High-Level Viremia in Adults and Children Infected with Human Immunodeficiency Virus: Relation to Disease Stage and CD4+ Lymphocyte Levels

1991 ◽  
Vol 164 (1) ◽  
pp. 72-80 ◽  
Author(s):  
M. S. Saag ◽  
M. J. Crain ◽  
W. D. Decker ◽  
S. Campbell-Hill ◽  
S. Robinson ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Disease Stage ◽  
Immunodeficiency Virus ◽  
Adults And Children ◽  
Cd4 Lymphocyte ◽  
High Level

scholarly journals High Levels of Human Immunodeficiency Virus Infection of CD8 Lymphocytes Expressing CD4 In Vivo

2004 ◽  
Vol 78 (18) ◽  
pp. 9862-9871 ◽  
Author(s):  
Alexandra Cochrane ◽  
Stuart Imlach ◽  
Clifford Leen ◽  
Gordon Scott ◽  
Dermot Kennedy ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Lymphocyte Function ◽  
Direct Role ◽  
Immunodeficiency Virus ◽  
Cd4 Lymphocyte ◽  
High Level ◽  
Memory Subset

ABSTRACT Human immunodeficiency virus (HIV)-infected CD8 lymphocytes have been reported in vivo, but the mechanism of infection remains unclear. Experiments using the thy/hu mouse model support export of intrathymically infected CD8 precursors, while recent in vitro data suggest that mature CD8 lymphocytes upregulate CD4 upon activation (generating a CD8bright CD4dim phenotype) and are susceptible to HIV infection. To determine whether these mechanisms operate in vivo and to assess their relative importance in the generation of circulating HIV-infected CD8 lymphocytes, we quantified HIV long terminal repeat (LTR) DNA in CD8+ CD4− and CD8bright CD4dim lymphocytes isolated from HIV-infected individuals by fluorescence-activated cell sorting. HIV infection of CD8 lymphocytes was demonstrated in 17 of 19 subjects, with a significant inverse relationship between level of infection and CD4 lymphocyte count (R = −0.73; P < 0.001). The level of HIV infection of CD8bright CD4dim lymphocytes was significantly higher (median, 1,730 HIV LTR copies/106 cells; n = 9) than that of CD8+ CD4− lymphocytes (undetectable in seven of nine individuals; P < 0.01) and approached that of CD4 lymphocytes from the same individuals (median, 3,660 HIV LTR copies/106 cells). CD8bright CD4dim lymphocytes represented 0.8 to 3.3% of total CD8 lymphocytes and were most prevalent in the memory subset. Thus, HIV-infected CD8 lymphocytes commonly circulate in HIV-infected individuals and are generated through infection of activated CD8 lymphocytes rather than through export of intrathymically infected precursors. The high level of infection of CD8bright CD4dim lymphocytes could have a direct role in the decline in CD8 lymphocyte function that accompanies HIV disease progression.

scholarly journals Subtypes of Human Immunodeficiency Virus Type 1 and Disease Stage among Women in Nairobi, Kenya

1999 ◽  
Vol 73 (5) ◽  
pp. 4393-4403 ◽  
Author(s):  
Joel R. Neilson ◽  
Grace C. John ◽  
Jean K. Carr ◽  
Paul Lewis ◽  
Joan K. Kreiss ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Disease Stage ◽  
Subtype C ◽  
Immunodeficiency Virus ◽  
Cd4 Lymphocyte ◽  
Subtype A ◽  
Hiv 1

ABSTRACT In sub-Saharan Africa, where the effects of human immunodeficiency virus type 1 (HIV-1) have been most devastating, there are multiple subtypes of this virus. The distribution of different subtypes within African populations is generally not linked to particular risk behaviors. Thus, Africa is an ideal setting in which to examine the diversity and mixing of viruses from different subtypes on a population basis. In this setting, it is also possible to address whether infection with a particular subtype is associated with differences in disease stage. To address these questions, we analyzed the HIV-1 subtype, plasma viral loads, and CD4 lymphocyte levels in 320 women from Nairobi, Kenya. Subtype was determined by a combination of heteroduplex mobility assays and sequence analyses of envelope genes, using geographically diverse subtype reference sequences as well as envelope sequences of known subtype from Kenya. The distribution of subtypes in this population was as follows: subtype A, 225 (70.3%); subtype D, 65 (20.5%); subtype C, 22 (6.9%); and subtype G, 1 (0.3%). Intersubtype recombinant envelope genes were detected in 2.2% of the sequences analyzed. Given that the sequences analyzed represented only a small fraction of the proviral genome, this suggests that intersubtype recombinant viral genomes may be very common in Kenya and in other parts of Africa where there are multiple subtypes. The plasma viral RNA levels were highest in women infected with subtype C virus, and women infected with subtype C virus had significantly lower CD4 lymphocyte levels than women infected with the other subtypes. Together, these data suggest that women in Kenya who are infected with subtype C viruses are at more advanced stages of immunosuppression than women infected with subtype A or D. There are at least two models to explain the data from this cross-sectional study; one is that infection with subtype C is associated with a more rapid disease progression, and the second is that subtype C represents an older epidemic in Kenya. Discriminating between these possibilities in a longitudinal study will be important for increasing our understanding of the role of specific subtypes in the transmission and pathogenesis of HIV-1.

