Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials

Eron, Joseph J.; Young, Benjamin; Cooper, David A.; Youle, Michael; DeJesus, Edwin; Andrade-Villanueva, Jaime; Workman, Cassy; Zajdenverg, Roberto; Fätkenheuer, Gerd; Berger, Daniel; Kumar, Princy; Rodgers, Anthony; Shaughnessy, Melissa; Walker, Monica L; Barnard, Richard; Miller, Michael D.; DiNubile, Mark J.; Nguyen, Bach‐Yen; Leavitt, Randi Y.; Xu, Xia; Sklar, Peter

doi:10.1016/s0140-6736(09)62041-9

Cited by 278 publications

(229 citation statements)

References 32 publications

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“…Switching of HAART may be associated with a risk of viral breakthrough. 123 In case of concern of drug resistance to antiretroviral drugs, use of DCV and SOF therapy may be optimal as it is compatible with most antiretroviral regimens and a switch of antiretroviral regimen may be avoided. DCV and SOF therapy is associated with significantly higher SVR12 rate and lower rate of discontinuation due to adverse effects than SOF and RBV in patients coinfected with HIV and HCV.…”

Section: Management Of Hcv In Hiv Coinfectionmentioning

confidence: 99%

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Puri

Saraswat

Dhiman

et al. 2016

Journal of Clinical and Experimental Hepatology

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India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects. ( J CLIN EXP HEPATOL 2016;6:119-145) T here have been revolutionary changes in the management of chronic hepatitis C (CH-C) over the last few years. Pegylated interferon alfa (Peg-IFNa) plus ribavirin (RBV) therapy, which till the recent past was the standard of care, has been eclipsed by the arrival of newer directly acting antiviral agents (DAAs). Not only do the DAAs have better efficacy, they are also associated with lower side effects, have better tolerability, a shorter duration of therapy, and have simpler administration.In the recent guidelines issued by the American Association for the study of Liver Diseases (AASLD), in collaboration with the Infectious Diseases Society of America 1 and the European Association for Study of the Liver z (EASL), 2 the role of Peg-IFNa/RBV therapy in the management of HCV has been relegated to second-line, backup status. These newer guidelines, however, cannot be implemented in India as many of the recommended drugs are yet to be marketed in India. Other considerations for the treatment of HCV in India are a predominance of

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Section: Management Of Hcv In Hiv Coinfectionmentioning

confidence: 99%

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Puri

Saraswat

Dhiman

et al. 2016

Journal of Clinical and Experimental Hepatology

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“…But simplification cannot be performed if compromising treatment efficacy. As an example, include two clinical trials recently presented, SWITCHMRK 1 and 2 51 . Two clinical trials are parallel, multicenter, double-blind, randomized studies encompassing virological controlled patients under treatment which included a Lopinavir/r stable, did not exclude patients who had failed other treatment regimens, provided that at the time of inclusion on CVP <50 copies / mL for at least 3 months.…”

Section: Other Simplificationmentioning

confidence: 99%

Simplification of Antiretroviral Therapy (ART)

Martinez¹

2011

Recent Translational Research in HIV/AIDS

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Recent Translational Research in HIV/AIDS 238 reintroducing the previously recalled. The data at 96 weeks confirmed the durability and safety of this estrategia 3 . After this study, is performed OK04 study including 205 patients with undetectable VL for at least 6 months (median 28), who were taking HAART including LPV/r associated with two NA. Is a randomized, open, non-inferiority comparing the strategy of continuation of triple therapy compared to monotherapy with LPV/r, followed by reinduction with 2 NA if viral rebound appeared. At 48 weeks the percentage of patients without virologic failure was 90 and 94% respectively (difference, -4%, upper limit 95% CI for difference 3.4%, meeting the criteria for noninferiority). The percentage of patients with VL <;50 copies/mL at 48 weeks (ITT), considering as failures reinduction was 85% in the monotherapy group and 90% in the continuation (p = 0.31). Episodes of low-level viremia between 50 and 500 copies / mL were more frequent in patients treated with monotherapy (4 vs. none) 4 . With patients in these two studies performed a multivariate analysis of predictors of loss of virologic response in the group treated with LPV/r monotherapy. Virologic failure was associated with lack of grip, low haemoglobin levels and nadir CD4 <100 cells/μL 5 . In another study of simplification to monotherapy with LPV/r was somewhat different strategy. We included 155 previously untreated patients who were randomized 2:1 to treatment with ZDV/3TC start with LPV / r (n = 104) or EFV (n = 51). Within 24 weeks of treatment and after at least 3 controls with VL < 50 copies / mL, patients taking LPV maintenance came to LPV/r monotherapy. Whereas failure to any positive viremia at 96 weeks of follow up, 48% of patients treated with LPV / r and 61% with EFV had CVP < 50 copies / mL (p = 0.17, 95% of the difference, -29% to 4%). In a new analysis that included patients as responders to reintroduce them after getting back NA CVP < 50 copies / mL, 60% of patients on LPV/r and EFV 63% responded to treatment ( p = 0.73, CI 95% -19% 13%). Have been observed low viral loads in patients on monotherapy. As for security, lipoatrophy was observed in 5% of the monotherapy arm, compared to 34% of the EFV group. There were no differences in lipohypertrophy. Grade 3-4 lipid abnormalities were more frequent in the group of LPV/r. In these two studies highlights the importance of the period during which the CVP remains undetectable prior to the step alone. This same strategy is being explored and DRV/r 6,7 ATV/r 8,10 . They have published the results at 48 weeks of a pilot study, single-arm open-simplification to ATV / r, the ACTG 5201. Were included in the same 34 patients who started treatment with 2 NA and IP, who were with undetectable viral load (<50 copies / mL) for at least 48 weeks, had not been treated with NN or prior virologic failure were HBsAg negative. Upon entering the study were switched to IP they were taking on ATV / r and 6 weeks after suspending the AN. The primary endpoint was time to ...

