This study tested whether donor-derived HIV-specific immune responses could be detected when viral replication was completely suppressed by the continuous administration of highly active antiretroviral therapy (HAART). A regimen of fludarabine and 200 cGy total body irradiation was followed by infusion of allogeneic donor peripheral blood cells and posttransplantation cyclosporine and mycophenolate mofetil. Viral load, lymphocyte counts, and HIV-1–specific CD8+ cell immune responses were compared before and after hematopoietic cell transplantation (HCT). Uninterrupted administration of HAART was feasible during nonmyeloablative conditioning and after HCT. The HIV RNA remained undetectable and no HIV-associated infections were observed. CD8+ T-cell responses targeting multiple epitopes were detected before HCT. After HCT a different pattern of donor-derived HIV-specific CTL responses emerged by day +80, presumably primed in vivo. We conclude that allogeneic HCT offers the unique ability to characterize de novo HIV-1–specific immune responses. This clinical trial was registered at ClinicalTrials.gov (identifier: NCT00112593).

Recent studies have shown that autologous hematopoietic cell transplantation (HCT) is feasible for treatment of HIV-associated lymphoma when HIV is controlled with highly active antiretroviral therapy (HAART).1  This study investigates a nonmyeloablative (NM) HCT regimen, NMHCT,2  combined with uninterrupted HAART to determine the effect on the control of HIV replication and on the development of HIV-1–specific immune responses.

Study population

Eligibility included HIV-1–infected patients with hematologic malignancies on suppressive HAART. The transplantation protocol was approved by the Institutional Review Board of the Fred Hutchinson Cancer Research Center (FHCRC). Written informed consent was obtained in accordance with the Declaration of Helsinki.

Transplantation

The preparative regimen, 90 mg/m2 total dose of fludarabine and 200 cGy total body irradiation, was administered as described.2  Patients received granulocyte colony-stimulating factor (G-CSF)–mobilized peripheral blood stem cells (PBSCs) from an HLA allele–matched related or unrelated donor. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine (CSP) and mycophenolate mofetil (MMF).2,3  HAART was given through conditioning and after HCT (Table 1).

Table 1

Patient characteristics and transplantation outcomes

Patient 1Patient 2
Age/sex 39/M 33/M 
Diagnosis AML AML 
CMV R/D +/− −/− 
Donor Unrelated Sibling 
Patient and donor HLA 
    A 2402, 0201 0101, 2601 
    B 2705, 3901 0801, 3502 
    C 0102, 1203 0701, 0401 
    DRB 1 0701, 1601 0301, 1104 
    DQB 1 0201, 0502 0201, 0301 
Cell dose/kg recipient 
    CD34+, ×106 4.58 10.63 
    CD3+, ×108 1.66 2.83 
HAART regimen Efavirenz, abacavir, tenofovir Efavirenz, abacavir, lamivudine 
GVHD prophylaxis CSP/MMF CSP/MMF 
Relapse (treatment) Cytogenetic relapse, day +44 (CSP/MMF withdrawn) None 
GVHD (treatment) Grade II skin/gut, day +56 (Pred/MMF/FK/B-B) BO, day +254 (Pred/Immuran/MMF/FK) None 
Survival Died, day +301 > 180 days 
Cause of death GVHD + BO NA 
HIV-related illness None None 
HIV RNA (copies/mL) 
    Pre < 30 < 30 
    Day +14 < 30 < 30 
    Day +28 < 30 < 30 
    Day +56 < 30 < 30 
    Day +100 < 30 < 30 
    Day 180 < 50 < 30 
HIV proviral DNA 
    Pre Positive Positive 
    Day +28 Positive Positive 
    Day +56 Negative Positive 
    Day +100 Negative Positive 
HIV culture 
    Pre Not isolated Not isolated 
    Day +14 Not isolated Not isolated 
    Day +28 Not isolated Not isolated 
    Day +56 Not isolated Not isolated 
    Day +100 Not isolated Not isolated 
CD4+ (cells/mL) 
    Pre 262 287 
    Day +14 63  
    Day +28 21  
    Day +56 78 315 
    Day +100 74 248 
    Day +180 56 NA 
CD8 (cells/mL) 
    Pre 391 381 
    Day +14 23  
    Day +28  
    Day +56 26 176 
    Day +100 141 128 
    Day +180 379 NA 
CD3+ % donor 
    Day +28 51% 48% 
    Day +56 69% 48% 
    Day +100 95% 49% 
    Day +180 100% 61% 
CD33+ % donor 
    Day +28 94% 100% 
    Day +56 99% 100% 
    Day +100 100% 100% 
    Day +180 100% 100% 
Patient 1Patient 2
Age/sex 39/M 33/M 
Diagnosis AML AML 
CMV R/D +/− −/− 
Donor Unrelated Sibling 
Patient and donor HLA 
    A 2402, 0201 0101, 2601 
    B 2705, 3901 0801, 3502 
    C 0102, 1203 0701, 0401 
    DRB 1 0701, 1601 0301, 1104 
    DQB 1 0201, 0502 0201, 0301 
Cell dose/kg recipient 
    CD34+, ×106 4.58 10.63 
    CD3+, ×108 1.66 2.83 
HAART regimen Efavirenz, abacavir, tenofovir Efavirenz, abacavir, lamivudine 
GVHD prophylaxis CSP/MMF CSP/MMF 
Relapse (treatment) Cytogenetic relapse, day +44 (CSP/MMF withdrawn) None 
GVHD (treatment) Grade II skin/gut, day +56 (Pred/MMF/FK/B-B) BO, day +254 (Pred/Immuran/MMF/FK) None 
Survival Died, day +301 > 180 days 
Cause of death GVHD + BO NA 
HIV-related illness None None 
HIV RNA (copies/mL) 
    Pre < 30 < 30 
    Day +14 < 30 < 30 
    Day +28 < 30 < 30 
    Day +56 < 30 < 30 
    Day +100 < 30 < 30 
    Day 180 < 50 < 30 
HIV proviral DNA 
    Pre Positive Positive 
    Day +28 Positive Positive 
    Day +56 Negative Positive 
    Day +100 Negative Positive 
HIV culture 
    Pre Not isolated Not isolated 
    Day +14 Not isolated Not isolated 
    Day +28 Not isolated Not isolated 
    Day +56 Not isolated Not isolated 
    Day +100 Not isolated Not isolated 
CD4+ (cells/mL) 
    Pre 262 287 
    Day +14 63  
    Day +28 21  
    Day +56 78 315 
    Day +100 74 248 
    Day +180 56 NA 
CD8 (cells/mL) 
    Pre 391 381 
    Day +14 23  
    Day +28  
    Day +56 26 176 
    Day +100 141 128 
    Day +180 379 NA 
CD3+ % donor 
    Day +28 51% 48% 
    Day +56 69% 48% 
    Day +100 95% 49% 
    Day +180 100% 61% 
CD33+ % donor 
    Day +28 94% 100% 
    Day +56 99% 100% 
    Day +100 100% 100% 
    Day +180 100% 100% 

AML indicates acute myelogenous leukemia; B-B, beclamethasone + budesnonide; BO, bronchiolitis obliterans; CMV R/D, cytomegalovirus serology of recipient/donor; CSP, cyclosporine; Dx, diagnosis; FK, FK506; GVHD, graft-versus-host disease; HIV-ID, HIV-associated; HLA, human leukocyte antigen; MMF, mycophenolate mofetil; MSD, HLA-matched sibling donor; MUD, HLA-matched unrelated donor; NA, not applicable; and Pred, prednisone.

HIV monitoring

Plasma HIV RNA levels, peripheral blood mononuclear cell (PBMC) HIV proviral DNA levels, and PBMC quantitative HIV cultures were obtained at least weekly.4-6 

IFN-γ ELISpot assays

Peptides based on optimal EBV- and CMV-derived HLA class I–restricted epitopes,7  obtained from Mabtech (Mariemont, OH) were tested individually and in pools. The ELISpot assay has been described.8  A positive response was defined as a 2-fold or greater increase in the mean number of spot-forming cells (SFCs) of experimental wells compared with negative controls, provided the mean SFC/106 cells in experimental wells was more than 50 after subtraction of negative controls.

CCR5 genotyping

HIV-1 coreceptor CCR5Δ32 genotype was determined using DNA restriction fragment length polymorphism analysis as previously described.8,9 

Feasibility of HAART administration and affect on viral replication during NMHCT

The choice of HAART took into consideration potency, adverse effects, and potential drug interactions. Patent 1 was switched to efavirenz to provide a more effective regimen and to avoid possible nevirapine-mediated hepatotoxicity associated with immune reconstitution.10  Protease inhibitors were not used, to avoid drug interactions causing toxic levels of CSP and the azoles.1  Although efavirenz induces P450 enzymes, we reasoned that the dosage of affected drugs could be adjusted upward. The risk of abacavir hypersensitivity was extremely unlikely, since neither patients nor donors expressed HLA-B*5701.11 

After transplantation, full donor CD33+ chimerism was established in both patients. The CD3+ subset of patient 1 converted from 51% donor at day +28 to 100% donor by day +80 after withdrawal of immune suppression for treatment of recurrent leukemia, detected at day +42. In patient 2, the proportion of donor CD3+ cells continues to increase. Reconstitution of CD4+ and CD8+ subsets (Table 1) was typical for NMHCT recipients, half of whom receive prolonged immunosuppressive therapy.2  Patient 2 has not experienced opportunistic infections or GVHD and remains alive more than 180 days after HCT. Patient 1 developed CMV reactivation on day +83, successfully treated with foscarnet. GVHD grade 3 developed on day +56, after sudden withdrawal of immune suppression to treat recurrent leukemia, and responded to additional immune suppression. On day +100, patient 1 was discharged home on MMF, tacrolimus, and tapering doses of prednisone. Seven months after HCT he developed severe bronchiolitis obliterans (BO) unresponsive to additional immune suppression. He died 3 months later of pulmonary failure related to BO, Pseudomonas aeruginosa sepsis, and mucormycosis of his sinuses while on multiple immune suppressive agents.

For both patients at all time points after HCT the plasma HIV RNA remained undetectable and no HIV was detected by viral cultures of PBMC (Table 1). In patient 1, PBMC proviral DNA was detected at baseline before HCT and at day +28, but thereafter became undetectable when he converted to 100% donor chimerism. In contrast, proviral DNA was detected at all time points evaluated in patient 2, who continued to have mixed donor-host chimerism of the T-cell subset. Both patients' donor cells expressed wild-type CCR5 coreceptor, not the CCR5Δ32 allele, which is associated with resistance to HIV infection.12 

These data show that HAART can be administered throughout NMHCT, including during conditioning, with control of plasma viral replication. Neither patient developed HIV-related complications, and, although our first patient did not survive, his death was due to transplantation-related complications of GVHD. In our experience before the advent of HAART, myeloablative HCT resulted in acceleration of HIV disease, persistent culturable virus, and high levels of HIV p24 antigen after transplantation.13  Other studies also demonstrated that myeloablative therapy alone did not eliminate viral reservoirs.14-19  In 2002, Kang et al reported on 2 patients given NMHCT with gene-modified sibling donor PBSC.20  HAART was discontinued 1 week before, then resumed after HCT. One patient developed an acute retroviral syndrome, with a 6-log rise in HIV load, which declined rapidly after reinstitution of HAART. He subsequently developed central nervous system toxoplasmosis and died of progressive Hodgkin lymphoma. The second patient developed no HIV-related complications and was alive at the time of report. Detailed immunologic studies were not reported.

Development of donor-derived antigen-specific T-cell responses

To determine whether HIV-naive donor cells could target HIV-epitope specificities, we examined T-cell responses to multiple optimal epitopes restricted by the patients' HLA class I alleles (Table 2). PBMCs obtained from patient 1 before transplantation reacted with 6 of 26 epitopes tested that spanned 6 proteins, including Nef, Vpr, Pol, Env, Gag, and Tat. Response frequencies to individual epitopes ranged from 100 to 805 SFC/106 PBMCs with a total response of 1545 SFCs/106 PBMCs. HIV-1–specific CD8+ T-cell responses were not detected on day +56, but were detected on day +81. The total magnitude of response frequency was 664 SFCs/106 PBMCs with response being targeted to 8 of 26 epitopes examined. The pattern of HIV-epitope specificities of posttransplantation donor cells was markedly different compared with pretransplantation recipient T cells. The inter-pretation of HIV-specific CD8 T-cell responses in patient 2, who has mixed donor-host CD3+ chimerism, is more complicated. Before transplantation, PBMCs reacted with 4 epitopes limited to Nef and Gag. After transplantation, 2 of these same epitopes were recognized, probably by residual host CD8 cells. In addition, T-cell responses were elicited by 2 new epitopes in RT and 1 new epitope involving Env.

Table 2

Interferon-γ ELISpot responses before and after allogeneic hematopoietic cell transplantation

VirusPatient 1
Patient 2
HLA restrictionProtein and regionPeptide sequenceIFN-γ SFC*
HLA restrictionProtein and regionPeptide sequenceIFN-γ SFC*
Pre-HCTDay +81Pre-HCTDay +81
CMV  Pool  678 487  Pool  ND 
EBV  Pool 1  435 1180  Pool 1  3017 980 
  Pool 2  1870 137  Pool 2  150 110 
  Pool 3  1013 620  Pool 3  171 130 
 A2 BMLFI (259-267) GLCTLVAML 120 120 B8 EBNA3A (158– 166) QAKWRLQTL 150 ND 
 A24 BRLFI (28-37) DYCNVLNKEF 955 503  BZLF1 (190–197) RAKFKQLL 3492 1110 
 B27 BRLFI (28-37) RRIYDLIEL 1455 237 B35 EBNA3A (458– 466) YPLHEQHGM 158 150 
FluA A2 Matrix 1 (58-66) GILGFVFTL 205 77 B8 NP (380–388) ELRSRYWAI 117 − 
 B27 NP (383-391) SRYWAIRTR 53 350      
HIV A2 Gag p17 (77-85) SLYNTVATL − 67 A26 Gag p24 (35-43) EVIPMFSAL 142 − 
  Env gp160 (311-320) RGPGRAFVTI 120 90 B8 Gag p17 (24-32) GGKKKYKL 129 50 
  RT(33-41) ALVEICTEM − 120  Gag p24 (128-135) EIYKRWII 54 − 
  Pol (22-31) MASDFNLPPV 195 63  Nef (90-97) FLKEKGGL 158 50 
  Vpr (59-67) AIIRILQQL 155 −  RT (118-127) VPLDEDFRKY − 100 
  Nef (136-145) PLTFGWCYKL 170 −  RT (18-26) GPKVKQWPL − 90 
 A24 Gag p17 (28-36) KYKLKHIVW − 53  Env gp41 (95-103) TAVPWNASW − 50 
 B27 Gag p24 (131-140) KRWIILGLNK 805 −      
  Env gp160 (786-795) GRRGWEALKY − 257      
  Nef (105-114) RRQDILDLWI − 77      
 Cw12 Tat (32-37) CCFHCQVC 100 67      
VirusPatient 1
Patient 2
HLA restrictionProtein and regionPeptide sequenceIFN-γ SFC*
HLA restrictionProtein and regionPeptide sequenceIFN-γ SFC*
Pre-HCTDay +81Pre-HCTDay +81
CMV  Pool  678 487  Pool  ND 
EBV  Pool 1  435 1180  Pool 1  3017 980 
  Pool 2  1870 137  Pool 2  150 110 
  Pool 3  1013 620  Pool 3  171 130 
 A2 BMLFI (259-267) GLCTLVAML 120 120 B8 EBNA3A (158– 166) QAKWRLQTL 150 ND 
 A24 BRLFI (28-37) DYCNVLNKEF 955 503  BZLF1 (190–197) RAKFKQLL 3492 1110 
 B27 BRLFI (28-37) RRIYDLIEL 1455 237 B35 EBNA3A (458– 466) YPLHEQHGM 158 150 
FluA A2 Matrix 1 (58-66) GILGFVFTL 205 77 B8 NP (380–388) ELRSRYWAI 117 − 
 B27 NP (383-391) SRYWAIRTR 53 350      
HIV A2 Gag p17 (77-85) SLYNTVATL − 67 A26 Gag p24 (35-43) EVIPMFSAL 142 − 
  Env gp160 (311-320) RGPGRAFVTI 120 90 B8 Gag p17 (24-32) GGKKKYKL 129 50 
  RT(33-41) ALVEICTEM − 120  Gag p24 (128-135) EIYKRWII 54 − 
  Pol (22-31) MASDFNLPPV 195 63  Nef (90-97) FLKEKGGL 158 50 
  Vpr (59-67) AIIRILQQL 155 −  RT (118-127) VPLDEDFRKY − 100 
  Nef (136-145) PLTFGWCYKL 170 −  RT (18-26) GPKVKQWPL − 90 
 A24 Gag p17 (28-36) KYKLKHIVW − 53  Env gp41 (95-103) TAVPWNASW − 50 
 B27 Gag p24 (131-140) KRWIILGLNK 805 −      
  Env gp160 (786-795) GRRGWEALKY − 257      
  Nef (105-114) RRQDILDLWI − 77      
 Cw12 Tat (32-37) CCFHCQVC 100 67      

CMV indicates cytomegalovirus; EBV, Epstein-Barr virus; HIV, human immunodeficiency virus; IFN, interferon; PBMC, peripheral blood mononuclear cell; and SFC, spot-forming cell.

*

The value of SFC/106 PBMC is shown for all positive responses. Negative responses are indicated by −. Patient 1 had no response in either the pre- or posttransplant samples to the following epitopes: HLA-A2–restricted: Env gp160 (813-822) SLLNATDIAV, RT (179-187) VIYQYMDDL, RT (309-317) ILKEPVHGV, Nef (180-189) VLEWRFDSRL; HLA-A2, A24 restricted: Nef (190-198) AFHHVAREL; HLA-A24–restricted: Gag p24 (162-172) RDYVDRFFKTL, Env gp160 (52-61) LFCASDAKAY, Env gp160 (585-593) RYLKDQQLL, Gag p17 (19-27) IRLRPGGKK; HLA-B39–restricted: Gag p24 (61-69) GHQAAMQML, HLA-Cw1–restricted: Gag p24 (36-43) VIPMFSAL, Gag_Pol_TF (24-31) NSPTRREL, Env gp160 (217-226) YCAPAGFAIL, Env gp160 (712-720) YSPLSLQTL, Vpu (74-82) HAPWDVNDL. Patient 2 had no response in either the pre or posttransplant samples to the following epitopes: HLA-B8–restricted: Gag p17 (74-81) ELRSLYNTV, Gag p24 (197-205) DCKTILKAL, Env gp120 (2-10) RVKEKYQHL, Env gp41 (75-82) YLKDQQLL, Nef (13-20) WPTVRERM, Env gp41 (337-345) LQGLERALL; HLA-B35–restricted: Gag p17 (36-44) WASRELERF, Gag p17 (124-132) NSSKVSQNY, Gag p24 (122-130) PPIPVGDIY, RT (107-115) TVLDVGDAY, RT (175-183) NPDIVIYQY, RT (175-183) HPDIVIYQY, Env gp120 (42-52) VPVWKEATTTL, Env gp120 (78-86) DPNPQEVVL, Nef (74-81) VPLRPMT.

T-cell responses to EBV, CMV, and FluA epitopes were used as controls. The CMV and EBV peptide pools consisted of published HLA class I–restricted CD8+ T-cell epitopes.

Allogeneic HCT provides a novel platform to study the development of HIV-1–specific T-cell responses generated from HIV-1–naive donor cells in the setting of chronic controlled infection. We found that new HIV-1–specific CD8+ T-cell responses were generated early after HCT, despite the absence of plasma HIV-1 RNA, suggesting that plasma viremia is not necessary for the development of an HIV-1 T-cell response and that T-cells can be primed by HIV antigens expressed in lymphatic tissue with limited HIV replication. The observed shift in recognized epitopes demonstrates that naive donor cells are capable of generating de novo HIV-1–specific immune responses under these conditions. Allogeneic HCT also provides a platform to study the effects of conditioning and the establishment of a new immune system, including antigen-presenting and -responding cells, on the latent HIV-1 reservoir. The gradual loss of detectable proviral DNA after HCT in patient 1, who achieved full donor chimerism, suggests that the pool of latently infected lymphocytes declined after HCT and that the priming of HIV-1–naive T-cells occurred with limited and localized HIV replication and antigen expression. These findings may provide insights for development of HIV-1 vaccines or immune-based therapies.

The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 USC section 1734.

The authors thank Deborah Sessions for assistance in preparation of the manuscript.

The study was supported by grants CA78902, CA18029, CA15704, AI64061, AI57005, and K08 AI 059173 from the National Institutes of Health (Bethesda, MD).

National Institutes of Health

Contribution: A.W. conceived and designed the study and wrote the manuscript; U.M. designed and performed research assays and analyzed data; R.H. wrote the manuscript; J.M. performed research assays and analyzed data; T.M. designed and performed research assays and analyzed data; S.R. provided analytical agents and analyzed data; R.C. designed and performed research assays and analyzed data; F.A. provided resources and critical review of the manuscript; L.C. designed and performed research assays and analyzed data; and R.S. provided resources and supervised the study.

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Ann Woolfrey, MD, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98115; e-mail: awoolfre@fhcrc.org.

1
Krishnan
 
A
Molina
 
A
Zaia
 
J
et al. 
Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas.
Blood
2005
, vol. 
105
 (pg. 
874
-
878
)
2
Maris
 
MB
Niederwieser
 
D
Sandmaier
 
BM
et al. 
HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies.
Blood
2003
, vol. 
102
 (pg. 
2021
-
2030
)
3
Maris
 
MB
Sandmaier
 
BM
Storer
 
BE
et al. 
Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning: the effect of postgrafting mycophenolate mofetil dosing.
Biol Blood Marrow Transplant
2006
, vol. 
12
 (pg. 
454
-
465
)
4
Zuckerman
 
RA
Lucchetti
 
A
Whittington
 
WL
et al. 
Herpes simplex virus (HSV) suppression with valacyclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized, double-blind, placebo-controlled crossover trial.
J Infect Dis
2007
, vol. 
196
 (pg. 
1500
-
1508
)
5
Jackson
 
JB
Drew
 
J
Lin
 
HJ
et al. 
Establishment of a quality assurance program for human immunodeficiency virus type 1 DNA polymerase chain reaction assays by the AIDS Clinical Trials Group.
J Clin Microbiol
1993
, vol. 
31
 (pg. 
3123
-
3128
)
6
Jackson
 
JB
Coombs
 
RW
Sannerud
 
K
Rhame
 
FS
Balfour
 
HH
Rapid and sensitive viral culture method for human immunodeficiency virus type 1.
J Clin Microbiol
1988
, vol. 
26
 (pg. 
1416
-
1418
)
7
Bihl
 
