An indirect comparison of efficacy and safety of elvitegravir/cobicistat/emtricitabine/tenofovir and dolutegravir + abacavir/lamivudine.
BACKGROUND
Integrase strand transfer inhibitors (INSTI) are the standard of care for naïve HIV-infected individuals due to their favourable efficacy and safety profile. The newest INSTIs, elvitegravir and dolutegravir, have not been evaluated in a head to head study; however, both have been compared to efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF) in phase III trials. Elvitegravir/cobicistat/emtricitabine/tenofovir DF (E/C/F/TDF) was compared to EFV/FTC/TDF for 144 weeks in Gilead Study 102 (GS-102), while dolutegravir (DTG) with the abacavir/lamivudine fixed-dose combination (ABC/3TC) was compared to EFV/FTC/TDF for 96 weeks in the SINGLE study. The objective of this analysis is to perform an indirect comparison at 48 and 96 weeks of E/C/F/TDF to DTG+ABC/3TC by using the two trials evaluating each of these regimens compared to EFV/FTC/TDF.


METHODS
An indirect comparison was performed by using Bucher's methodology to calculate risk differences based on the two phase III clinical trials described above.


RESULTS
At week 48 (snapshot analysis), 88% of the patients on E/C/F/TDF and DTG+ABC/3TC had HIV RNA <50 c/mL, while 84% and 81% of patients on EFV/FTC/TDF were suppressed in GS-102 and SINGLE, respectively. At week 96, 84% of patients receiving E/C/F/TDF compared with 80% of patients receiving DTG+ABC/3TC remained suppressed, while 82% and 72% on EFV/FTC/TDF maintained HIV RNA <50 c/mL in GS-102 and SINGLE. At week 144 80% of patients on E/C/F/TDF remained suppressed (vs. 75% of the patients on EFV/FTC/TDF). RESULTS of indirect comparison showed a risk difference of HIV RNA <50 copies per mL between E/C/F/TDF compared with DTG+ABC/3TC of -4% (CI 95%=-11 to 3) for the ITT 48 weeks (p=0.3) and -5% (95% CI=-13 to 3) for the ITT 96 weeks (p=0.2). In regards to safety, there was no significant difference between E/C/F/TDF and DTG+ABC/3TC for any adverse event (AE) (p=0.3), serious AEs (0.13), drug related AEs (0.7), or drug-related serious AEs (0.6).


CONCLUSIONS
In GS-102 and SINGLE, 88% of the patients on E/C/F/TDF and DTG+ABC/3TC were virologically suppressed at week 48. At week 96, these proportions were 84% for E/C/F/TDF and 80% for DTG+ABC/3TC. The indirect efficacy comparisons between EVG/COBI/FTC/TDF and DTG+ABC/3TC at week 48 and 96 revealed no statistically significant differences.
Medical Affairs, Gilead Sciences Europe, Uxbridge, UK.
Felipe
F
Rogatto
Pharmacoepidemiology, CEMKA, Bourg La Reine, France.
Stephane
S
Bouee
Pharmacoepidemiology, CEMKA, Bourg La Reine, France.
Vivianne
V
Jeanbat
Medical Affairs, Gilead Sciences, Foster City, CA, USA.
David
D
Piontkowsky
Medical Affairs, Gilead Sciences Europe, Uxbridge, UK.
Filipa
F
Aragao
Medical Affairs, Gilead Sciences, Foster City, CA, USA.
Matthew
M
Bosse