Increased antiretroviral potency by the addition of enfuvirtide to a four-drug regimen in antiretroviral-naive, HIV-infected patients.
OBJECTIVE
To assess if enfuvirtide (ENF) increases antiviral activity of a highly active four-drug antiretroviral (ARV) regimen containing lopinavir/ritonavir, efavirenz, lamivudine and tenofovir in ARV-naive, HIV-infected patients.


METHODS
Pilot study in ARV-naive, HIV-infected patients with viral load (VL) >10,000 copies/ml and no documented resistance to any of the study drugs. Patients were randomized to receive ENF (ENF Group) or not (Control Group) in combination with lopinavir/ritonavir, efavirenz, lamivudine and tenofovir as a backbone. The primary endpoint was to assess differences in the HIV-1 RNA decay rate during the first phase of viral decay. VL and treatment adherence were measured at baseline, every 6 h during the first 3 days, and once daily from day 3 to 6. Individual HIV-1 RNA decay rates were obtained using a non-linear least squares regression model.


RESULTS
Eight subjects were included in each study group. Mean (SD) baseline VL was 4.98 (0.38) log10 copies/ml in the ENF Group and 5.10 (0.49) log10 copies/ml in the Control Group (P=0.607). Baseline CD4+ cell count was 463 (306) and 362 (225) cells/mm3 in the ENF and the Control Group, respectively (P=0.484). First phase HIV-1 RNA decay rate was 0.802 (0.127) d(-1) in the ENF Group and 0.624 (0.182) d(-1) in the Control Group (P=0.045). By day 6, VL was 3.55 (0.40) and 3.92 (0.36) log10 copies/ml in the ENF and the Control Group, respectively (P=0.079).


CONCLUSIONS
The addition of ENF increased the antiviral potency of a highly active four-drug ARV regimen by 28.5% in ARV-naive, HIV-infected patients. The clinical impact of this finding should be assessed.
Moltó
José
J
Lluita contra la Sida Foundation, HIV Unit, Germans Trias i Pujol Hospital, Badalona, Spain. jmolto@ns.hugtip.scs.es
Ruiz
Lidia
L
Valle
Marta
M
Martinez-Picado
Javier
J
Bonjoch
Ana
A
Bravo
Isabel
I
Negredo
Eugenia
E
Heilek-Sneider
Gabrielle M
GM
Clotet
Bonaventura
B
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines; D003521:Cyclopropanes; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage* / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D061466:Lopinavir; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D010078:Oxazines / Q000008:administration & dosage / Q000627:therapeutic use; D010349:Patient Compliance; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000627:therapeutic use; D011744:Pyrimidinones / Q000008:administration & dosage / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D063065:Organophosphonates; D010078:Oxazines; D010446:Peptide Fragments; D011744:Pyrimidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000077560:Enfuvirtide; D061466:Lopinavir; D019259:Lamivudine; D000068698:Tenofovir; D000225:Adenine; C098320:efavirenz; D019438:Ritonavir