Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study.
BACKGROUND
Raltegravir is an HIV-1 integrase strand-transfer inhibitor with potent in vitro activity. This study explored the antiretroviral activity and safety of raltegravir in treatment-naive patients with plasma HIV-1 RNA levels > or = 5000 copies/mL and CD4 T-cell counts > or = 100 cells/mm.


METHODS
Multicenter, double-blind, randomized, controlled study of raltegravir at doses of 100, 200, 400, and 600 mg twice daily versus efavirenz at a dose of 600 mg/d, all in combination with tenofovir at a dose of 300 mg/d and lamivudine at a dose of 300 mg/d (clinicaltrials.gov identifier: NCT00100048).


RESULTS
In the 198 patients treated (160 on raltegravir and 38 on efavirenz), the mean HIV-1 RNA level ranged from 4.6 to 4.8 log10 copies/mL at baseline. At weeks 2, 4, and 8, the proportion of patients achieving an HIV-1 RNA level <50 copies/mL was greater in each of the raltegravir treatment groups than in the efavirenz group. By week 24, all treatment groups appeared similar, with plasma HIV-1 RNA levels <400 copies/mL in 85% to 98% of patients and <50 copies/mL in 85% to 95% of patients. These reductions were maintained through week 48 in 85% to 98% of patients and in 83% to 88% of patients, respectively. Five (3%) patients on raltegravir and 1 (3%) on efavirenz experienced virologic failure before week 48. Drug-related clinical adverse events were less common with raltegravir than with efavirenz. After 24 and 48 weeks of treatment, raltegravir did not result in increased serum levels of total cholesterol, low-density lipoprotein cholesterol, or triglycerides.


CONCLUSIONS
Raltegravir at all doses studied was generally well tolerated in combination with tenofovir and lamivudine. Raltegravir exhibited potent and durable antiretroviral activity similar to that of efavirenz at 24 and 48 weeks but achieved HIV-1 RNA levels below detection at a more rapid rate.
Markowitz
Martin
M
Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY, USA.
Nguyen
Bach-Yen
BY
Gotuzzo
Eduardo
E
Mendo
Fernando
F
Ratanasuwan
Winai
W
Kovacs
Colin
C
Prada
Guillermo
G
Morales-Ramirez
Javier O
JO
Crumpacker
Clyde S
CS
Isaacs
Robin D
RD
Gilde
Lucinda R
LR
Wan
Hong
H
Miller
Michael D
MD
Wenning
Larissa A
LA
Teppler
Hedy
H
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D001315:Australia; D002170:Canada; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D007843:Latin America; D008297:Male; D008875:Middle Aged; D009930:Organic Chemicals / Q000627:therapeutic use*; D063065:Organophosphonates / Q000627:therapeutic use; D011760:Pyrrolidinones; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D000068698:Tenofovir; D013785:Thailand; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D019428:HIV Integrase Inhibitors; D009930:Organic Chemicals; D063065:Organophosphonates; D011760:Pyrrolidinones; D012367:RNA, Viral; D019259:Lamivudine; D000068898:Raltegravir Potassium; D000068698:Tenofovir; D000225:Adenine