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Failure of Bone Marrow Transplantation to Eradicate HIV Reservoir despite Effective HAART
Véronique Avettand-Fenoel*1,2, Véronique Avettand-Fenoel*1,2, A Buzyn1, N Mahlaoui1, M L Chaix1,2, M L Chaix1,2, C Milliancourt1, M Burgard1,2, M Burgard1,2, M Cavazzana-Calvo1, C Rouzioux1,2, C Rouzioux1,2, S Blanche1,2, and S Blanche1,2
1Ctr Hosp Univ Necker, Paris, France and 2Univ Paris 5, Faculty of Med, Paris, France
Background: We explored the effect of bone marrow
transplantation (BMT) on HIV reservoir in a Romanian 17-year-old HIV-1-infected
man presenting a leukemia. This is the first case of
BMT performed on a patient on effective HAART for 18 months.
Methods: HIV infection occurred at 8 years of age by
transfusion. The patient developed a Burkitt’s lymphoma in June 2003 and
received effective HAART. He developed leukemia in April 2005 and BMT was
proposed in October. HAART was maintained except a short interruption due to
toxicity between day +114 and +134. We explored HIV DNA and HIV RNA by a
sensitive real time polymerase chain reaction (RT-PCR) (LTR region - ANRS) before and after BMT. The lowest threshold
possible for each sample was obtained even in cases with few cells, as the
maximum tests per sample were realized to explore all the available cells.
Results: Before BMT, HIV DNA was at 2.76 log copies/106
peripheral blood mononuclear cells (PBMC) and 1.77 log copies/106
bone marrow cells. After BMT, HIV RNA in plasma remained <1.7 log copies/mL;
HIV DNA was undetectable in PBMC during more than 4 months (<2 log copies/106
PBMC) although >1 million PBMC were explored. Chimerism study showed a 100%
donor phenotype. However, after HAART cessation, rebounds of HIV RNA (4.61 log
copies/mL) and HIV DNA (2.50 log) in blood were observed. Resumption of HAART
at day +134 returned viral loads to undetectable level at day +152. HIV DNA was
still detectable <1.5 to 2.5 log copies/106 PBMC, but not
detectable in esophageal, antral, duodenal, and rectal biopsies realized 12
days after HAART resumption. A phylogenetic analysis based on the gp120
C2-V3 sequences on 4 plasma viral strains (2 in 2003 and 2 in 2006 after BMT) confirmed
that the viral reservoir was not eradicated and was able to produce
quasispecies in 2006 different from those in 2003. The patient died in
multivisceral failure at day +191.
Conclusions: Despite BMT associated with the powerful
cytotoxic conditioning regimen, eradication was not observed in this patient
with long-term controlled viral replication. A short HAART interruption
revealed the persistence of an infectious archived viral reservoir previously
constituted in profound tissues. We hypothesized that some recipient
antigen-presenting cells can survive and play a critical role as a virus
reservoir. Moreover, totipotent hematopoietic progenitors may possibly survive
intensive pre-transplant conditioning regimen and support the failure of
eradication.
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