scholarly journals Persistence of Extraordinarily Low Levels of Genetically Homogeneous Human Immunodeficiency Virus Type 1 in Exposed Seronegative Individuals

2003 ◽  
Vol 77 (11) ◽  
pp. 6108-6116 ◽  
Author(s):  
Tuofu Zhu ◽  
Lawrence Corey ◽  
Yon Hwangbo ◽  
Jean M. Lee ◽  
Gerald H. Learn ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
High Risk ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Specific Cytotoxicity ◽  
Low Levels ◽  
And Control ◽  
Hiv 1

ABSTRACT Some individuals remain inexplicably seronegative and lack evidence for human immunodeficiency virus type 1 (HIV-1) infection by conventional serologic or virologic testing despite repeated high-risk virus exposures. Here, we examined 10 exposed seronegative (ES) individuals exhibiting HIV-1-specific cytotoxicity for the presence of HIV-1. We discovered HIV-1 DNA in resting CD4+ T cells (mean, 0.05 ± 0.01 copies per million cells) at multiple visits spanning 69 to 130 weeks in two ES individuals at levels that were on average 104- to 106-fold lower than those of other HIV-1-infected populations reported. Sequences of HIV-1 envelope and gag genes remained markedly homogeneous, indicating little to undetectable virus replication. These results provide the evidence for HIV-1 infection in ES individuals below the detection limit of standard assays, suggesting that extraordinary control of infection can occur. The two HIV-infected ES individuals remained healthy and were not superinfected with other HIV-1 strains despite continued high-risk sexual exposures to multiple HIV-infected partners. Understanding the mechanisms that confer diminished replicative capacity of HIV-1 in these hosts is paramount to developing strategies for protection against and control of HIV-1 infection.

scholarly journals Low Levels of Human Immunodeficiency Virus Type 1 DNA in High-Risk Seronegative Men

2005 ◽  
Vol 79 (10) ◽  
pp. 6551-6553 ◽  
Author(s):  
Fransje A. Koning ◽  
Teun J. K. van der Vorst ◽  
Hanneke Schuitemaker
Keyword(s):  
Human Immunodeficiency Virus ◽  
High Risk ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Peripheral Blood Mononuclear ◽  
Immunodeficiency Virus ◽  
High Prevalence ◽  
Low Levels ◽  
Hiv 1

ABSTRACT We detected human immunodeficiency virus type 1 (HIV-1) DNA at very low levels in sequential peripheral blood mononuclear cell samples of five out of six high-risk, seronegative, homosexual men and five out of five individuals 7.8 to 1.6 years prior to seroconversion. These data indicate a high prevalence of low-level HIV-1 DNA in exposed seronegative individuals.

scholarly journals Silent infections with human immunodeficiency virus type 1 are highly unlikely in multitransfused seronegative hemophiliacs [see comments]

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1924-1926 ◽  
Author(s):  
J Gibbons ◽  
JM Cory ◽  
IK Hewlett ◽  
JS Epstein ◽  
ME Eyster
Keyword(s):  
Human Immunodeficiency Virus ◽  
High Risk ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Immunodeficiency Virus ◽  
Contaminated Blood ◽  
Hiv 1

Abstract We used the polymerase chain reaction (PCR) to determine the frequency of silent human immunodeficiency virus type 1 (HIV-1) infections in seronegative high-risk individuals with hemophilia who had been exposed to contaminated blood products more than 3 years previously. In a cross- sectional study of a cohort of 57 prospectively followed seronegative hemophiliacs who received multiple transfusions before 1986, HIV-1 proviral DNA was found transiently in only one patient. These data suggest that the rate of HIV infection among high-risk antibody negative individuals with hemophilia is very low to absent, in the range of 0% to 2%. These findings should provide considerable reassurance to seronegative persons with hemophilia and their sexual partners.

scholarly journals Validation of a Modified Commercial Enzyme-Linked Immunoassay for Detection of Human Immunodeficiency Virus Type 1 Immunoglobulin G Antibodies in Saliva

