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

To determine the prognostic value of plasma viremia in long-term zidovudine (AZT)-treated HIV-infected patients, HIV-1 plasma viremia (PV) was quantified in 28 HIV-infected patients before and during AZT long-term treatment; the follow-up also included p24 antigenemia and CD4 cell counts. The variations of these markers during the follow-up period, the correlation with the clinical outcome (progressors versus nonprogressors), and the discrepancies between PV and surrogate markers were then analyzed. A significant and stable decrease in PV titer was observed in only nonprogressors (Friedman test, p < 0.005). At the end of follow-up, 11 (73%) of the 15 non-progressors were PV responders (patients who remained or became PV- long-term), whereas all the 13 progressors were PV nonresponders (patients who remained or became PV+). These results indicated a strong correlation between PV and clinical outcome (Fischer's exact test, p < 0.0001). The persistence, increase, or reappearance of viral replication appeared to be an important predictor of poor clinical outcome in HIV-infected patients under AZT treatment. This finding could provide a rational basis to help the clinician's decision in the clinical treatment of HIV-infected patients.
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PMID:The prognostic value of plasma viremia in HIV-infected patients under AZT treatment: a two-year follow-up study. 778 23

To define virologic and immunologic differences in patients with acute symptomatic and asymptomatic primary human immunodeficiency virus type 1 (HIV-1) infection, sequential plasma specimens were obtained longitudinally for 1-2 years postseroconversion from subjects with well-documented time of seroconversion. Thirteen of them had an acute symptomatic primary infection, eight subjects had asymptomatic primary infection and long-term follow-up, and 27 had asymptomatic seroconversion and short-term follow-up. Quantitative plasma HIV-1 RNA levels, CD4+ lymphocyte counts, and levels of antibodies to gp120, p66, p41, p31, p24, and p17 were measured. At the time of seroconversion, there was no significant difference in HIV-1 RNA levels and CD4+ counts between symptomatic (n = 13) and asymptomatic (n = 27) subjects. Subsequently, however, establishment of low levels of plasma HIV-1 RNA was seen significantly more frequently in asymptomatic (n = 8) than in symptomatic (n = 13) primary infection; this correlated with higher levels of some (anti-gp120 and anti-p31) anti-HIV-1 antibodies and a slower decline in CD4+ lymphocyte counts. These results indicate that immunologic control of viremia early after infection may be a critical determinant to subsequent clinical course of HIV-1 infection. They also suggest that persons with acute symptomatic primary infection may generally progress to having acquired immune deficiency syndrome (AIDS) more rapidly than people with low-grade symptoms or asymptomatic primary infection.
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PMID:Virologic and immunologic characterization of symptomatic and asymptomatic primary HIV-1 infection. 778 30

Macaca nemestrina has been described as an animal model for acute HIV-1 infection. This animal, unlike most infected humans, appears to contain HIV-1 replication. Therefore analysis of HIV-1-specific proliferative and cytotoxic T lymphocyte (CTL) responses following HIV-1 challenge of M. nemestrina may provide information into the role of such responses in both the control of acute HIV infection and protective immunity. Although CD4+ T cell responses to HIV-1 are generally difficult to detect in HIV-1-infected humans, early and persistent CD4+ T cell proliferative responses to HIV-1 antigens were detected in all HIV-1-inoculated M. nemestrina. HIV-1-specific CD8+ CTL responses were evaluated in PBMC by stimulation with autologous cells expressing HIV-1 genes, limiting dilution precursor frequency analysis, and T cell cloning. CTL reactive with gag, env, and nef were present 4-8 wk after infection, and persisted to 140 wk after infection. The presence of both CD4+ and CD8+ T cell responses before and after clearance of HIV-1 viremia is consistent with a role for these responses in the successful control of HIV-1 viral replication observed in M. nemestrina. Further studies of T cell immunity in these animals that resist disease should provide insights into the immunobiology of HIV-1 infection.
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PMID:Cytotoxic and proliferative T cell responses in HIV-1-infected Macaca nemestrina. 781 22

