The virus that causes AIDS is the human immunodeficiency virus, commonly known as HIV. After entering the body, HIV targets and gradually destroys immune cells called CD4 T cells, and without treatment, this destruction eventually leaves the immune system too weak to fight off infections and certain cancers. That advanced stage of immune failure is what clinicians call acquired immunodeficiency syndrome, or AIDS. The path from initial HIV infection to AIDS involves distinct phases, each with its own symptoms and timeline, and modern treatment can halt that progression entirely for most people who have access to it.
How HIV Gets Into Your Cells
HIV carries a surface protein called Env that acts like a key. It first latches onto a receptor called CD4, which sits on the surface of certain immune cells. That initial binding causes a shape change in the virus’s outer protein, exposing a second binding site that connects to a co-receptor on the cell, usually one called CCR5 or another called CXCR4.1PubMed Central. HIV: cell binding and entry Once both connections are made, the viral and cell membranes fuse together, and HIV’s genetic material slips inside.2PubMed. HIV-1 Entry Mechanisms: Protein-Host Receptor Interactions and Membrane Fusion Dynamics From there, the virus hijacks the cell’s own machinery to make copies of itself, which then spread to infect more CD4 cells.
This reliance on CD4 and a co-receptor explains why HIV primarily attacks the immune system rather than, say, the lungs or liver. CD4 T cells are the coordinators of your immune response. They tell other immune cells when and how to react to threats. Losing them is like pulling the general out of an army: the soldiers are still there, but nobody is directing the fight.
How CD4 Cells Are Destroyed
The story of immune collapse is more complex than “the virus kills every cell it infects.” Directly infected cells do die, sometimes by forming short-lived clumps of fused cells. But a large share of the CD4 cells that die are actually uninfected bystander cells. HIV proteins released from infected cells can trigger a self-destruct program in neighboring uninfected cells, and the chronic inflammation HIV causes pushes even more bystanders toward death.3PubMed. Mechanisms of CD4+ T lymphocyte cell death in human immunodeficiency virus infection and AIDS
Research has also shown that when HIV tries to infect resting CD4 cells in lymph tissue but fails to complete its replication cycle, the incomplete viral DNA fragments trigger a particularly inflammatory form of cell death called pyroptosis. This creates a vicious cycle: dying cells release signals that attract more immune cells to the area, which then become targets themselves.4PubMed Central. Dissecting How CD4 T Cells Are Lost During HIV Infection The result is a slow but relentless drain on the immune system that can take years to become critical.
HIV-1 and HIV-2
There are actually two species of the virus. HIV-1 is the one responsible for the vast majority of infections worldwide and the global AIDS pandemic. HIV-2, while it can also cause AIDS, behaves quite differently. It is far less transmissible, and most people infected with HIV-2 remain healthy for much longer, with many never progressing to AIDS at all. Plasma viral loads are consistently lower in HIV-2, as are levels of immune activation.5PubMed. Comparing HIV-1 and HIV-2 infection: Lessons for viral immunopathogenesis
HIV-2 remains largely confined to West Africa, while HIV-1 has spread across every continent. One reason for this difference in pathogenicity appears to involve how the two viruses interact with the innate immune system early on. HIV-2 steers certain immune cells toward a more effective antigen-presenting role rather than triggering the heavy interferon response that HIV-1 provokes, which may paradoxically leave the immune system better equipped to control the infection over time.6PubMed Central. HIV-1 and HIV-2 differentially mature plasmacytoid dendritic cells into interferon-producing or antigen-presenting cells
Treatment also differs. When HIV-2 patients do need antiretroviral therapy, CD4 counts recover more slowly, and the drop in viral load is less dramatic compared to HIV-1 patients on the same regimens. In one French cohort, the plasma viral load fell roughly three times faster in HIV-1 patients than in HIV-2 patients after starting treatment.7PubMed Central. Comparison of viro-immunological marker changes between HIV-1 and HIV-2-infected patients in France Certain drug classes that work well against HIV-1 are also less effective or entirely ineffective against HIV-2, which means clinicians need to choose regimens carefully.