2001 ◽  
Vol 8 (2) ◽  
pp. 346-348 ◽  
Author(s):  
Bhavna H. Chohan ◽  
Ludo Lavreys ◽  
Kishorchandra N. Mandaliya ◽  
Joan K. Kreiss ◽  
Job J. Bwayo ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
High Risk ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Predictive Value ◽  
Saliva Sample ◽  
High Risk Population ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT This study was performed to evaluate the performance of a saliva collection device (OmniSal) and an enzyme-linked immunoassay (EIA) designed for use on serum samples (Detect HIV1/2) to detect human immunodeficiency virus type 1 (HIV-1) antibodies in the saliva of high-risk women in Mombasa, Kenya. The results of the saliva assay were compared to a “gold standard” of a double-EIA testing algorithm performed on serum. Individuals were considered HIV-1 seropositive if their serum tested positive for antibodies to HIV-1 by two different EIAs. The commercial serum-based EIA was modified to test the saliva samples by altering the dilution and lowering the cutoff point of the assay. Using the saliva sample, the EIA correctly identified 102 of the 103 seropositive individuals, yielding a sensitivity of 99% (95% confidence interval [CI], 94 to 100%), and 96 of the 96 seronegative individuals, yielding a specificity of 100% (95% CI, 95 to 100%). In this high-risk population, the positive predictive value of the assay was 100% and the negative predictive value was 99%. We conclude that HIV-1 antibody testing of saliva samples collected with this device and tested by this EIA is of sufficient sensitivity and specificity to make this protocol useful in epidemiological studies.

scholarly journals CCR5Δ32 Protein Expression and Stability Are Critical for Resistance to Human Immunodeficiency Virus Type 1 In Vivo

2007 ◽  
Vol 81 (15) ◽  
pp. 8041-8049 ◽  
Author(s):  
Lokesh Agrawal ◽  
Qingwen Jin ◽  
Jeff Altenburg ◽  
L. Meyer ◽  
R. Tubiana ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protein Expression ◽  
Protective Effect ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Low Levels ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection of individuals carrying the two alleles of the CCR5Δ32 mutation (CCR5−/−) has rarely been reported, but how the virus overcomes the CCR5Δ32 protective effect in these cases has not been delineated. We have investigated this in 6 infected (HIV+) and 25 HIV− CCR5−/− individuals. CD4+ T lymphocytes isolated from HIV− CCR5−/− peripheral blood mononuclear cells (PBMCs) showed lower levels of CXCR4 expression that correlated with lower X4 Env-mediated fusion. Endogenous CCR5Δ32 protein was detected in all HIV− CCR5−/− PBMC samples (n = 25) but not in four of six unrelated HIV+ CCR5−/− PBMC samples. Low levels were detected in another two HIV+ CCR5−/− PBMC samples. The expression of adenovirus 5 (Ad5)-encoded CCR5Δ32 protein restored the protective effect in PBMCs from three HIV+ CCR5−/− individuals but failed to restore the protective effect in PBMCs isolated from another three HIV+ CCR5−/− individuals. In the latter samples, pulse-chase analyses demonstrated the disappearance of endogenous Ad5-encoded CCR5Δ32 protein and the accumulation of Ad5-encoded CCR5 during the chase periods. PBMCs isolated from CCR5−/− individuals showed resistance to primary X4 but were readily infected by a lab-adapted X4 strain. Low levels of Ad5-encoded CCR5Δ32 protein conferred resistance to primary X4 but not to lab-adapted X4 virus. These data provide strong support for the hypothesis that the CCR5Δ32 protein actively confers resistance to HIV-1 in vivo and suggest that the loss or reduction of CCR5Δ32 protein expression may account for HIV-1 infection of CCR5−/− individuals. The results also suggest that other cellular or virally induced factors may be involved in the stability of CCR5Δ32 protein.

scholarly journals Low TRBP Levels Support an Innate Human Immunodeficiency Virus Type 1 Resistance in Astrocytes by Enhancing the PKR Antiviral Response

2005 ◽  
Vol 79 (20) ◽  
pp. 12763-12772 ◽  
Author(s):  
Chi L. Ong ◽  
Janine C. Thorpe ◽  
Paul R. Gorry ◽  
Sylvie Bannwarth ◽  
Anthony Jaworowski ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Antiviral Response ◽  
Immunodeficiency Virus ◽  
Low Levels ◽  
Hiv 1

