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