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