摘要:

SummaryRecombinant human immunodeficiency virus type 1 (HIV-1) integrase was shown to bind ATP and other nucleoside triphosphates and nucleotide analogs in vitro. Cross-linking of ATP and the photoaffinity analog 8-azido-ATP to integrase occurred in a UV dose-dependent manner. Covalent binding of ATP to integrase was also achieved without UV irradiation when the nucleotide was oxidized to the 2',3'-dialdehyde derivative (oxidized ATP) prior to incubation with the protein, indicating the presence of a reactive lysine residue in the nucleotide binding region of the protein. A number of experimental observations indicate that nucleotides and DNA substrates bind at the same or overlapping site(s) on the integrase protein. For example, the binding of nucleotides or nucleotide analogs to integrase was blocked by prior incubation with DNA substrates, and the covalent cross-linking of 8-azido-ATP to integrase inhibited the DNA binding and oligonucleotide cleavage activities of the protein. Oxidized ATP inhibited the oligonucleotide cleavage activity of integrase at concentrations that had no effect on DNA binding, suggesting that oxidized nucleotides may specifically target the catalytic center of the enzyme. These studies indicate that nucleotide analogs may serve as probes for the DNA binding and catalytic sites of the enzyme and may serve as models for the design of active site inhibitors of retroviral integrase.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryWe compared the performance of a rapid and simple anti-CD4 antibody-coated microsphere assay with flow cytometry and immunofluorescence for quantitation of absolute count of CD4+T lymphocytes. A longitudinal evaluation of CD4+T lymphocytes by flow cytometry and microsphere assay in 10 human immunodeficiency virus (HIV)-seronegative and 59 HIV-seropositive individuals was conducted over a period of 9 months. Standard flow cytometry analysis was performed to establish the absolute CD4+T-lym-phocyte count. The microsphere assay uses whole blood; CD14+and CD4+cells are first blocked by small latex beads coated with anti-CD14 antibody, and remaining cells are stained with larger anti-CD4 antibody-coated beads. Cells rosetted with only anti-CD4 antibody-coated beads are counted with use of a hemacytometer. Immunofluorescence microscopy was performed by standard techniques with use of peripheral blood mononuclear cells. The predictive value for stratification of HIV-seropositive patients by CD4+T-lymphocyte values of <200/$$l was 95% when the microsphere method was compared with flow cytometry. A correlation coefficient of 0.91 between the two assay methods was demonstrated in 281 CD4+T-lymphocyte tests for absolute count. Finally, the flow cytometry method yielded better results than did the microsphere assay and immunofluorescence microscopy, in descending order of accuracy. The microsphere method should be effective in determining absolute CD4+T-lymphocyte count in developing countries where, for a variety of reasons, no other method can be reliably performed.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryTo investigate the function of the Vif protein of the simian immunodeficiency virus (SIV), mutations were introduced into the SIVmac239vifgene without affecting the reading frames of other overlapping genes. The phenotypes of these mutant viruses were examined with respect to viral replication and the expression and processing of viral proteins. Transfection of v/f-mutant proviral DNA into established T cell lines resulted in a significant delay in the onset of virus replication compared to that seen with the wild-type pro virus. The efficiency of replication of the v;/-mutant virus was dependent on cell type. MT-4 cells were permissive for replication of thevifmutant, while replication in CEMxl74 cells was severely restricted. Little or no virus replication was observed following cell-free infection of the CEMxl74 cell line and macaque peripheral blood mononuclear cells (PBMC). These results indicate that the requirement forvifduring the replication of SIVmac239 is dependent on cell type, as has been observed for HIV-1. Following cell-free infection, mutant viruses containing combined deletions invif andthe other regulatory genes (vpx, vpr, andnef) displayed replication kinetics similar to that of viruses containing the deletion ofvifalone. Viral protein expression and processing in MT-4 cells of vi/-deleted viruses were indistinguishable from those of the wild-type virus. The effects of two different point mutations invif wereexamined. One point mutant invifreverted to the genetic sequence of the wild-type virus within 2 weeks. A second point mutant that did not show genetic reversion displayed a similar kinetics of virus replication to that of thevifdeletion mutant. These data show that impaired replication ofvifmutant viruses results from mutation of thevifgene rather than the deletion of c/.?