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Better HIV Control, Better Bone Changes
After Switch From Atripla to E/C/F/TAF
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ICAAC 2015, September 17-21, 2015, San Diego
Mark Mascolini
People who switched from Atripla (coformulated efavirenz/tenofovir/emtricitabine [TDF/FTC]) to elvitegravir/cobicistat/FTC/tenofovir alafenamide (E/C/F/TAF) maintained virologic control through 48 weeks better than those randomized to stay on Atripla [1]. The E/C/F/TAF group also had significant gains in hip and spine bone mineral density (BMD). Total-to-high-density-lipoprotein (HDL) cholesterol ratio rose (worsened) slightly but significantly more with E/C/F/TAF than with Atripla.
TAF, the investigational tenofovir prodrug, puts more tenofovir in HIV target cells and less in blood than tenofovir disoproxil fumarate (TDF). At the 10-mg TAF dose in E/C/F/TAF, plasma tenofovir levels are about 90% lower than at the 300-mg TDF dose in Atripla or E/C/F/TDF (Stribild). Because blood carries less tenofovir to nontarget cells and organs after TAF dosing than TDF dosing, markers of kidney and bone toxicity have proved better with E/C/F/TAF than with E/C/F/TDF [2].
The study presented at ICAAC involved 1436 people with virologic suppression while taking Atripla, E/C/F/TDF, or ritonavir-boosted atazanavir plus TDF/FTC, two thirds of whom switched to E/C/F/TAF, while the rest stayed with their TDF regimen. This analysis focused on 376 people taking Atripla who stayed with that one-pill once-daily therapy or switched to one-pill once-daily E/C/F/TAF. All had a viral load below 50 copies for at least 48 weeks on Atripla, and all had an estimated glomerular filtration rate (eGFR) at or above 50 mL/min.
The 251 people switching to E/C/F/TAF and the 125 staying with Atripla had median ages of 41 and 39 years, two thirds in each group were white, 22% black, and 8% women. Median baseline CD4 count stood at 678 in the E/C/F/TAF group and 662 in the Atripla group. Respective median eGFRs were 116 and 121 mL/min.
After 48 weeks of follow-up, 241 of 251 people randomized to E/C/F/TAF (96%) and 112 of 125 maintaining Atripla (90%) still had a viral load below 50 copies, a significant difference (difference 6.4, 95% confidence interval 0.5 to 12.3, P = 0.015).
A higher proportion randomized to E/C/F/TAF than to Atripla had grade 2 to 4 creatine kinase abnormalities (14% versus 10%), and a higher proportion had neutropenia (5% versus <1%). Total cholesterol rose 10 mg/dL in the E/C/F/TAF group and 5 mg/dL in the Atripla group (P = 0.02), while "good" HDL cholesterol fell 2 mg/dL with E/C/F/TAF and rose 1 mg/dL with Atripla (P = 0.10). Total-to-HDL cholesterol ratio rose (worsened) from 3.4 to 3.8 with E/C/F/TAF and from 3.4 to 3.5 with Atripla, a significant difference (P < 0.001). Data from the Framingham Heart Study suggest that a ratio of 3.4 indicates about half the average risk of heart disease in men [3].
Through 48 weeks, serum creatinine climbed significantly more with E/C/F/TAF (+0.10 mg/dL) than with continued Atripla (+0.02 mg/dL). The investigators believe these changes reflect starting cobicistat and do not indicate impact on creatinine clearance. Four markers of proteinuria all fell (improved) in people who switched to E/C/F/TAF, while rising in the Atripla arm (P < 0.001 for all differences).
Five people stopped E/C/F/TAF and 4 stopped Atripla because of adverse events, and almost all these problems in both groups were neurologic/psychiatric. Frequency of central nervous system (CNS) side effects differed little between the E/C/F/TAF arm and Atripla arm. But results of a questionnaire about five CNS side effects indicated a 58% drop in the composite score in the E/C/F/TAF arm at week 48 versus a 5% drop in the Atripla arm. Symptoms began to improve 2 weeks into the study.
Spine BMD rose an average 0.86% with 48 weeks of E/C/F/TAF and fell 0.22% with 48 weeks of continuing Atripla (P < 0.05). Respective average 48-week changes in hip BMD also differed significantly (+1.44% versus -0.24%, P < 0.001). The proportion of people with normal BMD changed little through 48 weeks in the Atripla arm, while inching up in the E/C/F/TAF group (61.4% to 63.2% for spine, 67.9% to 71.7% for hip).
References
1. Shamblaw D, Van Lunzen J, Orkin C, et al. Switching from Atripla (ATR) to a tenofovir alafenamide (TAF)-based single tablet regimen: week 48 data in virologically suppressed adults. ICAAC 2015, September 17-21, 2015, San Diego.
2. Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet. 2015;385:2606-2615.
3. Harvard Health Publications. Making sense of cholesterol tests-the Family Health Guide. February 2005. http://www.health.harvard.edu/heart-health/making-sense-of-cholesterol-tests
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