Phenotypic or genotypic resistance testing for choosing antiretroviral therapy after treatment failure: a randomized trial

Meynard, Jean-Luc; Vray, Muriel; Morand‐Joubert, Laurence; Race, Esther; Descamps, Diane; Peytavin, Gilles; Matheron, Sophie; Lamotte, C.; Guiramand, Sonia; Costagliola, Dominique; Brun‐Vézinet, Françoise; Clavel, François; Girard, Pierre‐Marie

doi:10.1097/00002030-200203290-00008

Cited by 208 publications

(174 citation statements)

References 22 publications

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…Nevertheless, the advantage of genotyping information was lost after 12 months. These findings were similar to results from previous randomized studies [5][6][7][8][9], indicating that resistance testing helps to choose more effective regimens in patients failing previous antiretroviral regimens. Although group 2 patients had fewer mutations and viral samples with no mutations (wild type virus, Table 5), this group received less active drugs (Figure 2), thus emphasizing the importance of genotyping in salvage therapy.…”

Section: Discussionsupporting

confidence: 88%

See 1 more Smart Citation

Treatment switch guided by HIV-1 genotyping in Brazil

Tupinambás¹,

Ribeiro²,

Aleixo³

et al. 2006

Braz J Infect Dis

View full text Add to dashboard Cite

We assessed the performance of HIV-1 genotyping tests in rescue therapy. Patients were divided into two groups: group 1 (genotyped), included those switching to new antiretroviral drugs based on HIV-1 genotyping data, and group 2 (standard of care -SOC), comprised those in rescue therapy who had not used this test. This was an open and non-randomized study, with 74 patients, followed up for a mean period of 12 months, from February 2002 to May 2003. The groups differed in the duration of antiretroviral use, experience with diverse drug classes (non-nucleoside reverse transcriptase inhibitors and protease inhibitors) and viral load <2.6 log 10 copies/mL at any time during treatment. In 23 patients (group 1), the switch in antiretroviral (ARV) regimen was based on genotyping data; this test was not used for 51 patients (group 2). Two CD 4 + lymphocyte counts and viral load counts were made for each patient during the study. Data from the pharmacy where patients received antiretroviral agents, medical charts, and direct interviews with patients to assess compliance to treatment, were analyzed. In the genotyped group, the average drop in viral load was 2.8 log 10 , compared with a 1.5 log 10 difference in group 2; the difference was significant in the first assessment performed six months after switching (p=0.001). Considering the patients with viral load < 2.6 log 10 (400 copies/mL) after switching, the patients in group 1 had a better performance in the first assessment (73.9% versus 31.1% in groups 1 and 2, respectively); this difference was significant (p=0.001). In multivariate analysis, the variables associated with a greater drop in viral load in the first assessment were the patients whose switching was based on genotyping (group 1), those with a past history of viral load < 2.6 log 10 and correct use of antiretroviral agents. In conclusion, the genotyping test and adherence were found to be independent factors for success in the management of patients who failed treatment.

show abstract

Section: Discussionsupporting

confidence: 88%

“…Among others, the GART [6] and the NARVAL [7] studies demonstrated the usefulness of HIV genotyping, compared to phenotyping. The Argenta [8] and Havana [9] studies evaluated the effects of compliance and expert advice on HIV-1 genotyping.…”

mentioning

confidence: 99%

Treatment switch guided by HIV-1 genotyping in Brazil

Tupinambás¹,

Ribeiro²,

Aleixo³

et al. 2006

Braz J Infect Dis

View full text Add to dashboard Cite

show abstract

“…18,25,[30][31][32][33][34][35][36][37][38] Our analysis adds to several trials that have attempted to compare directly these two different methods. For the majority of these studies, the clinical outcomes have been similar regardless of the methodology: phenotype vs. virtual phenotype 39,40 and genotype vs. virtual phenotype; 33,41 however, in a subset of HIV-1-infected subjects with PI experience, a greater proportion of subjects achieved virologic suppression using genotypic testing vs. phenotypic testing 42 to guide antiviral selection. Although the optimum interpretation system has yet to be determined, our data suggest that the genotypic susceptibility scores perform similarly to the phenotypic susceptibility score in being correlated with virologic outcome.…”

Section: Comparison Of the Predictive Value Of Gss Versus Pssmentioning

confidence: 99%

Genotypic Susceptibility Scores and HIV Type 1 RNA Responses in Treatment-Experienced Subjects with HIV Type 1 Infection

