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4. HIV Cure Setbacks: Mississippi Baby and Bone Marrow Transplants

The quest for an HIV cure saw some setbacks in 2014, with further news about 2 stem cell transplant patients in Boston who experienced HIV rebound several months after interrupting antiretroviral therapy (ART). This was followed in July by an announcement that HIV was detected in a child in Mississippi who had maintained undetectable viral load for more than 2 years off treatment.

As previously reported, Timothy Ray Brown, known as the "Berlin Patient," appears cured of HIV 7 years after stopping antiretroviral therapy (ART) and undergoing bone marrow transplants totreat leukemia. Brown's doctor, Gero Hütter, found a donor with a double CCR5-delta-32 mutation, meaning they do not have the CCR5 co-receptors that most types of HIV use to enter T-cells. Brown recently described his experience as the only person known to be cured of HIV.

It is unclear what factors are responsible for Brown's sustained remission, with possibilities including the CCR5 mutation, the strong chemotherapy regimen used to kill off his cancerous blood cells, or a graft-versus-host reaction in which new immune cells reconstituted from the donor stem cells attack the patient's own body. Hütter recently reported that 6 other HIV positive cancer patients have received bone marrow transplants from CCR5-delta-32 homozygous donors; 1 experienced HIV relapse with virus using an alternate co-receptor and the rest died from cancer progression or complications after just a few months.

As Timothy Henrich reported in late 2013, with further details presented at the 2014 Retrovirus Conference, 2 HIV positive bone marrow transplant patients in Boston received stem cells from donors without the CCR5-delta-32 mutation, underwent a milder pre-transplant chemotherapy regimen, and remained on ART during the procedure. After they had been apparently HIV-free for 3-4 years they agreed to try a treatment interruption to see if the virus would return. Although the men maintained undetectable viral load longer than expected off treatment, both eventually experienced viral rebound, at 3 and 8 months after stopping ART.

The year's second big disappointment involved the "Mississippi Baby" -- now 4 years old-- who was born to an HIV positive mother who was not diagnosed until delivery and did not take prophylactic antiretrovirals. Because of the risk of transmission, the infant was started on combination ART around 30 hours after birth. After more than a year on treatment the baby was withdrawn from care and taken off ART. When she was brought back for care her viral load was still undetectable despite being off treatment for several months.

At the Retrovirus Conference in March researcher Deborah Persaud reported that the child still had undetectable HIV 2 years after interrupting ART. But by July it was a different story: during a routine clinical visit the child was found to have detectable HIV in her blood and a falling CD4 count, indicating that replicating virus was starting to kill off her T-cells. She was put back on ART and remains in good health.

Researchers also reported in 2014 that an Italian child who started ART soon after birth and had undetectable plasma viral load and no apparent HIV DNA also experienced viral rebound shortly after treatment interruption. A pair of HIV positive Australian patients who received bone marrow transplants for leukemia or lymphoma continue to show no evidence of infectious virus or HIV genetic material, but they have not yet undergone the ultimate test of ART interruption -- a step that increasingly appears risky.

At the annual IAS "Towards an HIV Cure" symposium and a companion press conference at the International AIDS Conference, experts put an optimistic spin on the recent developments, noting that while the HIV recurrences are disappointing, they reveal some valuable information about future approaches to curing HIV.

"We're looking at the moment at achieving long-term remission, and how long can we go [without antiretrovirals]," said conference co-chair Sharon Lewin. "We've realized in the past year that the virus can really hang around for a very long time and pop up unexpectedly...we need much better tools to detect HIV [in the body] and need to learn how to eliminate long-lived reservoirs."

NEXT: 5. HIV Treatment as Prevention: No Infections in PARTNER Study