Intensification of stable background therapy with abacavir in antiretroviral therapy experienced patients: 48-week data from a randomized, double-blind trial.
OBJECTIVE
To evaluate antiretroviral efficacy of abacavir (ABC) in antiretroviral-experienced patients, by intensifying current antiretroviral therapy (CART) in patients with stable, detectable plasma HIV-1 RNA.


METHODS
Thirty-two European centres recruited HIV-1 positive patients with < or = 36 months of CART experience. Patients were randomized to receive either ABC (300 mg twice daily) plus CART (ABC + CART) or ABC placebo plus CART (CART). We assessed efficacy as measured by plasma HIV-1 RNA and CD4+ cell counts and safety at baseline, weeks 2, 4 and every 4 weeks thereafter until week 48. Protocol-defined criteria enabled patients to switch to open-label ABC from week 8 onwards.


RESULTS
Ninety-two patients with a median plasma of 3.66 log10 HIV-1 RNA copies/mL and a median CD4+ cell count of 408 cells/microL were randomized to ABC + CART and 93 patients with a median plasma of 3.52 log10 HIV-1 RNA copies/mL and a median CD4+ cell count of 411 cells/microL were randomized to CART. From weeks 8-48, 11 (12%) patients in the ABC + CART group and 34 (37%) patients in the CART group switched to open-label ABC. At week 48, significantly more patients on ABC + CART (23/92, 25%) than on CART (5/93, 5%) had plasma < or =400 HIV-1 RNA copies/mL (P < 0.001, intent-to-treat switch = failure population). Neither duration of previous nucleoside reverse transcriptase inhibitor treatment (up to 18 months) nor prior lamivudine therapy affected ABC efficacy. In the ABC + CART group, 16/25 (64%) patients with the M184V mutation at baseline had < or = 400 copies/mL or a decrease > or = 1 log10 copies/mL at week 16. More patients (19/46, 41%) with baseline viral load < or = 5000 copies/mL had plasma < 400 HIV-1 RNA copies/mL at 48 weeks than those > 5000 copies/mL (4/44, 9%). CD4+ cell counts increased by 102 cells/microL and 57 cells/microL at week 48 for the ABC + CART and CART groups, respectively (intent-to-treat, switch included). ABC addition had minimal impact on the CART safety profile.


CONCLUSIONS
ABC intensification, in CART-experienced patients with low viral loads and limited reverse transcriptase mutations, most of whom had previously been on double-therapy, resulted in a significant and durable plasma HIV-1 reduction and concomitant increase in CD4+ cell count. The presence of M184V at baseline had minimal impact on the efficacy of ABC.
Katlama
C
C
Hôpital de la Pitie Salpetriere, Paris, France.
Clotet
B
B
Plettenberg
A
A
Jost
J
J
Arasteh
K
K
Bernasconi
E
E
Jeantils
V
V
Cutrell
A
A
Stone
C
C
Purdon
S
S
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019562:Viral Load; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir