HIV

Human immunodeficiency virus is the cause of acquired immunodeficiency syndrome (AIDS) and one of the defining pathogens of modern clinical virology. Four decades after its identification it remains a major global health problem, the source of much of the antiretroviral drug landscape and of the molecular diagnostic infrastructure the wider discipline now relies on, and the focus of one of the largest public-health programmes in history.

The pandemic is overwhelmingly the work of HIV-1, and almost entirely of its group M, with subtype C predominating across southern Africa and subtype B across the Northern hemisphere. HIV-2 is a distinct human immunodeficiency virus, sharing only about 50 to 60% of its sequence with HIV-1, descending from a separate primate cross-species transmission, and largely confined to West Africa. It transmits less efficiently and progresses to AIDS more slowly, but it is intrinsically resistant to the non-nucleoside reverse transcriptase inhibitors and is missed by most HIV-1 viral-load assays, both important when it is encountered. Outside those specific contexts, HIV means HIV-1.

The topic runs from the virus itself to operational practice across five pages.

→ See HIV-1 for the virus profile: classification within the genus Lentivirus, genome and virion structure, the replication cycle, pathogenesis, natural history and diagnosis.

→ See Ending the HIV Epidemic for the global pandemic in numbers, the 95-95-95 treatment cascade, the UNAIDS 2026 to 2031 Global AIDS Strategy, and the South African epidemic from SABSSM VI.

→ See Antiretrovirals for the drug classes and their mechanisms, characteristic toxicity and barriers to resistance, the major interactions, monitoring, and pre- and post-exposure prophylaxis.

→ See HIV drug resistance for why resistance arises, the mutation-naming convention, phenotypic and genotypic testing, the Stanford HIVdb interpretation tool, and the key South African mutations.

→ See South African HIV Guidelines for the operational programme: the 2026 National Consolidated Guidelines, the TLD framework, virological failure, tuberculosis co-treatment, advanced HIV disease, and prevention of vertical transmission.

Key terms

The vocabulary that recurs across the topic, grouped by theme.

Virus and pathogenesis:

Term	Definition
Group M, subtype C	The pandemic lineage of HIV-1; subtype C predominates in southern Africa and accounts for roughly half of infections worldwide.
Quasispecies	The swarm of related viral variants within one host, generated by an error-prone reverse transcriptase; the raw material for immune escape and drug resistance.
Latent reservoir	Integrated, replication-competent provirus in long-lived resting memory CD4+ T cells; established within days and the principal barrier to cure.
Set point	The viral load at which a partial immune response settles after acute infection, predicting the pace of progression.
Elite controller	A rare person who suppresses viraemia below detection without treatment, largely through favourable HLA-driven cellular immunity.

Diagnosis and monitoring:

Term	Definition
Fourth-generation assay	The standard screening test, detecting p24 antigen together with antibody and closing the diagnostic window to about two weeks.
Diagnostic window	The interval after infection before a given marker becomes detectable; preceded by an eclipse period in which nothing is detectable.
Early infant diagnosis (EID)	HIV PCR-based testing of infants under 18 months, who carry transplacental maternal antibody that makes serology uninterpretable.
Viral load (VL)	The quantitative HIV RNA measure used to monitor therapy; the suppression target is below 50 copies/mL.
Virological failure	Two consecutive viral loads at or above 1,000 copies/mL after at least nine months on a dolutegravir-based regimen with documented adherence support.

Treatment and prevention:

Term	Definition
Antiretroviral therapy (ART)	Combination therapy, most often two nucleoside reverse transcriptase inhibitors with an integrase inhibitor; it suppresses replication but does not cure.
TLD	The fixed-dose combination of tenofovir, lamivudine and dolutegravir, the South African and WHO-preferred first-line regimen.
U=U	Undetectable equals untransmittable: a sustained viral load below the limit of detection is not transmitted sexually.
Pre-exposure prophylaxis (PrEP)	Antiretroviral prevention taken before exposure: daily oral tenofovir/emtricitabine, long-acting cabotegravir, or six-monthly lenacapavir.
Post-exposure prophylaxis (PEP)	A 28-day course of triple therapy started within 72 hours of a discrete high-risk exposure.

Resistance:

Term	Definition
Genetic barrier	The number of mutations a virus needs to escape a drug; dolutegravir’s high barrier underpins the TLD framework.
Cross-resistance	Resistance to one drug reducing susceptibility to others that bind the same site; the rule within a drug class and the exception between classes, so losing a class means switching class.
Fitness cost	The replicative penalty a resistance mutation carries; it lets wild-type virus outcompete resistant variants off drug and underpins lamivudine recycling.
Archived resistance	Mutations retained in the integrated provirus for life; they re-emerge on drug re-exposure even when absent from the current consensus sequence.
Transmitted drug resistance	Resistance present at infection rather than acquired on treatment; rising pre-treatment resistance to the non-nucleoside class was a key driver of the shift to dolutegravir first-line.
Genotypic and phenotypic testing	Genotyping reads the sequence and predicts resistance (the clinical workhorse); phenotyping measures susceptibility directly in cell culture (the reference method).
Minority variants	Resistant sub-populations below the roughly 20% detection threshold of Sanger sequencing; next-generation sequencing detects them down to about 1%.
Non-canonical resistance mutations	Changes outside the classically scored positions, for example in the reverse transcriptase connection and RNase H domains or the protease cleavage sites, absent from standard interpretation lists yet able to lower susceptibility or offset a fitness cost; increasingly recognised as sequencing widens.
Stanford HIVdb	The dominant interpretation tool worldwide: it scores the mutations in a sequence and reports susceptibility per drug on a five-level scale.

Public health and programme:

Term	Definition
Reflex dolutegravir drug-level testing	The South African workflow that measures the drug level before genotyping, separating true resistance from non-adherence.
95-95-95	The treatment-cascade targets: 95% of people with HIV diagnosed, 95% of those on ART, and 95% of those suppressed.
Advanced HIV disease (AHD)	A CD4 count at or below 200 cells/µL, WHO clinical stage 3 or 4, or a child under 5, triggering an intensified care package.
Prevention of mother-to-child transmission (PMTCT)	Maternal ART with infant prophylaxis and early infant diagnosis to prevent vertical transmission.

References and recommended reading

• Bekker L-G, Beyrer C, Mgodi N, et al. HIV infection. Nature Reviews Disease Primers 2023;9:42. A comprehensive current overview of the virus and its management.
• National Department of Health, South Africa. 2026 National Consolidated Guidelines for the Prevention and Management of HIV. The operational reference for South African practice.
• UNAIDS. 2026 to 2031 Global AIDS Strategy: Towards Ending AIDS. The global strategic framework and cascade targets.
• Richman DD, Whitley RJ, Hayden FG, editors. Clinical Virology, 4th edition. ASM Press; 2016. The textbook source for HIV virology and antiretroviral principles.
• Human Sciences Research Council. South African National HIV Prevalence, Incidence, Behaviour and Communication Survey VI (SABSSM VI). 2024. The primary source for current South African epidemiology.