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Sustained Antiretroviral Efficacy of Raltegravir
as part of Combination ART in Treatment-Naive
HIV-1 infected patients: 144-week data
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Reported by Jules Levin
5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19-22, 2009, Cape Town
E. Gotuzzo1, B.-Y. Nguyen2, M. Markowitz3, F. Mendo4, W. Ratanasuwan5, C. Kovacs6, G, Prada7, J. Morales-Ramirez8,
C. Crumpacker9, C. Lu2, D. Brown2, R. Isaacs2, K. Strohmaier2, R. Danovich2, H. Teppler2, and the Protocol 004 Part II Study Team
1Hospital Nacionale Cayetano Heredia, Lima, Peru; 2Merck Research Laboratories, West Point, PA, United States; 3Aaron Diamond AIDS
Research Center, New York, NY, United States; 4Hospital Nacionale Edgardo Rebagliati, Lima, Peru; 5Siriraj Hospital, Bangkok, Thailand;
6Canadian Immunodefi ciency Research Collaborative, Toronto, Canada; 7Fundación Santafe de Bogota University Hospital, Bogota, Colombia;
8Clinical Research Puerto Rico, Inc., San Juan, Puerto Rico; 9Beth Israel Deaconess Medical Center, Boston, MA, United States
STUDY CONCLUSIONS
At 144 weeks, RAL had sustained antiretroviral effect similar to 96 week data and to EFV (both with TDF/3TC)
- 78% vs 76% (RAL vs EFV) with HIV RNA < 50 copies/mL
RAL was generally well tolerated at 144 weeks:
- Drug-related AEs appeared less frequent for RAL vs. EFV
- RAL had minimal effect on total cholesterol, LDL-C, and triglycerides
Defined as history of clinical diagnosis of AIDS at baseline, * With TDF/3TC, ** geometric mean
RAL/EFV (# of patients); Lack of effi cacy (4/2), AE (4/1), withdrew consent (9/4), Loss-to-follow up (6/1), Other reasons (13/2)
Protocol 004: 144 week Efficacy Summary
Percent of Patients with Virologic Suppression [Non-Completer=Failure]
Change from Baseline: CD4 and HIV RNA [Observed Failure Approach]
Protocol definition of virologic failure: (1) non-response: > 400 copies/ml at week 24 or early discontinuation, (2) virologic
relapse; > 400 copies/ml after initial response of < 400 copies/ml, or > 1.0 log10 increase above nadir level. (Percentage of
virologic failures in RAL: 8/160 (5%), and in EFV: 3/38 (7.9%).
*Failure occurred after Week 96, (--- indicates no mutations)
Mutation developed after patient was a virologic failure
Not known to be RAL resistance mutations - Monogram genotypic interpretation is "sensitive"
S230S/N is a common polymorphism that does not affect raltegravir sensitivity in phenotypic assays.
All four patients with Non-Response achieved >1.0 log10 decrease in HIV RNA at the nadir.
Protocol 004: 144 week Safety Summary
Cases included: 1 pt with B-cell lymphoma, 2 pts with Kaposi's sarcoma, 1 pt with both basal cell carcinoma and squamous cell
carcinoma (SC), 1 pt with both gastrointestinal carcinoma and SC
* Abnormal dreams, acute psychosis, adjustment disorder with depressed mood, auditory hallucination, completed suicide, concentration impaired, confusional state, delirium, depressed level of consciousness, depressed mood, depression, depressive
symptom, dizziness, dysthymic disorder, hallucination, hallucination visual, insomnia, major depression, nervous system
disorder, nightmare, psychotic disorder, somnolence, suicidal behavior, suicidal ideation, suicide attempt. Numbers are based
upon a list of neuropsychiatric AE terms associated with efavirenz.
RAL taken twice daily; EFV taken once daily; both with TDF/3TC.
*Incidence at least 10% in either treatment group; all intensity levels included.
Percent of Patients with Grade 3/4 Laboratory Abnormalities
No grade 3 or 4 abnormalities were reported in either treatment group for the following parameters: hemoglobin, platelet count, creatinine, and total bilirubin
Division of AIDS grading scale December 2004
RAL taken twice daily; EFV taken once daily; both with TDF/3TC
ULN - Upper Limit of Normal
Effect on Serum Lipids (144 weeks)
· LDL-cholesterol and triglycerides not increased by raltegravir
· Mean change from baseline (mg/dL) at week 144
* All RAL dose groups combined; all patients received TDF and 3TC
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