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Genotypic Resistance Testing Benefits:
Response to 'Limited benefit of antiretroviral resistance testing in treatment-experienced patients: a meta-analysis'
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AIDS: Volume 19(11) 22 July 2005
LETTER TO THE EDITOR
Badri, Sheila Ma,b,c; Adeyemi, Oluwatoyin Ma,b,c; Max, Blake Ec,d; Barker, David Ea,b,c
aDivision of Infectious Diseases, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA
bRush Medical College, Chicago, IL, USA
cCORE Center, Cook County Bureau of Health, Chicago, IL, USA
dUniversity of Illinois, Chicago College of Pharmacy, Chicago, IL, USA.
Received 2 March, 2005
Accepted 15 April, 2005
We read with interest about the meta-analysis performed by Panidou et al. [1] in a previous issue of AIDS, which appeared to demonstrate the limited utility of antiretroviral resistance testing and expert advice. We believe that this meta-analysis has several limitations, and that the conclusions reached by the authors cannot be generalized to all clinical situations. First, the analysis was not controlled for the number of active drugs available to the patients. More recent studies have documented this variable as a genotypic or phenotypic sensitivity score, which is unmeasured in the standard of care arms. In addition, studies included in the meta-analysis had a high proportion of patients who had failed several regimens and had very few active agents available to them, especially in the era studied 1997-1998 [2-4].
We have experience reviewing over 1000 genotypes for a large urban public HIV clinic in the United States. In our clinic, approximately one patient in four tested by genotypic resistance testing (GRT) has complete resistance to two or more classes of medications. The lack of useful agents would dampen the ability of any resistance testing method to affect virological outcome as we recently demonstrated [5]. Our experience suggests that patients who have failed one or two regimens benefit more from GRT than patients with a greater number of previous regimens, which logically correlates with a decreasing number of available antiretroviral agents. Similarly, there appears to be a range of the number of previous regimen failures in which expert advice contributes more and more as medication choices diminish, and then decreases again as the number of fully active choices dwindles towards zero. In our study, we demonstrated a highly statistically significant benefit for GRT plus expert advice versus GRT alone [6]. The study was not reviewed for meta-analysis, as it was a retrospective study. However, the study represents real world outcomes in our clinic. We agree with Panidou et al. [1] that phenotypic antiretroviral resistance testing (PART) is not very useful, and suspect that this is due to the tendency of PART and virtual PART to overestimate the activity of some nucleosides, as demonstrated by Haubrich et al. [7].
In conclusion, our experience suggests that GRT and expert advice are most useful for patients with limited antiretroviral exposure and fewer resistance mutations in choosing antiretroviral regimens for patients failing virologically on highly active antiretroviral therapy. Further studies are needed better to define the utility of GRT in patients who are highly drug experienced.
References
1. Panidou ET, Trikalinos TA, Ioannisis JPA. Limited benefit of antiretroviral resistance testing in treatment-experienced patients: a meta-analysis. AIDS 2004; 18:2153-2161.
2. Durant J, Clevenbergh P, Halfon P, Delgiudice P, Porsin S, Simonet P, et al. Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomized controlled trial. Lancet 1999; 353:2195-2199.
3. Melnick D, Rosenthal J, Cameron M, Snyder M, Griffith-Howard S, Hertogs K, et al. Impact of phenotypic antiretroviral resistance testing on the response to salvage antiretroviral therapy (ART) in heavily experienced patients. In: Seventh Conference on Retroviruses and Opportunistic Infections. San Francisco, February 2000 [Abstract 786].
4. Baxter JD, Mayers DL, Wentworth DN, Neaton JD, Hoover ML, Winters MA, et al. A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. CPCRA 046 Study Team for the Terry Beirn Community Programs for Clinical Research on AIDS. AIDS 2000; 14:F83-F93.
5. Badri SM, Adeyemi OM, Max BE, Hota BN, Barker DE. Does repeat genotypic resistance testing in patients with baseline three class resistance and virologic treatment failure provide new information? In: 42nd IDSA Conference. Boston, Massachusetts, 2004 [Abstract #908].
6. Badri SM, Adeyemi OM, Max BE, Zagorski BM, Barker DE. How does expert advice impact genotypic resistance testing in clinical practice? Clin Infect Dis 2003; 37:708-713.
7. Haubrich RH, Keiser P, Kemper C, Witt M, Leedom J, Forthol D, et al. CCTG 575: a randomized, prospective study of phenotype testine (PHENO) versus standard of care (SOC) for patients failing antiretroviral therapy (ARV). In: First International AIDS Society Conference on HIV Pathogenesis and Treatment. Buenos Aires, 2001 [Abstract 127].
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