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HIV and AIDS

Few diseases have reshaped modern medicine as profoundly as HIV. In four decades it went from a mysterious, uniformly fatal illness that killed young adults within a couple of years to a manageable chronic condition where a person diagnosed today, started on treatment promptly, can expect a near-normal lifespan and cannot transmit the virus to sexual partners. Understanding HIV means understanding immunology, virology, pharmacology, and public health all at once — which is exactly why it is a favourite of examiners and one of the most rewarding topics a clinician can master.

This page walks you through what the virus actually does inside the body, how infection is staged and diagnosed, how antiretroviral therapy works, and how the opportunistic infections that define AIDS are recognised and prevented. Along the way we keep coming back to two ideas that dominate real practice: get people tested and treated early, and remember that treatment is prevention.

Learning Objectives​

  • Explain how HIV infects and depletes CD4+ T lymphocytes and why this causes immunodeficiency.
  • Describe the natural history of untreated HIV: acute, clinical latency, and AIDS.
  • Interpret the modern diagnostic algorithm (fourth-generation antigen/antibody test, confirmatory assay, viral load).
  • Outline the principles of antiretroviral therapy (ART), the main drug classes, and the goal of viral suppression.
  • Recognise the major AIDS-defining opportunistic infections and the CD4 thresholds at which they occur.
  • Apply prevention strategies: PrEP, PEP, prevention of mother-to-child transmission, and the U=U message.

Quick Answer​

HIV (human immunodeficiency virus) is a retrovirus that infects CD4+ T helper cells, progressively destroying the immune system. Untreated, it passes through an acute flu-like illness, a long clinically latent phase, and finally AIDS — defined by a CD4 count below 200 cells/microlitre or an AIDS-defining opportunistic illness. Diagnosis uses a fourth-generation antigen/antibody test that detects infection within about 2–4 weeks, with viral load used to monitor disease and treatment. Antiretroviral therapy (ART) combines drugs from different classes to suppress viral replication to undetectable levels, restore CD4 counts, and prevent progression. A person with a durably undetectable viral load cannot transmit HIV sexually — the principle known as U=U (Undetectable = Untransmittable). Prevention includes pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), and treating pregnant women to prevent transmission to the baby.

Where It Came From​

In 1981 the US Centers for Disease Control reported clusters of two rare conditions — Pneumocystis pneumonia and Kaposi sarcoma — in previously healthy young gay men in Los Angeles and New York. These illnesses normally appeared only in people whose immune systems had collapsed, yet these patients had no obvious cause. The syndrome was soon named AIDS (acquired immunodeficiency syndrome), and the pressing need was to find what was destroying the immune system and how it spread.

The answer came in 1983–84, when Luc Montagnier and Françoise Barré-Sinoussi at the Institut Pasteur, and Robert Gallo at the US National Institutes of Health, isolated the retrovirus responsible. Montagnier and Barré-Sinoussi received the 2008 Nobel Prize for this discovery. Genetic detective work later traced HIV-1 to cross-species transmission from chimpanzees in west-central Africa in the early twentieth century — the virus is a descendant of simian immunodeficiency virus (SIV).

The early years were desperate: an HIV diagnosis was a death sentence, and the first drug, zidovudine (AZT, 1987), helped only briefly because the virus quickly mutated around a single agent. The turning point was 1996, when combining three drugs — highly active antiretroviral therapy (HAART) — proved able to suppress the virus below the level at which it could evolve resistance. Death rates fell dramatically almost overnight. The motivation running through this entire history is the same one that drives HIV medicine today: a fast-mutating virus can only be defeated by hitting it in several places at once, and by finding infected people before their immune system is destroyed.

How the Virus Works: Attacking the Immune Commander​

HIV is a retrovirus, meaning it carries its genome as RNA and copies it into DNA using the enzyme reverse transcriptase. Its surface glycoprotein gp120 binds the CD4 receptor together with a co-receptor (usually CCR5 or CXCR4) on the surface of T helper cells. The CD4+ T cell is the conductor of the immune orchestra — it coordinates B cells, cytotoxic T cells, and macrophages. By parasitising and destroying this one cell type, HIV disables immune responses across the board.

