Experts at Johns Hopkins say ability to go off antiviral treatment for an extended period of time is a critical goal.
Experts at Johns Hopkins say ability to go off treatment for long period of time is a critical goal.
In the wake of the landmark case involving a young child who was clear of HIV 2 years after ceasing treatment before detectable levels of the virus were found again, researchers are emphasizing the critical lessons learned from the child’s story.
In a commentary in the Aug. 28, 2014 issue of Science, leading HIV research experts Robert Siliciano, MD, PhD, and Janet Siliciano, PhD, of Johns Hopkins Medical Center, state that the cases of the child known as the “Mississippi baby” and 2 other HIV-infected adults who experienced “disease rebounds” are stepping stones to understanding how new therapies may be employed to push the virus into long-term remission.
“Heartbreaking as these three cases are clinically, they provide a dramatic illustration of the real barrier to an HIV cure and illuminate important therapeutic strategies,” said Robert Siliciano in a press release. “This is not the end of the story but the beginning of a new chapter.”
The Mississippi baby was born prematurely in July 2010 to a mother who had not seen a doctor during her pregnancy and was unaware she was infected with HIV. Her baby reportedly tested positive for the virus at 30 hours of age.
Soon thereafter, the infant began antiretroviral therapy with 3 drugs: zidovudine, lamivudine, and nevirapine, as opposed to the standard prophylactic treatment. One week after birth, the baby was discharged from the hospital and placed on antiretroviral therapy that included zidovudine, lamivudine, and co-formulated lopinavir-ritonavir.
Treatment of the infant ceased at the age of 18 months for undisclosed reasons. When the child returned for further evaluation 5 months later, doctors anticipated finding high levels of the virus but instead found it to be nonexistent on standard tests. The child was later found to be free of the virus on standard HIV tests at the ages of 24, 26, 28, and 30 months, even without continuing antiretroviral therapy.
However, it was announced on July 10, 2014, the child again had detectable levels of HIV in the blood (16,750 copies/mL). An additional viral load blood test 72 hours confirmed the finding (10,564 copies/mL of virus).
The child has since resumed antiretroviral therapy and is tolerating the treatment with decreasing viral levels and no side effects, according to the National Institute of Allergy and Infectious Diseases.
In their commentary, the Silicianos argue that putting the virus in remission and going off treatment for an extended period of time is an important goal, as it allows patients to avoid a lifetime of difficult to tolerate daily antiviral regimens. The pair finds the most important hurdle to eliminating HIV is an “extremely stable pool of virus” that remains hidden in a handful of cells known as memory CD4+ T cells.
While current therapies only target actively replicating virus, these hideouts remain out of reach for the drugs. As a result, reducing the number of infected cells or stopping their formation entirely is a new and realistic approach for future HIV therapies.
“These cases paint several clinical scenarios where a substantial reduction of viral reservoirs would allow some patients to come off treatment for prolonged yet uncertain periods of time, but they also raise the critical question of how to best monitor them for relapse so they can resume therapy swiftly when the virus rebounds,” said Janet Siliciano in a press release.