Where the Virus Came From
Both HIV-1 and HIV-2 originated from simian immunodeficiency viruses (SIVs) that naturally infect African primates. HIV-1 traces back to SIV strains carried by wild chimpanzees in west central Africa, with at least four separate cross-species transmission events giving rise to different lineages of HIV-1 in humans. One or two of those jumps may have passed through gorillas first.8PubMed Central. The evolution of HIV-1 and the origin of AIDS Most of these transmissions produced viruses that spread only to a limited extent. The exception was a single event, involving chimpanzees in southeastern Cameroon, that gave rise to HIV-1 group M, the strain behind the global pandemic.9PubMed Central. Origins of HIV and the AIDS pandemic
HIV-2 followed a similar pattern but with a different primate host: sooty mangabeys in West Africa. The limited geographic spread of HIV-2 compared to HIV-1 reflects both its lower transmissibility and the fact that its cross-species jumps happened in a more restricted region. Understanding these origins has been essential for tracing how the virus evolves and why certain strains are more dangerous than others.
Symptoms and Stages of Infection
HIV infection unfolds in three broad phases, each with different symptoms and levels of risk.
Acute HIV Infection
The first phase begins within days to weeks of exposure. The virus replicates explosively, and a prospective study in East Africa and Thailand found that peak viremia occurred about 13 days after the first detectable sign of infection on lab tests. Symptoms, when they appeared, clustered around this peak.10PubMed Central. Prospective Study of Acute HIV-1 Infection in Adults in East Africa and Thailand The acute phase is brief, and peak viremia predicts the viral set point that the body settles into about four to five weeks after infection.11PubMed Central. Lessons from acute HIV infection
Many people experience flu-like symptoms during this stage: fever, sore throat, swollen lymph nodes, rash, muscle aches, and fatigue. These symptoms are easy to mistake for a bad cold or mononucleosis. Not everyone has noticeable symptoms, but those who do tend to have higher initial viral loads, and more symptoms correlate with a higher set point afterward, which generally means faster disease progression if left untreated.12PubMed. The relation between symptoms, viral load, and viral load set point in primary HIV infection This is also the phase when a person is most infectious, because viral levels in the blood are at their highest.
Chronic (Latent) Infection
After the immune system mounts its initial response and brings viral levels down to the set point, HIV enters a long chronic phase. People often feel perfectly healthy during this period, which can last a decade or more without treatment. The virus is still replicating at low levels, though, and CD4 counts gradually decline. Some people develop mild symptoms like persistent swollen lymph nodes or recurring minor infections, but many have no symptoms at all.
One of the cruelest features of HIV is its ability to hide. The virus inserts its genetic material into the DNA of long-lived resting memory CD4 T cells, creating a latent reservoir that current treatments cannot reach. These cells can harbor dormant HIV for years or decades, which is why stopping antiretroviral therapy almost always leads to a viral rebound.13PubMed Central. Targeting HIV latency: resting memory T cells, hematopoietic progenitor cells and future directions
AIDS
If CD4 counts fall low enough, the immune system can no longer hold off infections that a healthy body handles routinely. This is AIDS. Clinically, it is defined as a CD4 count below 200 cells per microliter, or the presence of certain AIDS-defining illnesses, regardless of CD4 count. Symptoms at this stage are driven by the opportunistic infections and cancers that take hold. Common AIDS-defining conditions in the United States include esophageal candidiasis (a yeast infection of the food pipe), Pneumocystis pneumonia, cervical cancer, Mycobacterium avium complex infection, and cytomegalovirus disease.14AIDS. AIDS-defining opportunistic illnesses in US patients, 1994–2007: a cohort study Weight loss, chronic diarrhea, prolonged fevers, and night sweats are all common at this stage.
An often-overlooked finding from large U.S. cohort data is that over a third of opportunistic illness events occurred in patients whose CD4 counts were still above 200. That means some opportunistic conditions can develop before a person technically meets the clinical definition of AIDS, which underscores why monitoring and early treatment matter so much.
Neurological Effects
HIV does not limit its damage to the immune system. The virus crosses into the brain early in infection, and even with effective treatment, neurological complications remain common. A spectrum of cognitive problems collectively called HIV-associated neurocognitive disorders (HAND) affects up to half of all people living with HIV. HAND ranges from subtle impairments that a person might not notice, to mild cognitive difficulties that interfere with daily life, all the way to severe HIV-associated dementia.15PubMed Central. Global HIV Neurology: A Comprehensive Review
Antiretroviral therapy can stabilize or improve HAND, but it rarely resolves it completely, and new cases can emerge even in people whose blood tests show the virus is fully suppressed. Today the milder forms predominate rather than the devastating dementia that characterized the pre-treatment era, but the overall prevalence has stayed surprisingly steady. For people living with HIV, this means cognitive health is something to monitor alongside CD4 counts and viral load.
