Safety, tolerability, and antiretroviral effects of ritonavir-nelfinavir combination therapy administered for 48 weeks.
OBJECTIVE
To evaluate the safety, tolerability, and anti-HIV activity of ritonavir-nelfinavir (RTV-NFV).


METHODS
Single-site, open-label, nonrandomized, multiple-dose trial of RTV combined with two doses of NFV in protease inhibitor (PI)-naive, HIV-infected patients.


METHODS
Mean baseline HIV RNA was 39,500 copies/ml; mean baseline CD4 count was 323 cells/mm3. All patients received RTV at a dosage of 400 mg twice daily. Cohorts I (N = 10) and II (N = 10) received NFV at a dosage of 500 mg and 750 mg twice daily, respectively, for the initial 12 weeks of the study before allowing intensification with reverse transcriptase inhibitors.


RESULTS
The commonest effects of RTV-NFV therapy were study drug-related moderate-to-severe diarrhea (9 patients in cohorts I and II) and drug-related moderate-to-severe nausea (4 patients in cohorts I and II). HIV RNA was suppressed in a biphasic manner. At 48 weeks in cohort I, mean HIV RNA reduction was 2.82 log10 copies/ml (standard error [SE] =.61; p =.001; N = 4); mean CD4 cell count increase was 236 cells/mm3 (SE = 67.1; p =.006; N = 4). In cohort II, mean HIV RNA reduction at Week 48 was 2.21 log10 copies/ml (SE =.430; p =. 001; N = 8); mean CD4 cell count increase was 120 cells/mm3 (SE = 47. 5; p =.03; n = 8). In cohort I patients, 2 of 4 completing Week 48 had HIV RNA <20 copies/ml; and 3 of 4 had HIV RNA <400 copies/ml. In cohort II, 2 of 8 patients completing Week 48 had HIV RNA <20 copies/ml and 4 of 8 had HIV RNA <400 copies/ml. In addition, 3 patients in cohort I withdrew because of virologic failure not thought to be related to poor compliance. Moreover, 15 patients elected to add new reverse-transcriptase inhibitors (RTIs) after week 12.


CONCLUSIONS
RTV-NFV with concomitant reverse transcriptase inhibitors is a potential dual-PI option for PI-naive patients.
Raines
C P
CP
Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. CRaines410@aol.com
Flexner
C
C
Sun
E
E
Heath-Chiozzi
M
M
Lewis
R H
RH
Fields
C
C
Deetz
C
C
Apuzzo
L
L
Eshleman
S H
SH
Jackson
J B
JB
Gallant
J E
JE
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D004279:DNA, Viral / Q000737:chemistry; D005260:Female; D005838:Genotype; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy*; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000592:standards*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000592:standards*; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000592:standards*; D017422:Sequence Analysis, DNA; D019562:Viral Load
D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D016333:HIV Protease; D019888:Nelfinavir; D019438:Ritonavir