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Short-term HIV treatment interruption feasible for cure research
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Researchers at the National Institute of Allergy and Infectious Diseases found that a short-term interruption in ART during a closely monitored clinical trial did not increase the size of the HIV reservoir or cause irreversible damage to patients’ immune systems.
NIAID Director Anthony S. Fauci, MD, said the findings are not surprising; however, they have implications for future studies that will require short-term analytical treatment interruption (ATI).
“The important reason for doing the study is that there are a lot of other studies going on right now to determine if HIV can be cured,” Fauci told Infectious Disease News. “The only way to prove that you have indefinitely suppressed the virus is to actually take the patient off therapy. We wanted to determine whether there is any detrimental effect to study participants who are put back on therapy after their virus rebounds. The take-home message is no, there isn’t.”
Katherine E. Clarridge, MD, MSc , and colleagues at the NIAID examined the effect of ATI in 10 patients with HIV who previously participated in a study examining whether an anti-HIV antibody known as VRC01 could suppress their virus in the absence of ART. The participants were taken off therapy for a median of 57 days (range, 22-115 days).
“These individuals who volunteer for research studies are very well motivated,” Fauci said. “They know they are being watched very, very carefully and that if there is anything that even resembles there being a danger to them, we will intervene.”
All participants rebounded and were examined for approximately 1 year after reinitiating ART. The highest observed viremia during the ATI period was 30,950 copies of HIV RNA per mL of plasma, according to the researchers. Upon viral rebound, the level of HIV DNA was significantly higher than pre-ATI levels (P = .002). However, HIV DNA declined to pre-ARI levels within 6 to 12 months. The researchers found no evidence of irreversible immune system abnormalities, such as a reduction in CD4 T-cells or an increase in immune exhaustion and activation markers. In addition, ATI was not associated with drug resistance mutations that would compromise treatment responses upon reinitiation.
“There doesn’t seem to be any real danger or damage to patients when you let their virus rebound and put them back on therapy,” Fauci said. “The size of the reservoir remains the same. The level of virus in the cells stays the same. The CD4 cell count does not diminish. The participants looked exactly how they did before stopping therapy.”
Clarridge and colleagues noted that the participants’ previous exposure to VRC01 may have influenced their findings. However, the researchers reported that the antibody failed to neutralize all viral isolates, and that most patients were found to have VRC01-resistant replication-competent HIV, suggesting a significant impact was unlikely. Still, they concluded that additional studies that do not involve investigational treatments are needed to confirm their results.
“Nonetheless, our findings support the use of [ATI] 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,” they wrote. – by Stephanie Viguers
Disclosures: Clarridge and Fauci report no relevant financial disclosures.
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