Almost one in seven people in a Dutch HIV-positive population stopped treatment with integrase inhibitor dolutegravir HIV because of side effects, the researchers reported in the Netherlands in the online edition of AIDS. Approximately 14% of patients discontinued therapy with the drug because of tolerability issues, much higher than the rate seen in clinical trials. Dolutegravir caused twice as dropouts therapy when it was taken in combination with abacavir, but the side effects that led to a change in treatment were not associated with abacavir.
"In a clinic 'real' life DGV [dolutegravir] using the ART [antiretroviral therapy], we observed that in general the DGV was very well tolerated by most patients, but there were interruptions in a much higher rate than reported in trials randomized controlled clinical ", comment the authors.
Dolutegravir is recommended for first-line treatment against HIV. The product is available in a combination tablet with abacavir and lamivudine Triumeq () And as a tablet with 50mg single dose of the drug Tivicay (DGV). Dolutegravir is approved for treatment of people with HIV who have never taken before treatment (to antiretroviral naive) and those taking other treatment before the treatment (experienced).
In clinical trials, dolutegravir had a potent anti-HIV effect and was shown to be safe and tolerable, with a dropout rate 48 weeks no more than the 2 3%.
However, medical Netherlands observed that a significantly greater proportion of their patients to this therapy stopped DGV than the rate observed in clinical trials. Therefore conducted a study to determine the synchronization frequency, and reasons for the abandonment of therapies containing dolutegravir
The study population consisted of 556 people in Leiden and Amsterdam who initiated therapy between dolutegravir 2014 and 2016. The average age of 48 years 66% were men who have sex with men (MSM).
About one-fifth of the patients were naive to antiretroviral therapy (have never been subjected to any form of antiretroviral therapy). The combination pill Triumeq was prescribed to 57% of patients in all, 64% were taking dolutegravir in combination with abacavir.
A total of 85 people (15%) eventually abandoned the therapeutic regimens containing dolutegravir. In 76 patients (14%) there were reports of intolerable side effects as a reason for abandonment. Patients in these therapeutical modulations left the treatment and mean in the 73º days after the beginning; 95% dropped out within one year after starting their regimen containing dolutegravir Common reasons for not tolerating the use of dolutegravir were insomnia and sleep disturbances (6%), gastrointestinal complaints (4%) and neuropsychiatric symptoms such as anxiety and depression and psychosis (4%). In almost all cases, these side effects disappear as soon as the regimen containing dolutegravir was discontinued. There were no cases of virologic failure. Patients were about twice as likely to discontinue their treatments when taking Dolutegravir in combination with abacavir (RAR = 1,92%, IC 95%, 1,09-3,38, p = 0,01).
"We believe that there may be an interaction between drugs, leading to increased interruption of treatment, the authors write, adding that the two drugs are metabolized using the same route liver. They note, "the apparent interaction between DGV and abacavir mediated by this common degradation pathway does not appear to have been studied."
In contrast, taking dolutegravir in combination with a protease inhibitor was associated with a lower risk of dropping out of treatment (ARR = 0,20, 95% CI, 0,05-0,86; p = 0,03).
The authors call for further studies to determine the dropout rate of dolutegravir treatment due to side effects.
Translated by Claudio Souza Original in English Doctors in Netherlands note higher than expected dolutegravir treatment discontinuation rate written by Michael Carter Published: October 13 2016. Reviewed by Mara Macedo