HIV and AIDS

TL;DR. HIV is a virus that infects and destroys the exact immune cell that coordinates the immune response, the CD4 helper T cell. Over years, as those cells are depleted, the body loses the ability to fight infections it would normally ignore, and the resulting collection of illnesses is called AIDS. Untreated, it is nearly always fatal. Treated, it is a chronic condition with close to normal life expectancy, and a person on effective treatment cannot transmit the virus sexually at all. That last fact, established beyond reasonable doubt and summarised as Undetectable equals Untransmittable, is one of the most consequential findings in modern medicine and is still not widely known.

Key takeaways

• About 41 million people are living with HIV. Roughly 570,000 died of AIDS-related illness and 1.2 million newly acquired HIV in the most recent reporting year.
• HIV is not AIDS. HIV is the virus; AIDS is the advanced stage, defined by a CD4 count below 200 or by specific opportunistic illnesses. Most people living with HIV today will never develop AIDS.
• U=U. Someone with a sustained undetectable viral load on treatment does not transmit HIV sexually. This was demonstrated across thousands of couple-years with zero linked transmissions.
• The virus integrates into the DNA of long-lived cells, creating a latent reservoir. That reservoir is the reason treatment is lifelong and cure is hard.
• Prevention is now extraordinary. Daily oral PrEP, two-monthly injections, and six-monthly lenacapavir have each shown very high efficacy, with lenacapavir showing essentially complete protection in trials among young women.
• You cannot catch HIV from ordinary contact: not from sharing food, cups, toilets, hugging, kissing, coughing, insects, or swimming pools.

What it is

In short: A virus that destroys the immune cell that coordinates everything else, staged by CD4 count and viral load.

HIV (human immunodeficiency virus) is a retrovirus. Its genetic material is RNA, and it carries an enzyme, reverse transcriptase, that converts that RNA into DNA, which is then spliced permanently into the host cell's own chromosomes. Once integrated, the viral genome is part of that cell for the cell's life.

It targets cells carrying the CD4 surface protein, principally helper T cells, plus macrophages and dendritic cells. As Chapter 13 explains, the CD4 T cell is the coordinator of adaptive immunity. Removing it disables B cell antibody quality, macrophage activation, and killer T cell direction all at once.

Staging uses two numbers:

AIDS (acquired immunodeficiency syndrome) is diagnosed when the CD4 count falls below 200 or when one of a defined list of opportunistic conditions occurs.

Don't be confused: HIV-positive does not mean sick, and it does not mean infectious. A person diagnosed early, started on treatment, and virally suppressed has a near-normal life expectancy and cannot pass the virus to a sexual partner. Treating "HIV" and "AIDS" as synonyms, which most casual usage does, keeps alive a picture of the disease that has been out of date for two decades and drives stigma that measurably harms people.

The history

In short: From five case reports in June 1981 to combination therapy in 1996 and the proof in 2016 that treated people do not transmit it.

5 June 1981. The US CDC's Morbidity and Mortality Weekly Report described five cases of Pneumocystis pneumonia in previously healthy young gay men in Los Angeles, an infection that essentially never occurs in people with working immune systems. Similar clusters of Kaposi sarcoma followed. The syndrome was named AIDS in 1982.

1983 to 1984. The virus was isolated by Françoise Barré-Sinoussi and Luc Montagnier at the Institut Pasteur, with Robert Gallo's group in the US confirming its role. A blood test followed in 1985, which secured the blood supply after thousands of people with haemophilia had already been infected through contaminated clotting factor.

Origin. Genetic analysis traces HIV-1 group M, the pandemic strain, to a cross-species transmission from chimpanzees in south-eastern Cameroon, with the most likely entry into humans in the early twentieth century and establishment in Kinshasa around the 1920s, from where colonial-era urbanisation, transport, and possibly unsterile medical injection campaigns allowed it to spread.

The treatment arc.

What actually goes wrong

In short: The virus writes itself permanently into the DNA of long-lived cells, which is why treatment is lifelong and why cure is so hard.

Entry. The viral surface protein gp120 binds CD4, then a co-receptor, usually CCR5 early in infection and sometimes CXCR4 later. The viral envelope fuses with the cell membrane.

