New HIV Remissions Capture the Imagination of Specialists

Heather Boerner

July 25, 2017

PARIS — A 9-year-old South African girl has had an undetectable HIV viral load since she stopped treatment more than 8 years ago. This news highlights the importance of early treatment, and begs the question of how to turn such rare remissions into regular occurrences, experts said here at the International AIDS Society 2017 Conference.

It is exciting to think about the difference between viral rebound and viral remission, Anthony Fauci, MD, from the National Institute of Allergies and Infectious Diseases, told Medscape Medical News.

"Is it immunological response? Is there something special about the virus?" he asked. "Is there immune activation in one individual that you don't see in another individual?"

The hope is that when researchers study all these facets in each person who achieves long-term remission, they will "figure out how to predict remission before interrupting treatment," said Myron "Mike" Cohen, MD, from the University of North Carolina in Chapel Hill.

Eight Years and Counting

The girl's story was reported by Avy Violari, MD, from the University of the Witwatersrand in South Africa. After presentations describing cases of viral rebound, she took the podium and told the packed room, "After all that, I think we could all use a happy ending."

Dr Violari proceeded to describe the girl who was one of 5948 infants, 6 to 12 weeks of age, enrolled in the phase 3 Children with HIV Early Antiretroviral Therapy (CHER) trial (N Engl J Med. 2008;359:2233-2244).

Participants were randomly assigned to one of three treatment groups: early antiretroviral therapy for 96 weeks, early antiretroviral therapy for 40 weeks, or deferred therapy.

The girl was diagnosed with HIV when she was 32 days old. At day 39, her viral load was 750,000 copies/mL. At day 60, when antiretroviral therapy was initiated, her viral load was 151,000 copies/mL, but that dropped almost immediately to 915 copies/mL.

I think we could all use a happy ending.

By the time she was 40 weeks old, her viral load was below 20 copies/mL, and it remains undetectable. Ten other children in the CHER trial have low-level viremia, but she is the only child in remission.

The girl — who was in the 40-week treatment group — is now 9 and a half years old, and is still without symptoms. No replication-competent virus was found in her system on p24 ELISA and ultrasensitive nested RT-PCR testing, but DNA sequencing has confirmed that she still does have HIV.

At least for now, her system seems to have conquered the virus.

In answer to a question from the audience, Dr Violari confirmed that the child is not an elite controller.

A Larger Pattern

There were two other cases of remission reported at the meeting. A patient in San Francisco began treatment days after infection and achieved sustained remission for 7.4 months, after which the virus rebounded.

A 24-year-old Thai man had an undetectable viral load for 3 years before being enrolled in the RV397 vaccine trial. Despite recent detectable viral loads, his remission has been sustained for 10 months.

"There are multiple ways he can go from here," said Trevor Crowell, MD, from Johns Hopkins School of Medicine in Baltimore, who is an RV397 investigator.

"Many post-treatment controllers experience transient viremia before they demonstrate their own control," he told Medscape Medical News.

"He could stay where he's at — at a persistent, low-level viremia — or he could rebound," Dr Crowell explained.

The key takeaway is that remission is a clinical question. People must not stop treatment, Dr Violari told Medscape Medical News.

Physicians can help patients improve their likelihood of remission by explaining why the initiation of therapy as early as possible after infection is beneficial for now, and how that could set them up for remission later, if researchers succeed in finding a way to harness these rare remissions into a useable strategy.

"These data underscore the importance of identifying acute infection" and initiating "treatment as quickly as possible," said Dr Crowell.

CHER was funded through grants from the National Institute of Allergy and Infectious Disease, the Departments of Health of the Western Cape and Gauteng in South Africa, and GlaxoSmithKline. Dr Fauci has disclosed no relevant financial relationships. Dr Violari reports receiving lecture fees from Abbott Laboratories. Dr Cohen reports receiving advisory board honorariums or travel reimbursement from Janssen Global Services, Roche Molecular Systems, and Merck Research. Dr Crowell reports receiving speaking fees from Gilead Sciences.

International AIDS Society (IAS) 2017 Conference: Abstract TUPDB01LB. Presented July 25, 2017.

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