HIV (human immunodeficiency virus) is the sexually transmitted infection that directly attacks and destroys the immune system. It targets a specific type of white blood cell called the CD4 cell, which orchestrates the body’s defense against infections. A healthy person has between 500 and 1,500 CD4 cells per cubic millimeter of blood. Without treatment, HIV gradually destroys these cells until the immune system can no longer protect the body, a stage known as AIDS.
As of 2024, an estimated 40.8 million people worldwide are living with HIV, and about 1.3 million new infections occurred during the year. While other STIs like syphilis and hepatitis B can affect immune function in indirect ways, HIV is the only one that systematically dismantles the immune system itself.
How HIV Destroys Immune Cells
HIV specifically hunts CD4 T cells, the immune system’s coordinators. These cells signal other immune cells to respond when bacteria, viruses, or fungi enter the body. Without enough of them, even normally harmless microbes can cause life-threatening illness.
The virus latches onto the CD4 molecule on the cell’s surface, then connects with a second receptor (either CCR5 or CXCR4) to gain entry. Once inside, HIV hijacks the cell’s machinery to make copies of itself. The newly made viruses burst out, killing the host cell, and go on to infect more CD4 cells. HIV also triggers a self-destruct process in nearby uninfected CD4 cells. A protein on the surface of infected cells interacts with uninfected neighbors and activates a programmed cell death pathway, meaning HIV kills far more immune cells than just the ones it directly infects.
The Three Stages of HIV Infection
Acute Infection
Within two to four weeks of exposure, about two-thirds of people develop flu-like symptoms: fever, headache, rash, sore throat, swollen lymph nodes. During this phase, the virus multiplies rapidly and the level of HIV in the blood spikes, making transmission risk especially high. Many people mistake these symptoms for a cold or flu, and they typically resolve on their own within a few weeks.
Chronic (Latent) Infection
After the acute phase, HIV enters a quieter period. The virus continues replicating at low levels, but many people feel perfectly fine and have no symptoms at all. This stage can last 10 to 15 years without treatment. With modern antiretroviral therapy, people can remain in this stage for several decades, often with undetectable viral levels.
AIDS
AIDS is diagnosed when the CD4 count drops below 200 cells per cubic millimeter, or when certain dangerous infections appear. At this point the immune system is severely compromised. Symptoms can include rapid weight loss, recurring fevers, profuse night sweats, chronic diarrhea, persistent swollen lymph nodes, mouth or genital sores, pneumonia, and neurological problems like memory loss. Without treatment, survival after an AIDS diagnosis averages about three years.
What Happens When the Immune System Fails
As CD4 counts fall, infections that a healthy immune system easily controls become dangerous. These are called opportunistic infections, and specific ones emerge at specific CD4 thresholds. Below 200 cells per cubic millimeter, a type of pneumonia called Pneumocystis pneumonia becomes a serious risk. Below 150, a fungal infection called histoplasmosis can take hold in people living in certain regions. Below 100, toxoplasmosis (a parasitic brain infection) becomes a threat. At counts below 50, a bacterial infection called Mycobacterium avium complex can spread throughout the body.
Viral load matters alongside CD4 count. People with low CD4 counts but also low viral loads experience fewer opportunistic infections than people with the same CD4 count and high viral loads. This is one reason treatment that suppresses viral replication is so effective at preventing complications, even before CD4 counts fully recover.
How Treatment Rebuilds Immunity
Modern antiretroviral therapy doesn’t cure HIV, but it stops the virus from replicating. With viral levels suppressed, the immune system gets breathing room to rebuild. Most people on effective treatment see their CD4 counts rise over time, and many eventually recover to normal levels above 500 cells per cubic millimeter. Starting treatment early, before significant immune damage occurs, gives the best chance of full CD4 recovery. People who wait until counts are already low may see slower or incomplete rebuilding. Some experts consider a gain of fewer than 200 cells after two years of suppressed virus to be a suboptimal response.
In 2024, roughly 630,000 people still died from HIV-related causes globally, largely in populations without consistent access to treatment. For those who do have access, HIV has shifted from a fatal diagnosis to a manageable chronic condition.
Other STIs That Affect Immune Function
While HIV is the STI defined by immune destruction, a few others interact with the immune system in notable ways.
Syphilis, caused by the bacterium Treponema pallidum, doesn’t destroy immune cells the way HIV does, but advanced syphilis reflects a breakdown in the body’s immune response to the infection. In tertiary syphilis, which can develop years after the initial infection, the immune system shifts away from the type of response that effectively fights the bacterium. This leads to destructive inflammatory lesions called gummas in the skin, bones, liver, and other organs. Syphilis can also invade the nervous system, causing dementia, loss of sensation in the limbs, and inflammation of the membranes surrounding the brain.
Hepatitis B, a virus transmitted through sexual contact and blood, uses a different strategy. It has been called a “stealth” virus because it triggers almost no initial immune alarm. Early in infection, the virus replicates nearly unchecked, infecting up to 80 percent of liver cells while causing minimal inflammation or symptoms. It produces massive quantities of decoy particles that soak up the antibodies the body does make, preventing them from neutralizing the actual virus. Over time, the immune cells tasked with clearing hepatitis B become exhausted and stop functioning effectively. This is how chronic hepatitis B persists for years or decades, gradually damaging the liver while evading immune clearance.
Neither syphilis nor hepatitis B attacks the immune system as its primary target the way HIV does. But both exploit weaknesses in immune function, and both cause more severe disease when the immune system is already compromised, which is why co-infection with HIV makes these conditions significantly harder to control.