Raltegravir with optimized background therapy for resistant HIV-1 infection.
BACKGROUND
Raltegravir (MK-0518) is an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase active against HIV-1 susceptible or resistant to older antiretroviral drugs.


METHODS
We conducted two identical trials in different geographic regions to evaluate the safety and efficacy of raltegravir, as compared with placebo, in combination with optimized background therapy, in patients infected with HIV-1 that has triple-class drug resistance in whom antiretroviral therapy had failed. Patients were randomly assigned to raltegravir or placebo in a 2:1 ratio.


RESULTS
In the combined studies, 699 of 703 randomized patients (462 and 237 in the raltegravir and placebo groups, respectively) received the study drug. Seventeen of the 699 patients (2.4%) discontinued the study before week 16. Discontinuation was related to the study treatment in 13 of these 17 patients: 7 of the 462 raltegravir recipients (1.5%) and 6 of the 237 placebo recipients (2.5%). The results of the two studies were consistent. At week 16, counting noncompletion as treatment failure, 355 of 458 raltegravir recipients (77.5%) had HIV-1 RNA levels below 400 copies per milliliter, as compared with 99 of 236 placebo recipients (41.9%, P<0.001). Suppression of HIV-1 RNA to a level below 50 copies per milliliter was achieved at week 16 in 61.8% of the raltegravir recipients, as compared with 34.7% of placebo recipients, and at week 48 in 62.1% as compared with 32.9% (P<0.001 for both comparisons). Without adjustment for the length of follow-up, cancers were detected in 3.5% of raltegravir recipients and in 1.7% of placebo recipients. The overall frequencies of drug-related adverse events were similar in the raltegravir and placebo groups.


CONCLUSIONS
In HIV-infected patients with limited treatment options, raltegravir plus optimized background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks. (ClinicalTrials.gov numbers, NCT00293267 and NCT00293254.)
Steigbigel
Roy T
RT
State University of New York at Stony Brook, Stony Brook, USA.
Cooper
David A
DA
Kumar
Princy N
PN
Eron
Joseph E
JE
Schechter
Mauro
M
Markowitz
Martin
M
Loutfy
Mona R
MR
Lennox
Jeffrey L
JL
Gatell
Jose M
JM
Rockstroh
Jurgen K
JK
Katlama
Christine
C
Yeni
Patrick
P
Lazzarin
Adriano
A
Clotet
Bonaventura
B
Zhao
Jing
J
Chen
Joshua
J
Ryan
Desmond M
DM
Rhodes
Rand R
RR
Killar
John A
JA
Gilde
Lucinda R
LR
Strohmaier
Kim M
KM
Meibohm
Anne R
AR
Miller
Michael D
MD
Hazuda
Daria J
DJ
Nessly
Michael L
ML
DiNubile
Mark J
MJ
Isaacs
Robin D
RD
Nguyen
Bach-Yen
BY
Teppler
Hedy
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology; D009930:Organic Chemicals / Q000009:adverse effects / Q000627:therapeutic use*; D011760:Pyrrolidinones; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D016896:Treatment Outcome; D019562:Viral Load
D019428:HIV Integrase Inhibitors; D009930:Organic Chemicals; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium