CROI: Do boosted protease inhibitors have a lower risk of treatment failure than other regimens?

Anti-HIV treatment regimens including ritonavir (Norvir)-boosted protease inhibitors may be more forgiving of low adherence than those including unboosted protease inhibitors or non-nucleoside reverse transcriptase inhibitors, according to an observational study presented earlier this month at the Thirteenth Conference on Retroviruses and Opportunistic Infections in Denver.

HIV-positive patients taking antiretroviral therapy stand the best chance of treatment success if they take all of their medication at the correct times every day. While it is known that suboptimal adherence, typically below 95%, increases the risk of drug resistance and treatment failure, there have been few comparsions of the relative risk of poor adherence between different types of HIV treatment.

To assess the relative risk of treatment failure, investigators from the HOMER cohort examined the links between adherence and treatment failure in over 1630 Canadian patients from British Columbia. All of the patients had had at least two separate viral loads measurements below 500 copies/ml.

Over a median follow-up of 29 months, 606 (37%) of the patients experienced treatment failure, defined as two consecutive viral loads above 1000 copies/ml.

When they analysed the treatment failure rates separately by the drug class taken by the patients, the investigators found a significant association between treatment failure and adherence below 95% for the 752 patients taking an unboosted protease inhibitor as part of their HIV treatment combination (hazard ratio [HR] = 2.78; 95% confidence interval [CI]: 1.41 – 2.24). Adherence was measured by recording when the patients returned to collect their repeat prescriptions.

There was a similar relationship between failure and adherence for the 631 NNRTI-treated patients (HR = 1.47; 95% CI: 1.01 – 2.14).

However, there was no significant link between adherence below 95% and treatment failure in the 251 patients treated with ritonavir-boosted protease inhibitors (HR = 1.05; 95% CI: 0.46 – 2.42). This analysis was adjusted for sex, age, injection drug use, CD4 cell count, AIDS diagnosis and doctors’ experience.

Although a formal comparison failed to reveal a statistically significant difference between the three groups, the investigators conclude that boosted protease inhibitors may be more forgiving of low adherence.

“These results may be explained in part by higher trough concentrations with respect to the IC₉₀ of the virus, higher genetic barrier to resistance of protease inhibitors versus NNRTI, and prolonged half-lives due to the ritonavir boosting,” they explain. “For individuals at high risk of suboptimal adherence, using boosted protease inhibitor-based regimens may achieve higher effectiveness rates.”