Undetectable HIV Equals Zero Risk of Transmission

Ever since the human immunodeficiency virus (HIV) was first discovered in 1983, scientists have worked ceaselessly to find ways to prevent the further spread of the disease. Some of the interventions, like condoms, are effective but far from foolproof. Others, like pre-exposure prophylaxis (PrEP), are over 90% effective but have been poorly embraced by many high-risk groups, including African Americans. It was only in 2019 that scientists finally revealed the one intervention that can effectively reduce the risk of HIV to zero: an undetectable viral load.

The strategy, referred to by public health officials as "Undetectable = Untransmittable" (U=U), is based on evidence that antiretroviral therapy in people with HIV can altogether prevent infection if the viral load (the number of circulating virus) is fully suppressed.

It is a strategy that had been long debated prior to the release of the PARTNER 2 study 2019 and the earlier PARTNER 1 study in 2016. The landmark studies, which involved 1,570 gay and heterosexual serodiscordant couples (in which one partner is HIV-positive and other is HIV-negative) provided what health officials declared was the first sure-fire way to prevent transmission even when condoms were not used.

Despite the definitive results, there are some limitations to the U=U strategy, namely the low rate of undetectable viral loads among Americans living with HIV.

Background

The concept of U=U is not entirely new. In fact, it was in 2008 that experts with the Swiss Federal Commission for HIV/AIDS were the first to declare that "an HIV-infected person on antiretroviral therapy with completely suppressed (virus)... cannot transmit HIV through sexual contact."

It was a bold statement evidenced by an overwhelming body of epidemiological evidence but one that lacked the clinical research to show that it worked on a one-on-one basis. Even the Swiss Commission admitted that their statement, a compelling as it was, should not change prevention strategies currently in place.

Treatment as Prevention (TasP)

Around this same time, scientists with the HIV Prevention Trials Network (HPTN) decided to actively test the hypothesis, armed with a new and more durable generation of HIV drugs. Up until that point, the concept was considered inconceivable given that many of the early antiretrovirals were prone to high rates of drug resistance and early treatment failure.

However, with the release of tenofovir in 2001, scientists had a drug that could provide sustained control of the virus with less-than-perfect adherence.

The HPTN research team proposed that by maintaining an undetectable viral load with this newer, more durable form of therapy, the rate of transmission would not only be reduced in serodiscordant couples but in the larger population as well. It was a strategy popularly referred to as treatment as prevention (TasP).

The study, known as the HPTN-052, involved 1,763 serodiscordant couples who were given either immediate treatment or afforded treatment when the HIV-positive partner's CD4 count dropped to 350 or below (the prescribed starting point of therapy in 2011). What this meant was that HIV-positive partners without treatment would invariably have higher viral loads than those who did.

A 2016 follow-up study was able to show that TasP was not only effective intervention but durable, reducing the risk of transmission by 93% in the same group of couples after 10 years.

Concerns and Controversy

Despite the positive findings, many health officials remained dubious as to the effectiveness of TasP. Among their concerns, they asserted (correctly) that an undetectable virus is not the same thing as having no virus.

Even with the most sensitive viral load tests, HIV can persist below detectable levels. Current technologies define undetectable as being below 20 to 40 copies per milliliter of blood. What this means is that a test may read undetectable, but there may still be competent viruses in circulation. Might this be enough to establish infection?

Others expressed concerns that, of the 1,763 couples involved in the HPTN 052, the majority (97%) were heterosexual. Even the most open-minded pundits doubted that the results seen in heterosexuals would be mirrored in gay and bisexual men, who not only account for over 65% of new infections in the United States but also have vastly different vulnerabilities to HIV infection.

PARTNER 1 Study

In an effort to expand the scope of research, an international effort known as the PARTNER (Partners of People on Antiretrovirals—A New Evaluation of the Risks) study was launched in September 2010 to look at the effect of TasP in both heterosexual and gay male couples.

The study was conducted 14 European countries and involved 1,166 serodiscordant couples who had engaged condomless sex for an average of two years. What made the PARTNER study especially compelling was that only couples whose HIV-positive partner had a CD4 count under 200 (a clinical definition of AIDS) were eligible to participate.

Of the 888 couples able to sustain undetectable viral loads—548 of whom were heterosexual and 340 of whom were gay—only 11 infections occurred during the four-year study period. Of these, not one was genetically linked to the HIV strain of their partner (meaning that the infection occurred outside of the relationship).

Despite the positive findings, the statistical certainty was not as convincing for gay men (or anal sex) as it was for vaginal sex given that 10 of the 11 infections occurred in gay male couples.

PARTNER 2 Study

The PARTNER 2 study, launch in September 2010, was designed to evaluate the risk of transmission in serodiscordant gay male couples only. The study was specifically designed to assess the impact of a fully suppressed viral load in couples who did not consistently use condoms for anal sex.

Of the 997 couples recruited from 14 Europeans countries, 90 were excluded either because the HIV-positive partner failed to maintain an undetectable viral load or the HIV-negative partner used PrEP or HIV post-exposure prophylaxis (PEP) to prevent infection.

During the span of the seven-year trial, the 782 eligible couples reported condomless anal sex a total of 76,088 times. Moreover, no less than 288 of the HIV-negative men (37%) reported condomless sex with partners outside of the relationship.

In short, the risk of transmission in gay couples with an undetectable viral load was effectively zero, confirming U=U as an effective means of HIV prevention in serodiscordant partners, whether heterosexual, gay, or bisexual.

Policy and Action

As a result of the PARTNER trials and other landmark studies, the Prevention Access Campaign, a global community of health equity partners, launched the Undetectable = Untransmittable initiative to help undercut the fear and shame that promote HIV stigma and delay HIV care.

The initiative aims to encourage people with HIV to start and stay on antiretroviral therapy, to pursue pregnancy and family planning, and to feel less anxiety about infecting others.

It was an endeavor supported the International AIDS Society in its 2019 Annual Letter in which the committee called for a "shifting of our collective mindset" to embrace U=U as the new standard of HIV prevention.

A Word From Verywell

From the point of a view of a committed relationship, an undetectable viral load offers the most effective means of HIV protection, even greater than condoms or PrEP. But, it doesn't necessarily mean that you should give up condoms altogether.

It is also important to remember that being on antiretrovirals is not the same thing as being undetectable. In fact, according to the Centers for Disease Control and Prevention, fewer than 60 percent of people on HIV therapy in the United States have an undetectable viral load.

In the end, it is not enough to skip condoms simply because the person you're having sex with is "on treatment." Unless you are in a committed relationship and are fully aware of your partner's treatment status and viral load results, don't take anything for granted. Use condoms and other forms of safer sex to protect yourself.