The next-generation NNRTI Merck Doravirine (formerly known as MK-1439) was as effective as efavirenz at suppressing HIV replication, and although half of the many study participants with Doravirine have experienced adverse events related to medication - in particular side effects on the central nervous system (CNS) - they were less likely to stop prematurely treatment, according to the study results, reported in this week 8º Conference of the International AIDS Society (IAS) on HIV pathogenesis, treatment and prevention of this week in Vancouver.
NNRTIs are generally effective, easy to use and well suited for antiretroviral therapy (ART) for the first line. But the widely used drugs in this class, nevirapine (Viramune) are likely to generate resistance to HIV drugs, rilpivirine (Edurant) is less effective in people with high viral load, and efavirenz (Sustiva) may cause neuropsychiatric side effects such as dizziness and dreams abnormal. As such, these drugs are not recommended for first-line ART in US treatment guidelines
The approval of a potent and well tolerated new NNRTI that offers greater flexibility, especially for people with high drug resistance and limited treatment options. José Gatell of the University of Barcelona reported the latest results from the ongoing 007 study, which is comparing Doravirine against efavirenz, both taken once a day, to untreated people living with HIV.
2b this phase of the study included 2 parties. The 1 of this study evaluated doses of 25 mg, mg 50, 100 and 200 mg mg Doravirine in combination with tenofovir / emtricitabine (Truvada drug, a medication used in PrEP). As reported in Conference on retroviruses and opportunistic infections 2014 the 100Mg dose was selected because it offers the best balance of safety and efficacy based on an analysis 24 weeks.
At that time all participants of 1 phase remained or were associated with treatment with a dose of 100 mg Doravirine and monitoring was continued. More 132 people registered in the 2 the study and were randomly assigned to receive doses of 100 mg Doravirine or 600 mg efavirenz, both tenofovir / emtricitabine during 48 weeks.
In the treatment of HIV-drug Conference in Glasgow in the month of last November, Gatell reported that Doravirine was as effective as efavirenz in a study of 48 weeks of 1 phase. He also reported data in a preliminary study 8 week safety and tolerability from a pool of all participants 108 initiated at a dose of 100 mg Doravirine and 108 taking efavirenz in both phases of the study.
This week's meeting of the IAS, Gatell presented study findings of 24 weeks on efficacy and safety for this population combined 216 participants. More than 90% were male and 80% were white and the average age was approximately 35 years. The median cell count was approximately CD4 415 cells / mm3. Study participants were stratified by baseline viral load, with just over one third having RNA count the higher the HIV 100.000 copies / ml.
- The overall response rates were similar in both treatment groups, with only 73,1% of people who took Doravirine and 72,2% of participants who took efavirenz getting results as a viral load below 40 copies / ml (undetectable) in 24 weeks.
- 88,9 87,0% and%, respectively, had viral load below 200 copies / ml.
- Gains in CD4 cell counts were also similar, 154 and 146 cells / mm3 respectively.
- Looking response rates on viral function level pre-procedure, more than 90% of people who took the drug had reached HIV RNA counts down 200 copies / ml regardless of whether the treatment started with a low viral load or High.
- People who started with low viral load were more easily to suppress their HIV viral load to an undetectable level (below 40 copies / ml) (83,3% with Doravirine and 85,7% with efavirenz) than those who started with a higher level viral load (60,5 65,5% vs%).
- Participants in the treated arm Doravirine showed a potential of noncompliance around 50% of those who received treatment with efavirenz for any reason (4,6 11,9% vs.%, respectively).
- The difference was driven by a higher dropout rate due to adverse events Doravirine and Efavirenz (0,9 5,6% vs.%, respectively).
- While most people in both treatment arms had at least 1 serious adverse events, other events were less common in Doravirine (0,9 4,6% vs%). Moreover, people having had Doravirine half of side effects that many drugs in general (27,8 55,6% vs.%).
- The primary safety comparison showed that a significantly lower number of beneficiaries of Doravirine reported one or more events associated with the CNS week, the most frequent dizziness (9,3 27,8% vs), abnormal dreams (6,5 17,6% vs%), and nightmares (6,5 8,3% vs%).
- Depression was common in half of Doravirine users, for the users of Efavirenz, but the numbers were very small.
- Finally, the cholesterol levels "bad" LDL was found to be higher in efavirenz users.
Gatell noted that viral load was still falling in the week 24, and suggested that people with higher baseline levels probably still would not have enough time treatment to lower viral load to undetectable limit (40 copies of Viral RNA per cubic milliliter of blood ).
In summary, a daily dose of 100 mg of Doravirine in combination with tenofovir / emtricitabine "demonstrates antiretroviral activity and immunological effects similar to those of efavirenz" at 24a week, and "has much fewer CNS-related adverse events and fewer treatments linked to severe events "Than efavirenz, the researchers concluded. Gatell said that a Phase 3 study with a larger volume of Phase 3 Doravirine study is now underway.
Written by Liz Highleyman
Translated by Claudio Souza from the original IAS 2015: New NNRTI Doravirine Suppresses HIV as Well the Efavirenz CNS But with Fewer Side Effects by Claudio Souza.Reference Gatell J, F Raffi, The Plettenberg, et al. Efficacy and safety of doravirine 100 mg QD vs efavirenz 600 mg QD with TDF / FTC in ART-naive HIV-infected patients: week 24 results. 8th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Vancouver, July 19-22, 2015. Abstract TUAB0104.