Even though these days an HIV diagnosis is far from the perilous situation it was a few decades ago, it's still a chronic problem that can only be managed with large amounts of drugs – often several different pills taken daily, targeting specific mechanisms of the virus.
This is why the promising results of a new clinical trial investigating long-acting HIV management shots are kind of a big deal. A monthly injection is much easier to administer than a daily pill – which often drops in effectiveness as soon as you skip a dose. Easier treatment also means patients are better able to stick with the therapy.
The study, conducted by ViiV Healthcare in collaboration with Janssen Sciences Ireland, was a 96-week phase IIb trial, which means a rigorous demonstration of a medicine's efficacy in real patients, often a pivotal step in the process of developing a new treatment. Only 32 weeks in, the researchers were able to share the promising results.
The two drug companies collaborated to investigate whether a long-acting injectable combination of two separate drugs formulated by each company would be as effective in suppressing the virus as a daily pill combo – after initial trials showed this could be the case.
The drugs in question are cabetogravir and rilpivirine, and they each act on a different step of HIV's life cycle. The virus is so insidious because it turns our immune systems against us by infecting white blood cells. The virus enters our T4 white blood cells by binding to their specific surface receptors called CD4+. Once inside the cell, HIV's genetic material is copied from its RNA into human DNA via a process called 'reverse transcription'. This process uses the virus's own enzyme, called reverse transcriptase.
Rilpivirine belongs to a class of drugs that can block the reverse transcription process by binding to and blocking the enzyme doing the dirty work. It's already available in the US and EU as a daily tablet, but has now been developed into an injection.
The other drug, cabetogravir, is a newer type of medication that works one step down the track. It acts at the next stage of the infection – if reverse transcription does take place, the virus's DNA must be integrated into the human cell's DNA, again thanks to a handy HIV enzyme called integrase. Cabetogravir is a drug which can block this enzyme - and thus stop the virus from replicating.
Formulated to be long-acting and injected together, these two drugs suppressed the virus at a comparable rate to a combination of similar-acting pills taken daily. Patients received one shot either every four weeks, or every eight weeks, and the virus suppression rates were basically the same, although patients with monthly injections complained more about pain at the injection site – the most common side effect of this treatment.
"Going from many pills a day – like 10, 20 pills a day – to now one pill, to now one injection every two months is I think a huge medical technical achievement," said Paul Stoffels, Johnson & Johnson's (parent company of Janssen) chairman of pharmaceuticals, as reported by Bloomberg.
"Despite great progress in HIV treatments, the burden of treating HIV patients remains high. Long-acting injectable drug formulations may offer another option for HIV maintenance therapy," Stoffels added. The developers now hope to improve this experimental injection and bring it to the global market before 2020.