HIV/AIDS and Related Infections

HIV/AIDS is the prototypical acquired immunodeficiency: infection with the human immunodeficiency virus progressively depletes CD4 T-lymphocytes, undermining cell-mediated immunity and exposing the host to a characteristic set of opportunistic infections and malignancies that define the acquired immunodeficiency syndrome.

Definition

HIV infection is a chronic retroviral infection that targets and depletes CD4-positive T-lymphocytes; AIDS is its advanced stage, defined by profound cell-mediated immunodeficiency and the occurrence of specified opportunistic infections or malignancies.

Scope

This topic covers the virology and natural history of HIV infection, the mechanism of progressive CD4 depletion, the spectrum of related opportunistic and AIDS-defining infections, and the transformation of HIV into a manageable chronic condition with effective antiretroviral therapy. It is a reference overview of the disease and its immunologic consequences, not a treatment guide.

Core questions

• How does HIV cause progressive immunodeficiency?
• Why does the CD4 count predict the spectrum of related infections?
• How has antiretroviral therapy reframed HIV as a chronic disease?
• What distinguishes HIV infection from the AIDS-defining stage?

Key concepts

• CD4 T-lymphocyte depletion
• Viral load and immune status
• AIDS-defining illnesses
• Antiretroviral therapy and immune reconstitution
• Chronic immune activation
• HIV as a chronic disease

Mechanisms

HIV is a retrovirus that infects CD4-bearing T-cells and other immune cells, and through ongoing viral replication and immune activation it causes a progressive loss of CD4 T-lymphocytes and erosion of cell-mediated immunity (Maartens et al., 2014). As the CD4 count falls, the host becomes susceptible to a stage-dependent succession of opportunistic infections; severe immunosuppression can unmask latent pathogens, as in progressive multifocal leukoencephalopathy (Hall et al., 1998). Suppressing viral replication with antiretroviral therapy allows partial immune recovery and prevents progression, converting a once-fatal infection into a chronic, manageable condition (Deeks et al., 2013).

Clinical relevance

Because the degree of immunodeficiency in HIV tracks with the CD4 count, the disease is a clear example of how host immune status shapes infection risk, and it underlies the rationale for prophylaxis against opportunistic infection in advanced disease. This entry describes the disease and its immunology for reference; it is not a source of dosing, regimen selection, or individualised care.

Epidemiology

HIV/AIDS is a global pandemic affecting tens of millions of people, with the heaviest burden historically in sub-Saharan Africa. The advent and scale-up of antiretroviral therapy has profoundly altered its trajectory, reducing mortality and the incidence of AIDS-defining opportunistic infections and shifting the clinical focus toward long-term, chronic-disease management (Deeks et al., 2013; Maartens et al., 2014).

History

AIDS was recognised in the early 1980s as a cluster of opportunistic infections and unusual malignancies in previously healthy people, and HIV was subsequently identified as its cause. The development of combination antiretroviral therapy in the mid-1990s transformed prognosis, and by the 2010s HIV was increasingly framed as a chronic disease rather than a uniformly fatal one (Deeks et al., 2013).

Debates

When should antiretroviral therapy be started?

The relative emphasis on early universal treatment versus CD4-guided initiation evolved as evidence accumulated on the benefits of suppressing viral replication for both individual health and prevention of transmission.

Key figures

• Gary Maartens
• Steven Deeks
• Sharon Lewin
• Diane Havlir

Seminal works

• maartens-2014
• deeks-2013

Frequently asked questions

What is the difference between HIV and AIDS?

HIV is the virus that infects and gradually depletes immune cells; AIDS is the advanced stage of that infection, defined by severe immunodeficiency together with specific opportunistic infections or cancers. A person can live with HIV for years before, and ideally without ever, reaching the AIDS stage.

Why does the CD4 count matter in HIV?

The CD4 count reflects the strength of cell-mediated immunity, and as it falls the risk of particular opportunistic infections rises in a fairly predictable order. It is therefore a key marker of how advanced the immunodeficiency has become.