HIV

HIV is a retroviral infection targeting CD4-positive T lymphocytes. It produces progressive immune system depletion and, without effective treatment, susceptibility to a characteristic range of opportunistic infections and malignancies.

Combination antiretroviral therapy has transformed the natural history of this condition. A once uniformly fatal diagnosis is now a chronic, manageable condition. Life expectancy is near-normal for individuals achieving and maintaining effective viral suppression.

Pathophysiology and natural history

• HIV infects and progressively depletes CD4-positive T lymphocytes, the central coordinators of cell-mediated immunity.

• The resulting immunodeficiency produces susceptibility to a characteristic range of opportunistic infections and malignancies as CD4 count declines. Specific, well established CD4 thresholds correlate with the emergence of particular opportunistic conditions.

• Following initial infection, a period of acute retroviral syndrome may occur. This is followed by a variable, often prolonged asymptomatic period of chronic infection. Ongoing viral replication and progressive CD4 depletion continue despite the absence of overt symptoms.

• In the absence of effective treatment, infection eventually progresses to acquired immunodeficiency syndrome.

• Transmission occurs through sexual contact, blood and blood product exposure, and vertical transmission from mother to child. The relative risk varies with the route and, critically, the source individual's plasma viral load.

• Individuals maintaining an undetectable viral load on effective treatment carry negligible transmission risk through sexual contact.

• Acute retroviral syndrome occurs two to four weeks following initial infection in a substantial proportion of affected individuals. It presents as a non-specific, glandular fever-like illness comprising fever, lymphadenopathy, sore throat, and rash. It is frequently unrecognised or misattributed to a more common, self-limiting viral illness.
• Chronic, asymptomatic infection may persist for many years in the absence of treatment. CD4 count declines progressively, though silently, throughout this period. This underscores the value of testing-based diagnosis rather than reliance on symptomatic presentation.
• Advanced, untreated infection produces the characteristic range of opportunistic infections and malignancies, with specific conditions occurring at characteristic CD4 thresholds.
• Oral or oesophageal candidiasis and pulmonary tuberculosis occur at higher CD4 counts.
• Pneumocystis pneumonia and toxoplasma encephalitis occur at CD4 counts generally below 200 cells per microlitre.
• Cytomegalovirus retinitis and disseminated Mycobacterium avium complex infection occur at CD4 counts generally below 50 cells per microlitre.
• Kaposi sarcoma, primary central nervous system lymphoma, and an increased incidence of several other malignancies are additional manifestations of advanced, untreated infection. They reflect both direct immunodeficiency-related susceptibility and, for several specific malignancies, a relevant underlying viral co-factor.

• Combination antigen-antibody testing is the standard, first-line diagnostic approach. It offers earlier detection than antibody testing alone, because it detects the p24 antigen during the initial window period before antibody seroconversion has occurred. Confirmatory testing is performed on any initial reactive result.
• Viral load measurement and CD4 count assessment are essential components of baseline and ongoing evaluation once diagnosis is confirmed. Viral load is the marker of ongoing viral replication and treatment response. CD4 count is the marker of immune status and associated opportunistic infection risk.
• Baseline assessment following diagnosis includes screening for coexisting sexually transmitted infections, viral hepatitis, and tuberculosis, together with antiretroviral resistance testing. This directly informs treatment planning.
• Routine, opt-out HIV testing is a standard component of antenatal care and of a range of other relevant healthcare settings. It supports earlier diagnosis in populations who might not otherwise seek testing, given the substantial benefit of early diagnosis and treatment initiation to both individual and public health outcomes.

• Combination antiretroviral therapy, generally comprising three agents from at least two different drug classes, is standard, essential treatment for every individual diagnosed with HIV regardless of CD4 count. Early initiation has well established, substantial benefit for both individual health outcomes and prevention of onward transmission.
• Contemporary first-line regimens typically comprise two nucleoside reverse transcriptase inhibitors combined with an integrase strand transfer inhibitor. Agent selection is guided by resistance testing, coexisting conditions, and drug interaction considerations.
• Several effective, well tolerated single-tablet, once-daily combination regimens are now widely available, supporting adherence.
• The treatment goal is achievement and maintenance of an undetectable plasma viral load. This is generally achieved within several months of appropriately selected treatment initiation in the great majority of adherent individuals. Sustained viral suppression is associated with excellent individual health outcomes and negligible onward sexual transmission risk.
• Prophylaxis against specific opportunistic infections is indicated according to CD4 count. Co-trimoxazole prophylaxis against Pneumocystis pneumonia and toxoplasmosis is generally indicated at CD4 counts below 200 cells per microlitre. Azithromycin prophylaxis against Mycobacterium avium complex is considered at CD4 counts below 50 cells per microlitre.
• Prophylaxis is generally discontinued once sustained immune reconstitution is achieved on effective antiretroviral therapy.
• Pre-exposure prophylaxis comprises oral tenofovir-based combination therapy or, increasingly, long-acting injectable formulations. It is an effective prevention strategy for individuals at substantial ongoing risk of HIV acquisition.
• Post-exposure prophylaxis comprises a combination antiretroviral regimen commenced as soon as possible following a significant exposure and continued for twenty-eight days. It is an important intervention following a specific, recognised exposure event.
• Structured, lifelong follow-up underpins management of this now chronic, manageable condition. It incorporates regular viral load and CD4 monitoring, together with ongoing screening for and management of coexisting conditions and treatment-related considerations.
• Full psychosocial support addresses the substantial, though evolving, psychological and social impact of this diagnosis.