5th Conference on Retroviruses and Opportunistic Infections


Chicago, IL - February 1-5, 1998



COMBINATION ZIDOVUDINE (ZDV) AND STAVUDINE (D4T) THERAPY VERSUS OTHER NUCLEOSIDES: REPORT OF TWO RANDOMIZED TRIALS (ACTG 290 AND 298)

Conf Retroviruses Opportunistic Infect 1998 Feb 1-5; 5th:79 (abstract no. 2)

Havlir DV, Friedland G, Pollard R, Tierney C, Smeaton L, Fox L, Richman DD
NIAID Sponsored AIDS Clinical Trials Group, Bethesda, MD.

The combination of ZDV and d4T in vitro can exhibit pharmacologic antagonism and antiviral synergy depending on the conditions. To evaluate in vivo effects of these drug combinations, we initiated 1) a randomized study comparing 4 regimens- ZDV/d4T, d4T, ZDV/ddI, ddI- in ZDV experienced subjects with CD4 300-600 cells/mm3 (ACTG 290) and 2) a randomized study comparing d4T, d4T/ZDV, and 3TC/ZDV in treatment naïve subjects (ACTG 298). In ACTG 290, 144 subjects with median CD4 of 401 cells/mm3 and HIV RNA of 3.8 log copies/mL were followed for a median of 46 weeks. In ACTG 298, 128 subjects with a median CD4 of 407 cells/mm3 and HIV RNA of 4.0 log were followed for a median of 36 weeks.

ACTG 290 (48 weeks) ACTG 298 (48 weeks)
Regimen ΔCD4
(N=61)		 ΔRNA
(N=50)		 <500 RNA
(N=50)		 Regimen ΔCD4
(N=46)		 ΔRNA
(N=38)		 <500 RNA
N=38)
ZDV/d4T -45 0.01 0% ZDV/d4T +14 -0.33 8%
d4T +20 0.13 6% d4T +65 -0.47 31%
ZDV/ddI +5 -0.46 36% ZDV/3TC +101 -0.91 38%
ddI +70 -0.44 46%  
ΔRNA: ddI vs d4T arms (p=0.0008)
ddI vs ddI/ZDV (p<0.05)		 ΔRNA: d4T vs ZDV/3TC (p=0.03)
ZDV/d4T vs ZDV/3TC (p=0.02)

These data suggest a) ZDV/d4T does not have more potent antiviral effect than d4T alone, probably due to pharmacologic antagonism. ZDV/d4T is associated with CD4 cell decline in ZDV experienced patients. ZDV/d4T therefore should not be used in combination; b) ddI produces greater viral suppression than d4T in ZDV experienced patients; c) ZDV/ddI was not associated with virologic activity discernable from ddI in ZDV experienced patients.

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Keywords: AEGIS, Stavudine, Zidovudine, Didanosine, Lamivudine, Anti-HIV Agents, Reverse Transcriptase Inhibitors, HIV Infections, HIV Protease Inhibitors, HIV, HIV-1 Reverse Transcriptase, Antigens, CD4, In Vitro, Human, therapy, drug therapy, AIDS

1998-02-01
2

Copyright © 1998 - Foundation for Retrovirology and Human Health (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed from National Library of Medicine.