A virological benefit from an induction/maintenance strategy: the Forte trial.
OBJECTIVE
To evaluate whether the addition of a fourth drug for up to 32 weeks to a standard three-drug antiretroviral combination decreases the risk of virological failure without increasing toxicity in treatment-naive patients.


METHODS
Induction/maintenance (IM) therapy [two nucleoside reverse transcriptase inhibitors (NRTIs) + one non-NRTI (NNRTI) + one protease inhibitor for 24-32 weeks until plasma HIV RNA viral load (VL) < or =50 copies/ml then two NRTIs + NNRTI] was compared with standard therapy (ST) (two NRTIs + NNRTI). The primary endpoint was virological failure: VL >50 copies/ml at 32 (and 24) weeks or subsequent rebound to >400 copies/ml.


RESULTS
122 (62 IM, 60 ST) participants were randomized and followed for a median of 81 weeks (IQR 64-145). 52% were asymptomatic; median CD4+ T-cell count was 160 x 10(6)/l (IQR 92-260) and median VL 98,830 copies/ml (IQR 37,500-241,290). In an intent-to-treat analysis, the proportion of participants with virological failure at or after 32 weeks was higher in the ST arm [26 (43%) versus 11 (18%), P = 0.002]. The mean decrease in VL at 48 weeks was 0.84 95% confidence interval (CI) (0.15, 1.53) log10 copies/ml greater in the IM arm (P = 0.02). There were no significant differences between the two arms in the change in CD4+ T-cell count from baseline to 48 weeks, the number of participants with adverse events or the frequency of progression to AIDS/death. Drug resistance at failure was detected less frequently in the IM arm.


CONCLUSIONS
Starting antiretroviral therapy with an IM strategy improved virological outcomes compared with a three-drug regimen, without significantly increasing toxicity.
Asboe
David
D
Chelsea and Westminster Hospital, London, UK.
Williams
Ian G
IG
Goodall
Ruth L
RL
Darbyshire
Janet H
JH
Hooker
Malcolm H
MH
Babiker
Abdel G
AG
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000627:therapeutic use; D018450:Disease Progression; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019888:Nelfinavir / Q000627:therapeutic use; D019829:Nevirapine / Q000627:therapeutic use; D010349:Patient Compliance; D012367:RNA, Viral / Q000097:blood*; D012074:Remission Induction; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018119:Stavudine / Q000627:therapeutic use; D013997:Time Factors; D017211:Treatment Failure; D006113:United Kingdom; D019562:Viral Load
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D018119:Stavudine; D019888:Nelfinavir; D016049:Didanosine