ViiV Healthcare, the global specialist HIV company, majority owned by GlaxoSmithKline, with Pfizer Inc. and Shionogi Limited as shareholders, announced interim (Week 24) study results from INSPIRING, a phase IIIb study evaluating the safety and efficacy of dolutegravir in antiretroviral treatment-naive (ART-naïve) adults with HIV, co-infected with tuberculosis (TB).

Results presented at the annual Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, show that dolutegravir when administered at 50mg twice-daily with dual nucleoside reverse transcriptase inhibitors (NRTI), was effective and well-tolerated in HIV/TB co-infected adults receiving rifampin-based TB therapy.]

John C Pottage, Jr, MD, chief scientific and medical officer, ViiV Healthcare, said, “Tuberculosis remains the leading cause of death among people living with HIV, accounting for around one in three AIDS-related deaths. Concurrent treatment of TB and HIV remains a challenge as it is compounded by drug interactions, overlapping toxicities and immune reconstitution inflammatory syndrome. This is why the INSPIRING study is so important, as we look to provide this underserved population with as many effective treatment options as possible. The INSPIRING results add to the breadth and depth of data available for dolutegravir and support its use in the treatment of people living with HIV co-infected with TB.”

INSPIRING is a phase IIIb, non-comparative, active control, randomised, open-label study in HIV-1 infected ART-naive adults with drug-sensitive TB. Of the 113 enrolled participants on a rifampin-based TB treatment for up to 8 weeks, 69 were randomised to receive dolutegravir (50mg twice-daily during and for two weeks after TB therapy followed by 50mg once-daily) with two NRTIs and 44 to receive efavirenz (600mg once-daily) with two NRTIs. The primary endpoint of the study is the proportion of dolutegravir patients with HIV-1 RNA <50 copies per mL at week 48. The study, being conducted in Argentina, Brazil, Mexico, Peru, Russia, South Africa and Thailand, was not powered to show a difference between study arms and no formal statistical hypothesis was tested.

An interim analysis conducted at 24 weeks showed that the proportion of patients who maintained viral suppression (HIV-1 RNA less than 50 copies per ml) in the dolutegravir arm was 56/69 (81%) (95% confidence interval CI: 72%, 90%). In the efavirenz arm, 39/44 patients (89%) (95% CI: 79%, 98%) maintained viral suppression. No patients in the dolutegravir arm and two patients in the efavirenz arm discontinued due to adverse events, while five participants (7%) in the dolutegravir arm and none in the efavirenz arm discontinued due to non-treatment related reasons (loss to follow-up/protocol deviations). There were no reports of treatment emergent resistance in the dolutegravir arm and there was one report in the efavirenz arm. TB-associated immune reconstitution inflammatory syndrome (IRIS) rates were low in both arms (dolutegravir, n=4; efavirenz n=4) with no patients discontinuing due to IRIS or liver events. The INSPIRING study is ongoing and 48-week data will be presented at a future scientific meeting.

In 2016, there were an estimated 10.4 million cases of TB globally, including 1.2 million (11%) among people living with HIV (PLHIV). Although TB-related deaths among PLHIV have been steadily declining (33% decrease between 2005 and 2015), almost 60% of TB cases among PLHIV were not diagnosed or treated, resulting in 390,000 tuberculosis-related deaths among PLHIV in 2015.

INSPIRING is a phase IIIb, randomised, open-label, multicentre, parallel-group study to assess the antiviral activity of dolutegravir or efavirenz-containing regimens in HIV/TB co-infected patients undergoing rifampin-based TB therapy. The study includes a screening period, a randomised phase (Day 1 to 48 weeks plus a 4-week extension) and a dolutegravir open-label extension. During the dolutegravir open-label extension, patients were provided with dolutegravir until it is locally approved and commercially available, the patient no longer derives clinical benefit, or the patient meets a protocol-defined reason for discontinuation, whichever comes first.

The primary endpoint is the proportion of dolutegravir patients with plasma HIV-1 RNA <50 copies per millilitre (c/mL) at Week 48. Key secondary endpoints include the proportion of efavirenz patients with plasma HIV-1 RNA <50 c/mL at Week 48 and evaluation of both study arms at Week 24. Additional secondary endpoints include evaluation of the development of viral resistance, measurements of safety, tolerability and changes from baseline CD4+ counts.

Dolutegravir (Tivicay) is an integrase strand transfer inhibitor (INSTI) for use in combination with other antiretroviral agents for the treatment of HIV. Integrase inhibitors block HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection. Tivicay is approved in over 100 countries across North America, Europe, Asia, Australia, Africa and Latin America.