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  EACS - 12th European AIDS Conference
November 11-14, 2009
Cologne, Germany
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Study of Once-Daily Boosted Darunavir
Monotherapy as First-Line Therapy Had Difficulty

  12th European AIDS Conference, November 11-13, 2009, Cologne, Germany
Mark Mascolini
Darunavir/ritonavir once-daily monotherapy in this study in previously untreated people appeared to have some difficulties, according to results of a small and quickly aborted trial. Lopinavir/titonavir had more difficulty as firstline monotherapy[1].
Pedro Cahn and coworkers at Fundacion Huesped in Buenos Aires designed a study in which 11 antiretroviral-naive people with 10,000 to 100,000 HIV RNA copies/mL would start 800/100 mg of darunavir/ritonavir once daily with no other antiretrovirals. If 7 or more people had a viral load under 400 copies at week 8, the investigators planned to recruit 13 more people with viral loads between 20,000 and 500,000 copies. But the trial got off to a slow start when only 7 people could be recruited. Thirty-eight screened people did not qualify because of a high or low pretreatment viral load, pretreatment resistance mutations, or other disqualifications.
Study participants needed a CD4 count above 100 and could have no resistance mutations at screening. The Buenos Aires team mapped out a 48-week trial with three primary endpoints:
· Viral load drop of more than 1 log (10-fold) at week 4
· Viral load below 400 copies in 7 or more people at week 8
· Viral load below 50 copies at weeks 24 and 48
By treatment week 4, all 7 study participants had at least a 10-fold viral load decline, but by week 8 only 4 of 7 had a viral load below 400 copies. Two of 4 people who maintained monotherapy through 24 weeks had a viral load below 50 copies. The investigators stopped the trial because the week 8 endpoint was not reached with the first 7 people recruited and because further recruitment did not look promising. Cahn suggested that both the recruitment criteria and the stopping rules may have been too stringent.
At study week 12, the last time all 7 participants remained in the trial, the average CD4 count had climbed by 167 cells. No grade 3 or 4 laboratory or clinical problems arose. Genotyping of virus from 2 people detected no IAS-USA mutations or darunavir-related resistance mutations. All 7 study participants reached a viral load below 50 copies when they added nucleosides to darunavir/ritonavir.
"Based on results from this small, pilot study," the investigators wrote in the printed abstract, first-line once-daily darunavir/ritonavir monotherapy "cannot be recommended in antiretroviral-naive patients." But in his presentation Cahn suggested no firm conclusions can be drawn because of the trial's small size and brevity.
An on-treatment analysis of the lopinavir/ritonavir monotherapy trial, MONARK, determined that 80% of antiretroviral-naive people randomized to monotherapy had a viral load under 50 copies at week 48, compared with 95% of patients taking those protease inhibitors with zidovudine and lamivudine (P = 0.02) [2]. Major PI mutations arose in 5 of 83 people randomized to lopinavir/ritonavir monotherapy and in none randomized to triple therapy [3].
1. Patterson P, Krolewiecki A, Tomaka F, Miralles D, Spinosa S, Cahn P. A phase II, open-label trial in treatment-naive, HIV-1-infected subjects who received DRV/RTV as induction monotherapy. 12th European AIDS Conference. November 11-13, 2009. Cologne, Germany. Abstract PS4/4.
2. Delfraissy JF, Flandre P, Delaugerre C, et al. Lopinavir/ritonavir monotherapy or plus zidovudine and lamivudine in antiretroviral-naive HIV-infected patients. AIDS. 2008;22:385-393.
3. Delaugerre C, Flandre P, Chaix ML, et al; MONARK Study Group. Protease inhibitor resistance analysis in the MONARK trial comparing first-line lopinavir-ritonavir monotherapy to lopinavir-ritonavir plus zidovudine and lamivudine triple therapy. Antimicrob Agents Chemother. 2009;53:2934-2939.