterial bacteremias in human immunodeficiency virus (HIV)-infected patients from 1990 to 1991 to determine the incidence, risk factors, and outcome. Forty-five patients had a total of 63 episodes of bacteremia (9% of 689 HIV-related hospitalizations). In this cohort, the median CD4+lymphocyte count was 17 cells/mm3, 71% had AIDS, and 78% were homosexual men. The most frequently isolated bacteria wereStaphylococcus aureus(25%) and coagulase-negative staphylococci (22%). The most common site of infection was intravenous catheter-related, accounting for 35% of the bacteremias. Compared to HIV-infected, nonbacteremic controls, patients with bacteremia detected at admission were more likely to have an indwelling intravenous catheter (p= 0.003) and less likely to be taking zidovudine (p= 0.04). The overall in-hospital mortality rate was 24%. There was no significant difference in the in-hospital mortality rates in bacteremic patients with or without HIV infection. Seventeen patients had more than one episode of bacteremia (71% had recurrence with the same organism). We conclude that bacteremia is a significant problem in HIV-infected persons with low CD4+lymphocyte counts, often related to the presence of an intravenous catheter; recurrence is common. In addition, HIV infection does not appear to increase the mortality rate for bacteremia.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Among 178 HIV-infected men from the San Francisco City Clinic Cohort (SFCCC), we examined the association between health insurance and use of outpatient services and treatment. For men with private insurance, we also assessed the frequency of avoiding the use of health insurance. Men without private insurance reported fewer outpatient visits than men with fee-for-service or managed-care plans. Use of zidovudine for eligible men was similar for those with fee-for-service plans (74%), managed-care plans (77%), or no insurance (61%). Use ofPneumocystis cariniipneumonia prophylaxis was similar for those with fee-for-service (93%) and managed-care plans (83%) but lower for those with no insurance (63%). Of 149 men with private insurance, 31 (21%) reported that they had avoided using their health insurance for medical expenses in the previous year. In multivariate analysis, the independent predictors of avoiding the use of insurance were working for a small company and living outside the San Francisco Bay Area. Having private insurance resulted in higher use of outpatient services, but the type of private insurance did not appear to affect the use of service or treatment. Fears of loss of coverage and confidentiality may negate some benefits of health insurance for HIV-infected persons.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We tested the ability of a 0.04-μm nylon membrane filter to remove human immunodeficiency virus (HIV) from tissue culture media containing 10% fetal calf serum. Endpoint titrations of infectious virus (ID50) were performed on lymphocyte cultures. The presence of virus in the cultures was determined using an enzyme-linked immunoabsorbant assay (ELISA) of the HIV-1 P24 core antigen. In repeated experiments, filtration of the virus suspension resulted in the removal of HIV below detectable limits. The titer reduction was estimated to be greater than 8.5 × 102. These results suggest that this filter is effective in removing HIV from fluids containing serum or serum products.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Comparisons of human immunodeficiency virus (HIV) disease progression between risk groups are difficult primarily because of the long incubation period of acquired immune deficiency syndrome (AIDS) and unknown times of infection. This is believed to be the first study that directly compared changes in T-lymphocyte subsets following HIV-1 seroconversion between cohorts of predominantly black injecting drug users and predominantly white homosexual men. Longitudinal trends of CD4 and CD8 percentages of total lymphocytes during 4 years were modeled as piecewise linear functions with a two-parameter correlation structure to accommodate within-person repeated observations. Prior to seroconversion the 151 injecting drug users started with similar CD4% and CD8% levels compared with the 99 homosexual men. Following seroconversion, larger changes were observed overall in the homosexual men compared with the injecting drug users for both markers (p ≤ 0.001). The major discrepancies, however, were limited to the first 2 years. Subsequently, the CD4% levels of the two cohorts converged and then declined at similar rates. These comparative analyses of HIV seroconverters in homosexual men and injecting drug users suggest that risk group has only a minor effect on the initial course of HIV infection.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID