Interrupting HIV Treatment in Clinical Trials Okay, NIH Study Says

Analytical treatment interruption may not cause long-term damage to patients with HIV.

A new study funded by the National Institutes of Health suggests that a short discontinuation of treatment during clinical trials may not result in long-term increases in the HIV reservoir.

HIV treatment interruption was also not observed to cause irreversible damage to the immune system, according to a study published by PLOS Pathogens.

Much of the progress against HIV has been achieved due to advancements in antiretroviral therapy (ART) because it increases life expectancy and reduces the risk of transmission. When taken daily, ART reduces viral load to undetectable levels.

Because ART does not cure HIV, the latent virus persists in immune cells and patients have to take daily medication to prevent viral load expansion. It is well-known that if HIV-positive patients stop ART treatment, their viral load rebounds.

Researchers have been working towards developing treatment approaches that can lead to long-term ART-free remission; however, clinical trials that evaluate these strategies sometimes require patients to stop taking ART, which is called analytical treatment interruption (ATI).

“A major focus of current HIV research is the development of therapeutic strategies to achieve sustained virologic remission following discontinuation of ART either by eradication of viral reservoirs or enhancement of host immunity against HIV,” the authors wrote.

In the new study, NIH researchers evaluated the immunologic and virologic effects of ATI. To do so, they analyzed blood samples from 10 HIV-positive patients who participated in a clinical trial that explored whether infusions of a broadly neutralizing antibody could elicit ART-free remission.

During the trial, patients stopped taking ART, experienced a viral rebound, and restarted ART within 22 to 115 days posttreatment interruption.

When treatment was interrupted, HIV reservoirs and viral load were both observed to increase. The authors also found that there were abnormalities in immune cells during ATI, according to the study.

After the patients resumed ART for 6 months to 1 year, HIV reservoir size and immune cells normalized to levels pre-ATI, according to the study.

These findings confirm ATI use in clinical trials is safe when evaluating the efficacy of strategies for treatment-free remission, the authors reported.

The researchers noted that larger studies that do not include interventional drugs are necessary to confirm these results.

Currently, NIH researchers are conducting a clinical trial to determine the impact of short-term ATI on immunologic and virologic parameters in HIV-positive patients.

“Our findings support the use of antiretroviral treatment interruption in the setting of close monitoring of plasma viremia and concomitant strict ART restart guidelines as an integral part of determining the in vivo efficacy of therapeutic strategies aimed at achieving sustained ART-free virologic suppression in HIV-infected individuals,” the authors concluded.