Lifesaving HIV breakthroughs have changed the face of survival. But has it reshaped sexual behavior and also posed unforeseen public health challenges?
Study: An unintended consequence of a life-saving drug innovation: How HAART led to a resurgence of syphilis. Image credit: Sonis Photography/Shutterstock.com
Recent research published in health economics A breakthrough in antiretroviral therapy for HIV may have inadvertently sparked a resurgence of the sexually transmitted disease syphilis in the United States, researchers have revealed.
Improved HIV survival coincides with changing STI trends
The prevalence of penicillin and changing gender norms led to a more than 97 percent decline in the incidence of the sexually transmitted disease syphilis in the United States between 1943 and 2000.
During this period, human immunodeficiency virus (HIV) emerged as the leading cause of death, and by 1993 it was the most common cause of death among individuals aged 25 to 44 years, especially men aged 25 to 44 years who have sex with men.
The discovery of highly active antiretroviral therapy (HAART) was a major medical breakthrough in 1996 and has shown great promise in effectively suppressing HIV replication over long periods of time. With the use of HAART, medical professionals were finally able to transform HIV from a nearly fatal condition to a chronic, manageable condition. With the widespread use of HAART, the HIV-related death rate will reach an all-time low of 4,748 people in 2023.
Unfortunately, the introduction of HAART coincided with a sudden reversal of a long-standing downward trend in syphilis incidence, but the country continued to see a rapid increase in syphilis incidence, reaching a 60-year peak of 62.2 per 100,000 people in 2022.
Given this confluence of two major events, researchers from the University of Texas, Baylor University, and the University of North Carolina hypothesized that HAART-mediated transformation of HIV from a late stage state to a manageable chronic disease is partially responsible for the observed resurgence in syphilis incidence.
Mechanisms that may cause syphilis recurrence
The researchers considered two mechanisms that could potentially contribute to the resurgence of syphilis in the United States.
The first mechanism may be an increase in high-risk sexual behaviors among HIV-infected or uninfected individuals due to improved health status with HAART and treatment-related changes in perceived HIV risk. However, reducing the perceived risk of viral infection may be less relevant in this context, as until the late 2000s there was a lack of widespread public messaging emphasizing this risk reduction.
A second mechanism may be that the introduction of HAART increased the likelihood of acquiring sexually transmitted infections as a natural consequence of extending the lifespan of people with HIV. The introduction of HAART has saved the lives of thousands of people living with HIV, allowing them to lead relatively normal lives.
Evidence supporting these mechanisms
Researchers comprehensively analyzed information from the Centers for Disease Control and Prevention (CDC) and pharmaceutical industry sales data, providing evidence that both mechanisms likely contributed. However, increased lifespan alone cannot fully explain the observed trends.
The analysis found that with the introduction of HAART, syphilis prevalence began to increase by a differential among men in states that previously had high prevalence of acquired immunodeficiency syndrome (AIDS), the most advanced stage of HIV infection. These states had the most widespread prescribing of HAART and the greatest reductions in HIV-related mortality.
Specifically, the analysis showed that the introduction of HAART added approximately 71,190 syphilis diagnoses between 1996 and 2008. In a counterfactual scenario without HAART, the number of cases would have decreased by approximately 71,190 during this period, representing a decrease of approximately 81% compared to observed cases. Notably, syphilis incidence among women continued to decline.
Further analysis revealed that the observed increase in syphilis prevalence among men cannot be explained solely by the increased lifespan of people living with HIV, highlighting the important role of high-risk sexual behavior. It is inferred from the pattern of occurrence that causes such unintended consequences of major medical advances.
Additionally, several analyzes checking the robustness of the findings revealed that the observed increase in syphilis incidence was not caused by changes in drug use, changes in social attitudes toward sex with men, or changes in public health funding.
Findings highlight unintended public health trade-offs from innovation
The study highlights that not only increased longevity after the introduction of HAART, but also behavioral changes in people toward higher-risk sexual behaviors, such as unprotected sex, may have increased the risk of contracting sexually transmitted infections and caused a resurgence of syphilis.
Given these results, the researchers suggest developing complementary interventions to address behavioral changes unintentionally induced by HAART and alleviate some of its negative effects. They suggest expanding public health campaigns to promote safer sex practices and increasing testing for sexually transmitted diseases.
They particularly emphasize that the study results should not be interpreted as a criticism of HAART itself, as the life-saving benefits of HAART far outweigh the costs associated with the observed unintended consequences.
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Reference magazines:
- Beheshti, D., Cunningham, S., Eiram, N. (2026). An unintended consequence of a life-saving drug innovation: How HAART led to a resurgence of syphilis. Health economics. Doi: https://onlinelibrary.wiley.com/doi/10.1002/hec.70100. https://onlinelibrary.wiley.com/doi/10.1002/hec.70100
