Early initiation of HIV treatment reduces subsequent risk for cancers unrelated to AIDS

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  • Dutch researchers compared data between people who started HIV treatment early and late
  • Over 22 years, people who started HIV treatment early had a 40% reduced risk for many cancers
  • This study adds more evidence for the benefits of starting HIV treatment early

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When taken as directed, HIV treatment (antiretroviral therapy; ART) helps to reduce the amount of HIV in the blood. Over time, continued use of ART is usually able to suppress HIV to the point where it cannot be detected in blood samples with routine laboratory tests. This suppression of HIV allows the immune system to mostly repair itself. The result is that with continued care and monitoring, and all other things being equal, many people with HIV who use ART are living well into their senior years. 

The profile of cancers that people with HIV are at risk for developing has largely changed since 1996, when ART first became available in Canada and other high-income countries. Studies have found that the strengthening of the immune system caused by ART has led to a significant reduction in the risk for AIDS-related cancers. 

However, since 1996, there has been a gradual shift to a relatively increased risk for cancers unrelated to AIDS. Part of the reason for this shift is that as people with HIV live longer, they become at risk for certain cancers (unrelated to HIV). Another reason may be that viral coinfections in some people with HIV become chronic, and while these coinfections may be low-lying, they cannot be eradicated. Furthermore, research suggests that there are subtle immunological defects that persist despite the use of ART.

Some studies have found that waiting until CD4+ counts are low to initiate ART causes long-lasting injury to the immune system that cannot be fully reversed with ART. However, these studies have not provided precise timing as to what constitutes early or late HIV infection. Instead, such studies have largely relied on a person’s CD4+ count (and sometimes also viral load) and have assumed that, on average, lower CD4+ counts (prior to initiation of ART) are associated with long-lasting HIV infection, while higher CD4+ counts are associated with recent HIV infection.

A Dutch study breaks new ground

In an important development on how “early” and “late” HIV infection are defined for the purposes of a study, researchers in the Netherlands did something unique. They had access to the documented HIV testing history of many participants in a cohort called ATHENA. The researchers defined early initiation of ART as occurring within one year of HIV acquisition; people who started taking ART after this period were classed as late initiators of ART.

In the most recent analysis from their study, the Dutch researchers focused on 1,858 participants who began taking ART early and 17,995 participants who started ART late.

Participants were adults who were recruited from January 2000 to the end of 2022. 

People coinfected with hepatitis B or C virus were excluded from the study (because of their heightened risk for liver cancer), as were people with a prior history of cancer. The researchers also excluded people with AIDS-defining cancers (such as Kaposi’s sarcoma, B-cell non-Hodgkin lymphoma, cervical cancer) and non-melanoma skin cancer and Castleman’s disease.

On average, people who started ART early were more likely to have the following characteristics:

  • gay, bisexual and other men who have sex with men (89% vs. 59%)
  • younger (34 vs. 39 years) 
  • higher CD4+ counts (478 cells/mm3) compared to people who started ART later (260 cells/mm3)

Results

Over the course of the study, researchers found that a broad range of 25 cancers unrelated to AIDS developed in participants who initiated ART early. The most common were as follows:

  • stomach cancer – three cases 
  • melanoma – three cases

By contrast, among people who initiated ART late, there were 869 cancers unrelated to AIDS over the course of the study. The most common of these cancers were as follows:

  • lung cancer – 130 cases
  • prostate cancer – 110 cases
  • anal cancer – 86 cases

According to the research team, initiating ART early was associated with about a “40% reduced risk of any non-AIDS-defining cancer […] compared to starting ART later.”

They found that this impact of early ART initiation was independent of socioeconomic factors or the period when ART was initiated (current vs. past era).

There was no impact of early initiation of ART on cancers related to obesity. 

Why could early initiation of ART be helpful?

The scientists in ATHENA are uncertain exactly why early initiation of ART had such a profound benefit (as they did not conduct formal assessments of the functioning of the immune system in early vs. late ART initiators). However, they proposed the following points, based on other research:

  • Early ART “more strongly reduces the impact of HIV on [the aging of the immune system], sustained immune activation and inflammation, thereby reducing their pro-carcinogenic effects.”
  • Early ART helps to preserve the immune system’s ability to detect and delete pre-cancers and cancers.
  • By strengthening the immune system, early ART “may promote clearance of [cancer-causing viruses], particularly human papillomavirus (HPV).” This virus can cause cancer of the anus, cervix, lips, penis, throat, tongue, tonsils, vagina, and vulva. Past research has linked an increased risk of anal cancer in people with HIV with having a relatively low CD4 count prior to initiation of ART.

Bear in mind

The present study from the Netherlands is not a randomized, controlled clinical trial. As such, it is possible that unmeasured issues could have biased the interpretation of the results. For instance, there was inadequate data on smoking and problematic alcohol use by participants. However, the researchers conducted several sub-analyses to try to reduce the impact of potential sources of bias, and these analyses confirmed their main finding of a reduction in cancers unrelated to AIDS with the early initiation of ART.

As people with hepatitis B and C viruses were excluded from the study, its findings may not necessarily be relevant to people with HIV who are coinfected with these viruses.

Nevertheless, the study underscores the importance of HIV testing and early initiation of ART in people who test positive. 

The Dutch team notes that late-stage HIV remains common in the Netherlands and “accounted for 46% of all new HIV diagnoses between 2021 and 2023, with even higher percentages among heterosexual men and women. It remains a public health priority to facilitate access to HIV testing to improve the likelihood of early HIV diagnosis and immediate treatment, thereby reducing future [cancer] risk.”

—Sean R. Hosein

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