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Maintenance Therapy With 400/100 mg of Darunavir/Ritonavir for 48 Weeks
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9th IAS Conference on HIV Science (IAS 2017), July 23-26, 2017, Paris
Mark Mascolini
Darunavir/ritonavir at 400/100 mg daily usually maintained viral suppression achieved with the standard 800/100-mg dose in an open-label single-arm study [1]. In a 95-person analysis there were 8 treatment failures (8.4%), including 2 people whose darunavir dose changed without virologic failure.
French ANRS researchers noted that cutting the dose of a protease inhibitor (PI) could save money and broaden access in many countries, perhaps while decreasing toxicity. They conducted the ANRS 165 Darulight trial to determine whether cutting the darunavir/ritonavir dose from 800/100 to 400/100 mg once daily with two nucleos(t)ides) (NRTIs) would maintain viral suppression through 48 weeks.
The ANRS team enrolled people taking 800/100 mg of darunavir once daily plus two NRTIs for at least 6 months. Everyone had a viral load at or below 50 copies for at least 12 months No one ever had a virologic failure (viral load above 200 copies), no one had darunavir or NRTI mutations on a pretreatment genotype, and everyone had a CD4 count at or above 300. Among 100 enrolled participants, 5 were excluded from the modified intention-to-treat analysis because of protocol violations or withdrawn consent. Eight people stopped the 400/100-mg dose, 6 because of virologic failure, 1 based on the physician's decision, and 1 who became pregnant.
Among all 100 enrollees, 78 were men, 55 were men who have sex with men, and median age stood at 43. The group had taken antiretroviral therapy for a median of 46 months and had a viral load below 50 copies for a median of 35 months. Median baseline CD4 count stood at 633. Most participants (76%) took tenofovir/emtricitabine, while the rest took abacavir/lamivudine.
In the intention-to-treat analysis, 8 participants (8.4%) had treatment failure, which included virologic failure (above 50 copies) in 6 people and a change in darunavir dose without virologic failure in 2 people. Three successful genotypes after virologic failure detected no primary PI or NRTI mutations. Eleven people had a transient viral blip above 50 copies during follow-up. The only factor associated with viral load above 50 copies was a screening or baseline viral load above the study threshold (odds ratio 4.76, 95% confidence interval 1.47 to 15.4).
There were 9 serious adverse events but no adverse events leading to discontinuation. Twenty-three people had gastrointestinal problems, including diarrhea in 9 and abdominal pain in 5. Fourteen participants had a grade 2 or worse lab abnormality including neutrophils below 1000/mm(3) in 4 and glucose above 7 mmol/L in 3.
The researchers noted that an ongoing trial is comparing 400/100 mg of darunavir/ritonavir with 800/200 mg of lopinavir/ritonavir, both with NRTIs, in South Africans with well-controlled viremia on a second-line regimen [2].
References
1. Molina JM, El Abassi EM, Gallien S, et al. Efficacy and safety of darunavir dose reduction from 800 to 400 mg daily with ritonavir and TDF/FTC or ABC/3TC in virologically suppressed HIV-1-infected adults: an open-label study (ANRS-165 Darulight). 9th IAS Conference on HIV Science (IAS 2017), July 23-26, 2017, Paris. Abstract MOPEB0313.
2. ClinicalTrials.gov. Evaluation of low-dose darunavir in a switch study (DRV). ClinicalTrials.gov identifier NCT02671383. https://clinicaltrials.gov/ct2/show/NCT02671383
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