New data on HIV controllers highlight importance of personalized care

A large study on people living with HIV who innately keep viral replication at bay has found that antiretroviral therapy (ART) does not further reduce their risk for non-AIDS defining events, but that baseline viral load does. Although relatively specific to a small subset of patients, the findings nonetheless teach us some broader lessons about individualized approaches to HIV care.

Highlighted Study Population and Methods

The Dutch ATHENA cohort study evaluated more than 20,000 people with HIV over ~175,000 patient-years of follow-up. Of them, 1,007 were classified as HIV controllers (three consecutive viral load results below 10,000 copies/mL while off antiretroviral therapy); 1,510 were classified as early ART recipients (diagnosed with HIV and started ART within six months of a prior negative HIV test), and 15,437 were classified as “normal progressors” on ART.

The primary study end point was a composite of non-AIDS defining events (cardiovascular disease, non-AIDS malignancy, or all-cause mortality). Secondary end points were other non-AIDS illnesses such as pneumonia, severe liver disease, fractures, and chronic kidney disease.

Key Findings

• HIV controllers had 43%-45% lower risk of the primary end point relative to normal progressors.

• HIV controllers also had a lower risk of all-cause mortality and renal, bone, and cardiovascular disease—but not non-AIDS malignancy—compared with normal progressors.

• Among HIV controllers, lower baseline viral load further decreased the risk of a non-AIDS defining event.

• The use of ART by HIV controllers did not reduce their risk of a non-AIDS defining event.

• Early initiation of ART was associated with lower risk of all-cause mortality, non-AIDS malignancy, and non-AIDS defining events relative to normal progressors, but similar risk of cardiovascular disease.

Expert Analysis From Benjamin Young, M.D., Ph.D.

We have long known that people with HIV who were viral controllers (~1% of the population of people with HIV) were at lower risk for AIDS-related disease progression. We’ve also long known that, among people with typical HIV disease progression, early initiation of ART reduces long-term disease risk. So you might ask: What, exactly, is new here—and what impact would any of this have on my HIV treatment approach?

My answer: These study findings remind us how important a personalized approach to HIV care is.

We broadly employ a “test and treat” strategy when it comes to HIV: If a person is diagnosed, start them on treatment immediately. It’s an excellent strategy that has been widely endorsed for many important reasons, including prevention of disease progression, preservation of immune function, and prevention of onward transmission of HIV.

U.S. HIV guidelines strongly recommend ART for all patients, regardless of CD4 count. That is largely based on the results of two major studies—START and TEMPRANO—that were published roughly a decade ago. The thing is, those studies were underpowered to address the issue of viral controllers specifically (although START did find that, among a small group of viral controllers, ART did not affect their clinical outcomes).

These newly published ATHENA study results don’t diminish the importance of universal treatment for people with HIV. But they do allow us to at least take a moment to breathe when we’re faced with a patient who has been off treatment for some time (or is treatment naive) but whose viral load is atypically low.

Consider this scenario: A patient comes into your clinic. They were on ART before, but they’ve had a long break in therapy for some reason. For most of us, the immediate reaction would be: Put them on therapy immediately, and then worry about everything else later—including addressing the reasons why they stopped therapy in the first place (and may well stop therapy again in the future), which may have to do with social determinants of health, life priorities, housing insecurity, food insecurity, intimate partner violence, and so on.

But what if their viral load is 51 and their CD4 percentage is healthy? What if there’s a chance this person is one of that small-but-existent group of people whose immune systems can naturally prevent, or at least delay, HIV disease progression?

It’s notable that these new study data show that ART usage did not reduce the risk of non-AIDS-defining events among viral controllers. When coupled with the findings that viral controllers have a lower risk of both AIDS-related and non-AIDS related events compared with the general population of people with HIV—and importantly, appear to have lower risks of renal, bone, and cardiovascular disease—I would love to see these results facilitate more nuanced discussions with patients if they are within that small population of viral controllers. Among those patients, the conversation about ART can perhaps shift away from the prevention of illness and focus more on the potential benefits of preventing transmission, allowing them to make a more fully informed determination of the benefits versus the challenges of treatment in their unique case. (The data finding that baseline viral load affects non-AIDS event risk is an important part of the nuance in this discussion, and one that intersects with discussions about onward transmission risk, given the focus on 200 copies/mL as a U=U threshold.)

I want to underline that, as a person who has watched way too many patients get sick and die over the years due to inadequate or late receipt of HIV treatment, I remain a very strong proponent of ART. But I’m also a very strong proponent of getting to know my patients, and of treating them as a trustworthy partner in our medical relationship. Monolithic statements or policies may be useful for efficiency and for making simplified public health messaging—but they can also harm patient trust and undermine long-term success on an individual level.

At the risk of drawing too many broad conclusions from this one study, I found these results compelling because they remind us of the value of treating our patients like people, not data points.

About This Study

“Risk of Non–AIDS–Defining Events Is Lower in Antiretroviral Therapy (ART)–Naive HIV Controllers Than in Normal Progressors on Suppressive ART” was published in the March 15 issue of Clinical Infectious Diseases; it had originally published online ahead of print on Aug. 29, 2024. The primary author is Albert Groenendijk, M.D., of Erasmus University Medical Center in the Netherlands.