Once-Daily Dolutegravir Regimen Assists Women With HIV

Pam Harrison

July 25, 2016

DURBAN, South Africa — A fixed-dose single-tablet antiretroviral regimen for treatment-naïve HIV-positive women is successful in large part because of low rates of virologic nonresponse and of discontinuation related to adverse events, new research shows.

In the ARIA study, the once-daily combination of dolutegravir — an unboosted integrase strand transfer inhibitor with a high barrier to resistance — plus abacavir and lamivudine (Triumeq, ViiV Healthcare) was superior to a ritonavir-boosted regimen that consisted of atazanavir plus tenofovir disoproxil fumarate and emtricitabine.

"The superiority of the dolutegravir-based regimen does not appear to be attributable to a difference in adherence between the two treatment arms, so it's a regimen that works," said Catherine Orrell, MD, from the University of Cape Town in South Africa.

"If we look at all of the dolutegravir studies — whether they are comparing dolutegravir with darunavir or efavirenz — we see superiority in the dolutegravir arm. It's a robust efficacious drug and it's just plain easier for patients to take a single tablet once a day," she told Medscape Medical News.

Dr Orrell presented results from ARIA here at the International AIDS Conference 2016.

 
It's just plain easier for patients to take a single tablet once a day.
 

In the study, 248 treatment-naive women received the dolutegravir-based regimen and 247 received the atazanavir-based regimen. All participants tested negative for the HLA-B*5701 genetic variation, which is associated with susceptibility to abacavir hypersensitivity, and had a viral load above 500 copies/mL at study entry.

More than one-quarter of each treatment group had a viral load above 100,000 copies/mL at study entry, and about half had a CD4+ cell count below 350 cells/mm³.

The primary end point was an undetectable viral load (below 50 copies/mL) at week 48. And significantly more patients in the dolutegravir group than in the atazanavir group met the primary end point (82% vs 71%; P = .005).

In a per protocol analysis, the viral load was undetectable at week 48 in more patients in the dolutegravir group than in the atazanavir group (86% vs 76%). The same pattern was seen at week 48 in study participants who had a viral load above 100,000 copies/mL at baseline (80% vs 64%).

Virologic nonresponse was less common in the dolutegravir group than in the atazanavir group (6% vs 14%).

About one-third of the patients in the dolutegravir group experienced drug-related adverse events, as did about half the patients in the atazanavir group. Rates of psychiatric adverse events were similar — and low — in the two groups.

There were fewer discontinuations related to adverse events in the dolutegravir group than in the atazanavir group (4% vs 7%).

Importantly, participants who failed the dolutegravir regimen developed no significant mutations to dolutegravir or to any of the other components of the regimen. In contrast, one participant in the atazanavir group developed the M184v mutation, which confers a high level of resistance to lamivudine and emtricitabine.

At 48 weeks, the adjusted difference in favor of the dolutegravir regimen was 10.5%, Dr Orrell reported.

 
Our study provides important information to help guide treatment decisions in HIV-infected women.
 

"Our study provides important information to help guide treatment decisions in HIV-infected women," she said.

The current standard of care in HIV treatment involves a combination of at least two classes of antiretroviral agent, said session cochair Paula Munderi, MD, from the MRC/UVRI Uganda Research Unit on AIDS in Entebbe, Uganda.

"Improvements in overall adherence to treatment and in satisfaction with treatment when using a fixed-dose combination, especially single-tablet regimens, have been well documented," Dr Munderi told Medscape Medical News.

Not only is taking one pill once a day easier for patients, fixed-dose combinations also simplify the procurement process where there is only one bottle to fill, rather than three, she pointed out.

A "minor sacrifice" when using a fixed-dose formulation is the inability to adjust the dose of any of the drugs if a patient develops a unique adverse event related to one of them, she said.

"However, these instances are rare," Dr Munderi added, "and are usually taken into consideration in the dose-finding stages of any drug development process."

This study was funded by GlaxoSmithKline and ViiV Healthcare. Dr Orrell and Dr Munderi have disclosed no relevant financial relationships.

International AIDS Conference 2016: Abstract THAB0205LB. Presented July 21, 2016.

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