Suboptimal Adherence Has Less Effect on Boosted Darunavir (Prezista) than Lopinavir/ritonavir (Kaletra)

		SUMMARY: HIV positive individuals who are not able to achieve very good adherence to their antiretroviral therapy (ART) regimen may have a lower risk of treatment failure with ritonavir-boosted darunavir (Prezista) compared with lopinavir/ritonavir (Kaletra), according to 96-week data from the ARTEMIS trial published in the July 2010 Journal of Antimicrobial Chemotherapy. Highly adherent and suboptimally adherent patients had similar virological response rates in the darunavir/ritonavir arm, but those with poorer adherence had a lower response rate in the lopinavir/ritonavir arm.

By Liz Highleyman

Kaletra (lopinavir/ritonavir) • News Articles • Full US Prescribing Information Prezista (darunavir) • News Articles • Full US Prescribing Information

Mark Nelson from Chelsea and Westminster Hospital in London and colleagues conducted a study to examine how differences in treatment adherence affected clinical outcomes among participants in the ARTEMIS study, as well as to evaluate factors that influence adherence.

The Phase 3 ARTEMIS trial compared the safety and efficacy of boosted darunavir vs lopinavir/ritonavir.

The study enrolled nearly 700 treatment-naive HIV positive participants who were randomly assigned to receive darunavir/ritonavir at a dose of 800/100 mg once-daily, or lopinavir/ritonavir at doses of either 800/200 once-daily or 400/100 mg twice-daily. In addition, all participants received fixed-dose tenofovir/emtricitabine (Truvada).

Self-reported treatment adherence was assessed using the Modified Medication Adherence Self-Report Inventory (M-MASRI). In post-hoc analyses (done after the primary trial endpoints were evaluated), average adherence during weeks 4-96 was used to estimate overall adherence for each individual. Scores were converted to a binary variable: adherent (> 95%) or suboptimally adherent ( 95%). Some past research indicated that patients must achieve 95% adherence to get the most benefit from ART, but some later studies found that lower adherence could produce good outcomes under certain circumstances.

Results

	Overall adherence was high in both groups, with 83% in the darunavir/ritonavir arm and 78% in the lopinavir/ritonavir arm reporting > 95% adherence.
	The difference in virological response rates between the adherent and suboptimally adherent participants was smaller with darunavir/ritonavir than with lopinavir/ritonavir:
	Darunavir/ritonavir: 82% of adherent vs 76% of suboptimally adherent patients achieved undetectable viral load, a difference of 6% (P = 0.3312, not a statistically significant difference); Lopinavir/ritonavir: 78% vs 53%, respectively, achieved viral suppression, a difference of 25% (P < 0.0001, a highly significant difference).
	Among suboptimally adherent patients, those taking darunavir/ritonavir had a significantly higher virological response rate than those taking lopinavir/ritonavir (76% vs 53%, respectively; P < 0.01).
	In both treatment groups, suboptimally adherent patients reported more adverse events, including gastrointestinal side effects, than adherent patients.
	Among both adherent and suboptimally adherent patients, however, darunavir/ritonavir was associated with a lower rate of adverse events, including gastrointestinal symptoms, than lopinavir/ritonavir.

Based on these findings, the study authors concluded, "Suboptimal adherence had no significant effect on the virological response rate with once-daily darunavir/ritonavir treatment."

"In contrast, the lopinavir/ritonavir response rate was significantly reduced in suboptimally adherent patients compared with adherent patients," they continued. "Once-daily darunavir/ritonavir resulted in a higher virological response rate in suboptimally adherent patients compared with lopinavir/ritonavir."

Investigator affiliations: Chelsea and Westminster Hospital, London, UK; Hôpital Saint Antoine, Paris, Franc; Université Pierre et Marie Curie, Paris, France; INSERM Unit 707, Paris, France; Tibotec, Yardley, PA; Johnson & Johnson Pharmaceutical Services, Mechelen, Belgium; Tibotec BVBA, Mechelen, Belgium.

7/2/10

Reference
M Nelson, PM Girard, R Demasi, and others. Suboptimal adherence to darunavir/ritonavir has minimal effect on efficacy compared with lopinavir/ritonavir in treatment-naive, HIV-infected patients: 96 week ARTEMIS data. Journal of Antimicrobial Chemotherapy 65(7): 1505-1509 (Abstract). July 2010.

Other source
U.S. Department of Health and Human Services. Study Suggests Suboptimal Adherence Affects Efficacy of Lopinavir/ritonavir More than Darunavir/ritonavir. AIDSInfo-At-a-Glance 22. May 28, 2010.