Bictegravir matches dolutegravir in first-line treatment

Hans-Jürgen Stellbrink at HIV Glasgow 2018. Image credit: HIV Glasgow

A triple combination containing the new integrase inhibitor bictegravir proved just as effective as a dolutegravir-based combination in suppressing viral load over 96 weeks, but people taking bictegravir experienced significantly fewer adverse events related to treatment, Professor Hans-Jürgen Stellbrink of the University of Hamburg reported at the International Congress on Drug Therapy in HIV Infection (HIV Glasgow) on Tuesday.

Bictegravir is a new integrase inhibitor. It received regulatory approval in the European Union in July 2018 as part of a co-formulated, single-pill product called Biktarvy, combined with emtricitabine and tenofovir alafenamide. Biktarvy is also approved in the United States.

The GS-1490 study presented at HIV Glasgow compared Biktarvy to a regimen of dolutegravir, tenofovir alafenamide and emtricitabine in previously untreated people. Participants in this blinded study received matching placebos so that everyone took the same number of pills.

Glossary

endpoint

In a clinical trial, a clearly defined outcome which is used to evaluate whether a treatment is working or not. Trials usually have a single primary endpoint (e.g. having an undetectable viral load) as well as a few secondary endpoints, covering other aspects of treatment safety, tolerability and efficacy.

nausea

Feeling sick.

primary endpoint

The main result that is measured at the end of a clinical study to see if a given treatment worked (e.g., proportion of participants with viral suppression). What the primary endpoint will be is decided before the study begins.

protocol

A detailed research plan that describes the aims and objectives of a clinical trial and how it will be conducted.

secondary endpoint

Endpoints in a trial that provide supportive evidence to the primary endpoint.

The study recruited 645 participants in Europe and North America. People were eligible to join the study if they had normal-to-mildly impaired kidney function (eGFR > 30ml/min) and no previous history of antiretroviral treatment. People with hepatitis B or hepatitis C co-infection were eligible to join the study.

A primary endpoint analysis of the study was presented at the 9th International AIDS Society Conference on HIV Science (IAS 2017) in Paris in July 2017, showing no difference between the two regimens in rates of virological suppression after 48 weeks of treatment.

This week, Hans-Jürgen Stellbrink presented results of the secondary endpoint analysis of the study, rates of virological suppression at 96 weeks and adverse events.

Six hundred and fifty-seven participants were randomised and 645 began treatment in the study. Approximately one-third of study participants were black, a quarter were Hispanic or Latino and the remainder were white. The median baseline viral load was 4.43 log10 copies/ml in the bictegravir group and 4.45 log10 copies/ml in the dolutegravir group. The study population had relatively high baseline CD4 counts (a median of 440 cells/mm3), reflecting the trend towards earlier diagnosis.

The intent-to-treat analysis, covering everyone randomised to participate in the study, showed that after 96 weeks, 84.1% of those receiving Biktarvy and 86.5% of those receiving dolutegravir-based treatment had a viral load below < 50 copies/ml, a non-significant difference.

The per-protocol analysis, covering everyone who commenced treatment, showed that 100% of those receiving Biktarvy and 98.2% of those receiving dolutegravir-based treatment had a viral load below 50 copies/ml, a statistically significant difference (p = 0.03).

Five people taking dolutegravir-based treatment had detectable viral loads at week 96 but none had evidence of resistance to study drugs. Fourteen people in the bictegravir arm and seven in the dolutegravir arm discontinued treatment with a detectable viral load; in seven cases because they had no post-baseline visit, or because they did not wish to continue in the study, or due to pregnancy.

Participants randomised to dolutegravir had a significantly larger mean CD4 cell increase (+281 cells/mm3 vs 237 cells/mm3, p = 0.008), but Prof. Stellbrink noted that there was no significant difference in the absolute CD4 count at week 96 (733 cells/mm3 in the dolutegravir arm and 693 cells/mm3 in the bictegravir arm), nor in the change in CD4 cell percentage between the study arms.

Treatment-related adverse events were significantly more common in people receiving dolutegravir-based treatment than in the Biktarvy group (28 vs 20%, p = 0.02) but there was no difference in the rate of discontinuation due to adverse events (2%). The most common adverse events were nausea, diarrhoea and headache. No significant differences in the frequency of laboratory test abnormalities was observed.

References

Stellbrink H et al. Phase III randomized, controlled clinical trial of bictegravir coformulated with FTC/TAF in a fixed-dose combination (B/F/TAF) versus dolutegravir (DTG) + F/TAF in treatment naıve HIV-1 positive adults: Week 96 results. International Congress on Drug Therapy in HIV Infection (HIV Glasgow), Glasgow, 2018, abstract 0211.

View the abstract in the Journal of the International AIDS Society abstract supplement.

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