ABSTRACT Acute human immunodeficiency virus type 1 (HIV-1) replication in astrocytes produces minimal new virus particles due, in part, to inefficient translation of viral structural proteins despite high levels of cytoplasmic viral mRNA. We found that a highly reactive double-stranded (ds) RNA-binding protein kinase (PKR) response in astrocytes underlies this inefficient translation of HIV-1 mRNA. The dsRNA elements made during acute replication of HIV-1 in astrocytes triggers PKR activation and the specific inhibition of HIV-1 protein translation. The heightened PKR response results from relatively low levels of the cellular antagonist of PKR, the TAR RNA binding protein (TRBP). Efficient HIV-1 production was restored in astrocytes by inhibiting the innate PKR response to HIV-1 dsRNA with dominant negative PKR mutants, or PKR knockdown by siRNA gene silencing. Increasing the expression of TRBP in astrocytes restored acute virus production to levels comparable to those observed in permissive cells. Therefore, the robust innate PKR antiviral response in astrocytes results from relatively low levels of TRBP expression and contributes to their restricted infection. Our findings highlight TRBP as a novel cellular target for therapeutic interventions to block productive HIV-1 replication in cells that are fully permissive for HIV-1 infection.

scholarly journals Silent human immunodeficiency virus type 1 infection: a rare occurrence in a high-risk heterosexual population

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2396-2400 ◽  
Author(s):  
DB Brettler ◽  
M Somasundaran ◽  
AF Forsberg ◽  
E Krause ◽  
JL Sullivan
Keyword(s):  
Human Immunodeficiency Virus ◽  
High Risk ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Diagnostic Methods ◽  
Rare Occurrence ◽  
Immunodeficiency Virus ◽  
Additional Testing ◽  
Hiv 1

Abstract A group of 58 heterosexual female partners (FP) of human immunodeficiency virus type 1 (HIV-1)-seropositive hemophiliacs was studied by conventional diagnostic methods such as enzyme-linked immunosorbent assay (ELISA) and Western blot analysis to examine whether any had acquired HIV-1 infection through sexual transmission. A subset of 29 FP were asked to answer a detailed questionnaire concerning their health, use of “safer sex” techniques, and other risk factors for HIV-1 infection. They also had additional blood drawn for CD4 cell analysis, viral cultures, nef, gag, and env immunoblots, and polymerase chain reaction (PCR) analysis to assess the occurrence of “silent” HIV-1 infection in a high-risk seronegative population. Among the 58 FP, three were found to be HIV-1-seropositive on first testing, with no new seroconversions occurring with subsequent testing in the remaining 55. Two seropositive FP had the additional testing and were found to have positive viral cultures, as well as positive PCR results. All of the seronegative FP (n = 24) who had additional testing were negative in viral culture, had negative immunoblots, and had no HIV-1 nucleic acid sequences detected by PCR. Thus, in this population, silent HIV-1 infection appears to be a rare occurrence and antibody testing seems to correlate with the more sensitive techniques of PCR and viral cultures.

scholarly journals Diversity, Divergence, and Evolution of Cell-Free Human Immunodeficiency Virus Type 1 in Vaginal Secretions and Blood of Chronically Infected Women: Associations with Immune Status

2005 ◽  
Vol 79 (15) ◽  
pp. 9799-9809 ◽  
Author(s):  
Sharon T. Sullivan ◽  
Usha Mandava ◽  
Tammy Evans-Strickfaden ◽  
Jeffrey L. Lennox ◽  
Tedd V. Ellerbrock ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cell Level ◽  
Immunodeficiency Virus ◽  
Vaginal Secretions ◽  
Low Levels ◽  
Changes Over Time ◽  
Hiv 1

