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Switch From PI or NNRTI to Stribild in People 50
or Older Effective and Safe in Trials
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5th International Workshop on HIV and Aging. October 20-21, 2014. Baltimore
Mark Mascolini
Switching from a ritonavir-boosted protease inhibitor (PI) or a nonnucleoside (NNRTI) to single-tablet Stribild (elvitegravir/cobicistat/tenofovir/emtricitabine) proved effective and safe in people 50 or older enrolled in the STRATEGY-PI and STRATEGY-NNRTI trials [1]. Patient satisfaction scores were higher in people who switched to Stribild than in those who maintained their PI or NNRTI regimen, though the difference was significant only in the NNRTI trial. These analyses involved 77 people in STRATEGY-PI and 96 in STRATEGY-NNRTI.
STRATEGY-PI and STRATEGY-NNRTI randomized people taking a suppressive PI or NNRTI regimen including tenofovir/emtricitabine to switch to Stribild or maintain their current combination. After 48 weeks 94% randomized to Stribild in the PI trial maintained an undetectable viral load, compared with 87% randomized to continue their PI regimen, a significant difference (P = 0.025) [2]. After 48 weeks in STRATEGY-NNRTI, 93% in the switch group and 88% in the continued-NNRTI maintained an undetectable viral load, though that difference fell short of statistical significance (P = 0.066) [3].
To assess response rates and adverse events in people 50 or older, the investigators conducted this post hoc analysis. The trials randomized participants 2-to-1 to switch or maintain their initial regimen. Everyone had a viral load below 50 copies for at least 6 months, all were taking their first or second regimen, and no one had a history of virologic failure or resistance to tenofovir or emtricitabine. Everyone had an estimated glomerular filtration rate (eGFR) at or above 70 mL/min.
The analyses involved 54 people in the Stribild arm and 23 in the continued-PI arm in STRATEGY-PI, and 71 people randomized to Stribild and 25 to a continued NNRTI in STRATEGY-NNRTI. Age averaged about 53 across study groups and ranged from 50 to 76. Almost 90% of people in this analysis were men, and proportions of nonwhites across the four study arms ranged from 9% to 39%. About one third of participants had hypertension. Median time taking antiretrovirals stood at 3 or 4 years in the four arms and median CD4 count around 500.
Proportions of 50-and-older participants with a viral load below 50 copies at 48 weeks were 96% on Stribild in STRATEGY-PI versus 86% on a continued PI, and 92% on Stribild in STRATEGY-NNRTI versus 96% on a continued NNRTI. Neither of the differences within trials was statistically significant. Virologic failure rates were 2% and 3% in the Stribild arms of the PI and NNRTI trials, and 0% in the continued PI and NNRTI arms.
Median 48-week CD4 gains in these 50-and-older people measured 16 with Stribild and 29 with a continued PI in STRATEGY-PI and 38 with Stribild and 46 with a continued NNRTI in STRATEGY-NNRTI. Only the median 38-cell CD4 gain in the Stribild arm of the NNRTI trial was significant compared with baseline (P = 0.001).
In the continued PI or NNRTI arms of the two trials, eGFR remained nearly flat through 48 weeks in people 50 or older. In the 50-and older Stribild arms, median eGFR dropped 8.5 mL/min in the PI trial and 11.9 mL/min in the NNRTI trial through 48 weeks. Almost all of these declines occurred in the first few weeks after the switch, a result consistent with cobicistat's inhibition of renal creatinine secretion. Proximal renal tubulopathy developed in no one 50 or older in these trials.
In STRATEGY-PI median triglyceride levels fell 16 mg/dL in the 48 weeks after a switch to Stribild, but that change lacked statistical significance (P = 0.10). In STRATEGY-NNRTI median total cholesterol fell 11 mg/dL in the 48 weeks after a switch to Stribild, a significant drop (P = 0.036). "Good" high-density lipoprotein (HDL) cholesterol also fell significantly by 5 mg/dL among people who switched to Stribild in that trial (P = 0.007). Median changes in total-to-HDL cholesterol ratio through 48 weeks were small and similar across study arms (-0.3 with Stribild versus 0 with a continued PI, P = 0.23; 0.2 with Stribild versus 0.1 with a continued NNRTI, P = 0.92).
Among people 50 or older, patient HIV Treatment Satisfaction Scores were significantly higher with Stribild than a continued NNRTI through 24 weeks (P = 0.010). Satisfaction scores were modestly higher in older trial participants who switched to Stribild rather than staying with a PI, and that difference was not statistically significant (P = 0.44).
The STRATEGY trialists proposed that switching from a virologically effective boosted PI or an NNRTI to Stribild may be a reasonable option for older patients who need a treatment change or want a simpler regimen.
References
1. Ward DJ, McDonald CK, Markowitz MH, et al. Switching to Stribild from a RTV-boosted PI or NNRTI with TVD maintains HIV suppression at week 48 with no new safety signals in subjects age ≥50 years. 5th International Workshop on HIV and Aging. October 20-21, 2014. Baltimore. Abstract 17.
2. Arribas JR, Pialoux G, Gathe J, et al. Simplification to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of ritonavir-boosted protease inhibitor with emtricitabine and tenofovir in adults with virologically suppressed HIV (STRATEGY-PI): 48 week results of a randomised, open-label, phase 3b, non-inferiority trial. Lancet Infect Dis. 2014;14:581-589. http://www.natap.org/2014/HIV/060914_07.htm
3. Pozniak A, Markowitz M, Mills A, et al. Switching to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of non-nucleoside reverse transcriptase inhibitor with emtricitabine and tenofovir in virologically suppressed adults with HIV (STRATEGY-NNRTI): 48 week results of a randomised, open-label, phase 3b non-inferiority trial. Lancet Infect Dis. 2014;14:590-599. http://www.natap.org/2014/HIV/060914_08.htm
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