One of the most powerful strategies of HIV, the main barrier to its elimination, is the virus's ability to hide in hiding places that allow it to remain latent and waiting for an opportunity.
These viral reservoirs are what make it still necessary for HIV patients to take antiretroviral therapy for life. If they stop, the viruses come out of these hideouts and the infection resurfaces in a short period of time.
Innovations in the fight against HIV, however, have made an impact on the virus's ability to hide. As a recent Spanish research has shown, these viral reservoirs are up to four times smaller in patients who started their treatment from 2007 onwards, a key year in the fight against the virus.
"The evolution and advances in HIV treatment have allowed us to tame the viral reservoir," summarizes Javier Martínez-Picado, principal investigator at IrsiCaixa, ICREA professor, and head of the research just published in the Journal of Clinical Investigation.
The study, which has followed almost 900 patients diagnosed and treated in recent decades, clearly shows a change in the size of viral reservoirs from 2007 onwards, with figures four times smaller in patients who began treatment that year. This clear trend change is linked by researchers to innovations in patient treatment that occurred at that time. That year not only saw the introduction of key drugs in the treatment regimen, the integrase inhibitors; but also a change in treatment guidelines: from that date onwards, treatments were immediately initiated after diagnosis, without waiting for the patient's defenses to be affected.
"Integrase is a protein of the virus that integrates the virus into our DNA. Integrase inhibitors, therefore, work to stop the virus integration and, therefore, the formation of reservoirs," explains Martínez-Picado, who participated in the CIBER Congress held in Valencia these days.
Additionally, treatment initiation began that year, continues the researcher. Until then, it had not been the case. "Initially, people with HIV infection started treatment when they had less than 200 CD4, then it moved to less than 350, later to less than 500... and in 2007, immediate treatment began, as soon as the diagnosis was made."
So far, Martínez-Picado emphasizes, no one had previously noted this drop in the viral reservoir that occurred from 2007 onwards. The finding, he stresses, is important because it demonstrates that the new treatments have not only been effective in reducing viral load but have also opened a path to a cure "as they reduce the main obstacle to eradicating the virus definitively."
What led researchers to this trend change in the size of the viral reservoir was an analysis of patients with an extremely low reservoir. "In previous studies, we found that around 9% of people had this profile. But a couple of years ago, we expanded the study to more current samples and saw that the percentage of people with extremely low reservoirs increased to 20%. That's when we thought about considering the moment when these people started antiretroviral treatment," says Martínez-Picado.
"What we have discovered is important because as a researcher, I am convinced that curing HIV will involve at least two conceptual convergences. One of them is to reduce the viral reservoir as much as possible. The other will involve increasing the immunity of people with HIV," hints the researcher. And he concludes: "Research must continue, but there are already strategies in progress."