Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial
Raffi F.,University of Nantes |
Babiker A.G.,University College London |
Richert L.,French Institute of Health and Medical Research |
Molina J.-M.,University Paris Diderot |
And 15 more authors.
The Lancet | Year: 2014
Background Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen. Methods Between August, 2010, and September, 2011, we enrolled treatment-naive adults into this randomised, open-label, non-inferiority trial in treatment-naive adults in 15 European countries. The composite primary outcome was change to randomised treatment before week 32 because of insufficient virological response, no virological response by week 32, HIV-1 RNA concentration 50 copies per mL or higher at any time after week 32; death from any cause; any new or recurrent AIDS event; or any serious non-AIDS event. Patients were randomised in a 1:1 ratio to receive oral treatment with 400 mg raltegravir twice daily plus 800 mg darunavir and 100 mg ritonavir once daily (NtRTI-sparing regimen) or tenofovir-emtricitabine in a 245 mg and 200 mg fixed-dose combination once daily, plus 800 mg darunavir and 100 mg ritonavir once daily (standard regimen). This trial was registered with ClinicalTrials.gov, number NCT01066962. Findings Of 805 patients enrolled, 401 received the NtRTI-sparing regimen and 404 the standard regimen, with median follow-up of 123 weeks (IQR 112-133). Treatment failure was seen in 77 (19%) in the NtRTI-sparing group and 61 (15%) in the standard group. Kaplan-Meier estimated proportions of treatment failure by week 96 were 17·8% and 13·8%, respectively (difference 4·0%, 95% CI -0·8 to 8·8). The frequency of serious or treatment-modifying adverse events were similar (10·2 vs 8·3 per 100 person-years and 3·9 vs 4·2 per 100 person-years, respectively). Interpretation Our NtRTI-sparing regimen was non-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per μL. Funding European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories. © 2014 Elsevier Ltd.
Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial
PubMed | Service de Medecine Interne Immunologie Clinique, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Copenhagen University, University of Nantes and 8 more.
Type: Comparative Study | Journal: Lancet (London, England) | Year: 2014
Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen.Between August, 2010, and September, 2011, we enrolled treatment-naive adults into this randomised, open-label, non-inferiority trial in treatment-naive adults in 15 European countries. The composite primary outcome was change to randomised treatment before week 32 because of insufficient virological response, no virological response by week 32, HIV-1 RNA concentration 50 copies per mL or higher at any time after week 32; death from any cause; any new or recurrent AIDS event; or any serious non-AIDS event. Patients were randomised in a 1:1 ratio to receive oral treatment with 400 mg raltegravir twice daily plus 800 mg darunavir and 100 mg ritonavir once daily (NtRTI-sparing regimen) or tenofovir-emtricitabine in a 245 mg and 200 mg fixed-dose combination once daily, plus 800 mg darunavir and 100 mg ritonavir once daily (standard regimen). This trial was registered with ClinicalTrials.gov, number NCT01066962.Of 805 patients enrolled, 401 received the NtRTI-sparing regimen and 404 the standard regimen, with median follow-up of 123 weeks (IQR 112-133). Treatment failure was seen in 77 (19%) in the NtRTI-sparing group and 61 (15%) in the standard group. Kaplan-Meier estimated proportions of treatment failure by week 96 were 178% and 138%, respectively (difference 40%, 95% CI -08 to 88). The frequency of serious or treatment-modifying adverse events were similar (102 vs 83 per 100 person-years and 39 vs 42 per 100 person-years, respectively).Our NtRTI-sparing regimen was non-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per L.European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories.
PubMed | Hopitaux Universitaires, Bordeaux University Hospital Center, ANRS, French Institute of Health and Medical Research and 6 more.
