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Elvitegravir Regimen Maintains Virologic Control in Blacks After PI or NNRTI
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ICAAC 2014. September 5-9, 2014. Washington, DC
Mark Mascolini
Stribild, the single-tablet once-daily combination of elvitegravir/cobicistat plus tenofovir/emtricitabine (TDF/FTC), maintained virologic control somewhat better than a continued protease inhibitor (PI) or nonnucleoside (NNRTI) regimen among blacks in two open-label trials [1]. This post hoc analysis of outcomes in black and nonblack study participants recorded no virologic failures among blacks after a switch to Stribild.
The international, randomized, open-label STRATEGY-PI and STRATEGY-NNRTI trials demonstrated that switching to Stribild is noninferior to continuing a suppressive PI or NNRTI regimen for 48 weeks [2,3]. Previous antiretroviral research often found lower virologic response rates in African Americans than in others, but reasons for this difference remain unclear. To address the question of virologic response among blacks, STRATEGY investigators conducted this post hoc analysis of week-48 outcomes in black and nonblack participants of both trials.
The original trials included adults taking a ritonavir-boosted PI or an NNRTI--each with TDF/FTC--who had maintained a viral load below 50 copies for at least 6 months. Participants could be taking their first or second antiretroviral regimen. No one had a history of virologic failure and none had resistance to TDF or FTC. Everyone had an estimated glomerular filtration rate (eGFR) at or above 70 mL/min. For the race-based analysis, the investigators compared people who identified themselves as black or African in origin; all other study participants who described their race were classified as nonblack. The primary outcome was the proportion of black and nonblack participants who maintained a viral load below 50 copies through week 48 by FDA snapshot analysis, with a 12% noninferiority margin.
The analysis included 43 blacks and 248 nonblacks randomized to Stribild in the STRATEGY-PI and 20 blacks and 118 nonblacks randomized to continue their PI regimen in that trial. About two thirds of blacks in both treatment arms were men, as were almost 90% of nonblacks. Median age was 39 among blacks and 41 among nonblacks. Median baseline CD4 counts were close to 500 or higher in blacks and nonblacks in both trials.
STRATEGY-NNRTI included 49 blacks and 242 nonblacks randomized to Stribild and 23 blacks and 120 nonblacks randomized to continue their NNRTI. About three quarters of blacks in both treatment arms were men, and more than 95% of nonblacks were men. Median age stood at 42 among blacks in the Stribild arm and 34 in the NNRTI arm. Median age was about 42 among nonwhites in both treatment arms.
At week 48 the FDA snapshot algorithm determined sub-50-copy response rates among blacks of 95% with Stribild versus 89% with a continued PI for a difference of 5.9% favoring Stribild (95% confidence interval [CI] -8.5 to 28.5). Week-48 sub-50-copy response rates among blacks were 92% with Stribild versus 74% with a continued NNRTI for a difference of 17.9% favoring Stribild (95% CI -0.8 to 40). Among nonblacks at week 48 response rates were 93% with Stribild versus 87% with a continued PI (difference 6.2%, 95% CI -0.6 to 13.8) and 94% with Stribild versus 91% with a continued NNRTI (difference 2.9%, 95% CI -2.7 to 9.8). Treatment-emergent resistance mutations developed in no study participants in either arm of either trial or either racial group.
Considering blacks in the STRATEGY-NNRTI trial, the researchers found a significantly higher upper respiratory infection rate with Stribild than with a continued NNRTI (16% versus 0) and a significantly lower nasopharyngitis rate with Stribild than with a continued NNRTI (0 versus 13%). No adverse event rates differed significantly between Stribild and a continued PI among blacks. Among nonblacks, cough developed significantly more often with Stribild than with a continued PI (5% versus less than 1%). There were no other significant adverse event differences among nonblacks in either trial.
Among blacks median eGFR dropped more through 48 weeks with Stribild than with a continued PI (-11.1 versus -1.4 mL/min), a result reflecting cobicistat inhibition of renal creatinine transporters. eGFR decline was also greater with Stribild than with a continued NNRTI (-12.2 versus -3.0 mL/min). In both trials eGFR dropped through week 4 then stabilized through week 48. Among nonblacks median eGFR fell more with Stribild than with a continued PI (-6.7 versus -0.5) and with Stribild than with a continued NNRTI (-11.5 versus -0.2). Again the decline occurred in the first 4 weeks then leveled off. Proximal renal tubulopathy developed in no black study participants through week 48. Tubulopathy developed in 1 nonblack randomized Stribild who had abnormal baseline kidney measures.
The STRATEGY team concluded that Stribild may be "a viable switch option" for blacks taking a suppressive PI or NNRTI regimen.
References
1. Gathe J, Lewis S, Jordon W, et al. Switch to E/C/F/TDF from PI + RTV or NNRTI plus FTC/TDF maintains HIV suppression at week 48 and is safe in black subjects. ICAAC 2014. September 5-9, 2014. Washington, DC. Abstract H-1004.
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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