-acting elements, and also indicate that a strong selection exists against vi/-defective viruses.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryGood markers for monitoring the efficacy of antiretroviral therapy in children do not currently exist. This study examined the effect of antiretroviral therapy on human immunodeficiency virus (HIV-1) unintegrated DNA (uDNA), integrated DNA (iDNA), percent uDNA, immune complex dissociated (ICD) p24 antigenemia, and plasma viral titer. Seven children were followed at therapy initiation and at ~3− and 10-month intervals. HIV-1 uDNA was detected in all children prior to start of therapy (average percent uDNA, 43%). At 3 months, the percent HIV uDNA decreased in all patients to an average of 18% (p= 0.01) and at 10 months decreased to an average of 1%. In contrast, the amount of HIV iDNA was relatively constant after initiation of therapy. ICD HIV p24 antigen was detected in all patients prior to therapy (average, 538 pg/ml). Over the study period, the ICD p24 antigen level decreased in three patients and remained relatively unchanged in four patients. Plasma cultures of HIV-1 were positive in only one of the seven patients prior to therapy. Among the methods evaluated, measurement of uDNA was the only parameter which reliable decreased after initiation of nucleoside therapy.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryThe occurrence ofPneumocystis cariniipneumonia (PCP) in human immunodeficiency virus type 1 (HIV-1 )-infected individuals with high CD4+counts indicates poor immunologic function. Thrush and persistent fever, easily recognized clinically, are potential measures of immunocompetence. This analysis establishes the complex interactions of CD4+count, thrush, and persistent fever to predict the occurrence of PCP. Analyses used 20,632 person visits from 2,568 HIV-1-seropositive homosexual or bisexual men participating in the Multicenter AIDS Cohort Study (MACS). Comprehensive examinations were conducted semiannually, while occurrences of PCP were assessed continuously. The occurrence of thrush and fever increase in frequency as CD4+levels decrease. The relative hazard of PCP in the presence of thrush compared with the absence of thrush rises (p < 0.05) from 1 for the lowest CD4+category to approximately 5 in the highest categories. The relative hazard of PCP in the presence of fever compared with the absence of fever is above one (p< 0.05) in all CD4+categories. No cases of PCP occurred in individuals on PCP prophylaxis with CD4+counts >200/mm3These results suggest that HIV-1-related symptoms provide a measure of failing immune function that is not reflected by enumeration of CD4+lymphocytes alone and support the United States Public Health Service recommendation that symptomatic individuals with CD4+counts >200/mm3should be considered for PCP prophylaxis.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryThe aim of this study was to define predictors of survival for women and men after AIDS diagnosis. We examined health care delivery and drug therapy in the year before AIDS diagnosis for continuously enrolled New York State Medicaid beneficiaries with AIDS in 1988–1990. We examined the association of these factors with survival after AIDS diagnosis. Of 1,077 women and 1,871 men, 60% of both gender groups were drug users. In both risk groups, women had more outpatient visits than men but were equally likely to visit an AIDS specialist. In those who were not drug users, men were twice as likely as women to receive either zidovudine orPneumocystis cariniipneumonia prophylaxis. No difference appeared among drug users. Survival after AIDS diagnosis was similar by gender for those who were not drug users (RR = 1.09; 95% CI = 0.90–1.33). In drug users, women had a slightly lower risk of death than men (RR = 0.84; 95% CI = 0.72–0.98). Risk of death after AIDS diagnosis was higher for persons starting zidovudine earlier in both risk groups. Among drug users, women received more ambulatory care and survived slightly longer than men. Among those who were not drug users, survival was similar by gender even after adjusting for differences in care.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryMen from the Multicenter AIDS Cohort Study were classified as “susceptible” and “resistant” to HIV infection. Resistant men were still HIV antibody negative in 1993 and were estimated to have had >45 different anal intercourse partners (median, 92; range, 46–504) in the 2.5 years before visit 2 (1985). Susceptible men were seroconverters who were estimated to have had <13 different anal partners (median, 4; range, 0–12). Leukocyte groups were compared between the two groups of men. Values were excluded for 12 months before the first antibody-positive visit in the susceptible men. White blood cells, polymorphonuclear neutrophils, total lymphocyte count, CD8+percentage and number, and CD3+and CD4+number were higher in the resistant men. Logistic regression analyses were used to develop 50 bivariate models. Higher levels of neutrophils and CD8+cells were included in four of the six best-fitting bivariate models, suggesting that each is associated with resistance to HIV-1 infection. These results support the hypothesis that CD8+cells may modulate the outcome of HIV-1 exposure.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryRoyal Thai Army (RTA) enlistees were tested for HIV-1 seropositivity prospectively in order to explore their feasibility as a cohort in an HIV-1 preventive vaccine efficacy trial. The 17,615 seronegative enlistees, virtually all 21-year-old men, contributed 10,409 person-years (p-y) of follow-up. Cohorts were enlisted in November 1991 and May 1992 from northern Thailand and Bangkok. The follow-up rate was 50%, with loss to follow-up significantly associated with location of the base, marital status, and educational level. Seroincidence was 0.5/100 p-y for recruits stationed in Bangkok, 1.0/100 p-y in the lower north, and 3.2/100 p-y in the upper north. In a multiple regression model, the young man's birthplace was strongly associated with risk of infection, suggesting that transmission occurred during leave as well as during duty. Incidence rates were significantly lower in those who were married at the time of enlistment and in those with 3$$10 years of education. The seroincidence rates among recruits stationed in the upper north support vaccine trial feasibility, but follow-up rates need to be improved.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryWe examine changes and stability in risk behaviors and HIV-1 seroprevalence among heterosexual injection drug users (IDUs) over 13 cross-sectional surveys, 1986–1992. Interviews (n = 5,956) were conducted with IDUs in street settings and drug detoxification clinics over 6.5 years, and respondents were tested for HIV-1 antibody. Trends in use of condoms and bleach and HIV seroprevalence were assessed using multiple logistic and linear regression analyses. The percentage of time condoms were reportedly used during intercourse among men increased from 4.5% to 31.0%. Among the declining population of IDUs who reported needle sharing, reported use of bleach increased from 3% to 89%. Significant changes in use of bleach 100% of the time were reported: 29.8% in 1988, 52.8% in 1990, and 40.0% in 1992. HIV seroprevalence doubled from 7% in 1986 to 14% in 1987. Post-1987 fluctuations in HIV seroprevalence were not significant. Significant changes in risk behaviors among IDUs were reported over the study period. These changes coincided with the implementation of HIV prevention in San Francisco, including outreach programs, HIV testing and counseling, bleach distribution, and syringe exchange. The moderate and stable rate of HIV seroprevalence beginning in 1987 parallels self-reported reductions in risk behavior.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryData are presented from serologic screening for human immunodeficiency virus type 1 (HIV-1) in all blood donors (n = 3,696) in Gonder, Ethiopia, between 1989 and 1993. The crude seroprevalence was 10.6% in men (326 of 3,066) and 11.9% in women (75 of 630). Seroprevalence in male donors increased from 3.8% in 1989 to 16.0% in 1993 (p= 0.001); in female donors, seroprevalence increased from 7.0% in 1989 to 16.8% in 1992 (p= 0.002) and decreased to 13.4% in 1993. Syphilis seroreactivity increased from 4.8% in 1991 to 9.2% in 1993 (p= 0.02). HIV-1-seropositive donors were more likely to be seroreactive for syphilis than HIV-1-negative donors (odds ratio = 2.36; 95% confidence interval, 1.73–3.22). Therefore, there is an urgent need for control programs for both infections.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID