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HIV DNA Vanishes ["Cure"?] After CCR5-delta32
Stem Cell Transplant, But ART Continues
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HIV Drug Therapy, Glasgow 2016
Mark Mascolini
Another HIV patient with acute myeloid leukemia (AML) is responding to a CCR5-delta32 stem cell transplant with disappearance of proviral DNA from all samples scrutinized [1]. A delta32 stem cell transplant cured the Berlin patient of HIV infection [2], but the new "Dusseldorf patient" has yet to stop antiretroviral therapy (ART) to confirm a cure.
The Berlin patient apparently remains the only person cured of HIV infection after allogeneic stem cell transplantation (also for AML) from a donor homozygous for the delta32 deletion [2]. This well-known man has remained free from HIV for nearly a decade without ART. At the Glasgow meeting, researchers from the University of Cologne and other centers reported the case of a similar patient who has yet to suspend ART.
Like the Berlin patient, the Dusseldorf patient had AML, diagnosed in January 2011 only months after his HIV diagnosis. This 41-year-old man began ART with darunavir/ritonavir plus tenofovir/emtricitabine and in January 2011 had a plasma viral load of 44 copies and a CD4 count for 474. In March 2011 his clinicians switched from darunavir to raltegravir to avoid potential interactions during chemotherapy.
The man achieved complete remission of AML after two ICE induction courses and three consolidation courses. When AML relapsed in September 2012, the patient responded to A-HAM plus high-dose cytarabine. During a second complete remission, he received a transplant of unmodified peripheral blood stem cells from a donor homozygous for CCR5-delta32 in February 2013, after conditioning with fludarabine and treosulfan. Before the transplant HIV DNA measured 1.45 log10 copies/million peripheral blood mononuclear cells (PBMCs) and detectable western blot bands confirmed HIV infection.
A second AML relapse occurred in June 2013, and this time the patient responded to eight courses of 5-azacytidine and four donor lymphocyte transfusions. Since June 2014 the patient has taken dolutegravir plus abacavir/lamivudine and viral load remained undetectable in plasma.
All collected samples now test negative for proviral DNA by conventional PCR and digital droplet PCR performed at two different labs. Assayed samples include PBMCs (2014-2016), rectal biopsy (April 2015), and bone marrow (August 2015). The researchers saw incomplete patterns and fading bands on western blots done in 2014, 2015, and 2016. Viral outgrowth assays in PBMCs are negative. HIV LTR DNA cannot be detected in PBMCs by digital droplet PCR or quantitative PCR, but the assays see weakly positive signals in T-cell subsets.
The research team plans further assays including proviral DNA and quantitative viral outgrowth assays in lymph nodes, plus cellular immune response assays, before considering stopping ART. But they believe tests so far--in the 4 years since the stem cell transplant--"suggest that HIV may have been eradicated and that he may be the second individual cured from HIV by allogeneic CCR5-delta32" stem cell transplant.
References
1. Knops E, Kobbe G, Kaiser R, et al. Treatment of HIV and acute myeloid leukaemia by allogeneic CCR5-d32 blood stem cell transplantation. HIV Drug Therapy, Glasgow 2016. October 23-26, 2016. Abstract P077.
2. Hutter G, Nowak D, Mossner M, et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med. 2009;360:692-698. http://www.nejm.org/doi/full/10.1056/NEJMoa0802905
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