The advent of HIV/AIDS in 1981 transformed Kaposi’s sarcoma (KS) from a medical oddity to an epidemic [1
]. In resource-rich settings, the cumulative lifetime incidence of KS among HIV-infected homosexual men reached nearly 40% [2
]. In many resource-limited settings, particularly sub-Saharan Africa, the extent of the HIV epidemic resulted in KS becoming the most common malignancy not just among HIV-infected individuals but among all adults [3
]. Yet, just as abruptly as AIDS impacted KS, the advent of potent antiretroviral therapy (ART) has transformed HIV disease. In resource-rich areas where ART is routinely available, the lifespan of HIV-infected individuals has nearly normalized [4
]. ART has come more slowly to resource-limited settings, but by the end of 2010 over 5 million patients in sub-Saharan Africa alone had initiated ART [5
] with overall reduction in mortality comparable to resource-rich settings [6
While the general impact of ART on morbidity and mortality has been well documented, this review will summarize the specific influence of ART on KS incidence. We shall summarize the abundant data from resource-rich settings and examine emerging data from resource-limited settings. Importantly, we will clarify what is referred to as the “impact”, “influence” or “effect” of ART on KS occurrence. We believe that patients and practitioners may be interested in as many as five questions:
- Question 1. What is the individual patient-level efficacy of ART on KS incidence? This is akin to the question which would be addressed in a randomized trial of ART versus no ART in select HIV-infected patients with optimal adherence. It asks: what is the best effect on KS incidence that could be expected among ART users? While interesting, such a trial has never been conducted because it is now unethical, and the question has never been addressed with observational data. Hence, we will not summarize literature for this question.
- Question 2. What is the individual patient-level effectiveness of ART use on KS incidence? This is akin to the question in a randomized trial of ART versus no ART in “real world” clinical practice, which allows for variable ART adherence and other circumstances. Such a randomized trial also cannot be ethically performed today, but several observational studies have attempted to estimate this effect.
- Question 3. What is the population-level effectiveness of ART on KS incidence? This is what would be addressed in a randomized trial of “real world” communities of HIV-infected individuals comparing availability of ART in a community versus no availability. This question incorporates the answer to question 2 above (individual patient-level effectiveness), but it extends upon it by encompassing the act of starting therapy. In other words, population-level effectiveness is a function of starting ART, adhering to ART, and the inherent efficacy of ART.
- Question 4. How has KS incidence among HIV-infected persons changed since the availability of ART? While the randomized trial that addresses this question can be stated — what is the effect on KS incidence if one is randomized to live in the pre-ART era (up to 1996) versus the era when ART is available (after 1996) — it has no basis in reality. Yet, the question is relevant from a public health and population perspective in that it asks how KS incidence has changed among all HIV-infected individuals since ART has become available. While question 3 asks specifically whether ART per se is responsible for a change in KS incidence among the HIV-infected population (independent of other factors), question 4 simply asks whether KS incidence has changed since ART became available regardless of why.
In reviewing the impact of ART on KS incidence, we focused on the last four questions, namely individual patient-level effectiveness, population-level effectiveness, change in KS incidence in the ART era, and residual risk.