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HIV-1 viral load, phenotype, and resistance in a subset of drug-naive participants from the Delta trial
Ist Teil von
The Lancet (British edition), 1997-10, Vol.350 (9083), p.983-990
Ort / Verlag
London: Elsevier Ltd
Erscheinungsjahr
1997
Link zum Volltext
Quelle
EBSCOhost Business Source Ultimate
Beschreibungen/Notizen
The Delta trial showed that combination therapy (zidovudine plus didanosine and zidovudine plus zalcitabine) substantially lengthened life and reduced disease progression compared with zidovudine monotherapy. We did a nested virological study in three countries (France, the Netherlands, and the UK) to investigate changes in markers for viral load and antiretroviral-drug resistance during therapy.
240 zidovudine-naive HIV-1-infected patients were randomly assigned zidovudine only (n=87), zidovudine plus didanosine (n=80), or zidovudine plus zalcitabine (n=73). Viral load in peripheral-blood mononuclear cells and plasma was measured by quantitative culture. Plasma HIV-1 RNA was measured by reverse-transcriptase PCR amplification, and serum p24 antigen by ELISA. Resistance to antiretroviral drugs was measured phenotypically by culture and genotypically by detection and quantification of drug-related point mutations in the pol gene. Analyses were done by intention to treat.
The reduction in viral load was greatest 4-12 weeks after the start of therapy and was most pronounced in the combination-therapy study groups (median reductions of RNA at 4 weeks 1·58, 1·28, and 0·49 Iog10 copies/ml for zidovudine plus didanosine, zidovudine plus zalcitabine, and zidovudine only, respectively). RNA levels at 8 weeks were predictive of disease progression and death after allowance for baseline values.
At 48 weeks, the proportion of participants with phenotypic zidovudine resistance was similar in all three groups: didanosine and zalcitabine resistance were rare; zidovudine genomic resistance correlated with phenotypic resistance (r=0·54, p < 0·0001) and developed earlier in the combined-therapy groups. However, participants in the zidovudine monotherapy group had higher circulating loads of resistant virus than those in the combined-therapy groups.
Combined antiretroviral therapy was more efficient at lowering virus load than monotherapy. Although zidovudine resistance was common in monotherapy and combined-therapy groups, circulating concentrations of resistant virus were substantially lower in the combination groups, which is likely to be a result of the continued antiviral activity of didanosine or zalcitabine.