Responses to Switching to Maraviroc-Based Antiretroviral Therapy in Treated Patients with Suppressed Plasma HIV-1-RNA Load

Vitiello, Paola; Brudney, Daniel; MacCartney, Malcolm; Garcia, Anice; Smith, Colette; Marshall, Neal; Johnson, Margaret; Geretti, Anna María

doi:10.1159/000332023

Cited by 11 publications

(6 citation statements)

References 27 publications

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“…18 However, our case file included only patients on successful first-line therapy, who may not be representative of the more likely use of maraviroc as simplification strategy in more experienced patients. In addition, it is important to note that our patients were not subsequently treated with maraviroc, so it was not possible to verify the predictive power of genotypic coreceptor tropism testing with PBMC DNA.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal analysis of HIV-1 coreceptor tropism by single and triplicate HIV-1 RNA and DNA sequencing in patients undergoing successful first-line antiretroviral therapy

Meini¹,

Rossetti²,

Bianco³

et al. 2013

Journal of Antimicrobial Chemotherapy

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ObjectivesMaraviroc has been shown to be effective in patients harbouring CCR5-tropic HIV-1. While this CCR5 antagonist has initially been used in salvage therapy, its excellent safety profile makes it ideal for antiretroviral treatment simplification strategies in patients with suppressed plasma viraemia. The aim of this study was to compare HIV-1 tropism as detected in baseline plasma RNA and peripheral blood mononuclear cell (PBMC) DNA prior to first-line therapy and to analyse tropism evolution while on successful treatment.MethodsHIV-1 tropism was determined using triplicate genotypic testing combined with geno2pheno[coreceptor] analysis at a 10% false positive rate in 42 patients. Paired pre-treatment plasma RNA and PBMC DNA and two subsequent PBMC DNA samples (the first obtained after reaching undetectable plasma HIV-1 RNA and the second after at least 2 years of suppression of plasma viraemia) were evaluated.ResultsCoreceptor tropism was completely concordant in paired pre-treatment RNA and DNA, with 26.2% of HIV-1 sequences predicted to be non-CCR5-tropic. During follow-up, coreceptor tropism switches were detected in 4 (9.5%) patients without any preferential direction. Although false positive rate discrepancies within triplicates were common, the rate of discordance of coreceptor tropism assignment among triplicate results in this mostly CCR5-tropic dataset was only 2.1%, questioning the added value of triplicate testing compared with single testing.ConclusionsHIV-1 coreceptor tropism changes during virologically successful first-line treatment are infrequent. HIV-1 DNA analysis may thus support the choice of a CCR5 antagonist in treatment switch strategies; however, maraviroc treatment outcome data are required to confirm this option.

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Section: Discussionmentioning

confidence: 99%

Longitudinal analysis of HIV-1 coreceptor tropism by single and triplicate HIV-1 RNA and DNA sequencing in patients undergoing successful first-line antiretroviral therapy

Meini¹,

Rossetti²,

Bianco³

et al. 2013

Journal of Antimicrobial Chemotherapy

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“…In addition, the medication requires twice daily dosing, which is likely to cause an adherence issue [11]. There is, however, considerable evidence that for individuals requiring a switch in medications (due to toxicity with other regimens, poor tolerability with other regimens, or low CD4 counts), maraviroc may be advantageous [12,13]. More recently, there is considerable interest in another CCR5 antagonist, cenicriviroc, which is currently in clinical trials [14,15].…”

Section: Clinical Use Of Ccr5 Antagonists and Integrase Inhibitorsmentioning

confidence: 99%

New Antiretroviral Therapies and Potential Drug Interactions in HIVInfected Drug Abusers

