摘要:

Peripheral blood mononuclear cells from 12 asymptomatic human immunodeficiency virus (HIV)-1-seropositive and nine HIV-1-seronegative donors were screened for proliferative T-lymphocyte responses to peptides derived from a consensus sequence of the HIV-1envgene products from 25 HIV-1 isolates. Two hundred seventy-eight overlapping 17mer peptides, incremented by three residues each, were pooled into groups, each containing eight sequential peptides, for use in proliferation tests. Thirty-eight additional peptides containing variant amino acid residues also were tested. Proliferation data were analyzed using an algorithm that reduced subjective bias and estimated the responding cell frequencies. Peripheral blood mononuclear cells from a majority of donors, regardless of HIV-1 status, recognized peptides within two pools derived from the gp120 sequence and peptides from one pool in gp41. Pool 25 peptides from gp41 (centered around residue 600 of the gp160 consensus sequence) were recognized most frequently. The observed inability to differentiate between responses of HIV-1-seropositive and HIV-1-seronegative individuals implies either a lack of HIV-1 disease-related immunodominant env epitopes or functional abrogation of HIV-1 env-specific T-helper lymphocyte responses soon after infection. The observed proliferation of T lymphocytes from noninfected, low-risk individuals questions the origin of the responses to HIV-1 env-derived peptides and suggest that preexisting, cross-reactive immunity could influence responses to HIV-1.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The photosensitizer benzoporphyrin derivative monoacid ring A (BPD) has been investigated regarding its ability to destroy free and cell-associated human immunodeficiency virus type 1 (HIV-1) when activated by light. Experiments with free virus in tissue culture medium indicate that light-activated BPD was effective in rendering HIV uninfectious. Azidothymidine (AZT)-resistant strains of HIV appear equally susceptible to photodynamic inactivation under drug and light conditions that proved effective in inactivating AZT-sensitive strains of HIV. Experiments conducted on whole blood from individuals infected with HIV demonstrate that BPD and light treatment could significantly reduce cell-associated virus, under conditions that appear not to damage red blood cells. The amount of culturable virus from infected leukocytes surviving photodynamic treatment could be further reduced by the addition of AZT to the culture.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

HIV-1 envelope glycoprotein (gp120) may contribute to the magnitude of the immunological defects observed in the early stages of HIV-1 infection by modulating CD4 from the cell surface and altering the function of both CD4 and CD3 in uninfected cells. We investigated CD4 expression as well as CD3− and CD4-mediated cell migration in normal peripheral blood T lymphocytes exposed to recombinant gp120 in long-term cultures for ⩽6 days. Single low doses of gp120 (0.5 μg/ml) modulated CD4 by 4–6 h, reached a nadir at 24–72 h, and began to recover at 96 h. By day 6, surface expression of CD4 had rebounded to control levels. CD3 expression was unchanged at all time points. Concomitant with loss of surface CD4 was significant lessening of both anti-CD4 and anti-CD3 antibody-induced migration. Reexpression of CD4 at 96 h resulted in the recovery of both CD4− and CD3-mediated migration. Cycloheximide inhibited CD4 reexpression and both anti-CD4 and anti-CD3 antibody-induced migration in cells treated with gp120. These data suggest that CD4 modulation by gp120 results in loss of function, which persists until new membrane CD4 is generated. Persistent exposure of CD4+cells to gp120 in vivo may contribute to the disproportionately large immunological deficits seen in the early stages of HIV-1 infection, in which most CD4+cells remain uninfected.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The role ofvifduring the establishment of human immunodeficiency virus type 1 (HIV-1) infection of peripheral blood T lymphocytes and monocyte/macrophages was investigated usingvifmutants of three HIV-1 proviral DNAs.Vifwas found to be essential for the establishment of productive HIV-1 infection in peripheral blood T lymphocytes after cell-free infection with HXB2 and DFCI-HD, avpr-positive,vpu-positive,nef-positive derivative of HXB2. A chimeric HIV-1 provirus in which the T-cell line-tropicenvsequences in DFCI-HD were replaced with the macrophagetropicenvof the ADA strain was constructed for studies on the role ofvifduring the establishment of HIV-1 infection in primary monocyte/macrophages. These studies showed thatvifis also essential for the initiation of productive HIV-1 infection in primary monocyte/macrophage cultures after cell-free virus transmission. The DFCI-HD-ADA virus was shown to replicate in the CD4+T-cell line Molt 4 clone 8 but not in other T-cell or monocytic cell lines, as previously shown for another macrophagetropic strain YU-2 (1), suggesting that this cell line may be useful for future studies on at least some macrophagetropic strains of HIV-1. The finding thatvifis essential for the establishment of productive HIV-1 infection in primary T lymphocytes and monocyte/macrophages suggests thatvifmay be required for HIV-1 transmission and disease pathogenesis during natural infections and thus may be a good target for prophylactic or therapeutic intervention.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