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“…Пациенты либо продолжали прием лопинави-ра/р, либо переходили на ралтегравир. Несмотря на улучшение липидного профиля при смене лопинавира/р на ралтегравир, у 6% больных данной группы после 24 недель лечения вирусная нагрузка вновь стала опреде-ляемой, что свидетельствовало об осторожности замены бустированного ингибитора протеазы на ралтегравир у опытных пациентов [19]. Второе исследование включи-ло взрослых пациенты с ВИЧ-инфекцией и неопределя-емой вирусной нагрузкой в результате приема терапии с применением одного из ИП.…”

unclassified

“…В исследовании SWITCHMRK в группе пациентов с неопределяемой виру-сной нагрузкой, продолживших терапию лопинави-ром/р в сочетании с двумя НИОТ, частота нежелатель-ных явлений на 24-й неделе лечения, повлекших отмену терапии, составила 0,3%, а в группе ралтегравира с дву-мя НИОТ -0,6% [19]. Отметим, что на сегодняшний день совершенно ясно: минимальная частота отдаленных не-желательных явлений ралтегравира не идет ни в какое сравнение с высокими показателями метаболических нарушений на терапии лопинавиром/р.…”

unclassified

“…В исследовании SPIRAL у пациентов, перешедших с ИП/р на терапию ралтеграви-ром, наблюдали устойчивое снижение не только уровня липидов плазмы, но и соотношения общего холестерина к холестерину ЛПВП по сравнению с пациентами, про-должавшими лечение ИП/р, что указывает на сущест-венное улучшение липидного профиля при переключе-нии на ралтегравир [20]. В исследованиях SWITCHMRK также наблюдали статистически значимую разницу меж-ду группами терапии на основе ралтегравира и лопина-виром/р в изменении уровня триглицеридов и общего холестерина за 12 недель, однако изменения холестери-на ЛПНП и ЛПВП за тот же период времени не были ста-тистически значимыми [19]. Как и в предыдущих сооб-щениях о замене ИП другими препаратами [36], улучше-ние показателей липидного профиля у пациентов, пере-шедших на ралтегравир в исследовании SPIRAL, прояв-лялось быстро, и интенсивность динамики положитель-ных изменений оставалась относительно стабильной на всем протяжении исследования.…”

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Hiv Integrase Inhibitors: The Basis of Effective and Safe Antiretroviral Therapy

Шахгильдян

2017

Medicinskij sovet

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В статье рассматриваются вопросы эффективности и безопасности ингибиторов интегразы ВИЧ (ралте-гравира, долутегравира) в схемах антиретровирусной терапии (АРВТ) у больных ВИЧ-инфекцией разли-чных групп: с высокой концентрацией РНК ВИЧ в крови, низким количеством CD4-лимфоцитов в крови, беременных, при сочетании ВИЧ-инфекции с туберкулезом или хроническим гепатитом С, больных стар-шего возраста и/или с высоким кардиоваскулярным риском, нейрокогнитивными расстройствами. Осо-бое внимание уделяется минимальному риску развития поздних осложнений АРВТ при использовании в схемах АРВТ ралтегравира и возможности сочетания ралтегравира с лекарственными препаратами раз-личных классов.Ключевые слова: ингибиторы интегразы ВИЧ, ралтегравир, безопасность АРВТ.

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Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials

Cited by 278 publications

References 32 publications

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Simplification of Antiretroviral Therapy (ART)

Hiv Integrase Inhibitors: The Basis of Effective and Safe Antiretroviral Therapy

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