High risk of HIV-1 infection for first-born twins

167

134

We have compared the variable region 3 sequences from 10 human immunodeSciency virus type 1 (H1V-1)-infected infants to virus sequences from the corresponding mothers. The sequences were derived from DNA of uncultured peripheral blood mononuclear cells (PBMC), DNA ofcultured PBMC, and RNA from serum collected at or shortly after delivery. The infected infants, in contrast to the mothers, harbored homogeneous virus populations. Comparison of sequences from the children and clones derived from DNA of the corresponding mothers showed that the transmitted virus represented either a minor or a major virus population of the mother. In contrast to an earlier study, we found no evidence of selection of minor virus variants during transmission. Furthermore, the transmitted virus variant did not show any characteristic molecular features. In some cases the transmitted virus was more related to the virus RNA population of the mother and in other cases it was more related to the virus DNA population. This suggests that either cell-free or cell-associated virus may be transmitted. These data will help AIDS researchers to understand the mechanism of transmission and to plan strategies for prevention of transmission.

Section: Discussionmentioning

confidence: 99%

“…It has been recently suggested that transmission takes place at or shortly before delivery (3,4) and that mothers with low CD4+ lymphocyte counts and p24 antigenemia (2,5) have an increased risk of transmission.…”

mentioning

confidence: 99%

Comparison of variable region 3 sequences of human immunodeficiency virus type 1 from infected children with the RNA and DNA sequences of the virus populations of their mothers.

Scarlatti

Leitner

Halapi

et al. 1993

167

134

“…The ability of many infected infants to produce HIV-specific IgG at birth confirms that fetal B cells, which are normally "naive," are capable of responding to certain antigens or antigen-like moieties. It also implies that in utero transmission of perinatal HIV-1 infection, a possibility that remains controversial (24,25) birth may reflect the functional immaturity of neonatal B and helper T cells (26)(27)(28)(29), the increased suppressor activity of cord blood T cells (30,31), or insufficient antigenic stimulation. The amount of HIV-1 antigenic stimulation, as measured by p24 antigen levels in serum and the ability to culture virus, is low in the immediate newborn period but increases rapidly in the first 2 months of life (12,13).…”

Section: Discussionmentioning

confidence: 99%

Ontogeny of anti-human immunodeficiency virus (HIV) antibody production in HIV-1-infected infants.

Pollack

Zhan

Ilmet-Moore

et al. 1993

The early serologic response of infants to infection with human immunodeficiency virus type 1 (HIV-1) is normally obscured by the presence of transplacentally acquired maternal HIV antibody. By measuring HIV antibody produced in vitro by lymphocytes isolated from peripheral blood of infants and children of HIV-1-infected mothers, we have been able to study the natural acquisition of humoral immunity to perinatal HIV-1 infection. One hundred ninety-seven infants of HIV-1-infected women were studied prospectively and longitudinally from birth. In the neonatal period, infected infants produced only small amounts of HIV-specific IgG antibodies to a restricted number of antigens. The amount of immunoglobulin to HIV-1 and the number of HIV-1 antigens recognized increased with age. After 6 months of life 85% of infected infants made detectable antibody to two or more viral proteins. Antibody to gp160 appeared first and was the most frequently found at all ages, followed by antibody to the envelope proteins gp120 and gp41. The amount of HIV antibody produced correlated positively with the percentage of CD4+ T lymphocytes in peripheral blood. This assay provides a method of studying the immunogenicity of vaccines against HIV-1 in HIV-1-infected infants and of assessing the effect of early therapeutic interventions on the humoral response to HIV-1.

“…AZT-resistant virus in plasma or serum was detected by differential PCR to discern mutations at codon 215 of the HIV-1 RT gene (11); mutations at this site are often seen in clinical isolates resistant to AZT and are associated with clinical decline in patients receiving long-term AZT therapy (11,12). For [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] (Table 1) were reported previously (4).…”

Section: Methodsmentioning

confidence: 99%

Maternal plasma human immunodeficiency virus type 1 RNA level: a determinant and projected threshold for mother-to-child transmission.

Fang

Burger

Grimson

et al. 1995

151

To prevent mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission, it is important to identify its determinants. Because HIV-1 RNA levels can be reduced by antiviral therapy, we examined the role of maternal plasma HIV-1 RNA level in mother-to-child transmission. We used quantitative competitive PCR to measure HIV-RNA in 30 infected pregnant women and then followed their infants prospectively; 27% of the women transmitted HIV-1 to their infants and maternal plasma HIV-1 RNA level correlated strikingly with transmission. Eight of the 10 women with the highest HIV-1 RNA levels at delivery (190,400-1,664,100 copies per ml of plasma) transmitted, while none of the 20 women with lower levels (500-155,800 copies per ml) did (P = 0.0002). Statistical analysis of the distribution of HIV-1 RNA loads in these 30 women projected a threshold for mother-to-child transmission in a larger population; the probability of a woman with a viral RNA level of < or = 100,000 copies per ml not transmitting is predicted to be 97%. Examination of serial HIV-1 RNA levels during pregnancy showed that viral load was stable in women who did not initiate or change antiviral therapy. These data identify maternal plasma HIV-1-RNA level as a major determinant of mother-to-child transmission and suggest that quantitation of HIV-1 RNA may predict the risk of transmission.