Considerable progress has been made in the fight against HIV/AIDS since the first cases of the disease in the 1980s. Today, successful antiretroviral drug regimens are able to reduce viral loads to undetectable levels, cutting the risk of transmission almost to zero and effectively transforming AIDS into a chronic disease in many developed countries. However, despite improvements in combination therapies, treatment regimens can be complex, with some patients needing to take multiple pills daily for the rest of their lives. Moreover, missing doses increases both the risk of developing drug resistance and the chance of transmitting the virus. A need for better treatments remains, particularly those that are effective against resistant strains, simplify treatment regimens, and increase patient compliance.
One approach, taken by ViiV Healthcare, is a long-acting, fixed-dose combination of ViiV’s cabotegravir and Janssen’s rilpivirine, administered as a once-monthly intramuscular shot. Recent results from two Phase 3 trials (the ATLAS and the FLAIR studies) have shown that the injectable combo is as effective in suppressing viral replication as the current standard of care, which consists of daily doses of three oral drugs. Although neither trial evaluated the impact of the combo on transmission of the virus, extensive past research has shown that maintaining the viral load at undetectable levels (below 50 copies/ml) virtually eliminates the risk of passing on the virus.
While rates of serious adverse events and drug- or injection-related withdrawals were low in both studies, three-quarters of people in ATLAS and 82% of people in FLAIR reported injection site pain. The injection site reactions resolved over days and led to only a few withdrawals, but these events could put people off returning for subsequent shots. However, 98% of participants in the ATLAS study and 99% in FLAIR said that they were more satisfied with the monthly injection than with a daily pill regimen. Concerning, however, was the development of treatment-resistant viral strains in some trial participants who received the monthly injections.
From Suppression to Potential “Cure”?
While effective antiretroviral treatments have led to suppression of the viral load to virtually undetectable levels in many patients, eradicating the virus is still the holy grail of treatment. The so-called ‘Berlin patient,’ Timothy Brown, has been functionally cured of HIV – or to be more cautious, put into ‘sustained remission’ – since he received a stem cell transplant almost a decade ago as part of his cancer treatment. This year, a paper in Nature announced a second patient who has achieved such a sustained remission. The anonymous patient was diagnosed with Hodgkin’s lymphoma and underwent chemotherapy. As with Timothy Brown, the patient was given a transplant from a donor with a mutation in the CCR5 receptor, which prevents HIV from using the receptor to enter CD4-positive T cells.
While this is far too risky an approach to use for the vast majority of HIV-positive patients, it offers hope for those who require a stem cell transplant to address haemato-oncological conditions. It also gives researchers a starting point for developing new therapeutics, such as Sangamo Therapeutics’ CCR5-edited cell therapies and the CCR5 antagonists under development by ViiV and CytoDyn.
Will patients be willing to put up with injection site pain to avoid taking multiple pills every day? Will the risk of developing complications after a stem cell transplant be greater than the benefit of this approach? Will drugs targeting CCR5 enable sustainable remissions for the broader HIV-positive population? And could effective, consistent viral suppression eventually end the AIDS epidemic by preventing further transmission of HIV? We’ll be watching.