Type: Journal Article | Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | Year: 2015
Human immunodeficiency virus (HIV) infection is associated with a high risk of classical Hodgkins lymphoma (cHL) in the combined antiretroviral therapy (cART) era.We analyzed the characteristics and outcome of HIV-associated cHL diagnosed in the modern cART era. The French ANRS-CO16 Lymphovir cohort enrolled 159 HIV-positive patients with lymphoma, including 68 (43%) with cHL. HIV-HL patients were compared with a series of non-HV-infected patients consecutively diagnosed with HL.Most patients (76%) had Ann-Arbor stages III-IV and 96% of patients were treated with ABVD. At diagnosis, median CD4 T-cell count was 387/L and 94% of patients were treated with cART. All patients received cART after diagnosis. Five patients died from early progression (n = 2), sepsis (1) or after relapse (2). Two additional patients relapsed during follow-up. Two-year overall and progression free survivals (PFS) were 94% [95% CI, 89%, 100%] and 89% [82%, 97%], respectively. The only factor associated with progression or death was age with a relative risk of 8.1 [1.0; 67.0] above 45 years. The PFS of Lymphovir patients appeared similar to PFS of HIV-negative patients, 86% [82%, 90%], but patients with HIV infection displayed higher risk features than HIV-negative patients.Although high-risk features still predominate in HIV-HL, the prognosis of these patients, treated with cART and mainly ABVD, has markedly improved in the modern cART era and is now similar to non-HIV-infected patients.
PubMed | Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, ANRS, Oswaldo Cruz Foundation, U.S. National Institutes of Health and 4 more.
Type: Journal Article | Journal: Trends in microbiology | Year: 2015
The quest for a cure for HIV remains a timely and key challenge for the HIV research community. Despite significant scientific advances, current HIV therapy regimens do not completely eliminate the negative impact of HIV on the immune system; and the economic impact of treating all people infected with HIV globally, for the duration of their lifetimes, presents significant challenges. This article discusses, from a multidisciplinary approach, critical social, behavioral, ethical, and economic issues permeating the HIV-cure research agenda. As part of a search for an HIV cure, both the perspective of patients/participants and clinical researchers should be taken into account. In addition, continued efforts should be made to involve and educate the broader community.
PubMed | Biostatistics Unit, World Health Organization, Pham Ngoc Thach Hospital, Institute Pasteur in Cambodia and 7 more.
Type: Journal Article | Journal: PloS one | Year: 2014
Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured.This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir.Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 - 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations.Based on these findings, rifabutin 150 mg daily may be preferred when co-administered with lopinavir/ritonavir in patients with HIV-associated tuberculosis.ClinicalTrials.gov NCT00651066.
News Article | November 10, 2016
Industry veteran adds biotech innovation depth to Finn Partners' global reach and EU expertise in pharma and patient advocacy NEW YORK and PARIS, Nov. 10, 2016 /PRNewswire/ -- Finn Partners announced today the appointment of Mina Volovitch as Head of its Paris office and senior partner in the agency's Global Health Practice. Volovitch will be based in Paris and report to Chantal Bowman-Boyles, managing partner, leading Finn Partners Europe and Gil Bashe, managing partner, Global Health. Volovitch's more than 20 years' experience in health communications includes work with the globe's leading names in medicine and public health including bioMérieux, Bristol Myers-Squibb, Lilly, Novartis, Roche, Sanofi Pasteur, Transgene, the French Cancer Society, the National League Against Cancer (largest French patient group), the ANRS (National Agency for Research on Aids), the Mérieux Foundation and IAVI. "Our European offices are adding more and more health work encompassing biotechnology, patient advocacy and health technology assignments. Mina's dual-role as head of our Paris office and senior member of the global health practice demonstrates how our agency values and growth attract exceptional talent," said Bowman-Boyles. "Mina is among the great health communicators with knowledge and experience engaging some of the most influential players in medical innovation, patient advocacy and public health across Europe," said Bashe. "Her collaborative approach is already strengthening the service and insight Finn Partners offers health clients around the globe. Just as importantly, she lives the Finn Partners value of making a difference in the world through her professional and volunteer efforts." Volovitch began her career at Merck working in marketing, eventually becoming director of communications at MSD Paris. Following Merck, Volovitch joined the Mérieux Institute (the vaccine innovator that is today Sanofi Pasteur), where she served as director of communications. In 1987, she created Mynecom, a specialist healthcare communications agency. Her professional experience includes running national and global professional- and