Interruption of HIV treatment: a new study guides the design of future clinical trials for an HIV cure

Although antiretroviral therapy prevents HIV from replicating, it cannot eradicate it due to the persistence of the reservoir. For this reason, therapeutic alternatives are being explored to keep the virus under long-term control. Currently, the only strategy to study the efficacy of these alternatives is through a temporary interruption of antiretroviral treatment and comparing viral rebound in the absence of medication with a group of participants who have received a placebo. Both the inclusion of placebo groups and the interruptions of treatment themselves add significant complexity to all clinical trials in the search for a cure for HIV. Now, IrsiCaixa –a centre jointly supported by the "la Caixa" Foundation and the Health Department of the Generalitat of Catalonia– has participated in an international meta-analysis that sheds new light on HIV's behaviour after interrupting antiretroviral therapy. The study, published in Nature Communications, confirms that post-treatment control, the phenomenon by which the virus remains under control without medication, is very rare, but more frequent in people who start antiretroviral therapy shortly after diagnosis. The study also provides valuable information about the expected viral rebound in most people when they stop treatment.

"We wanted to use data from previous studies to define how people respond when treatment is interrupted in a clinical trial setting. Specifically, we analysed data from 382 people across 24 international studies and determined how long the virus can be controlled in the absence of drugs", explains Christian Brander, the article's author and ICREA researcher at IrsiCaixa.

Early treatment initiation improves HIV control

The meta-analysis revealed that, on average, viral load rebounds 16 days after stopping therapy, but a small percentage of the study participants achieve post-treatment control. This control consists of keeping the virus at very low levels in the blood for at least 84 days without antiretroviral drugs. Specifically, only 4% of participants managed to maintain this control; this percentage increases to 6% for people who started treatment within the first six months after acquiring HIV and decreases to just 1% for those who received a diagnosis and started antiretroviral therapy later.

In addition to early treatment initiation, another key factor in promoting post-treatment control is maintaining high levels of CD4⁺ T cells, which play a critical role in the immune response against HIV.

"The results show that interrupting treatment in a controlled manner can provide very valuable data on the virus's behaviour and the immune response", highlights Javier Martínez-Picado, study author and ICREA researcher at IrsiCaixa.

Implications for future clinical trials and innovative therapies

"The study provides essential tools for designing more efficient and safer clinical trials, reducing the number of participants needed for each study, optimizing resources, and minimizing risks for participants", comments Beatriz Mothe, study author, physician, and researcher at IrsiCaixa. Although it represents a significant advance, the scientific team highlights that the composition of the study population (91% men and 75% white individuals) underscores the need for future studies with more diverse populations and regions with high HIV prevalence to obtain a more comprehensive view of the results.

Thus, this work not only deepens our understanding of HIV dynamics but also paves the way for new therapeutic strategies, emphasizing the importance of diversity to ensure global applicability.