In Thailand, the human immunodeficiency virus (HIV) seropositivity rate in donated blood increased 150 times from 1987 to 1993, from 0.0065% to 0.95%. Although the National Blood Center and large hospitals initiated HIV antibody screening of all blood in 1987, HIV seronegative blood can pose a serious hazard to recipients because of the risk of viremia during the window period of early HIV infection. Transfusion-associated acquired immunodeficiency syndrome (AIDS) from seronegative blood was first reported in Thailand in 1990 in three thalassemic children. To reduce this risk, HIV P24 Ag screening has been mandatory since 1990 and is estimated to prevent about 180 cases of transfusion-associated HIV transmission from seronegative blood per year. Less effective, yet recommended, is donor self-exclusion. Other preventive measures recommended include exclusion of donors from high-risk groups, public education, sensitive and early detection of IgM antibodies, promotion of autologous blood transfusion, and the use of blood substitutes or blood stimulating factors.
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PMID:Transmission of HIV infection by seronegative blood in Thailand. 782 78

HIV PROTEINASE INHIBITORS: The HIV proteinase enzyme has been identified as a potential target for antiretroviral therapy, as inhibition of this enzyme leads to the generation of immature, non-infectious virions. There are several proteinase inhibitors in development; the first to enter clinical trials was saquinavir. DEVELOPMENT OF SAQUINAVIR: Saquinavir, a transition-stage analogue of an HIV proteinase cleavage site, was developed using computer-led rational design techniques. It is a highly specific inhibitor of HIV-1 and -2 proteinases, with antiviral activity at concentrations 1000-fold less than those causing cytotoxicity. EUROPEAN CLINICAL EXPERIENCE WITH SAQUINAVIR: Three European clinical studies involving 202 patients have been conducted with saquinavir at doses of 25, 75, 200 and 600 mg three times a day. Two studies were dose-ranging monotherapy trials, one in asymptomatic or mildly symptomatic patients not previously treated with zidovudine, the other in patients with advanced HIV infection who had been treated with zidovudine. The third study was a combination therapy trial with zidovudine in previously untreated patients with advanced infection. Saquinavir was well tolerated either alone or in combination with zidovudine. In the monotherapy studies, CD4 cell counts and estimates of viral load showed the best results with the 600-mg dose. The combination of saquinavir and zidovudine resulted in higher and more sustained increases in CD4 cell counts than with either drug alone. The CD4 cell counts favoured saquinavir at 200 and 600 mg in combination with zidovudine, although plasma viraemia and the RNA polymerase chain reaction indicated that the 600-mg dose (in combination) produced better responses.
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PMID:HIV therapy advances. Update on a proteinase inhibitor. 784 Sep 13

The idea is put forward and analysed numerically, that within an infected person HIV evolves to increase its reproductivity within the population of CD4+ cells. A mathematical model predicts initial viremia and CD4+ cell drop after HIV infection and thereafter a slow progressive decline in the number of CD4+ cells, although for an extended period HIV is kept at a relatively low level by an active immune response. The time span T until the number of CD4+ cells falls below 20 per cent of its normal value depends on several model parameters. Assuming Gaussian distributions for these parameters, the model predicts a distribution function for T which resembles the observed distribution function for the incubation period to AIDS.
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PMID:A model for AIDS pathogenesis. 784 11

We analyzed the kinetics of the virological and immunological events that occurred in four AZT-treated cynomolgus macaques during the acute infection that followed their exposure to the simian immunodeficiency virus (SIVmac251) grown on monkey PBMCs in a cell-free stock solution. These events included changes in the CD4+ and CD8+ T lymphocyte subsets, p27 antigenemia, infectious serum virus, and cell-associated virus loads. The kinetics of these changes proved strikingly similar to those reported in human HIV-1 infection. Four other SIV-exposed macaques were treated with placebo instead of AZT. We demonstrated that AZT does not prevent SIV infection, even when administered before SIV inoculation. However, the peaks of p27 antigenemia and of serum and cellular viremia were significantly smaller and occurred significantly later in the monkeys given AZT than in those given placebo.
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PMID:An animal model for antilentiviral therapy: effect of zidovudine on viral load during acute infection after exposure of macaques to simian immunodeficiency virus. 784 83

