Dolutegravir containing regimens can suppress HIV even with less than ideal adherence

Researchers have found that antiretroviral therapy (ART) regiments based on the the integrase inhibitor, dolutegravir (DTG) are more likely to lead to sustained viral suppression even in the face of poor adherence and treatment interruptions - compared to earlier drugs. The study was published at the Open Forum on Infection Diseases.

Dolutegravir is an agent for the treatment of HIV of the second-generation integrase inhibitors class. The World Health Organisation (WHO) recommends DTG as a first and second line therapy, as well as when treating patients with resistance to other drugs.

Problems related to poor adherence

Over the years, HIV treatment options have become ever more optimised and simplified - often with people taking just one pill, once a day. However compliance with treatment, on a daily basis, can remain a challenge for many people living with HIV.

Poor, or sub-optimal, adherence of HIV treatment can lead to a rebound of their viral load that can impact the person’s health - as well as provide ideal conditions for the development of drug-resistant strains of the virus.

When combination therapy first appeared in the nineties, almost perfect adherence was required to prevent resistance. According to several studies, the rate required to maintain viral suppression was around 80%.

In this new study, the researchers wanted to consider the factor low-adherence and termination of treatment would have in patients who were taking a second-generation integrase inhibitor such as dolutegravir.

Research

399 adults living with HIV from France and Switzerland participated in the multi-centre DOLUTECAPS study. The average age of the participants was 46 years, with 70% being men.

The study compared the a group receiving dolutegravir with previously collected data on the adherence of people living with HIV to older treatment methods:

• 100 were taking NNRTIs, 70 of which were taking nevirapine, 12 efavirenz, and 12 rilpivirine.
• 107 were taking boosted PIs, 54 were taking lopinavir, 48 atazanavir, 5 on other PIs.
• 90 participants were taking the first-generation integrase inhibitor, raltegravir.

Study results

Modelling showed that in people who were taking DTG, the nature of adherence did not have a significant impact on viral load - even when adherence was in the 60% - 80% range.

As expected, this wasn’t the case for the older drugs. For all other drugs tested adherence patterns were strongly associated with increased viral replication at the six-month end point.

With less than 95% adherence to treatment, people in the raltegravir group were 46 times more likely to not achieve viral suppression compared to 100% adherence.

When observing people with a high average adherence rate (>95%) there were no significant differences in viral load suppression between DTG containing regimens and other regimens.

Conclusion

The authors believe that a consistently high adherence rate should remain the goal of any HIV treatment. However, the results of their research make a compelling argument to recommend DTG containing regimens to people who’re finding it difficult to maintain a high level of adherence - or are at risk of a treatment interruption.