Reverse transcription and integration. Viral RNA is copied into DNA, transported into the nucleus, and integrated into the host genome by the enzyme integrase. The cell is now permanently carrying the instructions to build HIV.

Replication and destruction. Activated CD4 cells produce new virus and die, by direct viral killing, by immune attack, and by a form of inflammatory cell death (pyroptosis) in neighbouring cells that never became productively infected. Untreated, roughly a billion virions are produced daily, with an extremely high mutation rate, which is why monotherapy fails within weeks and why no vaccine has yet succeeded.

The reservoir. A small fraction of infected cells become long-lived resting memory T cells carrying integrated, silent virus. Antiretroviral drugs block replication, not integrated DNA, and the immune system cannot see a cell producing nothing. Stop treatment, and the reservoir reactivates and viral load rebounds within weeks. This single fact explains why treatment is lifelong.

Chronic immune activation. Even on suppressive treatment, HIV causes persistent low-grade inflammation, partly through damage to gut lymphoid tissue early in infection allowing bacterial products to leak into the circulation. This contributes to the higher rates of cardiovascular disease, kidney disease, bone loss, and some cancers seen in people living with HIV despite good viral control.

What it does to the body

In short: Years of nothing, then infections that appear at predictable CD4 thresholds as immune coordination collapses.

Acute infection (2 to 4 weeks after exposure): fever, sore throat, rash, swollen glands, muscle aches. It resembles glandular fever and is frequently missed, which matters because viral load is extremely high at this stage and transmission risk is at its peak.

Clinical latency: years, typically around 8 to 10 untreated, with few or no symptoms while CD4 cells decline steadily.

Advanced disease: as CD4 counts fall, characteristic infections appear at characteristic thresholds.

Plus HIV-associated wasting, HIV-associated neurocognitive disorder, and an increased risk of lymphoma, Kaposi sarcoma, and cervical and anal cancer, the last driven by HPV in the setting of poor immune surveillance.

Is it deadly?

Untreated, yes, in nearly all cases, with median survival from infection to death of roughly 10 to 11 years in adults and far shorter in infants.

Treated, the picture is unrecognisable. Large cohort studies show that a person diagnosed early, starting effective treatment with a preserved CD4 count and maintaining suppression, has a life expectancy approaching that of the general population. The remaining gap is attributable mostly to late diagnosis, smoking, substance use, comorbidities, and disparities in access.

Global figures: about 41 million people living with HIV, approximately 570,000 AIDS-related deaths and 1.2 million new infections in the most recent reporting year, down from a peak of roughly 2 million deaths a year in the mid-2000s. Around three quarters of people living with HIV are on treatment, which is both a remarkable achievement and a reminder that millions are not.

Is it contagious?

In short: Yes, by four specific routes and no others, and a person with an undetectable viral load does not transmit it sexually at all.

Yes, by specific routes, and by no others. This section is worth reading precisely, because misinformation here has caused more social damage than almost any other medical error in living memory.

HIV transmits through: unprotected anal or vaginal sex; sharing needles or injecting equipment; from mother to child during pregnancy, birth, or breastfeeding; through transfusion of unscreened blood or transplanted tissue; and through occupational needlestick injury (a low risk, roughly 0.3 percent per exposure).

HIV does not transmit through: touching, hugging, kissing (saliva contains too little virus and contains inhibitors), sharing dishes, cutlery, food, or drinks; toilet seats, swimming pools, showers, or gyms; coughing or sneezing; mosquitoes or any insect (the virus does not replicate in them and they do not inject blood from a previous host); or working alongside, caring for, or living with someone who has HIV.

Risk per exposure varies enormously by route, which is why prevention strategies differ:

And the single most important modifier: treatment. A person with a sustained undetectable viral load does not transmit HIV sexually. The PARTNER studies followed serodifferent couples through tens of thousands of condomless sex acts and recorded zero phylogenetically linked transmissions from a virally suppressed partner. This is not "low risk." It is the basis for the U=U consensus endorsed by public health agencies worldwide.