Three key modes of HIV transmission account for most HIV infections. They are sexual transmission, parenteral transmission, and perinatal transmission. Initially, homosexual transmission was the leading mode of HIV transmission in developed countries. Heterosexual transmission predominates in developing countries and is becoming more common in developed countries. 70% of all HIV infected persons worldwide are from sub-Saharan Africa. By January 1994, 86% of all AIDS deaths were in sub-Saharan Africa. Southeast Asia has had the most rapid growth of HIV infection during the 1990s. The number of HIV infected persons in Southeast Asia is greater than the total number of HIV infected persons in all developed countries. The US has the highest official number of AIDS cases in the world (by January 1994, 361,509 cases and 220,871 deaths). AIDS has become one of the leading causes of death for persons aged 25-44. In 1993, the increase in AIDS cases was greater among women than men and greater among Blacks and Hispanics than Whites. The greatest increase was among youth aged 13-19 and 20-24. Between 1992 and 1993, AIDS cases attributed to heterosexual activity increased 130%, while those attributed to homosexual activity fell from 66.5% to 46.6%. Risk factors are number of sex partners, frequency of unprotected sexual contact, anal intercourse, prostitution, sex with a prostitute, a history of sexually transmitted diseases (STDs), and, in the index case, level of CD4 lymphocytes, level of plasma viremia, use of antiretroviral therapy, genital ulcers or other STDs, no circumcision, or cervical ectopy. Zidovudine therapy during pregnancy reduces perinatal HIV transmission. Transmission of HIV through household contact is rare. HIV disease has five stages based on the CD4 count: acute infection, early disease, middle disease, late disease, and advanced disease. Symptoms within two to six weeks of exposure to HIV are fever, adenopathy, pharyngitis, and a transient skin rash. Risk reduction behavior is needed to prevent and control HIV disease.
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PMID:The epidemiology of the acquired immunodeficiency syndrome in the 1990s. 785 11

Fourteen patients previously treated with zidovudine were monitored for laboratory parameters and clinical events during 1 year after introduction of didanosine (ddI) monotherapy. Proviral human immunodeficiency virus type 1 (HIV-1) copy numbers (cell-associated DNA) and concentration of free virions (viremia) were determined using a semiquantitative polymerase chain reaction (PCR). High levels of circulating virus were detected in all patients (range, 17 to 5,934 x 10(3)/ml of serum). Within 4 weeks of therapy, a decrease of viremia (60 to 98%) was observed in nine patients. After 1 year of treatment, eight of these nine patients still had decreased viremia when proviral HIV DNA was decreased or stable, and CD4+ lymphocytes were stable or higher in seven of these eight patients. Antiviral effect was more pronounced in the six patients with CD4+ > 100/mm3 at entry, five of them belonging to the subgroup of the seven responding patients as compared to two of eight patients with CD4+ < 100/mm3. Clinical events in this small group were not statistically correlated with virologic parameters; however, responding patients had a tendency to stabilize or gain weight. This study suggests that measurement of viremia deserves further study as a marker of antiviral efficacy and might predict, even at 4 weeks, the beneficial potential of ddI.
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PMID:Early and prolonged decrease of viremia in HIV-1-infected patients treated with didanosine. 788

Nef of primate lentiviruses is required for viremia and progression to AIDS in monkeys. Negative, positive, and no effects of Nef have also been reported on viral replication in cells. To reconcile these observations, we expressed a hybrid CD8-Nef protein in Jurkat cells. Two opposite phenotypes were found, which depended on the intracellular localization of Nef. Expressed in the cytoplasm or on the cell surface, the chimera inhibited or activated early signaling events from the T cell antigen receptor. Activated Jurkat cells died by apoptosis, and only cells with mutated nef genes expressing truncated Nefs survived, which rendered Nef nonfunctional. These mutations paralleled those in other viral strains passaged in vitro. Not only do these positional effects of Nef reconcile diverse phenotypes of Nef and suggest a role for its N-terminal myristylation, but they also explain effects of Nef in HIV infection and progression to AIDS.
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PMID:HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization. 788 68


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