How HIV Is Diagnosed
Modern HIV testing uses a tiered approach. The standard starting point is a fourth-generation antigen/antibody test, which detects both HIV antibodies produced by the immune system and a viral protein called p24 antigen. These combination tests can identify infection earlier than older antibody-only tests because p24 appears in the blood before the body has made antibodies.16The Journal of Applied Laboratory Medicine. Real-World Clinical Performance Evaluation of a Fourth-Generation HIV Antigen/Antibody Differentiation Test
If a screening test comes back positive, a confirmatory test follows, typically a differentiation assay that can tell HIV-1 from HIV-2. In cases where very early infection is suspected and antibodies have not yet appeared, nucleic acid amplification testing (NAT) can detect the virus’s genetic material directly.17PubMed Central. HIV Nucleic Acid Amplification Testing Versus Rapid Testing: It Is Worth the Wait Rapid point-of-care tests, the kind offered at community clinics and health fairs, use finger-prick blood or oral fluid and return results within minutes. They are highly accurate for established infections but can miss very recent ones, which is why a negative rapid test after a known exposure may warrant follow-up lab testing a few weeks later.
How HIV Is Treated
Antiretroviral therapy (ART) cannot cure HIV, but it can reduce viral levels in the blood to the point where standard tests cannot detect the virus. Treatment typically involves a combination of drugs from different classes, each targeting a different step in the virus’s life cycle. The major categories include drugs that block the virus’s reverse transcriptase enzyme (both nucleoside and non-nucleoside types), protease inhibitors that prevent new viral particles from maturing, integrase inhibitors that stop the virus from inserting its DNA into the host cell, and entry inhibitors that block the virus from getting into cells in the first place.18PubMed Central. Mechanisms underlying of antiretroviral drugs in different cellular reservoirs with a focus on macrophages
Integrase strand transfer inhibitors are the newest class approved for HIV-1 and have become a backbone of most first-line regimens because of their potency and relatively mild side-effect profiles. Today, many people take a single pill once a day that combines two or three drugs from different classes. When taken consistently, ART keeps the virus suppressed indefinitely, preserves immune function, and allows people with HIV to live near-normal lifespans.
A concept that has reshaped both medicine and public perception is “Undetectable = Untransmittable,” often shortened to U=U. When a person on ART maintains an undetectable viral load, they effectively cannot transmit HIV sexually.19Clinical Chemistry. Undetectable Equals Untransmittable: A Game Changer for HIV Prevention This finding, backed by large studies involving thousands of couples, has been one of the most powerful motivators for early testing and treatment.
Prevention Beyond Treatment
Pre-exposure prophylaxis, or PrEP, is a prevention strategy for people who do not have HIV but are at higher risk of getting it. Across trials of daily oral PrEP based on tenofovir, the risk reduction ranged from roughly 49% to 86% in standard analyses, with effectiveness climbing above 90% in people who took the pills consistently.20PubMed Central. Effectiveness of Pre-exposure Prophylaxis (PrEP) in the Prevention of Human Immunodeficiency Virus (HIV): A Systematic Review of Randomized Controlled Trials With Narrative Synthesis More recently, a long-acting injectable form of PrEP (cabotegravir) given every two months has outperformed daily pills in large trials, with relative risk reduction as high as 89%. The injectable version sidesteps the adherence challenge entirely, since the clinic administers the shot.
Condoms, of course, remain effective at preventing sexual transmission. And for people who may have been exposed, post-exposure prophylaxis (PEP), which involves taking antiretroviral drugs within 72 hours and continuing for 28 days, can prevent infection from taking hold.
