Control groups for HIV prevention efficacy trials: what does the future hold?

Purpose of reviewEnding the HIV epidemic will require the development of additional effective immune-mediated and nonimmune-mediated means of HIV prevention. Evaluating novel interventions requires large, controlled trials demonstrating efficacy. Recent advances in the field of HIV prevention necessitate new approaches to efficacy trial design.Three classes of efficacy trial designs are possible: standard of prevention-controlled trials, active-controlled trials, and active-controlled trials augmented with external control data. Recent experience with these approaches provides lessons on considerations around and success of the designs. Additional experience and development is needed for the augmented active-controlled trial design.Efficacy trials of new HIV prevention interventions are feasible but require careful consideration, given the complexity and dynamic state of the prevention field. While standard of prevention-controlled efficacy trials are reasonable approaches for HIV vaccine and monoclonal antibody efficacy trials, trials of new antiretroviral agents may require active-controlled designs.Papers of particular interest, published within the annual period of review, have been highlighted as:Major advances in biomedical HIV prevention have occurred in the last two decades: research demonstrated that completely virally suppressed persons living with HIV cannot transmit HIV to their sexual partners [1-3], ('U = U') [4], and oral antiretrovirals (ARVs), when taken as preexposure prophylaxis (PrEP), are effective [5-7]. More recently, PrEP with long-acting injectable cabotegravir (CAB-LA) was found highly effective [8,9] and may circumvent some of the challenges associated with pill-taking adherence.These advances bode well for reducing population HIV incidence [10,11], but create challenges testing new interventions. Individual choice is critical in HIV prevention uptake [12,13], thus a portfolio of prevention options is required. However, an effective HIV vaccine, which may be necessary for ending the HIV epidemic, remains elusive [14,15,16].A standard of prevention-controlled efficacy trial including a placebo arm has traditionally been required for regulatory approval of new HIV prevention modalities. Although there are settings and populations in which this design remains appropriate, there are other settings where alternative control groups are needed.We overview three main study design options for future HIV prevention efficacy trials: standard of prevention-controlled, active-controlled, and active-controlled augmented with external control data. no caption availablePurpose of reviewEnding the HIV epidemic will require the development of additional effective immune-mediated and nonimmune-mediated means of HIV prevention. Evaluating novel interventions requires large, controlled trials demonstrating efficacy. Recent advances in the field of HIV prevention necessitate new approaches to efficacy trial design.Three classes of efficacy trial designs are possible: standard of prevention-controlled trials, active-controlled trials, and active-controlled trials augmented with external control data. Recent experience with these approaches provides lessons on considerations around and success of the designs. Additional experience and development is needed for the augmented active-controlled trial design.Efficacy trials of new HIV prevention interventions are feasible but require careful consideration, given the complexity and dynamic state of the prevention field. While standard of prevention-controlled efficacy trials are reasonable approaches for HIV vaccine and monoclonal antibody efficacy trials, trials of new antiretroviral agents may require active-controlled designs.Papers of particular interest, published within the annual period of review, have been highlighted as:Major advances in biomedical HIV prevention have occurred in the last two decades: research demonstrated that completely virally suppressed persons living with HIV cannot transmit HIV to their sexual partners [1-3], ('U = U') [4], and oral antiretrovirals (ARVs), when taken as preexposure prophylaxis (PrEP), are effective [5-7]. More recently, PrEP with long-acting injectable cabotegravir (CAB-LA) was found highly effective [8,9] and may circumvent some of the challenges associated with pill-taking adherence.These advances bode well for reducing population HIV incidence [10,11], but create challenges testing new interventions. Individual choice is critical in HIV prevention uptake [12,13], thus a portfolio of prevention options is required. However, an effective HIV vaccine, which may be necessary for ending the HIV epidemic, remains elusive [14,15,16].A standard of prevention-controlled efficacy trial including a placebo arm has traditionally been required for regulatory approval of new HIV prevention modalities. Although there are settings and populations in which this design remains appropriate, there are other settings where alternative control groups are needed.We overview three main study design options for future HIV prevention efficacy trials: standard of prevention-controlled, active-controlled, and active-controlled augmented with external control data. no caption availablePurpose of reviewEnding the HIV epidemic will require the development of additional effective immune-mediated and nonimmune-mediated means of HIV prevention. Evaluating novel interventions requires large, controlled trials demonstrating efficacy. Recent advances in the field of HIV prevention necessitate new approaches to efficacy trial design.Three classes of efficacy trial designs are possible: standard of prevention-controlled trials, active-controlled trials, and active-controlled trials augmented with external control data. Recent experience with these approaches provides lessons on