Alteration in the Proportion of CD4 T Lymphocytes in a Subgroup of Human Immunodeficiency Virus-Exposed-Uninfected Children

PEDIATRICS ◽  
1994 ◽  
Vol 93 (4) ◽  
pp. 624-630
Author(s):  
Matthew Gesner ◽  
Vana Papaevangelou ◽  
Song-He Chen ◽  
Tiina Moore ◽  
Keith Krasinski ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Statistical Significance ◽  
Weighted Average ◽  
Rate Of Change ◽  
Entire Study ◽  
Age Related ◽  
Wilcoxon Rank Sum Test ◽  
Immunodeficiency Virus ◽  
Cd4 Lymphocyte ◽  
Cd4 Percentage

Objective. The age-related changes in the proportion of CD4 and CD8 lymphocytes in human immunodeficiency virus (HIV)-seronegative children born to HIV-infected mothers (seroreverters) were compared with the changes in these lymphocyte subsets in children born to seronegative women to assess a possible effect of exposure to HIV without infection. Design. There were 146 seroreverter and 72 seronegative children. The median CD4 and CD8 percentages for each of these two groups of children were compared retrospectively at 3-month intervals from birth through 27 months and at a tenth interval for the time beyond 27 months. The weighted average of the within-subject rate of change of CD4 and CD8 percentages were also compared between the two groups. Finally, for each subject, the proportion of the subject's CD4 percentage assays which were &lt;10th percentile of the entire study population (30%) was calculated, and the distributions of the subject-specific proportions were then compared between the seronegative and seroreverter groups using the Wilcoxon rank sum test. The proportion of CD8 assays &lt;10th percentile (12%) or &gt;90th percentile (26%) were also computed for each subject, and the distributions of the proportions were compared similarily. Results. The median CD4 percentage for seroreverter children was lower than that for the seronegative children at every interval from birth through 27 months and for the last interval for values obtained at greater than 27 months, although the comparison was statistically significant only at the 4- to 6-month period. The weighted average of the within-subject rate of change of CD4 percentage was -0.09 and -3.0 per year (P .04), and of CD8 percentage was 1.3 and 1.0 (P = .67), for the seroreverter and seronegative children, respectively. There were significantly more children in the seroreverter group than in the seronegative group who had repeated assays in which the CD4 percentage was &lt;10th percentile for age (P &lt;.00005). In addition, there was a subset of 10 seroreverter children (6.8%) who had CD4 percentages &lt;30% on &gt;50% of their assays, as compared with only one (1.4%) seronegative child. The proportion of CD8 assays &lt;10th percentile or &gt;90th percentile were not significantly different between the two groups of children. Conclusions. The CD4 proportions were persistently lower in the seroreverter than in the seronegative population, although only reaching statistical significance in 1 of 10 3-month intervals. This finding may be due to a subgroup of seroreverter children who have persistently low CD4 lymphocyte percentages.

Combination Therapy With Stavudine and Didanosine in Children With Advanced Human Immunodeficiency Virus Infection: Pharmacokinetic Properties, Safety, and Immunologic and Virologic Effects

PEDIATRICS ◽  
1996 ◽  
Vol 97 (6) ◽  
pp. 886-890
Author(s):  
Mark W. Kline ◽  
Courtney V. Fletcher ◽  
Marianne E. Federici ◽  
Alice T. Harris ◽  
Kim D. Evans ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Combination Therapy ◽  
Lymphocyte Count ◽  
Hiv Disease ◽  
Hiv Rna ◽  
Immunodeficiency Virus ◽  
Pharmacokinetic Properties ◽  
Cd4 Lymphocyte Count ◽  
Cd4 Lymphocyte ◽  
Advanced Hiv Disease