The viral life cycle is worth knowing because every drug class targets a step in it:

  1. Attachment and entry — gp120 binds CD4 and a co-receptor; the viral and cell membranes fuse.
  2. Reverse transcription — viral RNA is converted to DNA.
  3. Integration — the enzyme integrase splices viral DNA into the host genome, creating a lifelong reservoir.
  4. Transcription and translation — the host cell manufactures new viral proteins.
  5. Assembly and budding — new virions form; the enzyme protease cleaves protein precursors so the virions mature and become infectious.

Reverse transcriptase is error-prone and has no proofreading, so HIV mutates rapidly. This is why single-drug therapy fails and why combination therapy is essential. Integration into host DNA also explains why HIV cannot yet be cured: the latent provirus hides silently in resting memory T cells, invisible to both drugs and the immune system, ready to rebound if treatment stops.

Natural History: From Infection to AIDS​

Without treatment, HIV follows a fairly predictable course over years.

Acute (primary) HIV infection occurs 2–4 weeks after exposure. Roughly half to two-thirds of people develop a seroconversion illness — fever, sore throat, generalised lymphadenopathy, a maculopapular rash, myalgia, and sometimes mouth ulcers — an illness easily mistaken for glandular fever or flu. Viral load is enormous at this stage, making the person highly infectious, and this is precisely when standard antibody tests may still be negative. Always keep acute HIV on the differential for a "flu-like" illness with rash and lymphadenopathy in someone with risk factors.

Clinical latency follows and can last around 8–10 years untreated. The person feels well, but the virus is far from dormant: billions of virions are produced and cleared daily, and the CD4 count declines gradually (typically from a healthy 500–1,500 cells/microlitre downward). Persistent generalised lymphadenopathy may be the only sign.

AIDS is diagnosed when the CD4 count falls below 200 cells/microlitre or an AIDS-defining illness develops. As immunity collapses, characteristic opportunistic infections and cancers emerge at recognisable CD4 thresholds (see below). Without ART, death typically follows within a couple of years of reaching AIDS.

Diagnosis: The Modern Testing Algorithm​

Testing has transformed. The recommended first-line assay is a fourth-generation combined antigen/antibody test, which detects both the viral p24 antigen (present early) and anti-HIV antibodies. This shortens the "window period" to roughly 2–4 weeks after exposure, much earlier than older antibody-only tests.

A rational algorithm:

  1. Fourth-generation Ag/Ab immunoassay — if negative and no recent high-risk exposure, HIV is excluded (repeat if within the window period).
  2. Reactive result — confirm with a differentiation assay (e.g. an HIV-1/HIV-2 antibody differentiation immunoassay).
  3. HIV RNA (viral load) — used if very early infection is suspected (antibodies not yet formed) and to quantify disease for management.

Once diagnosed, baseline work-up includes CD4 count (immune status), HIV viral load (replication level and treatment target), genotypic resistance testing, and screening for co-infections (hepatitis B and C, tuberculosis, syphilis and other STIs) and for latent conditions before starting therapy.

Worked example. A 26-year-old presents with 5 days of fever, sore throat, rash, and tender neck nodes. Monospot is negative. He reports condomless sex 3 weeks ago. A fourth-generation Ag/Ab test is reactive, driven by p24 antigen; the antibody differentiation assay is indeterminate, but HIV RNA is very high (over 1 million copies/mL). This is acute HIV infection — highly infectious, and an opportunity to start ART immediately, which improves outcomes and blunts onward transmission.

Treatment: Antiretroviral Therapy​

The modern standard is to start ART in everyone with HIV, as soon as possible after diagnosis, regardless of CD4 count. Early treatment preserves immune function, reduces the size of the viral reservoir, and prevents transmission.

ART combines drugs from different classes so the virus cannot mutate around all of them at once. The main classes, mapped to the life cycle:

Drug classTarget stepExamples
NRTIs (nucleoside reverse transcriptase inhibitors)Reverse transcriptiontenofovir, emtricitabine, abacavir, lamivudine
NNRTIs (non-nucleoside RTIs)Reverse transcriptionefavirenz, rilpivirine, doravirine
Integrase inhibitors (INSTIs)Integrationdolutegravir, bictegravir, raltegravir
Protease inhibitors (PIs)Maturationdarunavir, atazanavir (boosted with ritonavir/cobicistat)
Entry/fusion inhibitorsAttachment/entrymaraviroc (CCR5), enfuvirtide

A typical modern first-line regimen is two NRTIs plus an integrase inhibitor (for example, tenofovir + emtricitabine + dolutegravir/bictegravir), often available as a single daily pill. Integrase inhibitor-based regimens are favoured for potency, tolerability, and a high barrier to resistance. Long-acting injectable ART (cabotegravir plus rilpivirine every 1–2 months) is now an option for people with suppressed virus who prefer not to take daily pills.

