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Dolutegravir regimen highly effective in clinical trial for women
Liz Highleyman, 2016-11-07 07:40:00
A once-daily regimen containing the potent HIV
integrase inhibitor dolutegravir worked better than an older
atazanavir-containing regimen - with higher rates of viral suppression both
overall and across race subgroups - in the ARIA trial, one of the few antiretroviral
therapy studies to enrol only women, according to a presentation at IDWeek last
week in New Orleans.
Over the course of the HIV/AIDS epidemic white men
have been over-represented while women and people of colour have been
under-represented in clinical trials of new therapies. But worldwide, women
make up about half of all people living with HIV and people of African heritage
have the highest burden of disease, and it is important for new treatments to
be tested in all the groups that will ultimately use them.
Debbie Hagins of Chatham County Health Department in
Savannah, Georgia, presented findings from the ARIA trial, sponsored by
ViiV Healthcare, which enrolled 495 previously untreated women in 12 countries.
The study compared a fixed-dose combination of
versus ritonavir-boosted atazanavir (Reyataz)
plus tenofovir DF/emtricitabine (Truvada).
Dolutegravir has been shown to have a high barrier to resistance and is potent
enough to be used without a booster.
Nearly a third of trial participants were enrolled in
the UK and Europe, a quarter in the US, 13% in South Africa, and the rest in
Russia, Argentina, Thailand and Mexico. Just under half (46%) were white, 41%
were of African heritage and 13% were of other races/ethnicities, mostly Asian.
The median age was 37 years. The median baseline CD4 T-cell count was
approximately 350 cells/mm3 and over a quarter had a viral load
above 100,000 copies/ml.
Half the women were randomly assigned to receive
dolutegravir/abacavir/lamivudine and half to receive atazanavir/ritonavir plus
tenofovir/emtricitabine. The study's primary endpoint was the proportion in each arm with viral load below 50 copies/ml after 48
weeks on treatment.
After 48 weeks on treatment, 82% of women taking the
dolutegravir regimen and 71% taking the atazanavir regimen achieved viral
suppression in an intention-to-treat analysis. The difference was large enough
to show that the dolutegravir regimen was not only non-inferior, but also
superior to the atazanavir regimen. Response rates were similar when comparing
women with baseline viral loads above or below 100,000 copies/ml and CD4 counts
above or below 350 cells/mm3.
In a subgroup analysis by race, white women had higher
virological response rates on both dolutegravir and atazanavir (86% vs 80%)
compared to black women (74% vs 67%), but the difference between the two
regimens was similar for both groups.
Half as many women in the dolutegravir arm met the
criteria for virological non-response compared to
those in the atazanavir arm (6% vs 14% respectively). None of the women who
experienced virological failure while on dolutegravir/abacavir/lamivudine
developed resistance to these drugs.
The higher response rate in the dolutegravir arm was
largely driven by more discontinuations due to adverse events in the atazanavir
arm. About 20% of participants both arms stopped treatment before 48 weeks -
including 13 women who became pregnant - but the reasons for doing so differed.
About 80% of women in both treatment
arms experienced some adverse events, but those taking dolutegravir were less
likely to report moderate-to-severe events (46% vs 55%) and drug-related events
(33% vs 49%). Women in the dolutegravir arm had fewer serious adverse events (0
vs 3), drug-related serious adverse events (20 vs 12) and discontinuations due
to adverse events (17 vs 10) than those in the atazanavir arm. As expected, women
taking atazanavir were more likely to develop jaundice and yellowing of the
eyes due to elevated bilirubin. Patterns and frequency of adverse events were
similar when comparing black and white women.
Central nervous system side effects associated with
dolutegravir are an emerging concern,
but Hagins said that rate of neuropsychiatric events study were
the same in both treatment arms (14% overall, 4% insomnia, 2%-3% depression).
superior efficacy and a favourable safety profile compared to atazanavir plus
tenofovir/emtricitabine in treatment-naive women after 48 weeks of treatment,"
the investigators concluded in their study abstract. "Race subgroup
analyses were consistent with overall results."