French Study Offers Clues to Achieving a Functional Cure for HIV

A study assessing HIV treatment interruption in 14 French subjects suggests that early initiation of antiretroviral therapy may be associated with sustained virological remission.

Fresh on the heels of a report of a newborn who appears to have been functionally cured of HIV after being aggressively treated with antiretroviral therapy, researchers have released more evidence suggesting that early treatment for HIV may be crucial to achieving disease remission.

The study, published in the journal PLOS Pathogens, was based on a database of 3538 patients from the French Hospital Database on HIV. Approximately 1000 of the patients had begun taking drug cocktails within 6 months of having been infected, and 70 of these patients stopped taking the drugs when their viral load dropped below <50 copies/mL.

The researchers reported that, of the 70 patients who stopped therapy, 14 French adults achieved functional cures. The researchers described the individuals as “post-treatment controllers” because they had low viral blood levels despite having abandoned treatment 4 to 10 years earlier. The patients had been on drug therapy for 1 year to 7.5 years before treatment interruption.

One of the major hallmarks of the 14 participants who experienced virological remission is that they all started treatment very early after discovering they were infected. After stopping treatment with antiretrovirals (either because they were in studies that dictated they stop therapy or because they chose to abstain from treatment), the patients in the study “were able to maintain and, in some cases, further reduce an extremely low viral reservoir,” the researchers wrote.

The study authors were careful to point out that the patients in the study were not elite controllers; they “lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers.” However, they conceded that early therapy initiation could have potentially masked spontaneous control in some of the cases.

The researchers pointed out that not all patients would necessarily be capable of controlling the infection after therapy interruption, and initiating treatment with antiretrovirals during primary HIV-1 infection could potentially contribute to long-term toxicity. In addition, stopping treatment too soon could contribute to the development of resistant strains of the virus.

The researchers noted that achieving a functional cure requires a reduction in both the size and the distribution of HIV reservoirs. They concluded that initiation of antiretroviral therapy shortly after infection could “limit viral diversity and offer protection of innate and specific immunity from the deleterious effect of chronic immune activation.”