This study determined the in situ detection rate of polymerase chain reaction (PCR)-amplified human immunodeficiency virus type 1 (HIV-1) DNA and RNA in lymph nodes and peripheral blood CD4+cells in six patients with asymptomatic HIV-1 infection and from six people who died of advanced AIDS. The lymph nodes of patients with asymptomatic infection showed expanded germinal centers where, on average, 20% of the CD21+dendritic cells contained HIV-1 DNA. From 5 to 80% of the CD4+cells in these lymph nodes contained HIV-1 DNA, as compared with 1–11% of the CD4+peripheral blood mononuclear cells. The infection in most cells was latent in the asymptomatic group. In contrast, the lymph nodes of patients with advanced AIDS showed marked depletion of both dendritic and CD4+cells. The majority of the remaining CD4+cells in the lymph nodes and blood showed PCR-amplified viral DNA and cDNA sequences suggesting the presence of genomic and multiple spliced transcripts. It is concluded that asymptomatic HIV-1 infection is associated with a wide range of latent to active viral-positive CD4+lymphocytes and dendritic cells in the lymph nodes. Progression to AIDS is characterized by active viral replication in many of the remaining CD4+cells in the lymph nodes and blood.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The aim of this study was to ascertain the safety profile of didanosine (Videx; ddI) within the Canadian Open Treatment Program. Symptomatic HIV+subjects with AIDS or ARC or CD4 <200/mm3were eligible to receive didanosine if they were either (a) intolerant to zidovudine (Retrovir, ZDV) or (b) deteriorating despite ZDV therapy. The dose of didanosine (powder formulation) was based on body weight as follows: ⩾75 kg, 375 mg b.i.d.; 50–74 kg, 250 mg b.i.d.; 35–49 kg, 167 mg b.i.d. Participants were monitored with physical examinations and prespecified laboratory studies by their treating physicians on a monthly basis. Follow-up data were collected in a central database through five regional coordinators. A total of 168 physicians across Canada participated in the program, and 825 subjects who started didanosine after July 1, 1990, were included in the analysis. Of these, 97% were male, 88% homosexual, and 59% had a prior diagnosis of AIDS. Reasons for enrolling was ZDV intolerance in 39%, failure in 25%, both in 32%, and other in 4%. Data were prospectively collected until July 31, 1991. Total follow-up was 3,440 patient-months and median follow-up was 4.3 months. A total of 78 deaths were reported, 44 of which occurred within a month after the last dose of didanosine. Causes of death included AIDS-related unspecified causes (13 patients), MAC (11), wasting (7), AIDS-related CNS involvement other than OI's (7), Kaposi's sarcoma (7),Pneumocystis cariniipneumonia (6), sudden death, including suicides and accidents (6), lymphoma (5), toxoplasmosis (4), cryptococcosis (4), cytomegalovirus (3), unspecified causes (2), tuberculosis (1), PML (1), and disseminated histoplasmosis (1). Didanosine was discontinued in 140 (17%) subjects during the study period due to adverse events. The most common severe adverse events were diarrhea (16 patients), nausea and vomiting (11), peripheral neuropathy (7), and pancreatitis (6). We conclude that didanosine has a favorable safety profile, even among individuals with advanced HIV disease who have failed or are no longer tolerant of ZDV therapy.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The calcium-binding myelomonocytic protein calprotectin (L1 protein) was quantified in serum from 51 patients with HIV infection and in 20 HIV-seronegative blood donors. Significantly elevated levels were found both in asymptomatic patients and in people with AIDS compared with controls. The calprotectin level was not related to ongoing or recent opportunistic infections. For patients with CD4+counts above 50 x 106/L, a significant negative correlation was found between serum calprotectin levels and the CD4+counts. Serial samples from 24 patients during their first year of zidovudine (ZDV) treatment showed a further elevation of serum calprotectin during the first months of ZDV treatment, with a subsequent decline to pretreatment levels. A low calprotectin response during the first 6 months, determined as area under the curve, was associated with the occurrence of at least one AIDS-defining infection during the first year of antiviral treatment. Also, a low calprotectin maximal response during ZDV therapy was associated with short survival. Similar associations were not found for neopterin, β2-microglobulin, HIV p24 antigen, or CD4+or CD8+lymphocytes in blood. Our findings in a limited number of patients suggest that calprotectin levels may reflect immune activation and other immune mechanisms correlated with enhanced antimicrobial defense induced at least transiently by antiviral treatment.