Maraviroc versus Efavirenz, Both in Combination with Zidovudine‐Lamivudine, for the Treatment of Antiretroviral‐Naive Subjects with CCR5‐Tropic HIV‐1 Infection

Cooper, David A.; Heera, Jayvant; Goodrich, James; Tawadrous, Margaret; Saag, Michael S.; DeJesus, Edwin; Clumeck, Nathan; Walmsley, Sharon; Ting, Naitee; Coakley, Eoin; Reeves, Jacqueline D.; Reyes‐Terán, Gustavo; Westby, Mike; Ryst, Elna van der; Ive, Prudence; Mohapi, Lerato; Mingrone, Horacio; Horban, Andrzéj; Hackman, Frances; Sullivan, John; Mayer, Howard

doi:10.1086/650697

Cited by 241 publications

(239 citation statements)

References 26 publications

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“…Despite the exclusion of these patients from the reanalysis, virological success (HIV-1 RNA <50 copies/ml) to maraviroc-containing regimen was observed in 68.5% patients compared to 65.3% in the original analysis (Saag et al, 2008;Cooper et al, 2010). Thus, only a 3.2% improvement in virological response to maraviroc was observed despite this reclassification.…”

Section: Discussionmentioning

confidence: 94%

HIV-1 dual/mixed tropic isolates show different genetic and phenotypic characteristics and response to maraviroc in vitro

et al. 2011

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Section: Discussionmentioning

confidence: 94%

HIV-1 dual/mixed tropic isolates show different genetic and phenotypic characteristics and response to maraviroc in vitro

et al. 2011

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“…For instance, no clinical trials have, to date, proven the superiority of a PI-based or an NNRTIbased regimen, with respect to virological response, in the case of high pre-therapy viral load [44,45]. However, new retrospective and prospective studies may provide final results about whether PIs or NNRTIs should be selectively used according to pre-therapy viral load (and CD4 + T-cell number).…”

Section: Discussionmentioning

confidence: 99%

Impact of Pre-Therapy Viral Load on Virological Response to Modern First-Line Haart

et al. 2013

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Background: We tested whether pre-HAART viraemia affects the achievement and maintenance of virological success in HIV-1-infected patients starting modern firstline therapies. Methods: A total of 1,430 patients starting their first HAART (genotype-tailored) in 2008 (median; IQR: 2006-2009) were grouped according to levels of pre-HAART viraemia (≤30,000, 30,001-100,000, 100,001-300,000, 300,001-500,000 and >500,000 copies/ml). The impact of pre-therapy viraemia on the time to virological success (viraemia ≤50 copies/ml) and on the time to virological rebound (first of two consecutive viraemia values >50 copies/ml after virological success) were evaluated by Kaplan-Meier curves and Cox regression analyses. Results: Median pre-HAART viraemia was 5.1 log 10 copies/ml (IQR 4.5-5.5), and 53% of patients had viraemia >100,000 copies/ml. By week 48, the prevalence of patients reaching virological success was >90% in all pre-HAART viraemia ranges, with the only exception of range >500,000 copies/ml (virological success =83%; P<0.001). Higher pre-HAART viraemia was tightly correlated with longer median time to achieve virological success. Cox multivariable estimates confirmed this result: patients with pre-HAART viraemia >500,000 copies/ml showed the lowest hazard of virological undetectability after adjusting for age, gender, pre-HAART CD4 + T-cell count, transmitted drug resistance, calendar year and third drug administered (adjusted hazard ratio [95% CI]: 0.27 [0.21, 0.35]; P<0.001). Pre-HAART viraemia >500,000 copies/ml was also associated with higher probability of virological rebound compared with patients belonging to lower viraemia strata at weeks 4, 12 and 24 (P=0.050). Conclusions: At the time of modern HAART, and even though an average >90% of virological success, high pre-HAART viraemia remains an independent factor associated with delayed and decreased virological success. Patients starting HAART with >500,000 copies/ml represent a significant population that may deserve special attention.HAART has significantly extended the time to development of AIDS and to death in HIV-infected individuals [1,2]. Its efficacy in suppression of plasma HIV-1 RNA to undetectable levels, and in increasing CD4 + T-cell count, is well documented in several clinical trials [3][4][5][6].Despite years of great progress in treating AIDS, however, in some patients starting their first treatment; the effectiveness of HAART is still not sufficient, with consequent virological failures [7][8][9]. These failures can be caused by several factors, such as drug potency, drug

