Targeting Pre-Exposure Prophylaxis Among MSM
Figure 1 (left panel) gives the average over 10 simulations in the US model of the percent reduction in incident infections compared with no intervention across targeting strategies, plotted against PRPCR. As expected, effectiveness increases more or less monotonically in PRPCR under all targeting strategies. Percent of infections averted ranges from <1% with low uptake and adherence in the MAIN targeting strategy to ~50% with high uptake and adherence under the RECEP strategy. The right panel shows person-years on PrEP per infection averted for each targeting strategy. The reduction in infections for the RECEP strategy (targeting 91% of the population in the United States or 77% in Peru) is only modestly higher than for CAI40 (where only 40% of the population is targeted). These diminishing returns are reflected in the substantially greater efficiency of CAI40, measured by person-years on PrEP per infection averted. The MAIN strategy, however, is relatively ineffective in averting infections, with reductions ranging from 2% to 13%, but relatively efficient.
(Enlarge Image)
Figure 1.
Percent of new infections averted plotted against the population PRPCR in the targeted population (L) and person-years on PrEP per infection averted by targeting strategy (R) for scenarios in the United States.
Figure 1 also shows that the CAI20 strategy is less effective than CAI40, as measured by the percent of infections averted but with substantially greater efficiency. Indeed, the efficiency for CAI20 is even greater than that for MAIN. Also, targeting men in serodiscordant main partnerships (MAIN + CAI20) increases effectiveness to levels comparable with CAI40, whereas only decreasing efficiency to midway between CAI20 and CAI40.
Combining the MAIN and CAI20 interventions (MAIN + CAI20) results in an overall reduction in incidence that is slightly smaller than the sum of the effects of the 2 interventions alone. The slight penalty in net effectiveness is likely due to the fact that some men in serodiscordant main partnerships also have many casual CAI contacts and thus would be targeted by both strategies.
Notably, for the RECEP and CAI40 scenarios, the percent of new infections averted is greater than the PRPCR. For example, in the CAI40 strategy, with 20% uptake and the baseline (50-25-25) adherence profile, PRPCR is only 8.3% among the 40% of men in the targeted population, but incidence is reduced by 12.4%. This occurs despite the attenuation due to repeated exposures and is attributable to indirect long-term effects.
Figure 2 shows analogous results for Peru; they are broadly similar to results in Figure 1 for the Unites States. The CAI20 strategy seems to be somewhat less effective in reducing new infections at the population level than the same strategy in the United States. We again see MAIN + CAI20 as a targeting strategy giving similar reductions in incidence to CAI40 but at a level of efficiency more similar to CAI20. Overall, the reductions in incidence for any given scenario are slightly smaller in Peru, and the person-years on PrEP per infection averted are slightly higher, but substantively the conclusions remain the same.
(Enlarge Image)
Figure 2.
Percent of new infections averted plotted against the population PRPCR in the targeted population (L) and person-years on PrEP per infection averted by targeting strategy (R) for scenarios in Peru.
In assessing risk compensation, we focused on the most efficient scenario (MAIN + CAI20), with 40% uptake and an adherence profile of 25-50-25. Figure 3 is a contour plot showing the percent change in the number of new infections over 10 years for each risk compensation scenario for the United States. The contour at 0 indicates scenarios where PrEP has no net effect on incidence after accounting for risk compensation, whereas those with negative values indicate a decrease in incidence on average relative to no PrEP. Darker shading indicates stronger evidence for a net effect, whereas results in the white region are consistent with no PrEP effect. The figure shows evidence for a beneficial effect of PrEP despite increases of up to 150% in casual CAI for almost any level of increase in CAI in main partnerships, which has a much weaker effect. Significant harm is observed only with 3-fold increases in both. These results suggest that the benefits of PrEP would be quite robust to risk compensation in the United States.
(Enlarge Image)
Figure 3.
Effects of risk compensation on cases averted in the United States. Contour lines represent the expected percent change in the number of new infections, whereas the shading indicates the strength of evidence for the effect.
(Enlarge Image)
Figure 4.
Effects of risk compensation on cases averted in Peru. Contour lines represent the expected percent change in the number of new infections, whereas the shading indicates the strength of evidence for the effect.
