Decreased HIV diversity after allogeneic stem cell transplantation of an HIV-1 infected patient: a case report.
The human immunodeficiency virus type 1 (HIV-1) coreceptor use and viral evolution were analyzed in blood samples from an HIV-1 infected patient undergoing allogeneic stem cell transplantation (SCT). Coreceptor use was predicted in silico from sequence data obtained from the third variable loop region of the viral envelope gene with two software tools. Viral diversity and evolution was evaluated on the same samples by Bayesian inference and maximum likelihood methods. In addition, phenotypic analysis was done by comparison of viral growth in peripheral blood mononuclear cells and in a CCR5 (R5)-deficient T-cell line which was controlled by a reporter assay confirming viral tropism. In silico coreceptor predictions did not match experimental determinations that showed a consistent R5 tropism. Anti-HIV directed antibodies could be detected before and after the SCT. These preexisting antibodies did not prevent viral rebound after the interruption of antiretroviral therapy during the SCT. Eventually, transplantation and readministration of anti-retroviral drugs lead to sustained increase in CD4 counts and decreased viral load to undetectable levels. Unexpectedly, viral diversity decreased after successful SCT. Our data evidence that only R5-tropic virus was found in the patient before and after transplantation. Therefore, blocking CCR5 receptor during stem cell transplantation might have had beneficial effects and this might apply to more patients undergoing allogeneic stem cell transplantation. Furthermore, we revealed a scenario of HIV-1 dynamic different from the commonly described ones. Analysis of viral evolution shows the decrease of viral diversity even during episodes with bursts in viral load.
Kamp
Christel
C
Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany.
Wolf
Timo
T
Bravo
Ignacio G
IG
Kraus
Benjamin
B
Krause
Birgit
B
Neumann
Britta
B
Winskowsky
Gudrun
G
Thielen
Alexander
A
Werner
Albrecht
A
Schnierle
Barbara S
BS
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002460:Cell Line; D002478:Cells, Cultured; D016000:Cluster Analysis; D014644:Genetic Variation; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D010802:Phylogeny; D015728:Receptors, HIV / Q000032:analysis; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000821:virology
D019380:Anti-HIV Agents; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015728:Receptors, HIV; C514793:gp120 protein, Human immunodeficiency virus 1