The doravirin pill looks good as the initial HIV treatment
A single tablet regimen containing doravirin a Reverse Transcriptase Non-Nucleotide Inhibitor Reduced HIV viral load as well as an efavirenz-based co-formulation, but showed a more favorable side-effect profile, according to the results of the DRIVE-AHEAD study this week at 9A International AIDS Conference Society on HIV Science (IAS 2017) , Paris.
Current top-line antiretroviral therapy regimens are safe and highly effective. The integrase inhibitors have largely replaced reverse transcriptase inhibitors non-nucleotides (NNRTIs) as first-line treatment in recent years, but have multiple potent drugs and well tolerated antiretroviral drugs from different classes offers more options for individualized therapy.
Kathleen Squires Thomas Jefferson University in Philadelphia presented the results of study phase 3 DRIVE-AHEAD, which is evaluating a fixed dose co-formulation of 100 mg doravirina, 300 mg lamivudine (3TC) and 300 mg tenofovir disoproxil fumarate (TDF ).
Doravirin, a research NNRTI developed by Merck, has a unique resistance profile and is active against HIV with common mutations of NNRTI resistance including K103N. It can be taken with or without food and has low potential for drug interactions.
Previous studies have shown that doravirine suppresses viral load as well as efavirenz (Sustiva ou Stocrin®), But with fewer neuropsychiatric side effects, In an 2 phase study . Doravirine plus two Nucleoside Reverse Transcriptase Inhibitors of the researcher's choice - either TDF / emtricitabine (Truvada) Or abacavir / lamivudine (Kivexa® ou Epzicom) - worked as well as darunavir potentiated with ritonavir (Prezista®), But with a better lipid profile, In an 3 phase study.
DRIVE-AHEAD enrolled 728 people initiating HIV treatment for the first time. About 85% were men, Half were white and the average age was 31 years. The mean CD4 count was approximately 420 cells / Mm3, About 22% had a high viral load above 100.000 copies / ml and 14% had a Clinical history of AIDS.
The participants in this study double-blind Were randomly assigned to receive the doravirine combination tablet or a co-formulation of efavirenz, emtricitabine and TDF (Atripla®).
To "blind" the study, because drug dosing regimens are not the same, participants were given placebos for co-formulation that they were not taking. Doravirin allows a more flexible schedule: participants were invited to take doravirin or placebo co-formulation whenever they chose - but at the same time every day - with or without food. They were told to take the efavirenz pill or placebo on an empty stomach at bedtime, because it was thought to decrease the neurological side effects of efavirenz.
Treatment was planned for 96 weeks, the primary outcome being the proportion of people with HIV RNA below 50 copies / ml at 48th week (undetectable).
After 48 weeks of treatment, 84% of the persons in the arm of doravirin and 81% in the arm of efavirenz presented viral load Undetectable, showing that the new co-formulation was not inferior. Those who started with a higher viral load had higher response rates, but these did not differ according to the regimen. In a modified analysis, about 90% of people with low baseline viral load and about 80% of those with high baseline viral load reached an undetectable level in both treatment arms.
People who took doravirin were more likely to suffer from a protocol-defined therapeutic failure than those taking efavirenz, but this was uncommon in both arms (6% vs 4%). Among participants with therapeutic failure undergoing successful genotypic tests, 1,6% in doravirina arm and the 3,3% efavirenz arm had evidence of the NNRTI resistance mutations.
Both treatment regimens were generally safe and well tolerated, but there were some notable differences in side effects.
Half of many people in the arm of doravirin experienced drug-related adverse events in general (31% vs 63%, respectively), but serious events were rare in both arms (1% or less). Less than half of the arm of doravirin stopped treatment early due to adverse events (3% vs 7%). The most common adverse events in the doravirin arm were headache (13%), diarrhea (11%) and nasopharyngitis (11%), which occurred at similar rates in the efavirenz arm. The rash was less common with doravirin (5% vs 12%).
However, doravirin significantly Less side effects of the central nervous system. For example, 9% of people taking doravirin reported dizziness compared to 37% of those taking efavirenz. Looking at a set of pre-defined neuropsychiatric events, half of doravirina receivers reported sleep disturbances (12 26% vs%) and altered cognition (4 8% vs%). Depression and suicide or self-harm were also less frequent with doravirin (4% vs 7%).
Lipid profiles also favored doravirin. LDL cholesterol, total cholesterol and triglyceride levels decreased slightly after initiation of treatment on the doravirin arm, substantially increasing the efavirenz arm.
"Doravirin is taken once daily as a NNRTI for first-line treatment with consistent efficacy regardless of initial viral load and favorable safety profile tolerability in 3 two-phase clinical trials," the study's researchers concluded.
The DRIVE-AHEAD study had some limitations, including the fact that it compared doravirin against efavirenz, which is no longer recommended for first-line therapy in many treatment guidelines because of its adverse events. However, their low cost and wide availability explains why they are still commonly used in countries with limited resources.
In addition, session moderator to, Monica Gandhi, the University of California at San Francisco School, pointed out that the co-formulation of doravirina contains TDF instead of the new formulation of tenofovir alafenamida (TAF), which causes less toxicity and kidney In the bones. This was done because a generic version of the TDF is expected to be available soon, while the TAF will remain on the patent for another five years or more.
Doravirine combination pill looks good for initial HIV treatment written by Liz Highleyman Reviewed by Mara T de Macedo