Compact quadruple therapy with the lamivudine/zidovudine combination tablet plus abacavir and efavirenz, followed by the lamivudine/zidovudine/abacavir triple nucleoside tablet plus efavirenz in treatment-naïve HIV-infected adults.
OBJECTIVE
To assess efficacy, safety, and adherence with compact quadruple therapy comprising one lamivudine 150-mg/zidovudine 300-mg tablet (COM) twice daily + one abacavir (ABC) 300-mg tablet twice daily + three efavirenz (EFV) 200-mg capsules at bedtime for 24 weeks, followed by one lamivudine 150-mg/zidovudine 300-mg/ABC 300-mg triple nucleoside tablet (TZV) twice daily + three EFV 200-mg capsules at bedtime for 24 weeks.


METHODS
A pilot 48-week, prospective, open-label trial in which 38 antiretroviral-naïve HIV-infected adults (baseline median HIV-1 RNA 5.1 log(10) copies/mL, CD4+ cell count 285/microL) received the above treatment and were monitored regularly with respect to plasma HIV-1 RNA levels, CD4+ cell counts, T-cell receptor excision circles (TRECs), adherence, and adverse events.


RESULTS
At Week 48, intent-to-treat, switch-included analysis showed plasma HIV-1 RNA levels <400 copies/mL in 100% (29/29) of patients and <50 copies/mL in 93% (27/29); 59% of patients who achieved <50 copies/mL had <3 copies/mL (16/27). Similar virologic suppression was observed in patients with baseline HIV-1 RNA above or below 100000 copies/mL. HIV-1 RNA and CD4+ cell counts changed from baseline by a median of -3.4 log(10) copies/mL and +172 cells/microL, respectively. One virologic failure occurred at Week 16. Median TRECs/100000 peripheral blood lymphocytes increased 6-fold between baseline and Week 48. Median adherence rates were consistently 100% by self-report and 94% by pill count. Grade 2-4 treatment-related adverse events included dreams (16%), nausea (13%), decreased white cells (8%), dizziness (8%), sleep disorders (8%), and malaise and fatigue (8%). A suspected ABC hypersensitivity reaction occurred in 8% (3/38) of patients.


CONCLUSIONS
COM/ABC/EFV or TZV/EFV produced potent, durable virologic suppression and immunologic benefits, was associated with high adherence rates, and was generally well tolerated.
Ruane
Peter J
PJ
Tower Infectious Diseases Medical Associates, Inc, Los Angeles, California, USA. peter_ruane@towerid.com
Parenti
David M
DM
Margolis
David M
DM
Shepp
David H
DH
Babinchak
Timothy J
TJ
Van Kempen
Amy S
AS
Kauf
Teresa L
TL
Danehower
Susan A
SA
Yau
Linda
L
Hessenthaler
Siegrid M
SM
Goodwin
Diane
D
Hernandez
Jaime E
JE
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D048588:Benzoxazines; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010349:Patient Compliance; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000099227:Abacavir
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D019259:Lamivudine; D010078:Oxazines; D012367:RNA, Viral; D011948:Receptors, Antigen, T-Cell; D015215:Zidovudine; D000099227:Abacavir; C098320:efavirenz