Misinterpretation of HIV Preexposure Prophylaxis Findings

To the Editor—The analysis by Schneider and colleagues [1] raises two concerns—one methodological, one clinical—that undermine the policy conclusions of the article. A basic tenet of economic evaluation holds that mutually exclusive strategies should be compared based on their marginal contribution—not their absolute contribution—to both costs and benefits [2, 3]. Yet, the paper presents cost-effectiveness ratios that evaluate every strategy using the status quo as the basis of comparison. This error leads to a serious misinterpretation of findings, as noted in Table Table11. Table 1. Original and Corrected Versions of Schneider et al's Table 1 The corrected version highlights a critical finding that is not apparent in the original: Many strategies are dominated (ie, they cost more and deliver fewer benefits than 1 or more other strategies) and should therefore be eliminated from consideration. Indeed, there are only 4 nondominated strategies for which it is appropriate to report cost-effectiveness ratios. This mistake carries over to Figure 2 in Schneider et al's article. Although points on the figure are correctly arrayed, the 3 dark lines emanating from the origin (labeled “ICER Threshold”) have no interpretable meaning. Here again, the error lies in comparing everything to the status quo. By convention [2, 3], the figure should instead highlight the efficient frontier (ie, the convex envelope defined by the nondominated interventions); this outer boundary denotes the greatest possible quality-adjusted life-years that can be obtained for any given investment level. The correct interpretation of the output from the authors’ model is that preexposure prophylaxis (PrEP) meets Australian standards of cost-effectiveness only when targeted to the uninfected members of regular, serodiscordant partnerships (strategies 10 and 11). Closer examination of the modeling assumptions for these 2 strategies reveals the second concern—that the analysis does not appear to account for the potential of antiretroviral therapy (ART) to offset the benefits of PrEP in serodiscordant partnerships. Both Australian and international guidelines strongly recommend offering ART to human immunodeficiency virus (HIV)–infected partners in serodiscordant couples to reduce HIV transmission to uninfected partners [4, 5]. Concomitant ART will dramatically reduce the impact and the cost-effectiveness of targeting PrEP to the uninfected partner.