Results
Figure 1 (left panel) gives the average over 10 simulations in the US model of the percent reduction in incident infections compared with no intervention across targeting strategies, plotted against PRPCR. As expected, effectiveness increases more or less monotonically in PRPCR under all targeting strategies. Percent of infections averted ranges from <1% with low uptake and adherence in the MAIN targeting strategy to ~50% with high uptake and adherence under the RECEP strategy. The right panel shows person-years on PrEP per infection averted for each targeting strategy. The reduction in infections for the RECEP strategy (targeting 91% of the population in the United States or 77% in Peru) is only modestly higher than for CAI40 (where only 40% of the population is targeted). These diminishing returns are reflected in the substantially greater efficiency of CAI40, measured by person-years on PrEP per infection averted. The MAIN strategy, however, is relatively ineffective in averting infections, with reductions ranging from 2% to 13%, but relatively efficient.
(Enlarge Image)
Figure 1.
Percent of new infections averted plotted against the population PRPCR in the targeted population (L) and person-years on PrEP per infection averted by targeting strategy (R) for scenarios in the United States.
Figure 1 also shows that the CAI20 strategy is less effective than CAI40, as measured by the percent of infections averted but with substantially greater efficiency. Indeed, the efficiency for CAI20 is even greater than that for MAIN. Also, targeting men in serodiscordant main partnerships (MAIN + CAI20) increases effectiveness to levels comparable with CAI40, whereas only decreasing efficiency to midway between CAI20 and CAI40.
Combining the MAIN and CAI20 interventions (MAIN + CAI20) results in an overall reduction in incidence that is slightly smaller than the sum of the effects of the 2 interventions alone. The slight penalty in net effectiveness is likely due to the fact that some men in serodiscordant main partnerships also have many casual CAI contacts and thus would be targeted by both strategies.
Notably, for the RECEP and CAI40 scenarios, the percent of new infections averted is greater than the PRPCR. For example, in the CAI40 strategy, with 20% uptake and the baseline (50-25-25) adherence profile, PRPCR is only 8.3% among the 40% of men in the targeted population, but incidence is reduced by 12.4%. This occurs despite the attenuation due to repeated exposures and is attributable to indirect long-term effects.
Figure 2 shows analogous results for Peru; they are broadly similar to results in Figure 1 for the Unites States. The CAI20 strategy seems to be somewhat less effective in reducing new infections at the population level than the same strategy in the United States. We again see MAIN + CAI20 as a targeting strategy giving similar reductions in incidence to CAI40 but at a level of efficiency more similar to CAI20. Overall, the reductions in incidence for any given scenario are slightly smaller in Peru, and the person-years on PrEP per infection averted are slightly higher, but substantively the conclusions remain the same.
(Enlarge Image)
Figure 2.
Percent of new infections averted plotted against the population PRPCR in the targeted population (L) and person-years on PrEP per infection averted by targeting strategy (R) for scenarios in Peru.
In assessing risk compensation, we focused on the most efficient scenario (MAIN + CAI20), with 40% uptake and an adherence profile of 25-50-25. Figure 3 is a contour plot showing the percent change in the number of new infections over 10 years for each risk compensation scenario for the United States. The contour at 0 indicates scenarios where PrEP has no net effect on incidence after accounting for risk compensation, whereas those with negative values indicate a decrease in incidence on average relative to no PrEP. Darker shading indicates stronger evidence for a net effect, whereas results in the white region are consistent with no PrEP effect. The figure shows evidence for a beneficial effect of PrEP despite increases of up to 150% in casual CAI for almost any level of increase in CAI in main partnerships, which has a much weaker effect. Significant harm is observed only with 3-fold increases in both. These results suggest that the benefits of PrEP would be quite robust to risk compensation in the United States.
(Enlarge Image)
Figure 3.
Effects of risk compensation on cases averted in the United States. Contour lines represent the expected percent change in the number of new infections, whereas the shading indicates the strength of evidence for the effect.
(Enlarge Image)
Figure 4.
Effects of risk compensation on cases averted in Peru. Contour lines represent the expected percent change in the number of new infections, whereas the shading indicates the strength of evidence for the effect.