Human immunodeficiency virus (HIV) is an enveloped, positive-sense, single-stranded RNA virus belonging to the genus Lentivirus within the family Retroviridae. Two types are recognised, HIV-1 and HIV-2, of which HIV-1 is responsible for the global pandemic and is by far the more prevalent and clinically significant. HIV-1 is further classified into four groups, M, N, O, and P, with group M accounting for the vast majority of infections worldwide and comprising nine subtypes, or clades, with differing geographical distributions. Untreated HIV infection leads to the progressive depletion of CD4-positive T lymphocytes and, ultimately, to the clinical syndrome of acquired immunodeficiency syndrome (AIDS).

HIV enters host cells through high-affinity binding of the viral envelope glycoprotein gp120 to the CD4 receptor, which is expressed on the surface of helper T lymphocytes, macrophages, and dendritic cells. CD4 binding triggers conformational changes in gp120 that expose a second binding site for a co-receptor, either CCR5 or CXCR4, depending on the viral tropism. Co-receptor engagement induces further conformational changes in the transmembrane glycoprotein gp41, driving fusion of the viral and host-cell membranes and releasing the viral core into the cytoplasm. Following entry, the viral reverse transcriptase converts the RNA genome into double-stranded DNA, which is transported into the nucleus as part of the pre-integration complex and inserted into the host-cell chromosome by the viral integrase. The integrated provirus can then be transcribed by host-cell RNA polymerase II to produce new viral RNA genomes and mRNAs encoding all viral proteins. Progeny virions assemble at the plasma membrane and are released by budding, with final maturation driven by the viral protease.

The HIV genome encodes three major polyproteins, Gag, Pol, and Env, along with six regulatory and accessory proteins, Tat, Rev, Vif, Vpr, Vpu (HIV-1) or Vpx (HIV-2), and Nef.

Gag encodes the structural proteins of the viral core, including capsid, matrix, and nucleocapsid. Pol encodes the three essential viral enzymes, reverse transcriptase, integrase, and protease, all of which are established drug targets. Env encodes the envelope glycoproteins gp120 and gp41. The accessory proteins collectively serve to counteract host restriction factors, modulate immune responses, and optimise conditions for viral replication and immune evasion, with Vif in particular being essential for overcoming the antiviral activity of the host cytidine deaminase APOBEC3G.

HIV is transmitted through contact with infectious body fluids, primarily blood, semen, vaginal secretions, rectal secretions, and breast milk. The main routes of transmission are unprotected sexual contact, sharing of needles or syringes among people who inject drugs, transfusion of infected blood or blood products, and vertical transmission from mother to child during pregnancy, labour, delivery, or breastfeeding. Following transmission, HIV establishes a rapidly disseminating systemic infection, with an acute retroviral syndrome occurring in many individuals within two to four weeks of exposure, characterised by fever, lymphadenopathy, pharyngitis, rash, and myalgia. After the acute phase, a period of clinical latency lasting years follows, during which viral replication continues at lower levels, but CD4 cell counts progressively decline. Without treatment, immunosuppression eventually becomes severe enough to permit the opportunistic infections and malignancies that define AIDS.

HIV infection is a global pandemic of extraordinary scale. According to the most recent estimates, approximately 39 million people are living with HIV worldwide, with sub-Saharan Africa bearing the greatest burden. Around 1.3 million new infections occur each year, and approximately 630,000 people die annually from AIDS-related illnesses. Since the beginning of the epidemic, HIV has caused over 40 million deaths, making it one of the most lethal infectious diseases in recorded history.

Antiretroviral therapy (ART) has transformed HIV infection from a uniformly fatal disease into a manageable chronic condition. Current ART regimens typically combine two or more drugs from different mechanistic classes, including nucleoside and nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors, and entry inhibitors targeting CD4, CCR5, or gp41. When initiated promptly and taken consistently, ART suppresses viral replication to undetectable levels, prevents immune deterioration, restores CD4 counts, eliminates onward transmission, and allows people with HIV to have near-normal life expectancy. Long-acting injectable formulations of ART are now available, and broadly neutralising antibodies and other novel modalities are in clinical development. Despite these advances, a functional cure for HIV has not yet been achieved, and the latent viral reservoir established in resting CD4 T cells at the time of infection persists indefinitely in the absence of continuous treatment.

Prevention of new HIV infections relies on a combination of behavioural, biomedical, and structural approaches. Pre-exposure prophylaxis (PrEP), in which HIV-negative individuals at high risk take antiretroviral drugs before potential exposure, has become an important prevention tool and is highly effective when used consistently. Despite decades of intensive research, no broadly protective HIV vaccine has yet been licensed. Vaccine development has been hampered by the virus’s extraordinary genetic diversity, its ability to rapidly evolve under immune pressure, and the absence of a classical neutralising antibody response capable of controlling infection, though broadly neutralising antibody-based approaches continue to be investigated.

Overall, HIV remains one of the most significant infectious disease challenges of our time. The availability of highly effective ART has fundamentally changed the prognosis for people living with HIV, but eliminating the epidemic requires continued advances in prevention, diagnostics, and treatment, broader access to existing tools, and sustained research into curative strategies and a preventive vaccine.