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Mouse monoclonal antibodies with high human immunodeficiency virus type 1 (HIV-1) neutralizing titers were used for passive immunotherapy of eleven late-state HIV-infected patients. In five patients the serum level of the core protein p24 decreased, while in five cases it remained unchanged. The level of viral RNA in plasma as measured by quantitative polymerase chain reaction (PCR) decreased in four cases, was stable in another four, and increased in three cases. An anti-mouse (HAMA) response developed in eight patients and anti-idiotypic antibodies appeared in six. Immune complexes that formed in patient sera during the treatment were shown to contain mostly envelope glycoprotein gp120 which decreased in nine of the eleven treated patients toward the end of treatment. Antibodies inhibiting gp120 binding to CD4 became detectable or increased in six patients during immunotherapy. Serology of the HIV-1 V3 region was studied for both the HIV-1 IIIB and MN strains with no or very small changes in titer or avidity after treatment. No change in neutralizing titers to strain HTLVIIIB was observed in serum samples collected before and after treatment was terminated. In nine of the eleven patients stimulation of the T lymphocytes to proliferate in vitro when activated by phytohemagglutinin (PHA) was shown to be increased compared to before treatment. Increased T-cell proliferation was also noted with several antigens such as HIV-1 recombinant antigens, cytomegalovirus (CMV), tetanus toxoid (TT), and purified protein derivate of mycobacterium tuberculosis (PPD). These findings indicate a decreased total gp120 content in serum, permitting better T-cell activation.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To approximate the contributions of in utero, intrapartum, and postnatal transmission of human immunodeficiency virus type-1 (HIV-1) and to evaluate polymerase chain reaction (PCR) as a diagnostic tool for pediatric HIV infection, blood was collected at birth (cord blood), and at 3, 6–12, and 13–24 months in 218 children born to HIV-1-seropositive mothers in Kigali, Rwanda. Proviral DNA was detected by a double PCR using two sets of three primers (gag, pol, and env). Pediatric HIV-1 infection was defined according to serological and clinical criteria. The probability of having a positive PCR at a given time was calculated by a nonparametric method. Among children with unequivocal evidence of infection (n= 47), it was 30.5% on cord blood and 80.6% at 3 months. Thus, in children born to HIV-1-infected mothers, the estimated rate of transmission in the late postnatal period is 4.9%, and the rate of transmission in the intrapartum plus postnatal periods is 17.6%. Among 117 HIV-1-uninfected children born to HIV-1-infected mothers, six (5%) had a false-positive PCR on cord blood. These results should be taken into account in designing intervention trials aimed at reducing mother-to-child transmission of HIV-1.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To describe past risk behaviors among persons with heterosexually acquired human immunodeficiency virus (HIV) infection, we interviewed 497 persons ⩾18 years of age with heterosexually acquired HIV infection reported to 11 state and city health departments in the United States. Thirty-nine percent of persons reported using noninjection drugs in the past 5 years; noninjection drug use was highest among men whose sex partners injected drugs (53%). Sixteen percent of all persons used crack, and 17% were classified as potential alcoholics; among men, 29% were classified as potential alcoholics. Of the 49% of men who reported paying a woman for sex, 86% did so multiple times. Most persons had multiple sex partners in the past 5 years; however, 35% of the women had only one sex partner. Thirty-four percent of the women and 50% of the men had been treated for a sexually transmitted disease in the past 10 years. Seventy-four percent of the women and 68% of the men had never used condoms in the 5 years before they knew they were HIV positive. Among these people with heterosexually acquired HIV, noninjection drug use was common, many men have paid someone for sex, and many women have not had multiple sex partners. These findings have important implications for the types of prevention programs that can most successfully lessen the spread of HIV among heterosexuals.

ISSN:0894-9255    

出版商:OVID    

年代:1994

数据来源: OVID