Who gets it

In short: 41 million people, concentrated in eastern and southern Africa, and elsewhere among populations that legal and social barriers keep away from services.

Geography. Eastern and southern Africa carry the largest burden, with a substantial share of the world's people living with HIV. Epidemics are also significant in western and central Africa, Asia and the Pacific, Latin America, the Caribbean, and eastern Europe and central Asia, where new infections have been rising.

Who is most affected differs by region. In much of sub-Saharan Africa, adolescent girls and young women bear a disproportionate share of new infections, driven by age-disparate relationships, gender inequality, and limited negotiating power over condom use. Elsewhere, epidemics are concentrated among key populations: men who have sex with men, people who inject drugs, sex workers, transgender people, and prisoners, who together account for the majority of new infections outside sub-Saharan Africa and who face legal and social barriers to services that directly worsen outcomes.

Genetics. A minority of people of northern European descent carry a 32-base-pair deletion in the CCR5 gene. Two copies confer near-complete resistance to infection by the common CCR5-using strains; one copy slows progression. This variant is the reason the only people ever cured of HIV were cured: they received stem cell transplants for blood cancers from donors homozygous for CCR5-delta32.

Treatment, and how it works

In short: Three drugs in one daily tablet, started immediately at any CD4 count, plus prevention that now includes a twice-yearly injection.

Antiretroviral therapy (ART) combines drugs from different classes, each blocking a different step of the viral life cycle. Combination is essential for the same reason as in TB: the virus mutates so fast that any single drug is defeated within weeks.

Current standard first-line therapy in most of the world is a single daily tablet containing tenofovir, lamivudine, and dolutegravir (TLD), which is potent, has a high barrier to resistance, is well tolerated, and costs a few dollars per person per month in generic form. That combination of properties is why global scale-up became possible.

Treatment is started immediately after diagnosis, at any CD4 count. The START trial settled the question in 2015: immediate treatment reduced serious illness and death compared with waiting for CD4 decline.

Long-acting injectable therapy (cabotegravir plus rilpivirine every two months) offers an alternative for people for whom daily tablets are difficult, which is a significant real-world problem given stigma and unstable housing.

Prevention

• PrEP (pre-exposure prophylaxis): HIV-negative people take antiretrovirals to prevent infection. Daily oral tenofovir/emtricitabine is highly effective when taken consistently. Injectable cabotegravir every two months outperformed daily pills in trials, largely because adherence is built in. Lenacapavir, given twice a year, showed 100 percent efficacy among young women in the PURPOSE 1 trial and near-complete efficacy in PURPOSE 2, the strongest prevention results ever recorded.
• PEP (post-exposure prophylaxis): a 28-day course started within 72 hours of a possible exposure, and the sooner the better.
• Preventing mother-to-child transmission: maternal ART plus infant prophylaxis reduces transmission from 15 to 45 percent down to under 1 percent. Several countries have been certified as having eliminated vertical transmission.
• Voluntary medical male circumcision reduces female-to-male transmission by roughly 60 percent, established in three randomised trials in Africa.
• Needle and syringe programmes and opioid substitution therapy sharply reduce transmission among people who inject drugs, and remain politically restricted in many places despite consistent evidence.
• Treatment as prevention, which is U=U at population scale.

What treatment costs

In short: Modern regimens are well tolerated, with weight gain, bone and kidney effects, and one genetic test that prevents a dangerous reaction.

Modern regimens are far better tolerated than the early ones, which caused disfiguring fat redistribution, nerve damage, and severe metabolic effects.

• Integrase inhibitors: generally well tolerated; weight gain is a recognised effect, more marked in women and in people of African descent, and its long-term significance is under study. Insomnia and mood changes occur.
• Tenofovir disoproxil: kidney function decline and bone density loss with long use; the newer tenofovir alafenamide has less of both and more weight gain and lipid effect.
• Abacavir: a hypersensitivity reaction in people carrying HLA-B*57:01, which is why that genetic test is done before prescribing. This is one of medicine's cleanest examples of routine pharmacogenomic testing preventing serious harm.
• Efavirenz: vivid dreams, dizziness, and mood effects, which is why it has largely been displaced.
• Immune reconstitution inflammatory syndrome (IRIS): as the immune system recovers, it can mount a violent inflammatory response to an existing infection, particularly TB or cryptococcal meningitis, making the patient acutely worse. This is why treatment for those infections is often started before ART.

