Safety and antiviral activity at 48 weeks of lopinavir/ritonavir plus nevirapine and 2 nucleoside reverse-transcriptase inhibitors in human immunodeficiency virus type 1-infected protease inhibitor-experienced patients.
The safety and antiviral activity of lopinavir (Lpv), a protease inhibitor (PI) coformulated with ritonavir (Rtv) to enhance its pharmacokinetic properties, were evaluated in 70 patients with plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 1000-100,000 copies/mL on a first PI-containing regimen. Patients were randomized to substitute only the PI with Lpv/Rtv, 400/100 mg or 400/200 mg twice daily. On day 15, nevirapine (200 mg 2x/day) was added, and nucleoside reverse-transcriptase inhibitors were changed. Despite a >4-fold reduction in phenotypic susceptibility to the preentry PI in 63% of patients, mean plasma HIV-1 RNA levels declined by 1.14 log(10) copies/mL after 2 weeks of Lpv/Rtv. At week 48, 86% of subjects receiving treatment had plasma HIV-1 RNA levels of <400 copies/mL; 76% had levels <50 HIV-1 RNA copies/mL (intent-to-treat: 70% and 60%, respectively). Mean CD4 cell counts increased by 125 cells/muL. Three patients discontinued therapy for drug-related adverse events.
Benson
Constance A
CA
Department of Medicine, University of Colorado Health Sciences Center, 4200 E. 9th Avenue, B-168, Denver, CO 80262, USA. constance.benson@uchsc.edu
Deeks
Steven G
SG
Brun
Scott C
SC
Gulick
Roy M
RM
Eron
Joseph J
JJ
Kessler
Harold A
HA
Murphy
Robert L
RL
Hicks
Charles
C
King
Martin
M
Wheeler
David
D
Feinberg
Judith
J
Stryker
Richard
R
Sax
Paul E
PE
Riddler
Sharon
S
Thompson
Melanie
M
Real
Kathryn
K
Hsu
Ann
A
Kempf
Dale
D
Japour
Anthony J
AJ
Sun
Eugene
E
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000502:physiology; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000494:pharmacology / Q000627:therapeutic use; D011446:Prospective Studies; D011744:Pyrimidinones / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019829:Nevirapine; D019438:Ritonavir