Single-tablet dolutegravir-based therapy safe, effective for HIV-infected women

By Marilynn Larkin

NEW YORK (Reuters Health) - A single-tablet dolutegravir-based combination regimen given daily is noninferior to a multi-pill atazanavir-based regimen in previously untreated women with HIV infection, and has a similar safety profile, researchers say.

The randomized, open-label non-inferiority study was done specifically to address the efficacy and safety of the dolutegravir-based regimen in women, who are often under-represented in HIV clinical trials, according to the authors.

For the multinational phase IIIb trial, Dr. Catherine Orrell of the University of Capetown, South Africa and colleagues recruited 499 women between 2013 and 2015. The mean age was 38; 41% were black, 46% white, 9% Asian, and 4% other.

Participants had HIV-1 RNA viral loads of 500 copies per mL or greater, had received no more than 10 days of antiretroviral therapy, and had tested negative for the HLA-B*5701 allele, which confers hypersensitivity to abacavir. Pregnant women were excluded.

Half the women were assigned to the dolutegravir group; they took a single-tablet of dolutegravir plus abacavir and lamivudine once a day for 48 weeks. In the atazanavir group, women took a three-tablet combination of ritonavir-boosted atazanavir plus coformulated tenofovir disoproxil fumarate and emtricitabine once a day.

As reported in The Lancet HIV, online July 17, at week 48, 82% of participants in the dolutegravir group had HIV-1 RNA viral loads of less than 50 copies per mL versus 71% in the atazanavir group.

One participant in the atazanavir group had nucleoside reverse transcriptase inhibitor–associated resistance that led to reduced emtricitabine susceptibility.

Adverse events were similar between the groups. Most common were nausea (19% with dolutegravir versus 20% with atazanavir) and headache (11% versus 32).

Fewer participants in the dolutegravir group reported drug-related adverse events (33% for dolutegravir versus 49% for atazanavir) or adverse events that led to discontinuation (4% versus 7%). One non-treatment-related death was reported in each group.

“The non-inferior efficacy and similar safety profile of the dolutegravir combined regimen compared with the atazanavir regimen support the use of dolutegravir for HIV-1 infection in treatment-naive women,” the authors concluded.

Editorialist Dr. Susan Ellen Cohn of Northwestern University Feinberg School of Medicine in Chicago told Reuters Health by email, “Over half of all adults living with HIV globally are women, but we know less about the safety and efficacy of newer HIV treatment regimens in women since women are typically underrepresented in HIV clinical trials.”

“Adherence to ART has been shown to be crucially important for decreasing HIV-related morbidity and mortality, and for preventing HIV transmission,” she said. “Unfortunately, fewer than a third of all women with HIV in the US are virally suppressed.”

“To achieve an ‘AIDS Free Generation,’ it is essential to develop strategies to improve HIV medication adherence,” Dr. Cohn continued. “Strategies that focus on optimizing the ART regimen by making it simpler, with lower pill burden and better tolerated with fewer adverse effects have been helpful, but more is needed to combat the more challenging obstacles such as drug and alcohol use, intimate partner violence, depression and other psychologic issues, and HIV stigma and fear of disclosure.”

“By providing additional care and support services to maximize adherence to ART and tailoring interventions to be reflective of an individual’s needs,” she concluded, “we have the opportunity to help achieve the UNAIDS goal of 90-90-90 and, ultimately, bring about the end of the AIDS pandemic.”

The study was funded by ViiV Healthcare, which markets the dolutegravir combination tablet as Triumeq. Spokesperson Dr. Justin Koteff told Reuters Health by email, “Women account for over half of the almost 35 million adults living with HIV worldwide, yet unfortunately they are consistently under-represented in HIV clinical trials . . . This trial not only provides physicians with important additional information about Triumeq, but also builds on the strong body of evidence supporting the efficacy of dolutegravir-based regimens in a broad range of patient populations.”

Six coauthors are employees of ViiV Healthcare, one is an employee of GlaxoSmithKline, one is a former employee of GSK, and Dr. Orrell and four coauthors have received fees from ViiV/GSK and other pharmaceutical companies.

SOURCE: http://bit.ly/2v4AIIL and http://bit.ly/2v4XC2G

Lancet HIV 2017.

(c) Copyright Thomson Reuters 2017. Click For Restrictions - http://about.reuters.com/fulllegal.asp