Anderson

Jiang

Ding

et al. 2008

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

This study compared the role of genotypic susceptibility scores (GSS) as a predictor of virologic response in a group (n = 234) of HIV-infected, protease inhibitor (PI)-experienced subjects. Two scoring methods [discrete genotypic susceptibility score (dGSS) and continuous genotypic susceptibility score (cGSS)] were developed. Each drug in the subject's regimen was given a binary susceptibility score using Stanford inferred drug resistance scores to calculate the dGSS. In contrast to the dGSS, the cGSS model was designed to reflect partial susceptibility to a drug. Both GSS were independent predictors of week 16 virologic response. We also compared the GSS to a phenotypic susceptibility score (PSS) model on a subset of subjects that had both GSS and PSS performed, and found that both models were predictive of virologic response. Genotypic analyses at enrollment showed that subjects who were virologic nonresponders at week 16 revealed enrichment of several mutated codons associated with nucleoside reverse transcriptase inhibitors (NRTI) (codons 67, 69, 70, 118, 215, and 219) or PI resistance (codons 10, 24, 71, 73, and 88) compared to subjects who were virologic responders. Regression analyses revealed that protease mutations at codons 24 and 90 were most predictive of poor virologic response, whereas mutations at 82 were associated with enhanced virologic response. Certain NNRTI-associated mutations, such as K103N, were rapidly selected in the absence of NRTIs. These data indicate that GSS may be a useful tool in selecting drug regimens in HIV-1-infected subjects to maximize virologic response and improve treatment outcomes.

show abstract

“…Plasma HIV-1 RNA was <200 copies/mL at week 12 in 35% of patients in the phenotyping group, 44% in the genotyping group, and 36% in the standard-of-care group (phenotyping versus standard-of-care, P = 0.918; genotyping versus standard-of-care, P = 0.120). In a subset analysis of 179 patients experiencing a first protease inhibitor failure, the percentage of patients achieving HIV-1 RNA <200 copies/mL was significantly higher in the genotyping group (65%) than in the phenotyping (45%) and the standard-of-care groups (45%) (genotyping versus standard-of-care, P = 0.022) (13). Another study involving 450 participants failed to show that an overall improvement in the time to refractory treatment failure was associated with routine access to either genotype or phenotype resistance testing when used in a cohort of patients with a large number of enrollees with limited previous ART exposure (19).…”

Section: Discussionmentioning

confidence: 94%

“…Prospective studies have shown shortterm improvement in virus load suppression when genotype testing was used to guide therapy in naive and experienced patients (8)(9)(10)(11). Other recent studies have shown either transient improvement (12) or no benefit (13,14) associated with the use of genotype testing, i.e., resistance assays.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of genotype resistance testing for salvage antiretroviral therapy at AIDS care centers from Ribeirão Preto, São Paulo, Brazil

Neto

Colares

Fonseca

2008

Braz J Med Biol Res

View full text Add to dashboard Cite

The availability of HIV-1 genotype resistance testing (GRT) to clinicians has been insufficiently studied outside randomized clinical trials. The present study evaluated the outcome of salvage antiretroviral therapy (ART) recommended by an expert physician based on GRT in a non-clinical trial setting in Ribeirão Preto, Brazil. A prospective, open, nonrandomized study evaluating easy access to GRT at six Brazilian AIDS Clinics was carried out. This cooperative study analyzed the efficacy of treatment recommended to patients whose salvage ART was guided by GRT with that of treatment with ART based only on previous ART history. A total of 112 patients with ART failure were included in the study, and 77 of them were submitted to GRT. The median CD4 cell count and viral load for these 77 patients at baseline were (mean ± SD) 252.1 ± 157.4 cells/µL and 4.60 ± 0.5 log 10 HIV RNA copies/mL, respectively. The access time, i.e., the time elapsed between ordering the GRT and receiving the result was, on average, 71.9 ± 37.3 days. The study results demonstrated that access to GRT followed by expert recommendations did not improve the time to persistent treatment failure when compared to conventional salvage ART. Access to GRT in this Brazilian community health care setting did not improve the long-term virologic outcomes of HIV-infected patients experiencing treatment failure. This result is probably related to the long time required to implement ART guided by GRT.

show abstract

Phenotypic or genotypic resistance testing for choosing antiretroviral therapy after treatment failure: a randomized trial

Abstract: Overall, resistance assays did not demonstrate benefit over standard of care. In patients with the most limited protease inhibitor experience, a significant benefit was observed in the genotyping arm.

Cited by 208 publications

References 22 publications

Treatment switch guided by HIV-1 genotyping in Brazil

Treatment switch guided by HIV-1 genotyping in Brazil

Genotypic Susceptibility Scores and HIV Type 1 RNA Responses in Treatment-Experienced Subjects with HIV Type 1 Infection

Evaluation of genotype resistance testing for salvage antiretroviral therapy at AIDS care centers from Ribeirão Preto, São Paulo, Brazil

Contact Info

Product

Resources

About