The goal is an undetectable viral load (below about 50 copies/mL), which is usually achieved within 3–6 months. Adherence is everything: missed doses let the virus replicate and select for resistance. Monitoring uses viral load (efficacy) and CD4 count (immune recovery). The clinical payoff is enormous — and it extends beyond the patient, because durable viral suppression makes sexual transmission impossible (U=U).

Opportunistic Infections: When Defences Fail​

As CD4 counts fall, specific infections appear at fairly predictable thresholds — knowing these is high-yield.

  • CD4 below 200: Pneumocystis jirovecii pneumonia (PCP/PJP) — dry cough, exertional breathlessness, and low oxygen with a normal-sounding chest. Prophylaxis: co-trimoxazole.
  • CD4 below 100: cerebral toxoplasmosis (ring-enhancing brain lesions), oesophageal candidiasis.
  • CD4 below 50: disseminated Mycobacterium avium complex (MAC) and cytomegalovirus (CMV) retinitis (a cause of blindness).
  • Any CD4, but more common with immunosuppression: tuberculosis (a leading killer in people with HIV worldwide), oral candidiasis (thrush), Kaposi sarcoma (driven by HHV-8), and oral hairy leukoplakia (EBV).

Prophylaxis is CD4-driven — co-trimoxazole is started below 200 to prevent PCP (and it covers toxoplasmosis at lower counts). Once ART restores the CD4 count above threshold and holds it there, prophylaxis can usually be stopped.

A note of caution: starting ART when CD4 is very low can trigger immune reconstitution inflammatory syndrome (IRIS) — a paradoxical worsening as the recovering immune system mounts an inflammatory response against a pre-existing (sometimes hidden) infection such as TB or cryptococcus. This is managed, not prevented, by careful timing and screening before starting ART.

Real-World Applications​

  • Test-and-treat clinics: rapid diagnosis and same-day ART initiation are now routine in many settings, dramatically improving individual and population outcomes.
  • PrEP (pre-exposure prophylaxis): HIV-negative people at ongoing risk take daily tenofovir/emtricitabine (or long-acting injectable cabotegravir) to prevent acquisition — highly effective when taken as prescribed.
  • PEP (post-exposure prophylaxis): after a high-risk exposure (needlestick injury, sexual assault, condom failure), a 28-day course of ART started ideally within hours and no later than 72 hours can prevent infection. Every clinician should know how to access it.
  • Prevention of mother-to-child transmission (PMTCT): treating the mother to viral suppression, giving the infant prophylaxis, and managing delivery and feeding reduces transmission from around 25–40% to well under 1%.
  • Occupational health: understanding PEP protocols and the low but real risk from needlestick injuries is essential for all healthcare workers.

Common Mistakes​

  1. "A negative test just after exposure rules out HIV." Wrong — there is a window period. Even the fourth-generation test can be negative in the first 2 weeks. If exposure was recent, repeat testing at the appropriate interval and consider HIV RNA if acute infection is suspected.

  2. "HIV and AIDS are the same thing." They are not. HIV is the virus and the infection; AIDS is the advanced stage defined by CD4 below 200 or an AIDS-defining illness. With effective ART, a person with HIV need never develop AIDS.

  3. "Someone who is well and undetectable can still infect their partner, so no precautions matter." The evidence is clear: durably undetectable equals untransmittable (U=U) for sexual transmission. Undermining this message damages both accuracy and stigma reduction. (U=U applies to sexual transmission; separate measures still apply to areas such as breastfeeding, and consistent adherence is required to stay undetectable.)

  4. (Bonus) "Delay ART until the CD4 count drops." Outdated. Current guidance is to start ART in everyone at diagnosis, regardless of CD4, because early treatment improves outcomes and prevents transmission.

Comparison and Connections​

FeatureHIV infectionAIDS
What it isChronic viral infectionAdvanced stage of HIV
CD4 countVariable, often preserved earlyBelow 200 cells/microlitre
Defining featurePositive HIV testAIDS-defining illness or CD4 below 200
Reversible with ART?Kept in checkCD4 can recover; label persists but risk falls

HIV connects to many other topics. It is a classic cause of fever of unknown origin and a major risk factor for reactivation of tuberculosis. Its treatment is a central case study in antimicrobial resistance and stewardship, since resistance emerges when adherence lapses. Co-infection with viral hepatitis is common and shapes drug choice. For the immunology underpinning CD4 T-cell function, see the Immunology branch.

