We have presented an analysis of the effectiveness and cost-effectiveness of two promising antiretroviral-based HIV prevention technologies: ART and PrEP. We found that targeting PrEP to individuals at particularly high risk of infection may be cost-saving, but that if identifying high-risk HIV-negative individuals is not practical, then implementing universal treatment, regardless of scale, would be the most cost-effective ART intervention to reduce HIV transmission in South Africa. Our analysis is unique in considering the joint outcomes and cost-effectiveness of implementing ART and PrEP for HIV control.
We found that scaling up ART programs provided greater value than untargeted PrEP programs. Compared with the status quo, scaling up ART, either according to current guidelines or with universal treatment, appeared more cost-effective than scaling up untargeted PrEP. Moreover, implementing PrEP in the general population was never preferable to increasing ART coverage before ART coverage reached 100%.
We have also shown that scaling up ART according to current guidelines is less cost-effective than scaling up universal treatment. Universal treatment averted more infections than current guidelines even at relatively small program scales. Scaling up ART according to guidelines is still considered cost-effective in South Africa according to thresholds articulated in the Commission on Macroeconomics and Health . However, universal treatment was associated with a greater number of infections averted and a greater gain in QALYs for each unit investment in resources relative to the status quo, and the results got increasingly attractive as we considered longer planning horizons. When looking at the results for 10 years, Universal ART appeared less favorable (while still cost-effective), at $490 per QALY gained versus status quo. Taking into account benefits and costs over 20 years, this cost was $310 per QALY. Hence, Universal ART becomes more attractive if we consider the long-term impact, and the effects may become even stronger with longer horizons. We chose to use a 20-year time horizon because, unlike longer horizons, this time frame is still considered relevant for practical decision-making.
Our analysis suggests that despite the effectiveness of oral PrEP, its costs make it a relatively low-value alternative if used in the general population. If, however, it can be targeted to individuals at higher risk of acquiring HIV and adherence can be maintained, then PrEP can potentially be cost-saving. The effectiveness of PrEP remains uncertain, as suggested by the recent mixed results of clinical trials and the challenges with adherence. Our sensitivity analyses showed that providing PrEP to high-risk populations can be cost-saving as long as PrEP effectiveness is greater than 10%.
Our analysis has clear implications for resource prioritization between ART and PrEP; however, its limitations are important to note. Scaling up ART or PrEP programs requires a substantial budget investment at a time of global economic uncertainty. Our analysis cannot determine whether these resources would be available, only that some investments provide greater returns than others (for example, Universal ART relative to Guidelines ART). For those reasons, we explored a wide range of implementation scales. In addition, there is considerable uncertainty associated with the long-term epidemic impact of universal treatment . To explore this issue, we performed sensitivity analyses on parameters affecting the effectiveness of ART programs, such as reduction in infectivity if receiving ART, and the rates of attrition from the program. Additional uncertainty is related to the potential consequences of sustained PrEP, both in terms of individual toxicities and its implications for resistance and future treatment options. As more data become available, model assumptions and structure may need to be further refined to incorporate these findings. Finally, our model was based on South African data, where more people live with HIV than any other country. Our estimates of the relative effectiveness of alternative approaches can be generalized to many other areas of southern Africa, but additional work would be needed to apply this work to regions or countries with a different epidemic pattern and different costs of health care.
A proliferation of new strategies to control HIV are developed and tested in South Africa, but economic circumstances require judicious use of scarce resources. Developed countries have recently updated guidelines to recommend universal ART, and the Center for Disease Control has provided guidance on the use of PrEP in men who have sex with men [40, 41]. Our analysis supports the new World Health Organization recommendations on ART for sero-discordant couples, and estimates the value of extending universal treatment to all infected individuals . Our work provides new insights into the joint effects of ART and PrEP in a generalized HIV epidemic, and the cost-effectiveness of strategies for program scale-up in developing countries. Implementing the strategies outlined by these models can lead to better use of scarce resources and can prevent a significant proportion of new HIV infections, in the long term leading to epidemic control.