Open AccessDolutegravir treatment response by baseline viral load and NRTI backbone in treatment‐naïve HIV‐infected individuals
Author(s) -
Eron J,
Rockstroh J,
Pozniak A,
Elliott J,
Small C,
Johnson M,
Brennan C,
Pappa K,
Cuffe R
Publication year - 2012
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.7448/ias.15.6.18264
Subject(s) - dolutegravir , raltegravir , viral load , medicine , regimen , darunavir , integrase inhibitor , gastroenterology , human immunodeficiency virus (hiv) , pharmacology , virology , antiretroviral therapy
Background In two 48‐week studies in naïve subjects, dolutegravir with NRTI of choice has shown non‐inferiority to raltegravir and, with ABC/3TC, superiority to Atripla. Factors that influenced choice of NRTIs included viral load, resistance and safety. Methods We analysed response rates and time to virologic failure by NRTI backbone and baseline viral load in the pivotal DTG‐naïve studies. SPRING‐2 randomized participants to DTG 50 mg QD or RAL 400 mg BID, each in combination with investigator‐selected NRTIs (TDF/FTC or ABC/3TC). SINGLE randomised participants to DTG 50 mg+ABC/3TC QD or TDF/FTC/EFV (Atripla) QD. In SPRING‐2, changes in serum creatinine were examined by INI and NRTI backbone. Results The two studies randomized and treated 1655 subjects, of whom 249 (15%) were female, 388 (23%) non‐white, 495 (30%) had HIV‐1 RNA >100,000 c/ml, and 224 (14%) had CD4+ count <200 cells/mm 3 .Primary analyses demonstrated non‐inferiority of DTG to RAL in SPRING‐2 (Δ=2.5%; 95% CI:−2.2% to +7.1%, excluding −10%), and superiority of the DTG regimen in SINGLE (7.4%; +2.5% to +12.3%). In SPRING‐2, response rates by NRTI backbone were comparable in each viral load stratum. In SINGLE, a 7% difference in response (favoring DTG+ABC/3TC) was observed in each viral load stratum. Exploratory analyses examining time‐to‐virologic failure showed no difference in response rates between the NRTIs irrespective of baseline viral load or study. Resistance to INIs or NRTIs was not demonstrated in any subject on DTG‐based therapy through 48 weeks. Withdrawals due to AEs on DTG‐based regimen were few (2%) in both studies. In SPRING‐2, no significant differences were observed in serum creatinine change from baseline to Week 48 by NRTI backbones. Conclusions In SPRING‐2 and SINGLE, DTG was effective with both ABC/3TC and TDF/FTC, and in subjects with high and low viral load. DTG was well tolerated in both studies. Renal safety also was similar by NRTI backbone. DTG is a once‐daily, unboosted INI that can be used with either TDF/FTC or ABC/3TC backbone in treatment‐naïve, HIV‐infected individuals.