Cory¹

2014

J Antivir Antiretrovir

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Substance abuse remains a major obstacle in treating HIV-infected patients. The high prevalence of drug use is responsible for lack of adherence and severe drug interactions to antiretroviral therapy in HIV positive individuals. Over the past decade, newer therapies for HIV have been developed by targeting different stages of HIV life cycle. Of importance, targeting initial binding with receptor and genome integration by CCR5 antagonists and integrase inhibitors, respectively have been effective in reducing viral loads in clinical trials. However, most of these recently approved or investigational antiretroviral drugs are also metabolized by cytochrome P450 (CYP) enzymes. Thus, substance abuse mediated changes in level of CYP enzymes (induction or inhibition) may result in severe drug interactions, failure of therapy, rapid progression to AIDS, and increased mortality in HIV patients who are treated with regimens containing CCR5 antagonists and integrase inhibitors. In this review, we have discussed the pharmacokinetic data, efficacy, lack of adherence to these therapies in drug abusers, and CYP-mediated potential drug interactions for CCR5 antagonists and integrase inhibitors in HIV-infected drug abusers.

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“…Results from the smaller-scaled maraviroc “switch” studies demonstrated safety and efficacy [28]–[30], and it is hopeful that larger-scaled multicenter clinical trials such as the recruiting MARCH study [31] will shed more light on this knowledge gap. A second approach, the examination of pre-suppression HIV tropism from RNA, is considered in a few treatment guidelines [24], [26] based on small-scale studies that have shown limited evolution of plasma RNA tropism during HAART [10], [12], [32], [33].…”

Section: Introductionmentioning

confidence: 99%

Limited Evolution of Inferred HIV-1 Tropism while Viremia Is Undetectable during Standard HAART Therapy

Lee

Dong

et al. 2014

PLoS ONE

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BackgroundHIV patients on suppressive antiretroviral therapy have undetectable viremia making it impossible to screen plasma HIV tropism if regimen change is required during suppression. We investigated the prevalence and predictors of tropism switch from CCR5-using (“R5”) to non-CCR5-using (“non-R5”) before and after viral suppression in the initially therapy-naïve HOMER cohort from British Columbia, Canada.MethodsWe compared pre-therapy and post-suppression viral genotypic tropism in patients who initiated on PI/NNRTI-based antiretroviral regimens between 1996-1999 (n = 462). Virologic suppression was defined as having two consecutive viral loads of <500 copies/mL, which was the sensitivity limit of most viral load assays at the time. Viral tropism was inferred by V3-loop-population-sequencing and geno2pheno[coreceptor] with cutoff at 5.75% false positive rate (FPR).ResultsWhen virologic suppression was defined as two-consecutive viral loads <500 copies/mL, 34 (9%) of the 397 patients with pre-therapy R5-virus switched to non-R5 at viral load rebound after a median of 19 months (IQR 8–41 months) of undetectable viremia. Duration of viral load suppression was not a predictor of switch, but lower CD4 count during suppression (median 400 versus 250 cells/mL) and an increased prevalence of pre-therapy non-R5 HIV by “deep” sequencing (median 0.2% versus 3.2%) were independently associated with switch (p = 0.03 and p<0.0001, respectively).ConclusionR5-to-non-R5 tropism switches in plasma virus after undetectable viremia were relatively rare events especially among patients with higher CD4 counts during virologic suppression. Our study supports the use of pre-suppression tropism results if maraviroc is being considered during virologic suppression in this subgroup of patients.

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Responses to Switching to Maraviroc-Based Antiretroviral Therapy in Treated Patients with Suppressed Plasma HIV-1-RNA Load

Cited by 11 publications

References 27 publications

Longitudinal analysis of HIV-1 coreceptor tropism by single and triplicate HIV-1 RNA and DNA sequencing in patients undergoing successful first-line antiretroviral therapy

Longitudinal analysis of HIV-1 coreceptor tropism by single and triplicate HIV-1 RNA and DNA sequencing in patients undergoing successful first-line antiretroviral therapy

New Antiretroviral Therapies and Potential Drug Interactions in HIVInfected Drug Abusers

Limited Evolution of Inferred HIV-1 Tropism while Viremia Is Undetectable during Standard HAART Therapy

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