patient-communications programs; handling issues in pharmaceuticals and health products; and expertise across AIDS, biotech, cardiology, immunology, infectious disease, medical devices, oncology and vaccines. She is also a member of the National League Against Cancer communications working group. "I am energized and proud to join Finn Partners during this exciting time of growth for its global health practice and Paris office," said Volovitch. "I share the agency's commitment to make a difference in the world, and the icing on the cake is building upon professional relationships with colleagues with whom I've worked in the past. Quite simply, I have deep trust and respect for Finn Partners management team in building one of the world's fastest growing PR and marketing communications agencies," she added. About Finn Partners, Inc. Finn Partners was launched in late 2011 to realize Peter Finn's vision to create a leading communications agency dedicated to shaping a bold new future in which innovation and partnership are strong brand drivers. Finn Partners specializes in the full spectrum of marketing and public relations services, including digital and social media. Practice areas include arts, consumer, CSR and social impact, education, financial services, health, technology and travel & lifestyle. Since its inception four years ago, Finn Partners has received six agency awards that are indicators of client and cultural leadership: "Best Midsize Agency" in 2015, "Best Agency to Work For" in 2013 and "Best New Agency" in 2012 from the Holmes Report and "Midsize PR Firm of the Year" in 2015 and "Top Places to Work in PR" in 2013 from PR News. Headquartered in New York City, the company has approximately 550 employees, with offices in Chicago, Detroit, Fort Lauderdale, Jerusalem, London, Los Angeles, Munich, Nashville, Paris, Portland, San Francisco and Washington D.C., and offers international capabilities through its own global network and PROI Worldwide. Find us at www.finnpartners.com and follow us on Twitter @finnpartners.
Anderson J.L.,University of Melbourne |
Fromentin R.,Vaccine and Gene Therapy Institute Florida |
Corbelli G.M.,European AIDS Treatment Group |
Ostergaard L.,Aarhus University Hospital |
AIDS Research and Human Retroviruses | Year: 2015
Biomedical research has led to profound advances in the treatment of HIV infection. Combination antiretroviral therapy (ART) now provides the means to readily control viral infection, and people living with HIV who receive timely and effective ART can expect to benefit from a life expectancy comparable to uninfected individuals. Nevertheless, despite effective treatment, ART does not fully restore the immune system and importantly HIV persists indefinitely in latent reservoirs, resulting in the need for life-long treatment. The challenges and limits of life-long treatment have spurred significant scientific interest and global investment into research towards an HIV cure. The International AIDS Society (IAS) 2014 Towards an HIV cure symposium brought together researchers and community to discuss the most recent advances in our understanding of latency and HIV reservoirs, and the clinical approaches towards an HIV cure under current investigation. This report summarizes and reviews some of the major findings discussed during the symposium. © Mary Ann Liebert, Inc. 2015.
PubMed | Institute Pasteur, Institute Pasteur in Cambodia, World Health Organization, Pham Ngoc Thach Hospital and 7 more.
Type: Journal Article | Journal: Public health action | Year: 2015
Due to their nature and complexity, clinical trials often take some time to launch after the protocol has been designed and ethics approval obtained. During this time, there may be changes in international treatment guidelines and recommendations that result in a conflict between study protocol and recommended international best practice. Here, we describe the situation that arose in a pharmacokinetic study on the use of two different doses of rifabutin in patients with human immunodeficiency virus-associated tuberculosis who initiated antiretroviral therapy (ART) with a lopinavir-ritonavir-based regimen in South Africa and Viet Nam. The study protocol specified that ART should be started 10 weeks after the start of anti-tuberculosis treatment. The study in South Africa was approved in June 2008, went ahead as scheduled and was completed in August 2010. The study in Viet Nam was approved in October 2008 and was started in June 2010. A few weeks later, the World Health Organization released their 2010 guidelines for adult ART; one of its strong recommendations (with moderate quality of evidence) was that ART should be started 2-8 weeks after the start of anti-tuberculosis treatment. Emerging scientific evidence also supported this recommendation. The investigators felt that the Viet Nam study protocol was in conflict with recommended international best practice, and the trial was stopped in October 2010. An amended study protocol in which ART was started at 2 weeks was developed and implemented. The ethics issues around this decision and the need to change the study protocol are discussed in this article.
Borand L.,Institute Pasteur in Cambodia |
Laureillard D.,ANRS |
Madec Y.,Institute Pasteur Paris |
Chou M.,University of Health Sciences |
And 7 more authors.
