HIV Infection: Stages, Opportunistic Infections, and Antiretroviral Therapy

1. Pathogen and Epidemiology

HIV (Human Immunodeficiency Virus) is an RNA-containing retrovirus of the family Retroviridae, subfamily Lentivirinae. Two types are distinguished: HIV-1 (global pandemic) and HIV-2 (West Africa, slower progression). The genome consists of two copies of single-stranded RNA containing gag, pol, env genes and regulatory genes.

Key virion enzymes, all of which serve as targets for ART:

• Reverse transcriptase — DNA synthesis using an RNA template.
• Integrase — insertion of proviral DNA into the host cell genome.
• Protease — cleavage of polyproteins into functional proteins.

Transmission routes: sexual (>80% of cases), parenteral (injection drug use, blood transfusions), vertical (mother-to-child), occupational (healthcare workers).

2. Pathogenesis: Why CD4 Lymphocytes Die

HIV binds to the CD4⁺ cell membrane via the CD4 receptor and the CCR5 coreceptor (on macrophages, T-helper cells) or CXCR4 (late strains). Viral RNA → DNA (reverse transcriptase) → integration into the genome (integrase) → synthesis of viral proteins → assembly and budding from the cell.

Loss of CD4 lymphocytes occurs through three mechanisms: direct cytolysis, apoptosis of infected and uninfected ("bystander") cells, and CD8 cellular immune response against infected cells. The rate of CD4 decline correlates with the viral load.

3. Staging Classification

Pokrovsky Classification (Russia)

1. Incubation stage (2–4 weeks).
2. Primary manifestations stage:
   2A — asymptomatic;
   2B — acute HIV infection without secondary diseases (fever, lymphadenopathy, pharyngitis — "mononucleosis-like");
   2C — with secondary diseases.
3. Subclinical stage (from 6–7 years to decades).
4. Secondary diseases stage: 4A, 4B, 4C depending on severity.
5. Terminal stage (AIDS).

CDC Classification

Based on CD4 count and clinical categories A/B/C:

• CD4 ≥ 500 — category 1; 200–499 — 2; < 200 — 3 (AIDS).
• A — asymptomatic / acute infection / persistent generalized lymphadenopathy.
• B — non-AIDS-defining, but immunodeficiency-related (Herpes zoster, candidiasis, HPV dysplasia).
• C — AIDS-defining conditions (Pneumocystis pneumonia, cryptococcal meningitis, cerebral toxoplasmosis, Kaposi sarcoma, etc.).

4. Opportunistic Infections by CD4 Count

Knowing the CD4 thresholds is the key to clinical reasoning:

AIDS-defining conditions (at any CD4 count): Kaposi sarcoma, primary CNS lymphoma, Pneumocystis pneumonia, extrapulmonary TB, extrapulmonary cryptococcosis, disseminated histoplasmosis, HIV encephalopathy.

5. Diagnostics

Laboratory Algorithm

1. Screening: 4th generation ELISA (antibodies + p24 antigen) — window period 2–4 weeks.
2. Confirmation: immunoblot (detection of antibodies against gp160, gp120, gp41, p24).
3. Quantitative RNA PCR — viral load determination and ART monitoring.
4. CD4 lymphocytes — assessment of immune status.
5. Resistance genotyping — before initiating ART and in case of virological failure.

Serological window period: ELISA may be negative during the first 2–4 weeks. If acute HIV infection is suspected, order an RNA PCR immediately (becomes positive 5–10 days after infection).

6. Antiretroviral Therapy (ART)

Principle of modern ART: start immediately after diagnosis, regardless of CD4 count and clinical stage (the "treat-all" approach, WHO 2015).

Drug Classes

Standard first-line regimen

2 NRTIs + 1 integrase inhibitor. Most frequently: tenofovir + lamivudine (or emtricitabine) + dolutegravir (TLD — one tablet once daily). Alternative: bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).

Goals of therapy

• Decrease in viral load to undetectable (< 50 copies/mL) at 6 months.
• CD4 count increase of 50–100 cells/µL per year.
• Prevention of transmission: "U = U" (Undetectable = Untransmittable).

7. Prevention of opportunistic infections

• CD4 < 200 — trimethoprim/sulfamethoxazole (prophylaxis of Pneumocystis pneumonia and toxoplasmosis).
• CD4 < 50 — azithromycin (MAC), if IgG to Toxoplasma is positive — enhanced prophylaxis.
• TB contact — isoniazid for 6–9 months.
• Vaccination: inactivated vaccines are permitted; live vaccines (BCG, MMR) are contraindicated when CD4 < 200.

8. Post-exposure prophylaxis (PEP)

• Initiate as early as possible, optimally within the first 2 h, maximum 72 h.
• Regimen: tenofovir + emtricitabine + dolutegravir for 28 days.
• Laboratory tests: HIV test at weeks 0, 6, and 12; hepatitis B and C.

Pre-exposure prophylaxis (PrEP) — tenofovir/emtricitabine daily in individuals from high-risk groups, reduces the risk of infection by >90%.

9. Prevention of mother-to-child transmission

• ART for the mother — throughout pregnancy and labor.
• Elective Cesarean section if viral load > 1000 copies/mL.
• Avoidance of breastfeeding (in settings with access to formula).
• For the newborn — ART prophylaxis from the first hours of life (zidovudine ± nevirapine/raltegravir for 4–6 weeks).

With protocol adherence, the risk of transmission decreases from 15–45% to < 1%.

10. FAQ

What is the difference between HIV and AIDS?
HIV is an infection (virus in the body). AIDS is the end-stage defined by a CD4 count < 200/µL or the presence of an AIDS-defining condition.

What is an "undetectable viral load"?
< 50 copies of RNA/mL — indicates suppressed replication. A patient with such a load does not transmit HIV to a sexual partner (U=U principle).

Why is ART initiated regardless of CD4 count?
Early treatment reduces systemic inflammation, the risk of AIDS, cancer, cardiovascular diseases, and transmission to partners. WHO has recommended the "treat-all" strategy since 2015.

What to do in case of a needle-stick injury with an infected needle?
Wash with soap and water, consult an infectious disease specialist, and if risk is confirmed, receive post-exposure ART for 28 days. Follow-up ELISAs at weeks 6 and 12.

Is HIV transmitted through casual contact?
No. Transmission does not occur through casual contact (handshakes, dishware, toilets, swimming pools).

See also: Tuberculosis · Antibiotics · Immune cells · Gram staining of bacteria · Infectious diseases catalog · Clinical scales