The viral reservoir, the main obstacle to eradicating HIV, is up to four times smaller in those who started treatment after 2007

Antiretroviral therapy represents one of the greatest advancements in the history of HIV. A study led by IrsiCaixa—a center jointly supported by the “la Caixa” Foundation and the Health Department of the Government of Catalonia—and published in the Journal of Clinical Investigation supports this statement. The research links improvements in antiretroviral therapies and the immediate start of treatment after diagnosis to a reduction in the viral reservoir—the main barrier that has prevented the discovery of a definitive cure for HIV.

The analysis, which covers data from nearly 900 people diagnosed and treated over the past 30 years, reveals an encouraging trend: individuals who started treatment after 2007 have a considerably smaller viral reservoir compared to those diagnosed and treated earlier. This reduction coincides with the approval of drugs that prevent the integration of HIV into cells and the implementation of clinical guidelines recommending immediate treatment after diagnosis.

“The evolution and advancements in HIV treatment have allowed us to tame the viral reservoir,” explains Javier Martínez-Picado, lead researcher at IrsiCaixa and ICREA professor. “These findings demonstrate that new treatments are not only effective in reducing viral load, but also pave the way toward a cure, as they reduce the main obstacle to eradicating the virus definitively,” he adds.

Smaller reservoir, stronger immune system, and undetectable HIV in less time

The study’s graphs reveal a notable change starting in 2007. “Since then, people who started treatment not only show a lower viral reservoir—up to four times smaller compared to those who started treatment in earlier years—but they also have a stronger immune system,” says Maria Salgado, IGTP researcher at IrsiCaixa. Specifically, the study shows that immune cell levels remain significantly higher in those who began treatment after 2007. Moreover, the time needed to achieve undetectable HIV levels in the blood—and thus, make it non-transmissible—has decreased.

The team also identified how many patients had an extremely low reservoir, a profile called LoViReT (Low Viral Reservoir Treated), previously described by the research group led by Martínez-Picado at IrsiCaixa. “We were surprised to see a notable prevalence of this profile. In fact, in this study, 20% of participants are considered LoViReT, a figure that contrasts with the 9% observed in previous studies with patients who started treatment before 2011. This was the first indication that changes were occurring in the reservoir in recent years,” notes Irene González, a predoctoral researcher at IrsiCaixa.

Treatment, key in the search for an HIV cure

The study links the decrease in the viral reservoir to the introduction of integrase inhibitors, which prevent the virus from integrating into the DNA of cells. This strategy reduces the number of cells with “hidden” virus in the body. Today, first-line treatments include drug combinations that always include an integrase inhibitor, except in exceptional cases.

Additionally, the results emphasize the importance of starting treatment immediately after diagnosis. “In the early years, when information about HIV was limited and treatments had more severe side effects, treatment was delayed until the immune system was already severely weakened. Over time, the practice of starting treatment immediately after diagnosis was adopted, and we’ve seen that this decision has allowed us to reduce the size of the reservoir and better preserve immune system health,” explains Salgado.

These findings highlight how advances in HIV management have been crucial in the evolution of the virus. “Today, we have increasingly effective therapies, some of which don’t require daily administration, improving the quality of life for people with HIV. Moreover, these advancements in treatment are creating more favorable conditions for moving toward a potential cure,” concludes Martínez-Picado.