translation agency

Changes in viremia in patients receiving an alternating or simultaneous regimen of AZT and ddI as assessed by polymerase chain reaction combined with reverse transcription (RNA-PCR).
Kojima E; Shirasaka T; Anderson B; Chokekijchai S; Steinberg S; Broder
December 30, 1995
Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16;:131.

We quantified HIV-1 virions in serum from 26 patients (pts) with advanced HIV-1 infection randomized to receive an alternating (A) or simultaneous (S) regimen of AZT and ddI ([600 mg/day AZT for 3 weeks and 500 mg/day ddI for 3 weeks] and [300 mg/day AZT and 250 mg/day ddI], respectively) by performing polymerase chain reaction following reverse transcription of isolated viral RNA (RNA-PCR) and the nested PCR method. Thirteen pts on A-AZT/ddI and S-AZT/ddI arms had median entry CD4 counts of 227 and 174 cells/mm3, respectively. A pair of pol gene primers (AS61/62) and the gag primers (SK38/39) were employed and known numbers of HIV-1 virions were used as reference standards. Determination of virion number was not affected by the presence of certain known drug-related nucleotide substitutions including Asp-67 leads to Asn, Lys-70 leads to Arg, Leu-74 leads to Val, Lys-103 leads to Asp, Tyr-181 leads to Cys, Thr-215 leads to Tyr and Lys-219 leads to Glin, alone or in combination, when either of the primer pairs was used. Both A-AZT/ddI and S-AZT/ddI arms had a significant reduction in serum RNA copy numbers; however, the magnitude of the reduction (copy number at each time point/copy number at entry) was greater in S-AZT/ddI arm than in A-AZT/ddI arm during the first 2-3 months (p=0.013 at week 2; p=0.011 at week 9). After 1 year, the RNA copy numbers were still significantly lower than the entry levels in both arms (p=0.001 for A-AZT/ddI; p=0.016 for S-AZT/ddI), while there was no longer a statistically significant difference between the arms (p=0.48). The majority of pts developed the AZT-related mutation at codon 215 by 1 year in both arms. By contrast, the ddI-related Leu-74 leads to Val mutation was not detected or only transiently detected throughout the study. Our data suggest that S-AZT/ddI is more active in vivo than A-AZT/ddI and that the inclusion of AZT may block or retard the emergence of the Leu-74 leads to Val mutation. The data do not address whether the combination therapy is superior, inferior, or equivalent to monotherapy. Determination of the overall durability of the anti-viremic effect of both regimens and clinical implications of the results require further research.

Biological Availability Child Child, Preschool Clinical Trials, Phase I Human HIV Infections/*DRUG THERAPY Infant Zalcitabine/BLOOD/PHARMACOKINETICS/*THERAPEUTIC USE ABSTRACT