A randomized clinical trial comparing nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients (the Combine Study).
BACKGROUND
Non-nucleoside reverse transcriptase inhibitor-containing regimens may be a valid alternative to protease inhibitor-containing regimens for initial antiretroviral therapy, but to date few studies comparing these two strategies have been performed.


OBJECTIVE
To evaluate the efficacy and safety of nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients.


METHODS
Randomized, open-label, multicentre trial.


METHODS
Twelve centres in Spain (9) and Argentina (3).


METHODS
One hundred and forty-two HIV-infected naive patients without AIDS.


METHODS
Patients received combivir (zidovudine 300 mg/lamivudine 150 mg, twice-daily) plus either nelfinavir (1250 mg) twice-daily (zidovudine/lamivudine/nelfinavir, n=70) or nevirapine (200 mg) twice-daily (zidovudine/lamivudine/nevirapine, n=72), and were followed for 12 months. The primary endpoint was the proportion of patients with a plasma HIV-1 RNA (pVL) of less than 200 copies/ml by PCR at 12 months. pVL of less than 20 copies/ml (PCR), changes in CD4 counts, clinical progression and adverse events were also evaluated. Efficacy was assessed using intent-to-treat (ITT) (missing=failure) and on-treatment analysis.


RESULTS
At 12 months in the ITT analysis the proportion of patients with pVL below 200 copies/ml was 60% (95% CI 48.5-71.5) in the zidovudine/lamivudine/nelfinavir arm and 75% (95% CI 65-85) in the zidovudine/lamivudine/nevirapine arm (P=0.06), and the proportion below 20 copies/ml was 50% (95% CI 38.3-61.7) and 65% (95% CI 54.2-76.2), respectively (P=0.06). No differences were found when comparing the subgroup of patients with baseline pVL of more than 100,000 copies/ml. A gain of +173 and +162 CD4 cells/mm3, respectively, was observed. Zidovudine/lamivudine/nelfinavir was discontinued in 21% of patients, and zidovudine/lamivudine/nevirapine in 25%, due to toxicity (P>0.2).


CONCLUSIONS
Our results suggest that zidovudine/lamivudine/nevirapine is at least as effective as zidovudine/lamivudine/nelfinavir as first-line therapy for HIV disease.
Podzamczer
Daniel
D
Infectious Disease Service, Ciutat Sanitària de Bellvitge, L'Hospitalet, Barcelona, Spain. dpodzamczer@csub.scs.es
Ferrer
Elena
E
Consiglio
Ezequiel
E
Gatell
José Mariá
JM
Perez
Pepa
P
Perez
José Luis
JL
Luna
Elena
E
González
Alicia
A
Pedrol
Enric
E
Lozano
Luisa
L
Ocaña
Imma
I
Llibre
Josep María
JM
Casiró
Arnaldo
A
Aranda
Miquel
M
Barrufet
Pilar
P
Martínez-Lacasa
Javier
J
Miró
José María
JM
Badía
Xavier
X
Casado
Alfonso
A
Lupo
Sergio
S
Cahn
Pedro
P
Maños
Manel
M
Estela
Jordi
J
D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D001118:Argentina; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000009:adverse effects / Q000627:therapeutic use*; D019829:Nevirapine / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013030:Spain; D016896:Treatment Outcome; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine; D019888:Nelfinavir