Practice Questions​

Recall​

Q: What CD4 count defines AIDS, and name three AIDS-defining opportunistic infections. A: A CD4 count below 200 cells/microlitre (or an AIDS-defining illness). Examples: Pneumocystis pneumonia, cerebral toxoplasmosis, CMV retinitis, disseminated MAC, oesophageal candidiasis.

Understanding​

Q: Why is combination therapy (three drugs) used rather than a single antiretroviral? A: HIV's reverse transcriptase is error-prone and lacks proofreading, so the virus mutates rapidly. A single drug applies selection pressure the virus can escape within weeks. Combining drugs that hit different steps of the life cycle makes simultaneous resistance to all agents statistically very unlikely, allowing durable suppression.

Application​

Q: A nurse sustains a needlestick from a patient with untreated HIV. What do you do? A: Wash the wound, assess the exposure risk, and start PEP — a 28-day course of ART — as soon as possible, ideally within hours and no later than 72 hours. Perform baseline HIV testing on the nurse, arrange follow-up testing, and manage per occupational-health protocol.

Analysis​

Q: A patient with CD4 of 30 starts ART and two weeks later deteriorates with worsening fever and lymphadenopathy despite a falling viral load. What is happening and why? A: This is likely IRIS (immune reconstitution inflammatory syndrome). As the recovering immune system regains function, it mounts a vigorous inflammatory response against a pre-existing opportunistic infection (often TB or cryptococcus). It reflects immune recovery, not treatment failure — the falling viral load confirms ART is working. Management is to treat the underlying infection, continue ART, and add anti-inflammatory therapy if severe.

FAQ​

Is HIV curable? Not yet. ART controls the virus but cannot eliminate the latent reservoir integrated into resting cells. A very small number of people have been cured through stem-cell transplants for cancer using CCR5-deficient donor cells, but this is not a scalable treatment. Research into a cure and a vaccine continues.

How long can someone with HIV expect to live? Someone diagnosed early and treated effectively today can expect a life expectancy approaching that of the general population. Late diagnosis is now the main driver of poor outcomes — which is why testing matters so much.

Can HIV be transmitted through casual contact? No. HIV is not spread by hugging, sharing utensils, toilet seats, coughing, or insect bites. It is transmitted through blood, sexual fluids, and from mother to child during pregnancy, birth, or breastfeeding.

What does "undetectable" mean, and can they still pass it on? Undetectable means viral load is below the assay's detection limit (about 50 copies/mL). A person who is durably undetectable on treatment cannot transmit HIV sexually — this is U=U. Adherence must be maintained to stay undetectable.

Who should take PrEP? HIV-negative people at ongoing substantial risk — for example, those with an HIV-positive partner who is not yet suppressed, or people with multiple partners and inconsistent condom use. PrEP is highly effective when taken as prescribed and is combined with regular testing.

Why do people with HIV get tuberculosis so often? CD4 T cells are central to containing Mycobacterium tuberculosis within granulomas. As HIV depletes them, latent TB reactivates and new infection progresses more readily. TB is the leading cause of death among people with HIV worldwide, so screening and prevention are priorities.

Quick Revision​

  • HIV is a retrovirus that infects and destroys CD4+ T helper cells, causing progressive immunodeficiency.
  • Life cycle: entry → reverse transcription → integration → assembly → maturation (each a drug target).
  • Stages: acute seroconversion (highly infectious) → clinical latency (~8–10 years) → AIDS (CD4 below 200 or AIDS-defining illness).
  • Diagnose with a fourth-generation Ag/Ab test (window ~2–4 weeks); confirm and quantify with viral load.
  • Treat everyone at diagnosis with combination ART, typically 2 NRTIs + an integrase inhibitor; goal is undetectable viral load.
  • Opportunistic infections by CD4: PCP below 200, toxoplasmosis below 100, MAC/CMV below 50; co-trimoxazole prophylaxis below 200.
  • Prevention: PrEP, PEP, PMTCT, and the core public-health message U=U (Undetectable = Untransmittable).
  • Watch for IRIS when starting ART at very low CD4 counts.

Prerequisites​

Next Topics​