Transmission routes and general characteristics
HIV infection is transmitted primarily via the contact mechanism. Natural routes include sexual and vertical (mother-to-child), while artificial routes include parenteral. The pathogen is a retrovirus with a tropism for CD4+ T-lymphocytes, which determines the development of progressive immunodeficiency.
Clinical classification
The clinical classification distinguishes five stages of the disease.
- Stage 1 — Incubation. The period from infection to clinical manifestations or seroconversion lasts from 3 weeks to 6 months. Active viral replication occurs, and antibodies are not yet detectable. Diagnosis is possible only based on epidemiological data or PCR (viral RNA).
- Stage 2 — Primary manifestations. Includes the following variants: 2A — asymptomatic with seroconversion; 2B — acute infection without secondary diseases (fever, rash, lymphadenopathy, hepatosplenomegaly, tonsillitis, pharyngitis, occasionally atypical mononuclear cells — clinical picture resembles infectious mononucleosis; aseptic meningitis is possible); 2C — acute infection with secondary diseases (candidiasis, herpes, in severe cases — Candida esophagitis, Pneumocystis pneumonia).
- Stage 3 — Subclinical. Lasts on average 6–7 years (up to 20 years or more). The slow progression of immunodeficiency is compensated by excessive production of CD4 cells. The only possible symptom is persistent generalized lymphadenopathy: enlargement of lymph nodes in at least two groups, >1 cm in adults, >0.5 cm in children; nodes are elastic, painless, and mobile (not fused).
- Stage 4 — Secondary diseases. Depletion of compensatory reserves, sharp decline in CD4 count. 4A: weight loss <10%, recurrent skin and mucous membrane lesions, sinusitis, pharyngitis. 4B (after 7–10 years): weight loss >10%, prolonged fever and diarrhea, deep visceral lesions, localized Kaposi sarcoma, herpes zoster. 4C (after 10–12 years): cachexia, generalized infections, Pneumocystis pneumonia, esophageal, bronchial, or tracheal candidiasis, CNS lesions, malignant tumors. Progression and remission phases are distinguished.
- Stage 5 — Terminal. Irreversible course of secondary diseases, death within a few months.
Anamnesis and physical examination
Risk factors are clarified: sexual contacts, contraception methods, pregnancy, parenteral interventions, injection drug use. Diseases with a common transmission mechanism — hepatitis B and C, as well as possible secondary conditions (recurrent pneumonia, tuberculosis, night sweats, weight loss) — are investigated.
Physical examination assesses body weight (lipodystrophy is characteristic), skin and mucous membranes (rash, herpes zoster, seborrheic dermatitis, fungal infections, Kaposi sarcoma lesions, papillomas, condylomas, injection tracks), lymph nodes, liver, spleen, and oropharynx. Assessment of neurological and mental status, including cognitive functions (Montreal Cognitive Assessment), is mandatory.
Laboratory diagnostics
HIV testing is voluntary, requires informed consent, confidentiality, pre- and post-test counseling, and anonymity upon request. Diagnosis is carried out in two stages.
- Establishing infection status: ELISA to detect antibodies; immunoblotting determines the spectrum of antibodies to individual viral proteins (negative, indeterminate, positive result); PCR for viral RNA — most effective in stages 1–2 before seroconversion occurs; virological method — inoculation of a lymphocyte culture.
- Determining stage and prognosis: determination of immune status (normal CD4 count is 600–1200 cells/µL; severe immunodeficiency is <200 cells/µL or <15%, requiring urgent ART) and viral load — the number of RNA copies per mL of blood. During therapy, the goal is an undetectable level, at which HIV transmission is impossible.
Principles and drug classes of antiretroviral therapy
Treatment is based on the principles of voluntariness, timeliness, and continuity: therapy is lifelong, and no drugs exist that can eradicate the virus. Combination ART consisting of 3–4 drugs from different classes is used.
- Nucleoside and non-nucleoside reverse transcriptase inhibitors — competitive inhibition of the enzyme that synthesizes proviral DNA using an RNA template.
- Protease inhibitors — bind to the active site of the viral protease, disrupting polyprotein cleavage; immature, non-infectious virions are formed.
- Integrase inhibitors — block the integration of proviral DNA into the host cell genome.
- Fusion inhibitors — bind to the envelope glycoprotein, preventing the virus from penetrating the membrane.
- Coreceptor inhibitors — maraviroc alters the conformation of the CCR5 coreceptor; effective against R5-tropic strains (X4-tropic and dual-tropic strains are also distinguished).
Antiretroviral therapy regimens
Three levels of regimens are used.
- First-line regimen: two nucleoside reverse transcriptase inhibitors + one non-nucleoside reverse transcriptase inhibitor. In case of contraindications to non-nucleoside inhibitors, an alternative regimen consisting of three nucleoside inhibitors is used.
- Second-line regimen is prescribed when the first-line fails: two "new" nucleoside inhibitors (not used previously) + a protease inhibitor. Switching reduces the risk of developing resistance.
- Reserve regimens are used upon second-line failure: they include fusion inhibitors, one or two protease inhibitors; they require physician expertise and individualized selection.
Detailed protocols are outlined in the clinical guidelines for HIV infection in adults.
Key points
- HIV is transmitted through sexual, vertical, and parenteral routes.
- The clinical classification includes 5 stages: incubation, primary manifestations, subclinical, secondary diseases, and terminal.
- In the incubation stage, the diagnosis is made only by PCR, since antibodies have not yet been produced.
- Persistent generalized lymphadenopathy is the only possible symptom of the subclinical stage.
- A CD4 count <200 cells/µL is an indication for the urgent initiation of ART.
- Confirmation of infection: ELISA, immunoblotting, PCR, virological method.
- ART is a lifelong combination therapy consisting of 3–4 drugs from different classes.
- The goal of therapy is an undetectable viral load, which rules out virus transmission.