Antiviral Therapy | Year: 2013
Background: The optimal dose of efavirenz for HIV-infected patients receiving a tuberculosis regimen including rifampicin remains debated, especially for subjects weighing over 50 kg. To address this issue, we measured plasma efavirenz concentrations from Cambodian adults with tuberculosis enrolled in the CAMELIA randomized trial (ClinicalTrials.gov number, NCT01300481) 6 weeks after the onset of antiretroviral therapy. Methods: Efavirenz concentrations and proportions of patients with concentrations below 1,000 ng/ml were compared across patient body weight below or above 50 kg using a Student's t-test and a χ2 test, respectively. Factors associated with efavirenz concentrations below 1,000 ng/ml were identified by logistic regression analysis. Logistic regression analysis was also performed to check if efavirenz concentrations below 1,000 ng/ml were associated with virological failure. Results: Plasma efavirenz concentrations were higher in the 332 patients who weighed <50 kg compared with the 150 who weighed ≥50 kg (median [IQR] 2,859 [1,787-4,749] and 2,060 [1,425-3,575] ng/ml, respectively; P=0.02). However, the proportion of patients with efavirenz concentrations below 1,000 ng/ml was not different between those weighing less than or more than 50 kg (6% and 10%, respectively; P=0.13) and a body weight above 50 kg was not associated with a higher risk of plasma efavirenz concentrations below 1,000 ng/ml. When plasma efavirenz concentrations below 1,000 ng/ml were present, they were not associated with virological failure. Conclusions: The current WHO guidelines recommending 600 mg efavirenz daily irrespective of patient's body weight remains a safe and effective approach to treating coinfected adults needing simultaneous tuberculosis and HIV therapy. ©2013 International Medical Press.
Journot V.,French Institute of Health and Medical Research |
Perusat-Villetorte S.,French Institute of Health and Medical Research |
Bouyssou C.,French Institute of Health and Medical Research |
Couffin-Cadiergues S.,ANRS |
And 3 more authors.
Clinical Trials | Year: 2013
Background In biomedical research, the signed consent form must be checked for compliance with regulatory requirements. Checking usually is performed on site, most frequently after a participants final enrollment. Purpose We piloted a procedure for remote preenrollment consent forms checking. We applied it in five trials and assessed its efficiency to reduce form nonconformity before participant enrollment. Methods Our clinical trials unit (CTU) routinely uses a consent form with an additional copy that contains a pattern that partially masks the participants name and signature. After completion and signatures by the participant and investigator, this masked copy is faxed to the CTU for checking. In case of detected nonconformity, the CTU suspends the participants enrollment until the form is brought into compliance. We checked nonconformities of consent forms both remotely before enrollment and on site in five trials conducted in our CTU. We tabulated the number and nature of nonconformities by location of detection: at the CTU or on site. We used these data for a pseudo before-and-after analysis and estimated the efficiency of this remote checking procedure in terms of reduction of nonconformities before enrollment as compared to the standard on-site checking procedure. We searched for nonconformity determinants among characteristics of trials, consent forms, investigator sites, and participants through multivariate logistic regression so as to identify opportunities for improvement in our procedure. Results Five trials, starting sequentially but running concurrently, with remote preenrollment and on-site checking of consent forms from 415 participants screened in 2006-2009 led to 518 consent forms checked; 94 nonconformities were detected in 75 forms, 75 (80%) remotely and 19 more (20%) on site. Nonconformities infrequently concerned dates of signatures (7%) and information about participants (12%). Most nonconformities dealt with investigator information (76%), primarily contact information (54%). The procedure reduced nonconformities by 81% (95% confidence interval (CI): 73%-89%) before enrollment. Nonconforming consent forms dropped from 25% to 0% over the period, indicating a rapid learning effect between trials. Fewer nonconformities were observed for participants screened later in a trial (odds ratio (95% CI): 0.5 (0.3-0.8); p = 0.004), indicating a learning effect within trials. Nonconformities were more common for participants enrolled after screening (2.4 (1.1-5.3); p = 0.03), indicating a stricter scrutiny by form checkers. Limitations Although our study had a pseudo before-and-after design, no major bias was identified. Power and generalizability of our findings were sufficient to support implementation in future trials. © 2013 The Author(s).