considerations around and success of the designs. Additional experience and development is needed for the augmented active-controlled trial design.Efficacy trials of new HIV prevention interventions are feasible but require careful consideration, given the complexity and dynamic state of the prevention field. While standard of prevention-controlled efficacy trials are reasonable approaches for HIV vaccine and monoclonal antibody efficacy trials, trials of new antiretroviral agents may require active-controlled designs.Papers of particular interest, published within the annual period of review, have been highlighted as:Major advances in biomedical HIV prevention have occurred in the last two decades: research demonstrated that completely virally suppressed persons living with HIV cannot transmit HIV to their sexual partners [1-3], ('U = U') [4], and oral antiretrovirals (ARVs), when taken as preexposure prophylaxis (PrEP), are effective [5-7]. More recently, PrEP with long-acting injectable cabotegravir (CAB-LA) was found highly effective [8,9] and may circumvent some of the challenges associated with pill-taking adherence.These advances bode well for reducing population HIV incidence [10,11], but create challenges testing new interventions. Individual choice is critical in HIV prevention uptake [12,13], thus a portfolio of prevention options is required. However, an effective HIV vaccine, which may be necessary for ending the HIV epidemic, remains elusive [14,15,16].A standard of prevention-controlled efficacy trial including a placebo arm has traditionally been required for regulatory approval of new HIV prevention modalities. Although there are settings and populations in which this design remains appropriate, there are other settings where alternative control groups are needed.We overview three main study design options for future HIV prevention efficacy trials: standard of prevention-controlled, active-controlled, and active-controlled augmented with external control data. no caption availablePurpose of reviewEnding the HIV epidemic will require the development of additional effective immune-mediated and nonimmune-mediated means of HIV prevention. Evaluating novel interventions requires large, controlled trials demonstrating efficacy. Recent advances in the field of HIV prevention necessitate new approaches to efficacy trial design.Three classes of efficacy trial designs are possible: standard of prevention-controlled trials, active-controlled trials, and active-controlled trials augmented with external control data. Recent experience with these approaches provides lessons on considerations around and success of the designs. Additional experience and development is needed for the augmented active-controlled trial design.Efficacy trials of new HIV prevention interventions are feasible but require careful consideration, given the complexity and dynamic state of the prevention field. While standard of prevention-controlled efficacy trials are reasonable approaches for HIV vaccine and monoclonal antibody efficacy trials, trials of new antiretroviral agents may require active-controlled designs.Papers of particular interest, published within the annual period of review, have been highlighted as:Major advances in biomedical HIV prevention have occurred in the last two decades: research demonstrated that completely virally suppressed persons living with HIV cannot transmit HIV to their sexual partners [1-3], ('U = U') [4], and oral antiretrovirals (ARVs), when taken as preexposure prophylaxis (PrEP), are effective [5-7]. More recently, PrEP with long-acting injectable cabotegravir (CAB-LA) was found highly effective [8,9] and may circumvent some of the challenges associated with pill-taking adherence.These advances bode well for reducing population HIV incidence [10,11], but create challenges testing new interventions. Individual choice is critical in HIV prevention uptake [12,13], thus a portfolio of prevention options is required. However, an effective HIV vaccine, which may be necessary for ending the HIV epidemic, remains elusive [14,15,16].A standard of prevention-controlled efficacy trial including a placebo arm has traditionally been required for regulatory approval of new HIV prevention modalities. Although there are settings and populations in which this design remains appropriate, there are other settings where alternative control groups are needed.We overview three main study design options for future HIV prevention efficacy trials: standard of prevention-controlled, active-controlled, and active-controlled augmented with external control data. no caption availablePurpose of reviewEnding the HIV epidemic will require the development of additional effective immune-mediated and nonimmune-mediated means of HIV prevention. Evaluating novel interventions requires large, controlled trials demonstrating efficacy. Recent advances in the field of HIV prevention necessitate new approaches to efficacy trial design.Three classes of efficacy trial designs are possible: standard of prevention-controlled trials, active-controlled trials, and active-controlled trials augmented with external control data. Recent experience with these approaches provides lessons on considerations around and success of the designs. Additional experience and development is needed for the augmented active-controlled trial design.Efficacy trials of new HIV prevention interventions are feasible but require careful consideration, given the complexity and dynamic state of the prevention field. While standard of prevention-controlled efficacy trials are reasonable approaches for HIV vaccine and monoclonal antibody efficacy trials, trials of new antiretroviral agents may require active-controlled designs.Papers of particular interest, published within the annual period of review, have been highlighted as:Major advances in biomedical HIV prevention have occurred in the last two decades: research demonstrated that completely virally suppressed persons living with HIV cannot transmit HIV to their sexual partners [1-3], ('U = U') [4], and oral antiretrovirals (ARVs), when taken as preexposure prophylaxis (PrEP), are effective [5-7]. More recently, PrEP with long-acting injectable cabotegravir (CAB-LA) was found highly effective [8,9] and may circumvent some of the challenges associated with pill-taking adherence.These advances bode well for reducing population HIV incidence [10,11], but create challenges testing new interventions. Individual choice is critical in HIV prevention uptake [12,13], thus a portfolio of prevention options is required. However, an effective HIV vaccine, which may be necessary for ending the HIV epidemic, remains elusive [14,15,16].A standard of prevention-controlled efficacy trial including a placebo arm has traditionally been required for regulatory approval of new HIV prevention modalities. Although there are settings and populations in which this design remains appropriate, there are other settings where alternative control groups are needed.We overview three main study design options for future HIV prevention efficacy trials: standard of prevention-controlled, active-controlled, and active-controlled augmented with external control data. no caption availablePurpose of reviewEnding the HIV epidemic will require the development of additional effective immune-mediated and nonimmune-mediated means of HIV prevention. Evaluating novel interventions requires large, controlled trials demonstrating efficacy. Recent advances in the field of HIV prevention necessitate new approaches to efficacy trial design.Three classes of efficacy trial designs are possible: standard of prevention-controlled trials, active-controlled trials, and active-controlled trials augmented with external control data. Recent experience with these approaches provides lessons on considerations around and success of the designs. Additional experience and development is needed for the augmented active-controlled trial design.Efficacy trials of new HIV prevention interventions are feasible but require careful consideration, given the complexity and dynamic state of the prevention field. While standard of prevention-controlled efficacy trials are reasonable approaches for HIV vaccine and monoclonal antibody efficacy trials, trials of new antiretroviral agents may require active-controlled designs. Papers of particular interest, published within the annual period of review, have been highlighted as:Major advances in biomedical HIV prevention have occurred in the last two decades: research demonstrated that completely virally suppressed persons living with HIV cannot transmit HIV to their sexual partners [1-3], ('U = U') [4], and oral antiretrovirals (ARVs), when taken as preexposure prophylaxis (PrEP), are effective [5-7]. More recently, PrEP with long-acting injectable cabotegravir (CAB-LA) was found highly effective [8,9] and may circumvent some of the challenges associated with pill-taking adherence.These advances bode well for reducing population HIV incidence [10,11], but create challenges testing new interventions. Individual choice is critical in HIV prevention uptake [12,13], thus a portfolio of prevention options is required. However, an effective HIV vaccine, which may be necessary for ending the HIV epidemic, remains elusive [14,15,16].A standard of prevention-controlled efficacy trial including a placebo arm has traditionally been required for regulatory approval of new HIV prevention modalities. Although there are settings and populations in which this design remains appropriate, there are other settings where alternative control groups are needed.We overview three main study design options for future HIV prevention efficacy trials: standard of prevention-controlled, active-controlled, and active-controlled augmented with external control data. no caption availablePurpose of reviewEnding the HIV epidemic will require the development of additional effective immune-mediated and nonimmune-mediated means of HIV prevention. Evaluating novel interventions requires large, controlled trials demonstrating efficacy. Recent advances in the field of HIV prevention necessitate new approaches to efficacy trial design.Three classes of efficacy trial designs are possible: standard of prevention-controlled trials, active-controlled trials, and active-controlled trials augmented with external control data. Recent experience with these approaches provides lessons on considerations around and success of the designs. Additional experience and development is needed for the augmented active-controlled trial design.Efficacy trials of new HIV prevention interventions are feasible but require careful consideration, given the complexity and dynamic state of the prevention field. While standard of prevention-controlled efficacy trials are reasonable approaches for HIV vaccine and monoclonal antibody efficacy trials, trials of new antiretroviral agents may require active-controlled designs.Papers of particular interest, published within the annual period of review, have been highlighted as:Major advances in biomedical HIV prevention have occurred in the last two decades: research demonstrated that completely virally suppressed persons living with HIV cannot transmit HIV to their sexual partners [1-3], ('U = U') [4], and oral antiretrovirals (ARVs), when taken as preexposure prophylaxis (PrEP), are effective [5-7]. More recently, PrEP with long-acting injectable cabotegravir (CAB-LA) was found highly effective [8,9] and may circumvent some of the challenges associated with pill-taking adherence.These advances bode well for reducing population HIV incidence [10,11], but create challenges testing new interventions. Individual choice is critical in HIV prevention uptake [12,13], thus a portfolio of prevention options is required. However, an effective HIV vaccine, which may be necessary for ending the HIV epidemic, remains elusive [14,15,16]. A standard of prevention-controlled efficacy trial including a placebo arm has traditionally been required for regulatory approval of new HIV prevention modalities. Although there are settings and populations in which this design remains appropriate, there are other settings where alternative control groups are needed.We overview three main study design options for future HIV prevention efficacy trials: standard of prevention-controlled, active-controlled, and active-controlled augmented with external control data. no caption availablePurpose of reviewEnding the HIV epidemic will require the development of additional effective immune-mediated and nonimmune-mediated means of HIV prevention. Evaluating novel interventions requires large, controlled trials demonstrating efficacy. Recent advances in the field of HIV prevention necessitate new approaches to efficacy trial design.Three classes of efficacy trial designs are possible: standard of prevention-controlled trials, active-controlled trials, and active-controlled trials augmented with external control data. Recent experience with these approaches provides lessons on considerations around and success of the designs. Additional experience and development is needed for the augmented active-controlled trial design.Efficacy trials of new HIV prevention interventions are feasible but require careful consideration, given the complexity and dynamic state of the prevention field. While standard of prevention-controlled efficacy trials are reasonable approaches for HIV vaccine and monoclonal antibody efficacy trials, trials of new antiretroviral agents may require active-controlled designs.Papers of particular interest, published within the annual period of review, have been highlighted as:Major advances in biomedical HIV prevention have occurred in the last two decades: research demonstrated that completely virally suppressed persons living with HIV cannot transmit HIV to their sexual partners [1-3], ('U = U') [4], and oral antiretrovirals (ARVs), when taken as preexposure prophylaxis (PrEP), are effective [5-7]. More recently, PrEP with long-acting injectable cabotegravir (CAB-LA) was found highly effective [8,9] and may circumvent some of the challenges associated with pill-taking adherence.These advances bode well for reducing population HIV incidence [10,11], but create challenges testing new interventions. Individual choice is critical in HIV prevention uptake [12,13], thus a portfolio of prevention options is required. However, an effective HIV vaccine, which may be necessary for ending the HIV epidemic, remains elusive [14,15,16].A standard of prevention-controlled efficacy trial including a placebo arm has traditionally been required for regulatory approval of new HIV prevention modalities. Although there are settings and populations in which this design remains appropriate, there are other settings where alternative control groups are needed.We overview three main study design options for future HIV prevention efficacy trials: standard of prevention-controlled, active-controlled, and active-controlled augmented with external control data. no caption availablePurpose of reviewEnding the HIV epidemic will require the development of additional effective immune-mediated and nonimmune-mediated means of HIV prevention. Evaluating novel interventions requires large, controlled trials demonstrating efficacy. Recent advances in the field of HIV prevention necessitate new approaches to efficacy trial design. Three classes of efficacy trial designs are possible: standard of prevention-controlled trials, active-controlled trials, and active-controlled trials augmented with external control data. Recent experience with these approaches provides lessons on considerations around and success of the designs. Additional experience and development is needed for the augmented active-controlled trial design.Efficacy trials of new HIV prevention interventions are feasible but require careful consideration, given the complexity and dynamic state of the prevention field. While standard of prevention-controlled efficacy trials are reasonable approaches for HIV vaccine and monoclonal antibody efficacy trials, trials of new antiretroviral agents may require active-controlled designs.Papers of particular interest, published within the annual period of review, have been highlighted as:Major advances in biomedical HIV prevention have occurred in the last two decades: research demonstrated that completely virally suppressed persons living with HIV cannot transmit HIV to their sexual partners [1-3], ('U = U') [4], and oral antiretrovirals (ARVs), when taken as preexposure prophylaxis (PrEP), are effective [5-7]. More recently, PrEP with long-acting injectable cabotegravir (CAB-LA) was found highly effective [8,9] and may circumvent some of the challenges associated with pill-taking adherence.These advances bode well for reducing population HIV incidence [10,11], but create challenges testing new interventions. Individual choice is critical in HIV prevention uptake [12,13], thus a portfolio of prevention options is required. However, an effective HIV vaccine, which may be necessary for ending the HIV epidemic, remains elusive [14,15,16].A standard of prevention-controlled efficacy trial including a placebo arm has traditionally been required for regulatory approval of new HIV prevention modalities. Although there are settings and populations in which this design remains appropriate, there are other settings where alternative control groups are needed.We overview three main study design options for future HIV prevention efficacy trials: standard of prevention-controlled, active-controlled, and active-controlled augmented with external control data. no caption available