HIV: Viral Rebound After Bone Marrow Transplant

Veronica Hackethal, MD

July 22, 2014

Two patients with HIV who achieved transient remission after bone marrow transplant experienced viral load rebound after stopping antiretroviral (ART) medication, according to a case report published online July 21 in the Annals of Internal Medicine.

"[Hematopoietic stem cell transplant] may lead to loss of detectable HIV-1 from blood and gut tissue and variable periods of antiretroviral-free HIV-1 remission," write Timothy J. Henrich, MD, from the Division of Infectious Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, and colleagues, "but viral rebound can occur.... Long-lived tissue reservoirs may have contributed to viral persistence. The definition of the nature and half-life of such reservoirs is essential to achieve durable antiretroviral-free HIV-1 remission."

HIV that lurks inside cells poses a "major challenge" to eliminating the virus, the authors explain. Even though ART can reduce HIV found in the blood to levels virtually undetectable by laboratory tests, low levels of the virus still persist in most patients. Viral levels usually rebound within 1 to 8 weeks of stopping ART. This makes it challenging to achieve an ART-free remission, according to the authors.

Previously, a patient (known as the "Berlin" patient) attained long-term remission after receiving a bone marrow transplant with HIV-resistant donor stem cells. Whether or not patients can achieve remission with HIV-susceptible donor stems cells was unknown, however.

Therefore, the researchers analyzed immune responses and quantified blood and tissue levels of HIV in 2 men (Patient A and Patient B) who had received bone marrow transplants for lymphoma with HIV-susceptible donor stem cells. The 2 men had been receiving ART for at least 2 years before transplant. They had undetectable levels of HIV in blood and gut tissue while receiving ART after transplant. Patient A stopped ART about 2.5 years after transplant, whereas Patient B stopped ART about 4 years after transplant. The researchers analyzed blood and cerebrospinal fluid from both patients as well as lymph tissue from rectal biopsies provided by Patient B.

Blood and cerebrospinal fluid tests revealed HIV rebound at 12 weeks (Patient A) and 32 weeks (Patient B) after stopping ART. Both men developed symptoms associated with the acute retroviral syndrome associated with initial HIV infection. After restarting ART, these symptoms cleared up and HIV levels dropped in both men.

Despite receiving various immune-suppressing medications, both men developed graft-vs-host disease, indicating an immune reaction to the transplant. Both received additional treatment with prednisone.

The authors note that graft-vs-host disease may have played a role in the viral rebound. The role of anti-inflammatory medications also needs to be studied, the authors point out.

In an accompanying editorial, Sharon R. Lewin, FRACP, PhD, head of infectious disease at the Alfred Health, Monash University, and Burnet Institute in Melbourne, Australia, highlighted "the good news" from this study.

"[I]t is possible to significantly reduce the number of long-lived, latently infected T-cells that persist in patients receiving ART," Dr. Lewin writes. "[T]his reduction was associated with a significant delay in viral rebound once ART stopped."

On the flip side, Dr. Lewin points out the complicated relationship between HIV infectivity and human immune responses.

"[L]ong-term remission of HIV will likely need more than a very significant decrease in the number of latently infected T-cells," she notes. "The most sobering lesson was that these cases...have raised the possibility that total elimination of every last virus or infected cell to achieve lifelong remission may not be possible."

She concludes, "The amount of residual infectious virus left after ART and an effective immune response are both likely to be key in achieving long-term HIV remission."

One coauthor reports receiving honoraria from Gilead and Merck Sharp & Dohme; another coauthor reports receiving grants from the National Institutes of Health and the American Foundation for AIDS Research and honoraria from Abbott, Bristol Myers Squibb, Boehringer Ingelheim, Celera, Gilead, GlaxoSmithKline, Inna Virvax, Koronis, Merck, Roche, Sangamo, and ViiV; another author reports receiving other support from Ortho Clinical Diagnostics. The other authors have disclosed no relevant financial relationships. Dr. Lewin reports receiving grants from Merck and Gilead and other support or involvement with ViiV and Gilead.

Ann Intern Med. Published online July 21, 2014. Abstract


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