Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2006 Jul 28;1(3):e18.
doi: 10.1371/journal.pctr.0010018.

A randomised trial comparing genotypic and virtual phenotypic interpretation of HIV drug resistance: the CREST study

Gillian Hales  1 , Chris Birch, Suzanne Crowe, Cassy Workman, Jennifer F Hoy, Matthew G Law, Anthony D Kelleher, Douglas Lincoln, Sean Emery; CREST investigators
Affiliations

A randomised trial comparing genotypic and virtual phenotypic interpretation of HIV drug resistance: the CREST study

Gillian Hales et al. PLoS Clin Trials. .

Abstract

Objectives: The aim of this study was to compare the efficacy of different HIV drug resistance test reports (genotype and virtual phenotype) in patients who were changing their antiretroviral therapy (ART).

Design: Randomised, open-label trial with 48-week followup.

Setting: The study was conducted in a network of primary healthcare sites in Australia and New Zealand.

Participants: Patients failing current ART with plasma HIV RNA > 2000 copies/mL who wished to change their current ART were eligible. Subjects were required to be > 18 years of age, previously treated with ART, have no intercurrent illnesses requiring active therapy, and to have provided written informed consent.

Interventions: Eligible subjects were randomly assigned to receive a genotype (group A) or genotype plus virtual phenotype (group B) prior to selection of their new antiretroviral regimen.

Outcome measures: Patient groups were compared for patterns of ART selection and surrogate outcomes (plasma viral load and CD4 counts) on an intention-to-treat basis over a 48-week period.

Results: Three hundred and twenty seven patients completing >or= one month of followup were included in these analyses. Resistance tests were the primary means by which ART regimens were selected (group A: 64%, group B: 62%; p = 0.32). At 48 weeks, there were no significant differences between the groups for mean change from baseline plasma HIV RNA (group A: 0.68 log copies/mL, group B: 0.58 log copies/mL; p = 0.23) and mean change from baseline CD4+ cell count (group A: 37 cells/mm(3), group B: 50 cells/mm(3); p = 0.28).

Conclusions: In the absence of clear demonstrated benefits arising from the use of the virtual phenotype interpretation, this study suggests resistance testing using genotyping linked to a reliable interpretive algorithm is adequate for the management of HIV infection.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Participant Disposition
Figure 2
Figure 2. Comparison of Virological Response by Study Arm
Figure 3
Figure 3. Comparison of Genotype and Virtual Phenotype Reports for NRTIs
Figure 4
Figure 4. Comparison of Genotype and Virtual Phenotype Reports for PIs
Figure 5
Figure 5. Comparison of Genotype and Virtual Phenotype Reports for NNRTIs
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Larder BA, Darby G, Richman D. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science. 1989;243:1731–1734. - PubMed
    1. Smith M, Salomon H, Wainberg MA. Development and significance of nucleoside drug resistance in infection caused by the human immunodeficiency virus type 1. Clin Invest Med. 1994;17((3)):226–243. - PubMed
    1. Mayers DL. Prevalence and incidence of resistance to zidovudine and other antiretroviral drugs. Am J Med. 1997;102:70–75. - PubMed
    1. Condra JH, Schleif WA, Blahy OM, et al. In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature. 1995;374:569–571. - PubMed
    1. Hirsch MS, Conway B, D'Aquila RT, et al. Antiretroviral drug resistance testing in adults with HIV infection: Implications for clinical management. International AIDS Society—USA Panel. JAMA. 1998;24:1984–1991. - PubMed