In Pursuit of HIV Cure, NIAID Scientists Update Treatment Interruption Data for Modern ART

Thanks to advances in antiretroviral therapy (ART), most people living with HIV can maintain undetectable levels of virus in their blood with convenient one-pill-a-day regimens and fewer side effects compared to older drugs. While these individuals cannot sexually transmit HIV and benefit from improved health and prolonged life, stopping or pausing daily ART almost invariably leads to a rebound of detectable levels of the virus in the body. Scientists are therefore pursuing experimental strategies to achieve sustained ART-free HIV remission that would allow people with HIV to keep the virus suppressed without regular medication.

Clinical trials to evaluate such strategies may require participants to temporarily stop taking ART under careful monitoring from study investigators, an approach known as analytical treatment interruption, or ATI. Researchers can evaluate how well experimental HIV cure strategies are working based on how soon after ATI participants must restart ART compared to historical data from previous ATI studies. In a new study, NIAID researchers found that ATI following treatment with modern ART regimens results in similar viral rebound and immune responses compared to historical ATI data from participants treated with older ART regimens. Their findings, published last month in the Journal of Infectious Diseases, will support future HIV cure studies by updating the control group data to which experimental outcomes are compared.

Historical ATI data used in HIV cure research is often based on a patchwork of studies with variable intervals for monitoring participants’ immune systems and varying criteria for individuals to restart ART. Additionally, many participants included in such data sets had been on several different ART regimens and may have developed resistance to certain older classes of HIV drugs, which has an unknown effect on the time to viral rebound. Because of this, investigators led by Anthony S. Fauci, M.D., director of NIAID, and Tae-Wook Chun, Ph.D., chief of the HIV Immunovirology Unit in NIAID’s Laboratory of Immunoregulation, hypothesized that historical ATI data may be outdated and could skew results of ongoing HIV cure research.

To establish new benchmark data, researchers observed ATI among 22 participants who had taken only modern ART regimens and remained undetectable for a median of 7.7 years prior to ATI. All participants had the same criteria for restarting ART: after they experienced a viral load above 1,000 viral copies per mL for equal to or greater than 4 weeks, a defined decrease in CD4+ T cells, any HIV-related illness or symptoms, or pregnancy. Predictably, all participants experienced some viral rebound. Half of participants reached the ART restart criteria due to low CD4+ T-cell count, 35% based on sustained plasma viremia, and two because of HIV-related thrombocytopenia (low platelet count). The median time to restart ART was nearly 5 weeks. The findings suggest that modern ART does not alter the rate of viral rebound when compared to older ART regimens. By following the participants closely, investigators gained new insights into immune responses during ATI that may also inform future studies.

The findings affirm that ATI is safe in a controlled research environment and remains an effective way to evaluate potential ART-free HIV remission strategies. Researchers also note that these results underscore the importance of regular ART adherence in the absence of an HIV cure to benefit the overall health of people living with HIV. Read more about NIAID’s ongoing HIV cure research efforts.

Reference:

M Sneller et al. Kinetics of Plasma HIV Rebound in the Era of Modern Antiretroviral Therapy.  Journal of Infectious Diseases DOI: 10.1093/infdis/jiaa270 (2020).