What the person can do

• Test. Diagnosis is the gateway to everything, and late diagnosis is the main remaining driver of AIDS deaths in high-income countries. Testing is free, fast, and available as a self-test in many countries.
• Start treatment immediately and take it daily. Adherence is the entire game: it determines viral suppression, resistance, health, and transmission.
• Use PrEP if you are at ongoing risk, and know that PEP exists for emergencies.
• Address cardiovascular risk. Smoking is now a bigger threat to the life expectancy of a treated person with HIV than the virus is, and people living with HIV smoke at higher rates than the general population.
• Get vaccinated (hepatitis A and B, HPV, pneumococcus, influenza, COVID-19) and screened (cervical and anal cancer screening where recommended, TB, hepatitis C, other STIs).
• Tell people what U=U means, including clinicians in other specialties, who frequently do not know.

Living with it

The clinical problem has largely been solved for those with access; the social problem has not. Stigma remains the strongest predictor of late testing, poor adherence, and non-disclosure. Around 60 to 90 countries retain laws criminalising HIV non-disclosure, exposure, or transmission, many of which apply regardless of whether transmission occurred or whether the person was virally suppressed, and which public health bodies consistently find counterproductive because they deter testing.

The population living with HIV is also ageing. More than half of people living with HIV in several high-income countries are now over 50, and the clinical agenda has shifted to cardiovascular disease, kidney and bone health, cancer screening, polypharmacy, and loneliness in a cohort many of whom lost most of their friends in the 1980s and 1990s.

What's next

In short: Twice-yearly prevention, cure research aimed at the latent reservoir, and a vaccine that has defeated four decades of attempts.

• Lenacapavir for prevention at scale. Twice-yearly injections with essentially complete efficacy would change the epidemic if priced and distributed to reach the people who need it, which is currently the entire question.
• Cure research. A handful of people have been cured, all via stem cell transplants from CCR5-delta32 donors for cancers they had anyway. That approach is far too dangerous for general use. Current strategies target the latent reservoir: "shock and kill" (reactivating latent virus so it can be cleared), "block and lock" (permanently silencing it), gene editing of CCR5 or of integrated provirus, and engineered immune cells.
• Broadly neutralising antibodies, both as long-acting prevention and as part of remission strategies.
• A vaccine, still absent after four decades. Every large efficacy trial has failed, and the reasons (viral diversity, the shielded envelope protein, integration before immunity can act) are precisely the ones that make this virus difficult in every other respect.
• Sustained funding, which is again the structural risk. Recent reductions in international HIV financing have prompted warnings that infections and deaths could rise substantially if programmes contract.

Sources and notes

Epidemiological figures are from UNAIDS: approximately 41.0 million people living with HIV, 570,000 AIDS-related deaths, and 1.2 million new infections in the most recent global update. First AIDS report: MMWR, 5 June 1981. Virus isolation: Barré-Sinoussi et al., Science, 1983 (Nobel Prize 2008). Origin and dating of HIV-1 group M: Worobey et al., Nature, 2008, and Faria et al., Science, 2014. HPTN 052: Cohen et al., NEJM, 2011. PARTNER and PARTNER2: Rodger et al., JAMA, 2016 and The Lancet, 2019 (zero linked transmissions). START trial: NEJM, 2015. Per-act transmission risks: CDC estimates, which carry wide confidence intervals. Male circumcision trials: Auvert et al. 2005; Bailey et al. and Gray et al., 2007. PURPOSE 1 and 2 lenacapavir results: NEJM, 2024. Berlin, London, and subsequent cured patients: published case reports, 2009 onward. Life expectancy in treated HIV: Antiretroviral Therapy Cohort Collaboration analyses.

Open questions. No strategy has yet cleared the latent reservoir safely. Whether an effective vaccine is achievable remains unknown. The long-term significance of integrase-inhibitor-associated weight gain is not settled.

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