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“…4,5 If the cost of such an agent can be reduced by 50%, however, the CD4 count increase required would be 19 cells/μL, which is closer to the additional increase reported in the MERIT study of a maraviroc-based regimen (compared to an efavirenz-based regimen) in treatment-naïve patients. 8 …”

Section: Discussionmentioning

confidence: 99%

“…For example, in the MERIT trial of antiretroviralnaïve patients, CD4 count increases after 48 weeks were significantly higher in patients treated with maraviroc+zidovudine/lamivudine than with efavirenz/zidovudine/lamivudine (+170 vs +144 cells/μL: difference +26 [95% CI, +7 to +46]), despite a lower degree of virologic suppression (65% vs 69% with HIV RNA <50 copies/mL), and the CD4 count difference was maintained at 96 weeks. 8,9 The clinical benefit of this additional CD4 count improvement is not known and will need to be tested in future clinical studies. 9 Similarly, the cost of immune-enhanced initial ART will depend on whether the immune-enhancing agent can be subsequently withdrawn without losing this clinical benefit.…”

mentioning

confidence: 99%

Cost-effectiveness of Adding an Agent That Improves Immune Responses to Initial Antiretroviral Therapy (ART) in HIV-Infected Patients: Guidance for Drug Development

Morris¹,

Scott²,

Wilkin³

et al. 2012

HIV Clinical Trials

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Purpose Adding an immune-enhancing agent to initial antiretroviral therapy (ART) for HIV is a potential strategy to ensure that patients achieve optimal immune response. Method Using a mathematical model of HIV disease and treatment, we evaluated the treatment benefits and cost-effectiveness of adding a hypothetical immune-enhancing agent to the initial 6 months of ART. We assumed that the additional agent would result in a higher CD4 increase that would provide clinical benefit. The additional cost ($1,900/month) was based on the cost of a drug currently under investigation for immune enhancement. Outcomes included projected life expectancy and cost-effectiveness in 2009 US dollars/quality-adjusted life year (QALY) with costs and QALYs discounted at 3% annually. Results Compared to standard ART, immune-enhanced ART resulting in an additional 40 CD4 cell/μL increase at 6 months yields a 2.4 month projected undiscounted life expectancy increase with a cost-effectiveness ratio of $107,600/QALY. Achieving a cost-effectiveness ratio <$100,000/QALY requires a >43 CD4 cell/μL improvement, or >19 cells/μL if immune-enhancing agent costs are halved. Conclusions In addition to showing clinical efficacy, investigational immune enhancement agents need to increase CD4 counts more than has been previously observed or have a lower cost to be considered cost-effective in the United States.

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Maraviroc versus Efavirenz, Both in Combination with Zidovudine‐Lamivudine, for the Treatment of Antiretroviral‐Naive Subjects with CCR5‐Tropic HIV‐1 Infection

Cited by 241 publications

References 26 publications

HIV-1 dual/mixed tropic isolates show different genetic and phenotypic characteristics and response to maraviroc in vitro

HIV-1 dual/mixed tropic isolates show different genetic and phenotypic characteristics and response to maraviroc in vitro

Impact of Pre-Therapy Viral Load on Virological Response to Modern First-Line Haart

Cost-effectiveness of Adding an Agent That Improves Immune Responses to Initial Antiretroviral Therapy (ART) in HIV-Infected Patients: Guidance for Drug Development

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