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Response Rates Similar With Rilpivirine and Efavirenz Above and Below 50 Years of Age
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ICAAC: Older Patients Showed Similar Efficacy and Safety Results Compared With Younger Patients Over 96 Weeks in the Phase III ECHO and THRIVE Trials of Treatment-Naïve HIV-1-Infected Patients Treated With Rilpivirine or Efavirenz - (09/13/12)
3rd International Workshop on HIV and Aging, November 5-6, 2012, Baltimore
Mark Mascolini
Being 50 or older did not impair virologic or CD4 responses to rilpivirine- or efavirenz-based first-line therapy through 96 weeks, according to a post hoc analysis of the ECHO and THRIVE trials [1]. A slightly higher proportion of over-50 people assigned to efavirenz than to rilpivirine had an undetectable viral load at 96 weeks, but the difference could not be weighed statistically because of the nature of this analysis. As in the primary trial analyses [2,3], certain toxicity outcomes were worse with efavirenz than with rilpivirine.
As people age with HIV infection, the impact of antiretroviral therapy may change because of declining liver, kidney, and immune function, and because of more frequent non-HIV illnesses. To assess the effect of age on response to first-line regimens built on the nonnucleosides rilpivirine and efavirenz, ECHO and THRIVE investigators ran this comparison of outcomes in trial participants younger than 50 or 50 and older. The initial ECHO and THRIVE analyses at 48 weeks established that rilpivirine with standard nucleoside combinations is noninferior to efavirenz in previously untreated people [2,3]. Virologic failure rates were higher with rilpivirine, but safety outcomes were better with rilpivirine.
Tenofovir/emtricitabine was the only nucleoside combination in ECHO; in THRIVE participants could take tenofovir/emtricitabine, abacavir/lamivudine, or zidovudine/lamivudine. Of the 1368 people considered in this analysis, 126 (9%) were 50 or older (69 rilpivirine, 57 efavirenz) and 1242 were younger than 50 (617 rilpivirine, 625 efavirenz). Median ages were 35-36 in the combined under-50 group and 54 in the over-group. About one quarter of participants across arms and age groups were women, and about one quarter were black.
Pretreatment viral load averaged 100,000 copies, with little difference by age or treatment assignment. Median CD4 count stood at 253 in under-50s on rilpivirine, 220 in 50+ on rilpivirine, 261 in under-50s on efavirenz, and 257 in 50+ on efavirenz. Median overall HIV infection duration was only 1 year, and fewer than one third of study participants had AIDS symptoms or diagnoses.
At week 96 a snapshot analysis determined that the following proportions had a viral load below 50 copies:
Under 50 years old:
-- Rilpivirine 76% (471 of 617) below 50 copies
-- Efavirenz 76% (474 of 625) below 50 copies
50 or older:
-- Rilpivirine 77% (53 of 69) below 50 copies
-- Efavirenz 84% (48 of 57) below 50 copies
Median CD4 gains were similar in both age groups, regardless of treatment arm: 263 and 237 in younger and older people randomized to rilpivirine, and 251 and 278 in younger and older people randomized to efavirenz.
Small proportions of younger and older trial participants assigned to rilpivirine stopped treatment because of adverse events (3.9% younger and 5.8% older), while slightly greater proportions in the efavirenz arm stopped for that reason (8.5% younger and 10.5% older). Age did not affect rates of possibly drug-related grade 2 or worse adverse events, but those rates were lower in the rilpivirine group (17% younger and 13% older) than in the efavirenz group (33% younger and 39% older).
Grade 2 or worse central nervous system side effects developed in 4% and 1% of younger and older rilpivirine participants, and in 10% and 9% of older and younger efavirenz participants. Grade 2 or worse psychiatric side effects at least possibly related to study drugs affected 9.1% of younger participants and 14.0% of older participants randomized to efavirenz. In contrast, rates in the rilpivirine arm were 6.3% among younger people and 2.9% among older people. Similarly, grade 2 or worse skin and subcutaneous tissue problems affected 8.2% and 15.8% of younger and older people assigned to efavirenz versus 1.6% and 1.4% assigned to rilpivirine. Rash arose in 5% and 9% of younger and older people taking efavirenz and in 1% of younger and older people taking rilpivirine.
Total and "bad" low-density lipoprotein cholesterol rose in both younger and older people taking efavirenz for 96 weeks, while levels of these lipids changed minimally in younger and older people taking rilpivirine. "Good" high-density lipoprotein and triglycerides changed little through follow-up and did not appear to be affected by age. Creatinine, aspartate aminotransferase, and alanine aminotransferase had similar small changes in both treatment arms and both age groups. At week 96 estimated glomerular filtration rate (eGFR) in older people dropped 9.2 mL/min in the efavirenz group and 11.0 mL/min in the rilpivirine group. eGFR declines in younger people measured 3.9 mL/min with efavirenz and 13.6 mL/min with rilpivirine.
Rilpivirine full prescribing information notes that virologic failure in ECHO and THRIVE was more common in the rilpivirine arm than in the efavirenz arm among people with a pretreatment viral load above 100,000 copies [4]. This higher failure rate resulted in more nucleoside and nonnucleoside resistance in the rilpivirine arm. The age-related analysis did not stratify participants by pretreatment viral load and did not assess resistance rates.
References
1. Anderson D, Dayaram YK, Schaible D, Coate B, Ryan R. Similar outcomes in older versus younger patients over 96 weeks in treatment-naive, HIV-1-infected patients treated with rilpivirine or efavirenz.3rd International Workshop on HIV and Aging. November 5-6, 2012, Baltimore. Abstract O_16.
2. Molina JM, Cahn P, Grinsztejn B, et al. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Lancet. 2011;378:238-246.
3. Cohen CJ, Andrade-Villanueva J, Clotet B, et al. Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial. Lancet. 2011;378:229-237.
4. Edurant. (rilpivirine) [Tablets]. Full prescribing information. http://www.edurant.com/hcp/sites/www.edurant-info.com.hcp/files/EDURANT-PI.pdf
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