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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).




 

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



 




Information in this article was accurate in December 30, 1995. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.