ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Zidovudine-resistant strains of HIV have recently been isolated from individuals during prolonged treatment. Analysis of the HIV reverse transcriptase (RT) gene from clinical isolates revealed that resistance was due to multiple nucleotide changes conferring specific amino acid substitutions in this enzyme. In order to correlate the degree of resistance with these amino acid changes, we constructed a series of infectious HIV variants with specific combinations of mutations in the RT gene and assessed their sensitivity to zidovudine. The reproducible nature of the mutations seen in clinical isolates has enabled the polymerase chain reaction to be used to identify lesions associated with resistance. This procedure was validated by analysis of sensitive and resistant clinical isolates with RT genes of known DNA sequence. Using a 'double' amplification procedure, zidovudine sensitivity was assessed by direct detection of specific mutations in DNA from peripheral-blood lymphocyte samples. This should make it possible to test large numbers of individuals receiving zidovudine therapy, with the aim of establishing the clinical significance of the resistant isolates.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Antisense RNA can inhibit the expression of messenger RNAs (mRNAs) to which they are complementary by a variety of mechanisms and might provide the basis for antiviral therapies of high selectivity. In a previous study of six retrovirally expressed antisense RNAs targeted to HIV-1IIIB, we found that two significantly reduced HIV-1IIIBreplication. Here we test the degree to which this inhibitory effect tolerates the natural variation found in the nucleotide sequence of different strains of HIV-1. We show that the longer of the two inhibitory antisense RNAs (600 bases) inhibits replication of HIV strains RF, MN and SF2 to at least as great an extent as it does the homologous strain. In contrast, the shorter (71 bases) does not inhibit replication of the heterologous strains. An examination of the predicted positions of the mismatches in the duplexes formed between the IIIB antisense RNAs and the mRNAs of heterologous strains suggests that one requirement of an inhibitory antisense RNA is that it can form a perfect duplex with its target mRNA of at least some 51–64 base-pairs. Although the observations presented here are not definitive proof of this, they are reminiscent of the structural requirements deduced for the double-stranded RNA-mediated induction of interferon and the activation of interferon-induced 2′, 5′-oligo(A) synthetase and protein kinase. We tested the ability of antisense RNA to inhibit HIV replication in Jurkat, CEM, U937 and HeLa-T4 cells. The level of inhibition of HIV-1IIIBreplication varied according to the cell line in which it was expressed, but in all cases was significant.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

A simple quantitative bioassay for infectious HIV-1 has been developed. The assay is based on adherent CD4+ HeLa cell lines stably transfected with episomal vectors carrying theEscherichia coliβ-galactosidase gene under the control of the HIV long terminal repeat (LTR) promoter. HIV infection of these cell lines transactivates the LTR promoter inducing β-galactosidase production. Infected cells and virus foci can be stained dark blue by the addition of the chromogenic substrate X-Cal. Alternatively, a readily automatable quantitative enzyme assay can be performed on the infected cultures. Because of its simplicity the bioassay may be useful for routine quantification of HIV-infected cultures, plaque purification, virus neutralization studies and for the screening of antiviral agents.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Data from the Multicenter AIDS Cohort Study (MACS) of 1637 gay men, recruited in 1984 and 1985 in Los Angeles and followed at 6-monthly intervals, are used to develop a computer simulation model of the typical pattern of CD4 T-cell number changes in HIV-infected AIDS-free subjects. The empirical model incorporates the following features: (1) within-person and between-person variability in CD4 measurements; (2) variation in the rates of decline of CD4 values; (3) variation in the level of CD4 at which clinical AIDS is diagnosed, and (4) greater absolute variation in CD4 values in men with high CD4 levels compared with men with low CD4 values. Three applications of the model to assist in the design and interpretation of clinical trials are given. Further applications to clinical trials and to estimate the current and future spectrum of HIV-mediated immunological disease in the USA, as measured by the CD4 values, are discussed.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