F
Narayan
 
M
Chisholm
 
JV
et al. 
Lytic and latent antigens of the human gammaherpesviruses Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus induce T-cell responses with similar functional properties and memory phenotypes.
J Virol
2007
, vol. 
81
 (pg. 
4904
-
4908
)
8
Larsson
 
M
Jin
 
X
Ramratnam
 
B
et al. 
A recombinant vaccinia virus based ELISPOT assay detects high frequencies of Pol-specific CD8 T cells in HIV-1-positive individuals.
AIDS
1999
, vol. 
13
 (pg. 
767
-
777
)
9
Quillent
 
C
Oberlin
 
E
Braun
 
J
et al. 
HIV-1-resistance phenotype conferred by combination of two separate inherited mutations of CCR5 gene.
Lancet
1998
, vol. 
351
 (pg. 
14
-
18
)
10
Baylor
 
MS
Johann-Liang
 
R
Hepatotoxicity associated with nevirapine use (Review).
J Acquir Immune Defic Syndr
2004
, vol. 
35
 (pg. 
538
-
539
)
11
Phillips
 
E
Mallal
 
S
Drug hypersensitivity in HIV [review].
Curr Opin Allergy Clin Immunol
2007
, vol. 
7
 (pg. 
324
-
330
)
12
Huang
 
Y
Paxton
 
WA
Wolinsky
 
SM
et al. 
The role of a mutant CCR5 allele in HIV-1 transmission and disease progression.
Nat Med
1996
, vol. 
2
 (pg. 
1240
-
1243
)
13
Bowden
 
RA
Coombs
 
RW
Nikora
 
BH
et al. 
Progression of human immunodeficiency virus type-1 infection after allogeneic marrow transplantation.
Am J Med
1990
, vol. 
88
 (pg. 
49N
-
52N
)
14
Aboulafia
 
DM
Mitsuyasu
 
RT
Miles
 
SA
Syngeneic bone-marrow transplantation and failure to eradicate HIV.
AIDS
1991
, vol. 
5
 pg. 
344
 
15
Gabarre
 
J
Leblond
 
V
Sutton
 
L
et al. 
Autologous bone marrow transplantation in relapsed HIV-related non-Hodgkin's lymphoma.
Bone Marrow Transplant
1996
, vol. 
18
 (pg. 
1195
-
1197
)
16
Davis
 
KC
Hayward
 
A
Ozturk
 
G
Kohler
 
PF
Lymphocyte transfusion in case of acquired immunodeficiency syndrome.
Lancet
1983
, vol. 
1
 (pg. 
599
-
600
)
17
Lane
 
HC
Zunich
 
KM
Wilson
 
W
et al. 
Syngeneic bone marrow transplantation and adoptive transfer of peripheral blood lymphocytes combined with zidovudine in human immunodeficiency virus (HIV) infection.
Ann Intern Med
1990
, vol. 
113
 (pg. 
512
-
519
)
18
Vilmer
 
E
Rhodes-Feuillette
 
A
Rabian
 
C
et al. 
Clinical and immunological restoration in patients with AIDS after marrow transplantation, using lymphocyte transfusions from the marrow donor.
Transplantation
1987
, vol. 
44
 (pg. 
25
-
29
)
19
Verdonck
 
LF
de Gast
 
GC
Lange
 
JM
Schuurman
 
HJ
Dekker
 
AW
Bast
 
BJ
Syngeneic leukocytes together with suramin failed to improve immunodeficiency in a case of transfusion-associated AIDS after syngeneic bone marrow transplantation.
Blood
1988
, vol. 
71
 (pg. 
666
-
671
)
20
Kang
 
EM
De Witte
 
M
Malech
 
H
et al. 
Nonmyeloablative conditioning followed by transplantation of genetically modified HLA-matched peripheral blood progenitor cells for hematologic malignancies in patients with acquired immunodeficiency syndrome.
Blood
2002
, vol. 
99
 (pg. 
698
-
701
)
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