Mother-to-Child Transmission
HIV can pass from mother to baby during pregnancy, labor, delivery, and breastfeeding. Without intervention, transmission rates are significant. But antiretroviral strategies during pregnancy have dramatically reduced this risk. Compared with placebo, zidovudine (one of the earliest HIV drugs) cut mother-to-child transmission roughly in half, and nevirapine reduced the risk even further when compared to zidovudine alone. Elective cesarean delivery also substantially lowered transmission risk.21Cochrane Database of Systematic Reviews. Interventions for reducing the risk of mother‐to‐child transmission of HIV infection
Current practice goes well beyond single-drug prophylaxis. Pregnant women with HIV now typically receive full combination ART, and infants receive short-course antiretroviral prophylaxis as well.22PubMed. Prevention of mother-to-child transmission of HIV: antiretroviral strategies With these combined approaches, transmission rates in high-resource settings have dropped below 1%. In parts of the world where access to testing and treatment remains limited, though, mother-to-child transmission is still a meaningful driver of new pediatric infections. Researchers are exploring whether adding immune-based strategies, like maternal vaccination or passive antibodies, to ART might help close the remaining gap, particularly during breastfeeding when residual transmission risk persists.23PubMed Central. Maternal Interventions to Prevent Mother-To-Child Transmission of HIV: Moving Beyond Antiretroviral Therapy
The Tuberculosis Connection
Tuberculosis is the most dangerous co-infection for people living with HIV, and it works both ways. HIV is the single most important risk factor for developing active TB in high-burden settings, because the loss of CD4 cells cripples the immune response that normally keeps TB bacteria in check. Meanwhile, TB infection speeds up HIV’s progression toward AIDS by further disrupting immune function.24PubMed Central. Tuberculosis and HIV Coinfection
The death toll reflects this synergy. In 2023, about 24% of individuals with both TB and HIV died, compared with 11% of TB patients who were HIV-negative.25PubMed Central. Tuberculosis and HIV coinfection: Progress and challenges towards reducing incidence and mortality Treating both infections at the same time is necessary but complicated, because antiretroviral drugs and anti-TB drugs interact with each other in ways that can reduce effectiveness or increase side effects.26PubMed Central. HIV-TB Coinfection: Current Therapeutic Approaches and Drug Interactions Clinicians managing co-infected patients have to carefully sequence and adjust regimens to balance both treatments.
A Natural Genetic Shield
A small fraction of people carry a genetic mutation that provides natural resistance to HIV. The mutation is a 32-base-pair deletion in the gene that codes for the CCR5 co-receptor, the same doorway HIV uses to enter cells. People who inherit two copies of this deletion (one from each parent) produce no functional CCR5 protein on their cell surfaces, and the virus simply cannot get in.27Gene Reports. The CCR5Δ32 allele as an HIV infection resistance marker: Possible evolutionary theories of origin
A meta-analysis confirmed this protective effect quantitatively: people homozygous for the deletion had a roughly 75% lower risk of HIV-1 infection, while carriers of a single copy (heterozygotes) saw a more modest but still statistically meaningful reduction in susceptibility.28PubMed Central. The CCR5-Delta32 Genetic Polymorphism and HIV-1 Infection Susceptibility: a Meta-analysis The mutation is most common in people of Northern European descent and is rare or absent in most African and Asian populations. This discovery has directly influenced both drug development and cure research, since blocking CCR5 pharmacologically (with drugs like maraviroc) mimics what the mutation does naturally.29PubMed Central. CCR5: From Natural Resistance to a New Anti-HIV Strategy
Progress Toward a Cure and a Vaccine
Since 2009, seven people have been declared cured of HIV after receiving stem cell transplants from donors who carried the CCR5 deletion. The transplants were done to treat blood cancers, not HIV itself, and the procedure is far too risky and expensive for general use. But those cases proved that eliminating HIV from the body is biologically possible, and they energized research into gene therapy approaches that could achieve the same result more safely. Current strategies focus on either cutting the viral DNA out of infected cells using gene-editing tools or disabling the CCR5 co-receptor in a patient’s own cells.30PubMed Central. In pursuit of an HIV cure: from stem cell transplants to gene therapies
A vaccine, meanwhile, has remained stubbornly elusive. Prototype candidates designed to stimulate antibody or cellular immune responses have failed to prevent infection or meaningfully reduce viral loads in clinical trials.31PubMed Central. Challenges in the development of an HIV-1 vaccine HIV’s extraordinary genetic diversity, its ability to mutate rapidly, and its trick of hiding inside the very immune cells that should be fighting it all make vaccine design uniquely difficult. Recent years have brought renewed interest in broadly neutralizing antibodies and mRNA vaccine platforms, but no candidate has yet succeeded in a large efficacy trial. For now, prevention rests on the tools already in hand: testing, treatment, PrEP, and condoms.