A Systematic Review of the Use of Atazanavir in Women Infected with HIV-1

Johnson, Margaret; Walmsley, Sharon; Haberl, Annette

doi:10.3851/imp2742

Cited by 4 publications

(4 citation statements)

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“…The rate of discontinuation caused by rash was high compared with historical rates reported for men, showing sex differences in reported severities of adverse events associated with antiretroviral drugs. 13,19,21–23 Pharmacokinetic studies are pending and will delineate whether increased atazanavir concentrations were associated with study-drug discontinuation.…”

Section: Discussionmentioning

confidence: 99%

“…Current guidelines for first-line treatment of HIV-1 infection include the use of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a third active drug from a different class. 10–12 The integrase strand transfer inhibitor (elvitegravir, 150 mg) coformulated with cobicistat (150 mg), emtricitabine (200 mg), and tenofovir disoproxil fumarate (300 mg) in a single-tablet regimen is a preferred ART regimen in treatment-naive patients and atazanavir (300 mg) boosted by ritonavir (100 mg) plus a preferred two-NRTI backbone (emtricitabine plus tenofovir disoproxil fumarate) is well tolerated in HIV-infected women 13 and remains a preferred regimen during pregnancy. 10,11,14 …”

Section: Introductionmentioning

confidence: 99%

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Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study

et al. 2016

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Summary Background Women are under-represented in HIV antiretroviral therapy (ART) studies. Guidelines for selection of ART as initial therapy in patients with HIV-1 infection do not contain sex-specific treatment. We aimed to assess the safety and efficacy of the single tablet integrase inhibitor regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate compared with a boosted protease inhibitor regimen of ritonavir-boosted atazanavir with emtricitabine and tenofovir disoproxil fumarate. Methods In this international, randomised, controlled, double-blind, phase 3 study (Women AntiretroViral Efficacy and Safety study [WAVES]), we recruited treatment-naive HIV-infected women with an estimated creatinine clearance of 70 mL/min or higher from 80 centres in 11 countries. Women were randomly assigned (1:1) to receive elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (integrase inhibitor regimen) or ritonavir-boosted atazanavir with emtricitabine and tenofovir disoproxil fumarate (protease inhibitor based regimen); regimens were masked with matching placebos. Randomisation was done by a computer-generated allocation sequence (block size four) and was stratified by HIV-1 RNA viral load and race. Investigators, patients, study staff, and those assessing outcomes were masked to treatment group. All participants who received one dose of study drug were included in the primary efficacy and safety analyses. The main outcome was the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48 as defined by US Food and Drug Administration snapshot algorithm (prespecified non-inferiority margin of 12%). This study is registered with ClinicalTrials.gov, number NCT01705574. Findings Between Nov 28, 2012, and March 12, 2014, 575 women were enrolled. 289 were randomly assigned to receive the integrase inhibitor regimen and 286 to receive the protease inhibitor based regimen. 252 (87%) women in the integrase inhibitor group had plasma HIV-1 RNA less than 50 copies per mL at week 48 compared with 231 (81%) women in the protease inhibitor group (adjusted difference 6·5%; 95% CI 0·4–12·6). No participant had virological failure with resistance in the integrase inhibitor group compared with three participants ([1%]; all Met184Val/Ile) in the protease inhibitor group. 19 women in the protease inhibitor group discontinued because of adverse events compared with five in the integrase inhibitor group. Interpretation WAVES shows that clinical trials of ART regimens in global and diverse populations of treatment-naive women are possible. The findings support guidelines recommending integrase inhibitor based regimens in first-line antiretroviral therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study

et al. 2016

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“…This may affect tolerability, toxicity, and potentially the efficacy of antiretroviral therapy, and this should be considered when selecting drug regimens. Previous studies have indicated that women have an increased risk of antiretroviral therapy toxicity and treatment interruption following an adverse event . While some of these data were obtained with older regimens, two recent studies that only enrolled women also showed differences in efficacy/tolerability of current regimens .…”

Section: Resultsmentioning

confidence: 99%

Promoting high standards of care for women living with HIV: position statement from the Women Against Viruses in Europe Working Group

et al. 2017

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“…(10-12) The single-tablet regimen (STR) containing the integrase strand transfer inhibitor (INSTI) elvitegravir (EVG) with the NRTIs emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), and the pharmacoenhancer cobicistat (COBI) is an approved regimen for treatment-naïve individuals with HIV, and the protease inhibitor atazanavir (ATV) boosted by ritonavir (RTV) with FTC/TDF is another regimen option that is well tolerated in HIV-1 infected women and is a recommended regimen during pregnancy. (10, 11, 13, 14)…”

Section: Introductionmentioning

confidence: 99%

Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128)

Kulkarni

Hodder²,

Cao

et al. 2017

HIV Clinical Trials

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Background Women and those with non-B subtype HIV-1 are typically underrepresented in clinical trials. WAVES (GS-US-236-0128) was a double-blind phase 3b study among treatment-naïve HIV-1-infected women that demonstrated that elvitegravir/cobicistat/emtricitabine/tenofovir DF (EVG/COBI/FTC/TDF; N=289) was superior to atazanavir+ritonavir+FTC/TDF (ATV+RTV+FTC/TDF; N=286) for HIV-1 RNA <50 copies/mL by FDA snapshot analysis at Week 48. Here, we describe resistance development through Week 48 in women with virologic failure and determine the impact of pre-existing mutations and HIV-1 subtype on viral suppression. Methods Genotypic analyses (population and deep sequencing) and phenotypic analyses of HIV-1 protease, reverse transcriptase (RT), and integrase (IN) were performed. The resistance analysis population (participants with HIV-1 RNA ≥400 copies/mL at confirmed virologic failure, at discontinuation ≥Week 8, or at Week 48) had genotypic and phenotypic analyses at failure and baseline. Results The proportion of women qualifying for resistance analyses was similar between treatment groups (6.2% EVG/COBI/FTC/TDF; 7.3% ATV+RTV+FTC/TDF). Emergent resistance was rare (0% EVG/COBI/FTC/TDF; 1% ATV+RTV+FTC/TDF—3 with M184V/I in RT). Deep sequencing of HIV-1 did not detect additional resistance development. Pre-existing mutations did not lead to virologic failure; most with the polymorphic primary IN substitution T97A, or with substitutions in RT (i.e. A62V, V90I, K103N, or E138) demonstrated virologic suppression at Week 48, with no resistance development. Most participants (74%) had non-B HIV-1, and subtype did not affect outcome. Conclusions Emergent resistance to study drugs was rare in this global study of women, and no resistance was observed among EVG/COBI/FTC/TDF-treated participants, despite a high proportion of participants with natural or transmitted viral mutations and non-B HIV-1 subtypes.

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A Systematic Review of the Use of Atazanavir in Women Infected with HIV-1

Abstract: As part of a combination antiretroviral therapy regimen, ATV/r appears to be a safe, effective and durable option for treatment-naive and early treatment-experienced patients with HIV-1 infection, including non-pregnant and pregnant women.

Cited by 4 publications

References 73 publications

Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study

Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study

Promoting high standards of care for women living with HIV: position statement from the Women Against Viruses in Europe Working Group

Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128)

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