Nonnucleoside Reverse-transcriptase Inhibitor- vs Ritonavir-boosted Protease Inhibitor–based Regimens for Initial Treatment of HIV Infection: A Systematic Review and Metaanalysis of Randomized Trials

Borges, Álvaro H.; Lundh, Andreas; Tendal, Britta; Bartlett, John A.; Clumeck, Nathan; Costagliola, Dominique; Daar, Eric S.; Echeverría, Patricia; Gisslén, Magnus; Huedo‐Medina, Tania B.; Hughes, Michael D.; Hullsiek, Katherine Huppler; Khabo, Paul; Komati, Stephanus; Kumar, Princy; Lockman, Shahin; MacArthur, Rodger D.; Maggiolo, Franco; Matteelli, Alberto; Miró, José M.; Oka, Shinichi; Petoumenos, Kathy; Puls, Rebekah; Riddler, Sharon A.; Sax, Paul E.; Sierra‐Madero, Juan; Torti, Carlo; Lundgren, Jens D

doi:10.1093/cid/ciw236

Cited by 14 publications

(9 citation statements)

References 34 publications

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“…A recent comprehensive metaanalysis found no difference in clinical or viro-immunological outcomes between NNRTIs and PIs but did not address resistance development. 10 Genotype analysis in our study of samples from patients failing treatment revealed NNRTI or NRTI resistance mutations in nearly three of four patients in the NNRTI-arm, which is even higher than that reported in other studies, 12,29 and reflect poor adherence. The high proportion of pre-therapy resistance can be due to transmitted resistance or previous ART exposure.…”

Section: A C C E P T E Dcontrasting

confidence: 68%

“…This problem is even more pronounced in Black Africans, who more frequently harbour a polymorphism in cytochrome P450 2B6 associated with slower plasma clearance of efavirenz (EFV). 4 Large randomised trials comparing NNRTIs with protease inhibitors (PIs) have been conducted in Europe and the United States of America, [5][6][7][8][9][10] but these results are not generalisable to an African setting due to differences in genetics, sex distribution, and adherence. 4,11 Most studies comparing NNRTIs with PIs in adults that have been conducted in Africa have indicated equivalent efficacy; however, most of these studies only included women and treatment procedures were supported economically and practically to a larger extend than is common in the vast majority of centers in Sub-Saharan Africa.…”

Section: Introductionmentioning

confidence: 99%

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Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA): A Randomized Controlled Trial

Jespersen¹,

Hønge²,

Krarup³

et al. 2018

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Section: A C C E P T E Dcontrasting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA): A Randomized Controlled Trial

Jespersen¹,

Hønge²,

Krarup³

et al. 2018

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Since its initial approval in 2006, substantial clinical trial data and clinical experience with darunavir have accumulated, demonstrating the potent and durable virologic response, high genetic barrier to resistance, and favorable safety profile in ART-naive, HIV-1-infected patients [ 4 , 5 ]. A substantial proportion of newly diagnosed patients in the United States and Europe are treated with a boosted protease inhibitor [ 6 , 7 ], and darunavir is the recommended protease inhibitor in treatment guidelines [ 8 – 10 ]. United States guidelines recommend two nucleoside or nucleotide analogue reverse transcriptase inhibitors (NRTIs) combined with an integrase strand transfer inhibitor (INSTI), or in certain clinical situations boosted darunavir 800 mg once daily or a nonnucleoside reverse transcriptase inhibitor (NNRTI) [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients

Eron

Orkin

Gallant

et al. 2018

Aids

102

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Objectives:To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naive, HIV-1-infected adults.Design:Phase-3, randomized, active-controlled, double-blind, international, multicenter, noninferiority study (NCT02431247).Methods:Seven hundred and twenty-five participants were randomized (1 : 1) to D/C/F/TAF (362) or control (363). The primary objective was to demonstrate noninferiority of D/C/F/TAF vs. control for percentage viral load less than 50 copies/ml (FDA-snapshot analysis) at 48 weeks (10% margin).Results:At week 48, D/C/F/TAF was noninferior to control (91.4 vs. 88.4% achieved viral load <50 copies/ml, respectively; difference 2.7%; 95% CI −1.6 to 7.1; P < 0.0001), with 4.4 vs. 3.3% of patients, respectively, having viral load greater or equal to 50 copies/ml. No treatment-emergent mutations associated with darunavir or TAF/TDF resistance were observed in either group. One patient (D/C/F/TAF) was identified with M184I/V conferring resistance to emtricitabine. Incidences of grades 3 and 4 adverse events (5 vs. 6%), serious adverse events (5 vs. 6%) and adverse event-related discontinuations (2 vs. 4%) were low and similar between groups. Mean decrease in urine protein/creatinine ratio was greater with D/C/F/TAF than control (−22.42 vs. −10.34 mg/g, P = 0.033). Mean percentage change in bone mineral density with D/C/F/TAF vs. control was 0.21 vs. −2.73%, P < 0.0001 (hip), −0.68 vs. −2.38%, P = 0.004 (lumbar spine), and −0.26 vs. −2.97%, P < 0.0001 (femoral neck). Median change from baseline in total cholesterol/HDL-cholesterol ratio was 0.20 vs. 0.08, P = 0.036.Conclusion:D/C/F/TAF achieved a high virologic suppression rate (91.4%) and was noninferior to darunavir/cobicistat with F/TDF. D/C/F/TAF also demonstrated the bone and renal safety advantages of TAF in combination with darunavir/cobicistat.

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“…While a recent meta-analysis did not find differences between NNRTI- and PI/r-based regimens in terms of clinical outcomes such as death or progression to AIDS, it was found that trial-defined virological failure was higher with a NNRTI-based regimen [6]. Also, toxicity of certain NNRTIs were found to be inferior to PI/r-based regimen [7].…”

Section: Introductionmentioning

confidence: 99%

The choice between a ritonavir-boosted protease inhibitor- and a non-nucleoside reverse transcriptase inhibitor-based regimen for initiation of antiretroviral treatment – results from an observational study in Germany

Mahlich

Gross

Kuhlmann³

et al. 2016

J of Pharm Policy and Pract

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BackgroundThis study aims at identifying predictors of the treatment decision of German physicians with regard to a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r) -based initial treatment regimen.MethodsThe study is based on a sub analysis of a nation-wide multi-centre, non-interventional, prospective cohort study. 133 patients were identified, who received antiretroviral first-line therapy. By means of a logistic regression, factors that determine the treatment strategy for treatment-naïve patients were analysed.ResultsCompared to patients receiving a NNRTI-based initial regimen, patients treated with PI/r are slightly younger, less educated, in a later stage of HIV and have more concomitant diseases. Regression analysis revealed that being in a later stage of HIV (CDC-C) is significantly associated with a PI/r-based treatment decision.ConclusionsOur analysis is the first study in Germany investigating sociodemographic and disease-specific parameters associated with a NNRTI- or a PI/r-based initial treatment decision. The results confirm that the treatment decision for a PI/r strategy is associated with disease severity.

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Nonnucleoside Reverse-transcriptase Inhibitor- vs Ritonavir-boosted Protease Inhibitor–based Regimens for Initial Treatment of HIV Infection: A Systematic Review and Metaanalysis of Randomized Trials

Abstract: We found no difference in clinical and viro-immunologic outcomes between NNRTI- and PI/r-based therapy.

Cited by 14 publications

References 34 publications

Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA): A Randomized Controlled Trial

Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA): A Randomized Controlled Trial

A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients

The choice between a ritonavir-boosted protease inhibitor- and a non-nucleoside reverse transcriptase inhibitor-based regimen for initiation of antiretroviral treatment – results from an observational study in Germany

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