ABSTRACT Most human immunodeficiency virus type 1 (HIV-1) infections are believed to be the result of exposure to the virus in genital secretions. However, prevention and therapeutic strategies are usually based on characterizations of HIV-1 in blood. To understand better the dynamics between HIV-1 quasispecies in the genital tract and blood, we performed heteroduplex assays on amplified env products from cell-free viral RNA in paired vaginal secretion (VS) and blood plasma (BP) samples of 14 women followed for 1.5 to 3.5 years. Diversity and divergence were less in VS than in BP (P = 0.03 and P < 0.01, respectively), and divergence at both sites was correlated with blood CD4+ cell levels (VS, P = 0.05; BP, P = 0.01). Evolution of quasispecies was observed in 58% of the women; the loss or gain of quasispecies in VS or BP was always accompanied by such changes at the other site. In addition, sustained compartmentalization of quasispecies in VS was found for four women, even as CD4+ cell levels decreased to low levels (<50 cells/μl). Quasispecies changes over time were associated with fluctuations in CD4+ cell levels; concordant increases or decreases in VS and BP divergence had greater CD4+ cell level changes than intervals with discordant changes (P = 0.05), and women with evolving quasispecies had greater decreases in CD4+ cell levels compared to that for women who maintained the same quasispecies (P < 0.05). Thus, diversity, divergence, and evolution of cell-free HIV-1 in VS can be different from that in BP, and dynamics between their respective quasispecies are associated with changes in CD4+ cell levels.

scholarly journals Silent infections with human immunodeficiency virus type 1 are highly unlikely in multitransfused seronegative hemophiliacs [see comments]

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1924-1926 ◽  
Author(s):  
J Gibbons ◽  
JM Cory ◽  
IK Hewlett ◽  
JS Epstein ◽  
ME Eyster
Keyword(s):  
Human Immunodeficiency Virus ◽  
High Risk ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Immunodeficiency Virus ◽  
Contaminated Blood ◽  
Hiv 1

We used the polymerase chain reaction (PCR) to determine the frequency of silent human immunodeficiency virus type 1 (HIV-1) infections in seronegative high-risk individuals with hemophilia who had been exposed to contaminated blood products more than 3 years previously. In a cross- sectional study of a cohort of 57 prospectively followed seronegative hemophiliacs who received multiple transfusions before 1986, HIV-1 proviral DNA was found transiently in only one patient. These data suggest that the rate of HIV infection among high-risk antibody negative individuals with hemophilia is very low to absent, in the range of 0% to 2%. These findings should provide considerable reassurance to seronegative persons with hemophilia and their sexual partners.

scholarly journals Silent human immunodeficiency virus type 1 infection: a rare occurrence in a high-risk heterosexual population

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2396-2400
Author(s):  
DB Brettler ◽  
M Somasundaran ◽  
AF Forsberg ◽  
E Krause ◽  
JL Sullivan
Keyword(s):  
Human Immunodeficiency Virus ◽  
High Risk ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Diagnostic Methods ◽  
Rare Occurrence ◽  
Immunodeficiency Virus ◽  
Additional Testing ◽  
Hiv 1

A group of 58 heterosexual female partners (FP) of human immunodeficiency virus type 1 (HIV-1)-seropositive hemophiliacs was studied by conventional diagnostic methods such as enzyme-linked immunosorbent assay (ELISA) and Western blot analysis to examine whether any had acquired HIV-1 infection through sexual transmission. A subset of 29 FP were asked to answer a detailed questionnaire concerning their health, use of “safer sex” techniques, and other risk factors for HIV-1 infection. They also had additional blood drawn for CD4 cell analysis, viral cultures, nef, gag, and env immunoblots, and polymerase chain reaction (PCR) analysis to assess the occurrence of “silent” HIV-1 infection in a high-risk seronegative population. Among the 58 FP, three were found to be HIV-1-seropositive on first testing, with no new seroconversions occurring with subsequent testing in the remaining 55. Two seropositive FP had the additional testing and were found to have positive viral cultures, as well as positive PCR results. All of the seronegative FP (n = 24) who had additional testing were negative in viral culture, had negative immunoblots, and had no HIV-1 nucleic acid sequences detected by PCR. Thus, in this population, silent HIV-1 infection appears to be a rare occurrence and antibody testing seems to correlate with the more sensitive techniques of PCR and viral cultures.

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