How HAART (Highly Active Antiretroviral Therapy) Works

The Triple Therapy That Turned the HIV Epidemic Around

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HAART is the acronym for "highly active antiretroviral therapy," a term coined in the late 1990s to describe the effectiveness of combination drug therapies used to treat HIV. The term is less commonly used today given that modern antiretrovirals are more than just "highly active" but able to afford people with HIV near-normal life expectancy and prolonged, disease-free health.

Even so, HAART remains a seminal turning point in the HIV pandemic and the foundation on which modern antiretroviral therapies are built.

3 pill bottles of antiretrovirals
SIA KAMBOU / Getty Images

Background

Prior to HAART, the use of one or two antiretroviral drugs afforded limited control of the virus, resulting in rapid treatment failure and the development of multi-drug resistance.

It was with the introduction of a class of drugs called protease inhibitors in 1995 that doctors were able to combine three or more drugs in a way that stopped HIV from replicating at different stages of its life cycle.

With the advent of HAART, the number of HIV-related deaths in the United States and Europe plummeted by more than 50% within the span of three short years.

Those gains have been seen in other parts of the world as well, with the United Nations now aiming to place the majority of the world's HIV-positive population on antiretrovirals and effectively end the pandemic by 2030.

How Antiretrovirals Works

Antiretroviral drugs do not kill HIV; rather, they block different stages in the virus's life cycle—from the time it attaches to a cell to the time it creates new copies of itself to infect other cells.

The combination of drugs works as something of a biological "tag team," suppressing a wide range of HIV variants that can exist within a single population. If one drug is unable to suppress a certain viral type, the others usually can.

By keeping the viral population fully suppressed (undetectable), there are fewer circulating viruses in the bloodstream and fewer opportunities for the virus to mutate into a drug-resistant variant.

Drug Classes

In the past, HAART was equated to triple-drug therapy. Today, because of improved pharmacokinetics, some antiretroviral therapies consist of only two drugs.

There are currently six classes of antiretroviral drugs able to treat HIV, each of which inhibits a specific stage in the virus's life cycle:

  • Entry/attachment inhibitors
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
  • Nucleoside reverse transcriptase inhibitors (NRTIs)
  • Protease inhibitors (PIs)
  • Integrase inhibitors (INIs)
  • Pharmacokinetic enhancers ("booster drugs")

As of 2021, there are 26 individual antiretroviral drugs licensed by the Food and Drug Administration (FDA) as well as 22 fixed-dose combination drugs comprised of two or more antiretroviral agents.

While antiretrovirals typically require daily dosing, an injectable option called Cabenuva (cabotegravir + rilpivirine) was approved by the FDA in 2021, requiring only two shots once monthly to keep the virus fully suppressed.

Benefits

In addition to preventing disease progression in people with HIV, the widespread use of antiretrovirals can reverse infection rates in many high-risk populations. The strategy, known as treatment as prevention, aims to reduce the "community viral load" within a population, making it more difficult to spread infection.

The same aims can be achieved on an individual level. According to a landmark study published in the May 2019 issue of The Lancet, achieving and sustaining an undetectable viral load reduces the risk of HIV transmission to zero.

With the appropriate precautions, heterosexual couples can even have babies safely when one partner has HIV and the other doesn't.

Moreover, when antiretroviral therapy is started early, the risk of severe HIV-associated diseases and non-HIV-associated illnesses (like cancers and heart disease) is reduced by as much as 72%, according to research published in the New England Journal of Medicine.

Findings like these only punctuate the need for early testing and treatment.

A Word From Verywell

HAART altered the course of the AIDS pandemic in the late-20th and early-21st centuries. The benefits extended not only to people with HIV but to others around them.

Today, antiretrovirals can even be used in non-infected people to further reduce their risk of infection. By taking one pill a day, an HIV-negative person can reduce their risk of getting the virus by as much as 99%.

The strategy, known as pre-exposure prophylaxis (PrEP), is currently recommended for people at high risk of infection, including serodiscordant (mixed-status) couples, injecting drug users, and those who engage in protected anal or vaginal sex.

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