Objectives. To obtain preliminary information on the pharmacokinetic properties, tolerance, safety, and antiviral activity of combination therapy with stavudine and didanosine in children with advanced human immunodeficiency virus (HIV) infection. Methods. Eight children (median age, 6.6 years; range, 2.8 to 12 years) with advanced HIV disease (median CD4+ lymphocyte count at baseline, 42 cells/µL; range, 8 to 553 cells/µL) were treated with stavudine (2 mg/kg per day in two divided doses) and didanosine (180 mg/m2 per day in two divided doses) for 24 weeks. Seven children had histories of prior zidovudine therapy. All children had received stavudine alone for 19 to 33 months before the addition of didanosine to the treatment regimen. Children were assessed clinically and with laboratory studies at baseline, weekly through week 4 of combination therapy, and every 4 weeks thereafter. Results. Analysis of stavudine and didanosine plasma half-life values, clearances, and area under the plasma concentration-versus-time curves revealed no obvious clinical pharmacokinetic interaction between the drugs through study week 12. Combination therapy was well tolerated, and there were no drug-associated clinical or laboratory adverse events. Signs and symptoms of peripheral neuropathy were not observed. All three children with baseline CD4+ lymphocyte counts greater than 50 cells/µL had greater than 20% increases in their counts within the first 12 weeks of therapy; CD4+ lymphocyte count increases were not observed in the other children. Plasma HIV RNA concentrations showed median declines of 0.88 log10 (range, -3.41 log10 to 0.31 log10) and 0.30 log10 (range, -0.63 log10 to 0.89 log10) at study weeks 12 and 24, respectively. Conclusions. Combination therapy with stavudine and didanosine was well tolerated and safe in this small group of children with advanced HIV disease. Plasma HIV RNA concentration declines suggest a favorable effect of therapy on virus load. These findings should be confirmed, and the regimen's clinical efficacy should be examined, in controlled studies of HIV-infected children with less-advanced disease.

scholarly journals The presence of hepatitis C virus (HCV) antibody in human immunodeficiency virus-positive hemophilic men undergoing HCV "seroreversion"

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 1010-1015 ◽  
Author(s):  
MV Ragni ◽  
OK Ndimbie ◽  
EO Rice ◽  
FA Bontempo ◽  
S Nedjar
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Second Generation ◽  
Hcv Rna ◽  
Negative State ◽  
Immunodeficiency Virus ◽  
Before And After ◽  
Hcv Antibody ◽  
Cd4 Lymphocyte

Abstract Hepatitis C virus (HCV) is a major cause of transfusion-induced chronic liver disease in hemophiliacs, with 70% to 90% being anti-HCV positive. Seroreversion or loss of antibody response to HCV has been observed in a small proportion of human immunodeficiency virus-positive [HIV(+)] anti-HCV(+) hemophilic men. Despite the seroreversion to an anti-HCV- negative state, such patients continue to show serum alanine aminotransferase (ALT) elevations and biopsy evidence of cirrhosis and/or chronic active hepatitis. To determine the cause for the loss of anti-HCV antibody, we compared first- and second-generation anti-HCV enzyme immunosorbent assay (EIA 1.0 and 2.0), second-generation recombinant immunoblot (RIBA 2.0), and HCV-RNA amplification using polymerase chain reaction (PCR) in 19 “seroreverters” before and after seroreversion. There was no difference between 19 seroreverters and 59 persistently anti-HCV-positive hemophiliacs in mean ALT (1.1 +/- 0.1 XUL v 2.0 +/- 0.2 XUL; chi 2 = 1.80, P > .05), in mean CD4 (188 +/- 36/microL v 232 +/- 28/microL; t = 0.965, P > .05), or in the rate of progression to acquired immunodeficiency syndrome (13 of 19 [68.4%] v 30 of 59 [50.9%]; chi 2 = .987, P > .05, respectively). Before seroreversion, all 19 seroreverters (100%) were positive for EIA 1.0 and 2.0 and PCR, and all but 2 of 19 (89.5%) were RIBA 2.0 positive, whereas, after seroreversion, none were positive for EIA 1.0, 15 of 19 (78.9%) were positive for EIA 2.0, 8 of 18 (44.4%) were positive for RIBA 2.0, and 18 of 19 (94.7%) were positive for PCR. There was a lower CD4 lymphocyte number after seroreversion in those who were RIBA 2.0 negative as compared with those who were RIBA 2.0 positive (32 +/- 10/microL v 171 +/- 52/microL; t = 2.638, P > .05). These results indicate that HIV(+) anti-HCV(+) hemophilic men who undergo “HCV seroreversion” are truly infectious and anti-HCV positive by second- generation tests. Anti-HCV detection in immunosuppressed hosts is significantly improved by second-generation EIA and RIBA assays.

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