Document 2854
 DOCN  M94A2854
 TI    HIV-1 viremia changes and development of drug-related viral mutations in
       patients (pts) receiving long-term combination therapy with AZT/ddI.
 DT    9412
 AU    Kojima E; Shirasaka T; Anderson BD; Chokekijchal S; Steinberg S; Broder
       S; Yarchoan R; Mitsuya H; National Cancer Institute, Bethesda, MD.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):21 (abstract no. 056B). Unique
       Identifier : AIDSLINE ICA10/94369721
 AB    OBJECTIVE: To investigate viremia changes and the development of
       drug-related viral mutations in pts with advanced HIV-1 infection
       receiving AZT and ddl in combination. METHODS: HIV-1 virion numbers in
       serum (VPs) from a subset of 26 pts randomized to received AZT and ddl
       in an alternating (A: 600 mg/day AZT for 3 wk and 500 mg/day ddl for 3
       wk) or simultaneous (S: 300 mg AZT plus 250 mg ddl daily) regimen (see
       J. Infect. Dis. 169:9, 1994) were determined by PCR following reverse
       transcription of viral RNA. RESULTS: 13 pts in A and S arms had median
       entry CD4 counts of 227 and 174/mm3, respectively. Both arms had a
       significant reduction in VPs during the first 2-3 mos (approximately 8x
       (p = 0.0002) and approximately 31x (p = 0.0005) lower than at entry for
       A and S, respectively); however, the reduction was greater in S arm than
       in A arm (p = 0.0051 both at wk 2 and 9). After 1 yr, VPs remained
       significantly lower in both arms (13x (p = 0.0005) for A; 9x (p =
       0.0024) for S), but there was no difference between the arms (p = 0.37).
       The reduction was still present after 1.5 and 2 yrs (5x and 19x lower (p
       = 0.039 and 0.039) for A; 8x and 8x lower (p = 0.0049 and 0.014) for S,
       respectively). 18/26 (69%) pts developed the mutation at codon 215 by 1
       yr. By contrast, only 1/26 (4%) pts had the Leu74-->Val mutation,
       although 8/9 (89%) pts receiving ddl monotherapy in other NCl trials
       developed this mutation (p = 0.00005). DISCUSSION/CONCLUSIONS: The data
       suggest that S is more active than A in vivo for 2 to 3 mos and that the
       inclusion of AZT blocks or retards the emergence of the Leu74-->Val
       mutation. Determination of the overall durability of the anti-viremic
       effect of A and S regimens and clinical implications of the results
       require further research.
 DE    Acquired Immunodeficiency Syndrome/*DRUG THERAPY/MICROBIOLOGY
       Didanosine/*ADMINISTRATION & DOSAGE  Drug Administration Schedule  Drug
       Therapy, Combination  Human  HIV-1/*DRUG EFFECTS/GENETICS  Mutation/DRUG
       EFFECTS  Viremia/DRUG THERAPY  Virion/DRUG EFFECTS
       Zidovudine/*ADMINISTRATION & DOSAGE  CLINICAL TRIAL  MEETING ABSTRACT
       RANDOMIZED CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).