A strategy for accelerating the development of preventive AIDS vaccines
None of the current vaccine candidates is likely to prevent infection completely, because they do not induce potent neutralizing antibodies against primary HIV isolates [4,5]. The failure to protect by antibodies against the HIV envelope may be the result of HIV antigenic variation, a lack of neutralization potency, or additional factors . Most of the current candidate vaccines  are designed to induce cell-mediated immunity, which is expected to decrease the HIV viral load in vaccinated individuals who become infected, thereby potentially slowing or preventing progression to AIDS and decreasing infectiousness [8–11]. In HIV-infected individuals, the time to key clinical events in HIV-1 disease progression was significantly longer for those with viral load setpoints 0.5–1.25 log10 copies/ml lower than the reference group [12,13]. Studies in non-human primates have demonstrated that vaccine-induced viral load reduction accompanies increased survival . By quantifying the anticipated clinical benefits of reducing the viral load at setpoint, Gupta and colleagues  have supported the use of virological end points in HIV-1 vaccine trials.
Given the hypothesis that the primary effect of current vaccines will be to reduce viral load, we propose a more efficient strategy for determining the value of various vaccine approaches: screening test of concept (STOC) trials. The primary endpoint of a STOC trial is plasma HIV-RNA viral load at setpoint in individuals who acquire HIV. Approximately 30 total HIV infections are required to detect a 1.0 log10 reduction in viral load with adequate statistical power. Data from these trials can demonstrate biological plausibility that a cell-mediated immunity-based vaccine has a meaningful effect, although if the reduction were only 1.0 log10, the next step might be to begin an interactive process, improving the vaccine and conducting another trial. Along with evidence of efficacy in animal models, safety and immunogenicity data, and feasibility of vaccine manufacture and distribution, these trials could serve to accelerate promising candidates to phase III trials, or limit the use of resources on less effective candidates.