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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study set out to characterize the unique features of natural lentivirus infection in chimpanzees over time. The virologic and serologic characteristics of this infection were followed longitudinally in a naturally infected chimpanzee together with a small cohort of experimentally HIV-1-infected chimpanzees. The subsequent isolates from the naturally infected chimpanzee were all non-syncytium forming (NSI) versus syncytium forming in the experimentally infected animals. In contrast to HIV-1-infected chimpanzees virus load was higher and plasma viremia occurred but in a cyclic pattern. Serologic follow-up suggested the development of neutralizing antibodies with subsequent escape of new isolates. Interestingly, the sequence of the principal neutralizing (V3 loop) domain (of HIV-1) remained constant over time. Antibodies to peptides from the V3 loop were type specific. The occurrence of persistent, fluctuating plasma viremia and NSI-type virus variants of this natural lentivirus infection are unique characteristics not previously reported in experimentally infected chimpanzees.
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PMID:Virologic and serologic characteristics of a natural chimpanzee lentivirus infection. 764 27

Cytotoxic T lymphocytes (CTL) play an important role in the immune response to viral infection by recognizing and destroying infected cells. HIV-1 elicits an unusually strong CTL response in infected individuals and clearance of the viremia of acute infection coincides with the development of HIV-specific CTL. Because HIV-specific CTL may provide protection against de novo viral infection, we compared the CTL response in seronegative volunteers treated with two vaccination approaches. Seven volunteers were immunized with a live recombinant vaccinia virus expressing the HIV envelope protein gp160LAI (HIVAC-1e) and boosted with 640 micrograms recombinant baculovirus-expressed gp160LAI in alum 1-13 months later. In a second study, three volunteers underwent four successive immunizations with 640 micrograms subunit gp160LAI in alum at 0, 1, 6, and 12 months. The first vaccination strategy using a liver vector would be expected to generate gp160-specific CTL, while for the second, using only whole-protein subunit, the generation of specific CTL would be unlikely. Predominantly CD8+ T-cell lines generated from PBMC by nonspecific stimulation with PHA and IL-2 were screened after three to four weeks of culture for cytolytic activity against autologous targets infected with vaccinia vectors encoding envLAI, RT, gag, and lacZ control. A strong gp 160-specific CTL response was detected in two vaccines in the recombinant vaccinia plus subunit boost study. Modest responses were seen in four of the other five live vector-primed vaccinees. No significant gp160-specific CTL were observed in three volunteers given only subunit rgp160 or in five control subjects.
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PMID:A vaccinia-gp160-based vaccine but not a gp160 protein vaccine elicits anti-gp160 cytotoxic T lymphocytes in some HIV-1 seronegative vaccinees. 764 81

A nonselective ex vivo assay was used to directly detect and quantify zidovudine (AZT)-resistant human immunodeficiency virus type 1 (HIV-1) in the blood of treated and untreated patients. In contrast to previous reports, drug-resistant virus was detected in peripheral blood mononuclear cells of a few of the patients who had never received AZT. The AZT resistance of HIV-1 isolates from one untreated individual was confirmed by further susceptibility studies in vitro and by the finding of a characteristic mutation (Lys-->Arg at codon 70) in the reverse transcriptase. In patients who were clinically stable while on AZT, HIV-1 titers in plasma and mononuclear cells were generally low but resistant viruses already predominated. In those individuals who were deteriorating despite AZT administration, high levels of viremia were observed, and the resistance phenotype was nearly universal. These findings serve to emphasize the magnitude of the AZT-resistance problem in patients on drug treatment.
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PMID:Quantitation of zidovudine-resistant human immunodeficiency virus type 1 in the blood of treated and untreated patients. 767 40

The prevalence and characteristics of hepatitis C virus (HCV) infection in 226 patients who were seropositive for human immunodeficiency virus (HIV) were determined. Antibody to HCV (anti-HCV) was detected by enzyme immunoassay (EIA), and positive results were confirmed by a neutralization EIA or recombinant immunoblot assay. The prevalence of anti-HCV was 8%. Intravenous drug use was the most common risk factor for HCV infection (61.1% of patients), and 52.4% of intravenous drug users were seropositive for anti-HCV (HCV+). Only 16.7% of HCV+ patients had AIDS, as compared with 37.4% of anti-HCV-seronegative (HCV-) patients (P = .04). The prevalence of hepatitis B virus markers in patients with and without anti-HCV was similar. The CD4+ lymphocyte counts were higher for HCV+ patients than for HCV- patients (P = .001), and the prevalence of anti-HCV decreased in parallel with CD4+ counts. Elevated liver function test values were more common for HCV+ patients than for HCV- patients (61.1% vs. 26.0%; P < .01), but abnormalities were usually slight (< 2-fold elevation in values). HCV viremia was detected by the polymerase chain reaction in 88.2% of HCV+ patients. Despite the coexistence of HIV and HCV infection, liver disease appeared to be mild, and HCV infection did not appear to increase the severity of HIV infection. Serological tests for HCV appear to underestimate the prevalence of HCV infection in patients with advanced HIV infection or AIDS.
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PMID:Hepatitis C virus infection in patients infected with the human immunodeficiency virus. 768 86

