This story is over 5 years old.


Promising Antibody Therapy Wakes Up HIV Just To Kill It

A recent trial finds hope for a cloned natural antibody in fighting dormant HIV.

It's frequently remarked that, since the development of antiretroviral medications, HIV has become a chronic, manageable illness. What was only recently a death sentence to be preceded by months or years of agonizing, debilitating opportunistic infections can now be treated more or less indefinitely with medication. In this sense, HIV is by now a lot more like diabetes—given proper treatment adherence, someone with the infection can live as long and with the same quality of life as anyone else.


This doesn't come free, however. Treatment adherence for an HIV patient means taking from three to six or more different medications daily without fail. Given the high cost of the drugs and the potential for side effects and drug resistance, managing HIV is a dangerous chore. Some large part of the problem is that if treatment is even briefly discontinued, HIV is always ready to make a sudden comeback from its repressed/latent state to its quickly multiplying supervirus state.

Based on a small trial of 13 participants, researchers from Harvard Medical School, Rockefeller University, and several other institutions have found that an antibody known as 3BNC117 is effective in restraining the virus for up to 19 weeks following the discontinuation of highly-active retroviral therapy (ART). This is in contrast to historical control models indicating a viral rebound within just two and a half weeks in patients receiving neither ART nor antibody treatment. What's more, this delay can be achieved with between two and four antibody doses spaced two to three weeks apart, a far cry from the daily rigors of antiretrovirals.

HIV is frustrating (and impressive) for many reasons, including its ability to retreat into hidden reservoirs when threatened. Given antiretroviral treatment, it's possible to cut viral loads in a patient to beneath detectable levels, but without treatment HIV always manages to claw its way back to threaten and eventually kill its host.


When dormant, the virus exists quietly within the nuclei of long-lived immune cells called CD4+ memory T cells where it lives not so much as a hijacker, but as an innocuous passenger. All the body's immune system sees are normal T cells, unaware that those cells may have been genetically compromised by HIV. Targeting the virus then means drawing it out of hiding, possibly by discontinuing antiretroviral therapy as in what's properly known as analytical treatment interruption (ATI).

The idea behind employing 3BNC117 against HIV is based on a small subset of HIV-infected individuals known as "elite controllers" that come equipped with a natural resistance to the virus thanks to the activity of broadly-neutralizing antibodies (bNAbs) against the protein envelope surrounding viral DNA. 3BNC117, which had already shown some success in earlier trials, is one such antibody.

In a few cases, however, viral suppression persisted as long as the antibodies were around, indicating that no resistance was developed.

Without antiretrovirals, latent HIV hiding out in a patient eventually figures out that are safe to get back to the unceasing work of infection (albeit in molecular terms). But, here they would have been greeted by new antibodies, which would have kept the virus suppressed for as long as it took to develop a resistance to 3BNC117. This is what happened in most of the patients studied—the latent HIV eventually became resistant.

In a few cases, however, viral suppression persisted as long as the antibodies were around, indicating that no resistance was developed. Outlier or not, that's a very exciting result.

Also exciting is the observation that, once the virus began to reappear following antibody administration, it was mostly just a single version of the virus. This is in contrast to viral rebound following ART discontinuation, in which many different genetic variants of the virus re-emerge. Given that mutation and hyperactive evolution is a very large part of what makes HIV so challenging, this is very promising.

In any case, this is all still pretty preliminary. Thirteen subjects is not very many, and, moreover, they were preselected for having viral variants susceptible to 3BNC117, in particular. Not every patient is. To this effect, the study notes that, as with the combinations of drugs employed in ART, antibody therapy will likely require combinations of different antibodies to be effective rather than just a single silver bullet.

The study also hints at one other thing worth mentioning. It's possible that the antibodies are, unlike antiretrovirals, capable of attacking dormant reservoirs themselves. This is the route toward an actual HIV cure, though there are many more studies to be done before you're likely to even see the c-word in print.