Net benefits of resistance testing directed therapy compared with standard of care in HIV-infected patients with virological failure: A meta-analysis

Ena, Javier; Apodaca, Rosa F. Ruiz de; Amador, Concepción; Benito, Concepción; Pasquau, Francisco

doi:10.1016/s0213-005x(06)73768-5

Cited by 12 publications

(8 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The introduction of highly active antiretroviral therapy (HAART) consisting of nucleoside and non‐nucleoside reverse transcriptase (RT) inhibitors (NRTIs and NNRTIs) and protease inhibitors (PI) has led to significant reductions in HIV morbidity and mortality [Mocroft et al, 2003]. Nevertheless, drug resistance can jeopardize the efficacy of HAART regimens [Turner and Wainberg, 2006; Wainberg and Friedland, 1998]: this has made genotyping drug resistance an essential tool in patient management [Bracciale et al, 2009; Brenner et al, 2002b; Castor et al, 2009; De Luca et al, 2006; Ena et al, 2006; Zaccarelli et al, 2009].…”

Section: Introductionmentioning

confidence: 99%

Subtype diversity associated with the development of HIV‐1 resistance to integrase inhibitors

Brenner

Lowe

Moïsi

et al. 2011

Journal of Medical Virology

View full text Add to dashboard Cite

We used genotypic and phylogenetic analysis to determine integrase diversity among subtypes, and studied natural polymorphisms and mutations implicated in resistance to integrase inhibitors (INI) in treatment-naïve persons (n = 220) and -experienced individuals (n = 24). Phylogenetics revealed 7 and 10% inter-subtype diversity in the integrase and reverse transcriptase (RT)/protease regions, respectively. Integrase sequencing identified a novel A/B recombinant in which all viruses in a male-sex-male (MSM) transmission cluster (n = 12) appeared to possess subtype B in integrase and subtype A in the remainder of the pol region. Natural variations and signature polymorphisms were observed at codon positions 140, 148, 151, 157, and 160 among HIV subtypes. These variations predicted higher genetic barriers to G140S and G140C in subtypes C, CRF02_AG, and A/CRF01_AE, as well as higher genetic barriers toward acquisition of V151I in subtypes CRF02_AG and A/CRF01_AE. The E157Q and E160Q mutational motif was observed in 35% of INI-naïve patients harboring subtype C infections, indicating intra-subtype variations. Thirteen patients failed raltegravir (RAL)-containing regimens within 8 ± 1 months, in association with the major Q148K/R/H and G140A/S (n = 8/24) or N155H (n = 5/24) mutational pathways. Of note, the remaining patients on RAL regimens for 14 ± 3 months harbored no or only minor integrase mutations/polymorphisms (T66I, T97A, H114P, S119P, A124S, G163R, I203M, R263K). These results demonstrate the importance of understanding subtype variability in the development of resistance to INIs.

show abstract

Section: Introductionmentioning

confidence: 99%

Subtype diversity associated with the development of HIV‐1 resistance to integrase inhibitors

Brenner

Lowe

Moïsi

et al. 2011

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…To this end, testing for resistance to antiretrovirals is standard of care, and current guidelines recommend resistance testing for treatment failure during chronic infection. 9,10 Resistance testing is important in guiding the medical management of HIV-1-infected individuals and has been shown to improve virologic response, [11][12][13][14][15] but it remains unclear which method of resistance testing is most useful. Currently, there are three methods to evaluate HIV-1 resistance: genotype, phenotype, and virtual phenotype.…”

Section: Introductionmentioning

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

“…The distribution of patients across CD4 cell counts and viral load at the end of the two-year follow-up period was used to populate the model for projecting long-term costs and clinical outcomes over a patient's lifetime. In this subsequent model, the relative risk of experiencing treatment failure when expert opinion alone was used versus GRT in virologically suppressed patients was derived from published randomized controlled trials [8], [10], [11], [26], [27].…”

Section: Methodsmentioning

confidence: 99%

“…It has been documented in randomized controlled trials that GRT based treatment optimization leads to a higher viral load reduction than standard care alone in treatment-experienced patients [8], [10], [11]. Published clinical guidelines now recommend GRT in patients with antiretroviral treatment failure or in recently infected patients who may have acquired drug-resistant virus [12]–[14].…”

Section: Introductionmentioning

confidence: 99%

Cost-Effectiveness of Genotypic Antiretroviral Resistance Testing in HIV-Infected Patients with Treatment Failure

et al. 2007

View full text Add to dashboard Cite

BackgroundGenotypic antiretroviral resistance testing (GRT) in HIV infection with drug resistant virus is recommended to optimize antiretroviral therapy, in particular in patients with virological failure. We estimated the clinical effect, cost and cost-effectiveness of using GRT as compared to expert opinion in patients with antiretroviral treatment failure.MethodsWe developed a mathematical model of HIV disease to describe disease progression in HIV-infected patients with treatment failure and compared the incremental impact of GRT versus expert opinion to guide antiretroviral therapy. The analysis was conducted from the health care (discount rate 4%) and societal (discount rate 2%) perspective. Outcome measures included life-expectancy, quality-adjusted life-expectancy, health care costs, productivity costs and cost-effectiveness in US Dollars per quality-adjusted life-year (QALY) gained. Clinical and economic data were extracted from the large Swiss HIV Cohort Study and clinical trials.ResultsPatients whose treatment was optimized with GRT versus expert opinion had an increase in discounted life-expectancy and quality-adjusted life-expectancy of three and two weeks, respectively. Health care costs with and without GRT were $US 421,000 and $US 419,000, leading to an incremental cost-effectiveness ratio of $US 35,000 per QALY gained. In the analysis from the societal perspective, GRT versus expert opinion led to an increase in discounted life-expectancy and quality-adjusted life-expectancy of three and four weeks, respectively. Health care costs with and without GRT were $US 551,000 and $US 549,000, respectively. When productivity changes were included in the analysis, GRT was cost-saving.ConclusionsGRT for treatment optimization in HIV-infected patients with treatment failure is a cost-effective use of scarce health care resources and beneficial to the society at large.

show abstract

Net benefits of resistance testing directed therapy compared with standard of care in HIV-infected patients with virological failure: A meta-analysis

Cited by 12 publications

References 21 publications

Subtype diversity associated with the development of HIV‐1 resistance to integrase inhibitors

Subtype diversity associated with the development of HIV‐1 resistance to integrase inhibitors

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

Cost-Effectiveness of Genotypic Antiretroviral Resistance Testing in HIV-Infected Patients with Treatment Failure

Contact Info

Product

Resources

About