Methods for the absolute quantitation of nucleic acids present in small amounts in biological samples (competitive PCR and competitive reverse transcription PCR) were applied to the direct monitoring of specific anti-human immunodeficiency virus type 1 (HIV-1) therapy. With these techniques, different parameters of HIV-1 activity (including genomic RNA copy numbers in plasma, proviral and late transcript copy numbers in peripheral blood lymphocytes, and mean transcriptional activity per each HIV-1 provirus) were monitored during therapy with azidothymidine or ddI. In most of these treated patients, a direct response to the antiretroviral compounds employed was detected during the first few weeks of treatment, as documented by a fast decrease of all molecular indexes of HIV-1 activity. However, residual viral replication (albeit at minimal levels) was documented during therapy in all subjects monitored in this study. In a minority of the patients under study (3 of 12), the drug-dependent viral inhibition was maintained throughout the observation time (213 to 791 days), but in 9 patients a rebound in viremia level was detected during therapy with competitive reverse transcription PCR. Sequencing analysis of a portion of the HIV-1 gene pol from cell-free virions showed that circulating viral variants bearing at least two mutations compatible with azidothymidine or ddI resistance were detectable in the patients who exhibited a rebound in cell-free HIV-1 genomic RNA copy numbers in plasma but not in one patient who maintained (for 455 days) lowered levels of viral load during ddI treatment.
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PMID:Quantitative molecular monitoring of human immunodeficiency virus type 1 activity during therapy with specific antiretroviral compounds. 769 34

Periodic quantitative HIV-1 plasma cultures were performed on 28 seropositive individuals who had CD4 cells < or = 300/mm3 and who were enrolled in three clinical trials testing the efficacy of didanosine versus zidovudine monotherapy. Most plasma cultures were negative or of low titer (1-100 tissue culture infective dose/ml of plasma), but there were 14 instances of high-titered plasma viremia (> or = 1,000 tissue culture infective dose/ml of plasma) seen in 11 individuals. These peaks in plasma culture titers were significantly associated either with rapidly decreasing CD4 cell numbers or with CD4 cells already < 50/mm3. In addition, patients who experienced these episodes of high-titered plasma viremia were more apt to have clinical complaints of fever, rash, flu-like illness, and/or opportunistic infection and also the syncytium-inducing HIV-1 phenotype and progression of disease.
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PMID:Transient high titers of HIV-1 in plasma and progression of disease. 771 35

We evaluated saquinavir, an orally active, selective inhibitor of HIV proteinase, in a randomised, double-blind, dose-ranging study in 49 zidovudine-naive HIV-positive patients with few or no symptoms and CD4 cell counts of 500 or less. The study was designed to assess the antiviral activity and tolerability of saquinavir. Patients were randomised to receive 25, 75, 200, or 600 mg of saquinavir three times daily for 16 weeks. No serious adverse events occurred. CD4 cell counts showed a trend indicative of a dose response in favour of the 600 mg dosage, the maximum increase being seen around week 4. In none of the 8 patients with positive plasma viraemia at baseline did cultures become negative after treatment; peripheral blood mononuclear cell and plasma-viral load by culture and DNA and RNA PCR all showed a trend towards reduction at higher doses of saquinovir. Saquinavir was well tolerated in this group of previously untreated patients with few or no symptoms; this study shows that an HIV-proteinase inhibitor is active in HIV-infected patients.
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PMID:Safety and activity of saquinavir in HIV infection. 771 88

Epidemiologically, the Acquired Immune Deficiency Syndrome, AIDS, is transmitted and distributed in the USA and Europe almost entirely in well-defined subsets of populations engaging in, or subjected to, the effects of behaviours which carry high risks of genital and systemic infections. The persons predominantly affected are those engaging in promiscuous homosexual and bisexual activity, regular use of addictive drugs, and their sexual and recreational partners. In such persons and in subsets of populations with corresponding life-styles, the risk of AIDS increases by orders of magnitude. Because of continuity of risk behaviour and of associated indicator infections, the incidence of AIDS over 3-5 year periods is predictable to within 10% of actual totals of registered cases in the USA and UK. Secondary transmission of AIDS beyond these groups is minimal or, in many locations, absent. There is no indication of appreciable spread by heterosexual transmission to the general population. The Human Immunodeficiency Virus, HIV, is transmissible to some extent in general populations, and more so among promiscuous persons. It may cause viraemia, lymphadenopathy and latent infection (HIV disease) in anyone. In persons engaging in risk behaviours which themselves alter or suppress immune responses, it can interact with MHC, antibodies to other organisms and to semen, and other allogenic antigens to initiate a programmed death of CD4 lymphocytes and other defensive cells, as in graft-host rejections. This occurs also in haemophiliacs receiving transfusions of blood products, and is more pronounced in persons with reactive HLA haplotypes. The susceptibility of particular subsets of populations to AIDS is thereby largely explained. But these changes occur in the absence of HIV, and so do Kaposi's sarcoma, lymphadenopathies and opportunistic infections which are regarded as main indicators of AIDS. The hypothesis that HIV-1 can do all this by itself and thereby cause AIDS is falsifiable on biological as well as epidemiological grounds. An alternative hypothesis is proposed, linking the incidence of AIDS to the evolution of contemporary risk behaviour in particular communities and locations in the USA, UK and probably in most of Europe. It does not pretend to explain the reported incidence of AIDS in Africa and other developing regions where data are insufficient to provide validation of the pattern of disease and contributory variables. The immediate, practical implication of this alternative hypothesis is that existing programmes for the control of AIDS are wrongly orientated, extremely wasteful of effort and expenditure, and in some respects harmful.
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PMID:The epidemiology and transmission of AIDS: a hypothesis linking behavioural and biological determinants to time, person and place. 774 60

PBL from HIV-infected patients were engrafted into CB-17 SCID mice to develop a novel small animal model for the study of HIV pathogenesis and therapy. Engraftment was achieved in 84% of mice, with human Ig (hu-Ig) levels and total human mononuclear cell recovery by peritoneal wash similar to those in control hu-PBL-SCID mice engrafted with uninfected donor cells. The hu-Ig produced by hu-HIV/PBL-SCID mice had broad reactivity against HIV. Virus could be detected in 98% of mice by polymerase chain reaction and/or viral coculture. Viremia was first detected by quantitative polymerase chain reaction on day 7 (approximately 10,000 copies of viral RNA/ml of plasma) and persisted through day 17. Quasispecies analysis of amplified, cloned, proviral DNA of the V3 region of the env gene showed that nucleotide sequences from hu-HIV/PBL-SCID mouse peritoneal wash cells on day 17 were not significantly changed from those derived from donor PBL at the time of injection. Relative to human CD4+ T cell recovery by peritoneal wash in control hu-PBL-SCID mice (CD4 = 19 +/- 2%; n = 40), severe CD4+ lymphocyte depletion (CD4 = 5 +/- 0.5%; n = 59; p < 0.001) was observed in untreated hu-HIV/PBL-SCID mice 18 to 25 days after engraftment. Treatment with 2'-beta-fluoro-2',3'-dideoxyadenosine, a nucleoside analogue, significantly reduced CD4+ T cell depletion (CD4 = 13 +/- 1; n = 59; p < 0.001) and the frequency of virus isolation (70%; p = 0.015) in the hu-HIV/PBL-SCID model. Boosting hu-Ig levels in the mice by injection of purified donor Ig with neutralizing activity did not affect the frequency of CD4+ lymphocyte recovery or virus isolation. The administration of a mAb to TNF had minimal effects. These studies demonstrate that PBL from HIV-infected donors can engraft SCID mice; that HIV can be detected in the spleen, peritoneal wash cells, and blood of these mice; that HIV infection within the model results in rapid CD4+ T cell depletion; and that anti-retroviral therapy is effective in improving CD4+ T cell recovery and reducing the frequency of virus isolation. The hu-HIV/PBL-SCID mouse model thus represents a potentially useful model in which to study HIV pathogenesis and therapy.
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PMID:The human HIV/peripheral blood lymphocyte (PBL)-SCID mouse. A modified human PBL-SCID model for the study of HIV pathogenesis and therapy. 775 95

We studied the perinatal transmission of hepatitis C virus (HCV) in 70 high risk mother/infant pairs. Seventy-six percent of the mothers (53 of 70) were coinfected with human immunodeficiency virus (HIV) and 79% (55 of 70) had a history of drug addiction. During the follow-up HCV RNA was detected in 14 of 70 (20%) infants: 12% (2 of 17) in infants born to HIV-negative mothers; and 23% (12 of 53) in infants to HIV-positive mothers. The rate of vertical transmission was significantly higher in vaginally delivered infants than in those delivered by cesarean section (32% vs. 6%; P < 0.05). All 56 uninfected infants lost passively acquired anti-HCV by age 9 +/- 4 months and only 2 of 56 infants (4%) had evidence of HIV infection. Four of 14 HCV RNA-positive infants (29%) had evidence of HIV coinfection. We observed 3 clinical patterns of HCV infection: a transient viremia in 2 infants; an acute pattern in 2 infants; and a chronic pattern in 10 infants. All 4 HIV-coinfected infants had chronic HCV infection. All infants with a chronic pattern, had increased alanine aminotransferase values for more than 6 months and 5 had a liver biopsy that showed signs of chronic persistent hepatitis. HCV perinatal transmission was more frequent in infants born to HIV-coinfected mothers than in infants born to HIV-noninfected women, particularly when delivered vaginally.
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PMID:Perinatal transmission and manifestation of hepatitis C virus infection in a high risk population. 776 Nov 84


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