Efficacy and safety of once-daily combination therapy with didanosine, lamivudine and nevirapine in antiretroviral-naive HIV-infected patients.
BACKGROUND
Simplified antiretroviral regimens are needed to improve patient adherence and quality of life. The purpose of this study was to evaluate the efficacy and safety of a once-daily regimen consisting of didanosine (ddI), lamivudine (3TC) and nevirapine (NVP) for adult antiretroviral-naive patients with HIV-1 infection.


METHODS
This was a prospective, one-arm, multicentre pilot study. Daily drug dosage was 250 or 400 mg didanosine, 300mg lamivudine and 400 mg nevirapine. The primary outcome measure was the percentage of patients with a plasma HIV-RNA level <50 copies/ml at 12 months on an intention-to-treat (ITT) basis.


RESULTS
Seventy patients were enrolled in the study. At baseline, mean plasma HIV-1 RNA was 5.10log10 copies/ml, and mean CD4 cell count was 262 cells/microl. At month 12, 67% (95% CI: 56-78) of patients maintained a viral load of <50 copies/ml in the ITT analysis and CD4 counts increased a median of 201 cells/microl. The treatment was more effective in patients with baseline CD4 counts >100 cells/microl than in those with a poorer immunological status at baseline, although the number of patients with CD4 counts <100 was low. Four patients died during the study period. Therapy was discontinued in 18 patients due to virological failure in 11, adverse events in seven, loss to follow-up or withdrawal of consent in four and death in one. Eight out of nine patients with available genotype after virological failure showed resistance mutations to NVP (Y181C and others) and 3TC (M184V/I), and four of them also had ddI resistance (L74V). The lipid profile was favourable, with a decrease in the ratio of total-to-high density lipoprotein cholesterol.


CONCLUSIONS
A once-daily combination of ddI, 3TC and NVP seems to be an effective, safe and easy-to-take regimen in antiretroviral-naive patients, at least in those who do not have severe immunodepression at baseline.
Ribera
Esteban
E
Infectious Diseases Service, Hospital Universitari Vall d'Hebron, Barcelona, Spain. eribera@vhebron.net
Rodríguez-Pardo
Dolors
D
Rubio
Manuel
M
Soler
Anna
A
Pedrol
Enric
E
Blanco
José L
JL
González
Alicia
A
Crespo
Manel
M
Falcó
Vicenç
V
Ocaña
Imma
I
Deig
Elisabeth
E
Miró
Jose M
JM
Pahissa
Albert
A
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D013030:Spain
D019380:Anti-HIV Agents; D012367:RNA, Viral; D019259:Lamivudine; D019829:Nevirapine; D016049:Didanosine