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Combination therapy with anti-HIV-1 antibodies maintains viral suppression.

ABSTRACT: Individuals infected with HIV-1 require lifelong antiretroviral therapy, because interruption of treatment leads to rapid rebound viraemia. Here we report on a phase 1b clinical trial in which a combination of 3BNC117 and 10-1074, two potent monoclonal anti-HIV-1 broadly neutralizing antibodies that target independent sites on the HIV-1 envelope spike, was administered during analytical treatment interruption. Participants received three infusions of 30 mg kg-1 of each antibody at 0, 3 and 6 weeks. Infusions of the two antibodies were generally well-tolerated. The nine enrolled individuals with antibody-sensitive latent viral reservoirs maintained suppression for between 15 and more than 30 weeks (median of 21 weeks), and none developed viruses that were resistant to both antibodies. We conclude that the combination of the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 can maintain long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.

SUBMITTER: Mendoza P

PROVIDER: S-EPMC6166473 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Combination therapy with anti-HIV-1 antibodies maintains viral suppression.

Mendoza Pilar P Gruell Henning H Nogueira Lilian L Pai Joy A JA Butler Allison L AL Millard Katrina K Lehmann Clara C Suárez Isabelle I Oliveira Thiago Y TY Lorenzi Julio C C JCC Cohen Yehuda Z YZ Wyen Christoph C Kümmerle Tim T Karagounis Theodora T Lu Ching-Lan CL Handl Lisa L Unson-O'Brien Cecilia C Patel Roshni R Ruping Carola C Schlotz Maike M Witmer-Pack Maggi M Shimeliovich Irina I Kremer Gisela G Thomas Eleonore E Seaton Kelly E KE Horowitz Jill J West Anthony P AP Bjorkman Pamela J PJ Tomaras Georgia D GD Gulick Roy M RM Pfeifer Nico N Fätkenheuer Gerd G Seaman Michael S MS Klein Florian F Caskey Marina M Nussenzweig Michel C MC

Nature 20180926 7724

Individuals infected with HIV-1 require lifelong antiretroviral therapy, because interruption of treatment leads to rapid rebound viraemia. Here we report on a phase 1b clinical trial in which a combination of 3BNC117 and 10-1074, two potent monoclonal anti-HIV-1 broadly neutralizing antibodies that target independent sites on the HIV-1 envelope spike, was administered during analytical treatment interruption. Participants received three infusions of 30 mg kg<sup>-1</sup> of each antibody at 0, ...[more]

PMID: 30258136

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Project description:BACKGROUND:Protease inhibitor monotherapy is a simplified treatment strategy for virally suppressed HIV-positive patients that has the potential for cost savings, as fewer drugs are used than with combination therapy. However, evidence for its economic value is limited. OBJECTIVES:We assessed the cost-effectiveness of lopinavir/ritonavir monotherapy followed by treatment intensification in case of viral load rebound versus combination antiretroviral therapy (cART) with efavirenz/emtricitabine/tenofovir in HIV-1 infected patients with viral suppression in the ANRS 140 DREAM trial. METHODS:DREAM was conducted in 36 French Hospitals between 2009 and 2013. For each treatment strategy, we estimated the unadjusted and multivariate-adjusted mean costs (in €, year 2010 values) and quality-adjusted life-years (QALYs) per patient, as well as incremental costs and QALYs per patient. We then assessed uncertainty using the cost-effectiveness acceptability curve, scenario analyses and cost-effectiveness price-threshold (CEPT) analysis. RESULTS:In the base-case analysis considering 2009-2013 antiretroviral drug (ARV) prices, adjusted incremental costs and QALYs were - €3296 (95% confidence interval [CI] - 5202 to - 1391) and 0.006 (95% CI - 0.021 to 0.033), respectively, over 2 years, suggesting that monotherapy was cost-effective with a probability of 100% at various cost-effectiveness thresholds. In scenario analyses considering 2018 ARV prices, monotherapy remained cost-effective but with a lower probability (94% vs. 100% in the base-case analysis). The current price of cART would have to decrease by 34% to be cost-effective with a probability of 95%. CONCLUSION:Monotherapy appears to be cost-effective compared with cART for virologically suppressed HIV-positive patients in France. CEPT analysis is a useful tool to identify the preferred strategy to adopt given that ARV prices change rapidly. TRIAL REGISTRATION:Clinicaltrials.gov identifier: NCT00946595.

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Combination therapy with anti-HIV-1 antibodies maintains viral suppression.

Publications

Combination therapy with anti-HIV-1 antibodies maintains viral suppression.

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