704
Analysis of HIV Tropism in HIV-infected Ugandan Infants
Jessica D. Church*1, W Huang2, J Toma2, L Guay1, F Mmiro3, P Musoke3, J Jackson1, N Parkin2, A Mwatha4, and S Eshleman1
1Johns Hopkins Univ, Baltimore, MD, US; 2Monogram Biosci, South San Francisco, CA, US; 3Makerere Univ, Kampala, Uganda; and 4Fred Hutchinson Cancer Res Ctr, Seattle, WA, US
Background: HIV-1 may utilize the CXCR4 co-receptor, the
CCR5 co-receptor, or both (dual-tropic virus). HIV-1 infection usually initiated
with CCR5-using virus. Evolution to CXCR4-using virus is associated with more
rapid progression to AIDS. We analyzed HIV-1 tropism in samples from HIV-1-infected
Ugandan infants.
Methods: Plasma or serum samples (100 µL)
collected at 6 to 14 weeks of age were available from 75 of 106 HIV-1-infected
Ugandan infants in the HIVNET012 trial who were HIV-infected by 14 weeks of
age. HIV tropism was analyzed using a commercial co-receptor tropism
assay. Additional samples were tested
from infants who had evidence of CXCR4-using strains, and from their mothers.
Results: Of 75 samples, 57 (76%) were successfully analyzed. Inability
to obtain results on the other 18 samples most likely reflected the low sample volumes
available for testing. Of the 57 samples, 52 (91.2%) had the CCR5-using (R5)
phenotype, and 5 (8.8%) had evidence of CXCR4-using (X4) virus, including 1
infant with predominantly X4 tropic virus and 4 infants with dual or mixed
tropism. Of the 5 infants, 4 were diagnosed with HIV infection at birth, and 1
at 6 to 8 weeks of age. Results from maternal samples collected at delivery,
infant samples collected at the time of birth, follow-up samples (available for
2 of 5 infants), and the age at death are shown in the table. The median
survival of these 5 infants (24.3 months) was not significantly different from
the median survival of the 52 infants who had CCR5-using virus at 6 to 14 weeks
of age (23.6 months, log-rank p
=0.293). The 2 infants with CXCR4-using virus or dual or mixed tropic virus
that used CXCR4 efficiently died within 14.5 months.
Conclusions: CCR5 tropic virus was detected in the majority
of HIV-infected infants at 6 to 14 weeks of age. However, 5 (8.8%) of 57
infants had evidence of infection with either CXCR4-using virus or dual or
mixed tropic tropic virus. Further studies are needed to define the tropism of
strains in newly infected infants and its effect on disease progression in
infants.
|
|
Delivery
|
Birth
|
6-8
weeks
|
14
weeks
|
12-18
months
|
Age at death
|
|
197
|
X4
|
DM
|
X4
|
X4
|
|
14.5 months
|
|
185
|
DM
|
DM
|
NA
|
DM a
|
|
10.5 months
|
|
223
|
DM
|
NA b
|
DM
|
DM
|
R5
|
2.5 years
|
a This sample had a high efficiency of replication in cells
with CXCR4.
b HIV infection was diagnosed in this infant at 6 to 8 weeks
of age.
c A minor population of dual-tropic clones was identified in
this sample.
DM = dual or mixed tropism.
|