After immunization of chimpanzees against HIV antigens, antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC) were evaluated and compared with anti-HIV-antibody levels detected by enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers. Adult chimpanzees were immunized with different HIV-1 (LAV-BRU) antigen preparations: recombinant vaccinia virus (rVV) expressing gp160, p25 or p27nef;formalin- and β-propiolactone-inactivated whole virus (inHIV); soluble recombinant gp160 either associated or not associated with other HIV proteins; a 25-mer peptide from the V3 region of gp120 coupled with KLH (V3-KLH). Immunization with the various rVV mixtures induced no or borderline ADCC increase above preimmune serum levels. Stronger and more sustained reactivity was elicited by inHIV. Purified HIV antigens elicited ADCC activity when the chimpanzees were naive; ADCC increased or remained at the same level when the animals had been preimmunized with rVV and/or inHIV. This type of reactivity apparently did not depend on whether gp160 alone or mixed with other proteins was used for immunization. The injection of V3-KLH resulted in only little, if any, recall ADCC response. ELISA antibody titers significantly correlated with ADCC and neutralizing antibody titers, but serum ADCC was independent of neutralizing antibody titers, an indication that the two latter serum activities are mediated by independent antibodies. Therefore, ADCC is elicited in the same manner as other antibody activities by the immunization of chimpanzees with inHIV or with purified recombinant HIV antigen preparations. The results obtained from the three chimpanzees of this series, which were subsequently challenged with infectious virus through the intravenous route, suggest that serum ADCC may be considered for vaccination purposes.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We compared the prevalence of HIV p24 antigenemia in black and white US patients with HIV infection. The prevalence of HIV antigenemia increased with severity of HIV disease (P< 0.001). In all clinical categories, whites were more likely to be HIV-antigenemic than blacks (overall prevalence 38 versus 18%;P< 0.01). Anti-p24 antibodies were detected in a higher proportion of blacks (84%) than whites (65%;P= 0.02). Blacks had significantly higher total serum immunoglobulin levels than whites (median 3.8 versus 3.2mg/dl;P< 0.00001). Racial differences in HIV antigen expression may result from differences in humoral response to HIV infection. These differences should be considered when HIV antigen is used as a surrogate marker in clinical trials.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The initiation and maintenance of substantial behaviour change is required to reduce the spread of HIV infection among the intravenous drug-using population. In order to ascertain the efficacy of interventions aimed at reducing HIV-related risk-taking behaviour among this population, valid and reliable (yet preferably short) instruments for measuring such behaviour are required. The HIV risk-taking behaviour scale (HRBS) is a brief 11-item interviewer-administered scale which examines the behaviour of intravenous drug users in relation to both injecting and sexual behaviour. This paper describes the construction of the scale, in addition to data evaluating its reliability and validity. Initial analyses indicate that the scale has satisfactory psychometric properties.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Needle-use practices of intravenous drug users (IVDUs) were examined in a region (Seattle, King County, Washington State, USA) where needle purchase is legal. IVDUs in treatment (n = 313) were administered extensive structured interviews concerning drug and injection equipment-use practices. Of the 80.2% reporting intravenous drug use in the previous year, 78.3% reported sharing needles. Of the 47.7% reporting intravenous use in the previous 30 days, only 40.5% shared needles, with 59.3% sharing with only one other person. Most needle-sharing partners were very well known (63%) or well known (17%) to the subjects. The most frequent method for obtaining needles was 'buying in a drug store', ranked first by 65% of the sample. Subjects whose primary source was 'buying in a drug store' shared equipment less frequently during drug-use events in the previous year (mean: 16.2%) than those with other primary sources (mean: 28.5%). Compared with findings from other regions where needle purchase and possession are illegal without a prescription, fewer subjects in the current investigation shared needles, and those who did shared with a smaller number of people. The apparent association between legalized injection equipment and reduced sharing of equipment among IVDUs should be further examined in longitudinal studies of needle-sharing before and after legalization is instituted.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

During the prospective follow-up of 64 babies at risk for perinatal HIV-1 infection because their mothers were seropositive, and of 130 control babies whose mothers were seronegative, we studied the occurrence of complications of bacillus Calmette–Guérin (BCC) immunization and its ability to induce cutaneous reactivity to tuberculin. Babies born both to HIV-1-positive and HIV-1-negative mothers received BCG immunization during their first month of life according to the Expanded Programme on Immunization (EPI) recommendations. Local and regional complications of BCG vaccine were looked for at 3, 6 and 9 months after inoculation. A tuberculin skin test was performed at 6 or 9 months of age. Most babies born to HIV-1-positive mothers were later classified as infected or uninfected according to their clinical condition and/or serological status at 18 months of age. The mean duration of the follow-up was 36 months (range 30–40 months). No chronic or deep ulcerations at the site of injection or disseminated forms of BCG infection were observed. The frequency of BCG-related lymphadenitis in the group of HIV-1-infected children (24%) did not differ significantly from the group of uninfected children (19%; Fisher test:P= 0.73). In contrast, the tuberculin skin test responses were positive less often in the group of HIV-1-infected children (33%) than in the uninfected group (83%; Fisher test:P= 0.007). Because BCG vaccine appears to be safe — even when given to perinatally infected babies — continuation of the BCG immunization policies of the EPI is justified, especially in view of the growing incidence of tuberculosis as a complication of HIV infection.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID