7.3 Introduction to HIV, AIDS, and Antiretrovirals

HIV is a retrovirus that attacks the immune system, specifically CD4+ T cells. Without treatment, it progresses to AIDS. Antiretroviral therapy (ART) has transformed HIV from a fatal diagnosis into a manageable chronic condition, but effective treatment depends on understanding how the virus works, how drugs target it, and how nurses support adherence.

HIV Pathophysiology and Progression

Mechanisms of HIV infection

HIV targets CD4+ T cells, which are central to coordinating the immune response. The virus gets inside these cells through a specific sequence:

1. HIV attaches to the CD4 receptor on the cell surface, then binds a co-receptor (either CCR5 or CXCR4) to gain entry.
2. Once inside, the enzyme reverse transcriptase converts the viral RNA into DNA.
3. The viral DNA integrates into the host cell's genome using the enzyme integrase.
4. The host cell then produces new viral particles, which bud off and infect other CD4+ cells.

Each round of replication kills the host cell and spreads infection further. Over months to years, the CD4+ count drops steadily. As the immune system weakens, opportunistic infections (like pneumocystis pneumonia) and cancers (like Kaposi's sarcoma) emerge because the body can no longer fight them off.

Symptoms of HIV/AIDS

HIV progresses through three stages:

• Acute HIV infection (2–4 weeks after exposure): Flu-like symptoms including fever, fatigue, sore throat, rash, headache, and lymphadenopathy. This is when viral load is extremely high and the person is very contagious.
• Chronic HIV infection (clinical latency): Can last years with few or no symptoms. Persistent generalized lymphadenopathy may be present, with gradual onset of fatigue, weight loss, and low-grade fevers. The virus is still replicating and CD4+ counts are declining.
• AIDS (CD4+ count below 200 cells/mm³ or presence of AIDS-defining conditions):
  • Opportunistic infections: toxoplasmosis, cryptococcal meningitis, pneumocystis pneumonia
  • Cancers: non-Hodgkin's lymphoma, cervical cancer, Kaposi's sarcoma
  • Wasting syndrome, HIV-associated dementia, and other neurological complications

HIV Transmission and Diagnosis

Risk factors for HIV transmission

HIV is transmitted through specific body fluids: blood, semen, pre-seminal fluid, rectal fluids, vaginal fluids, and breast milk. The main routes are:

• Sexual contact with an HIV-positive person. Receptive anal intercourse carries the highest per-act risk, followed by vaginal intercourse. Oral sex carries a much lower risk.
• Sharing needles, syringes, or other injection equipment among people who inject drugs.
• Mother-to-child (perinatal) transmission during pregnancy, childbirth, or breastfeeding. ART during pregnancy dramatically reduces this risk (from ~25% to less than 1%).
• Occupational exposure through needlestick injuries or contact with infected blood/body fluids.

Diagnostic tests for HIV

• Antibody tests (ELISA, rapid tests): Detect antibodies the immune system produces in response to HIV. The window period is up to 12 weeks after exposure, meaning a test taken too early may give a false negative.
• Antigen/antibody combination tests (4th generation): Detect both HIV antibodies and the p24 antigen, a viral protein present early in infection. This shortens the window period to 2–6 weeks, making earlier detection possible.
• HIV RNA tests (viral load): Measure the actual amount of HIV RNA in the blood. Used to confirm infection, detect very early infection (before antibodies develop), and monitor how well treatment is working.
• CD4+ T cell count: Not a diagnostic test for HIV itself, but it assesses immune system status. A count below 200 cells/mm³ defines AIDS. CD4+ counts guide when to start treatment and help monitor disease progression.

Antiretroviral Therapy

Classes of antiretroviral drugs

Each drug class targets a different step in the HIV life cycle. Understanding which step each class blocks helps you remember both the mechanism and why combination therapy works.

• Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): Act as faulty building blocks that get incorporated during reverse transcription, terminating the DNA chain. Examples: tenofovir, emtricitabine, abacavir. NRTIs form the "backbone" of most ART regimens.
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs): Bind directly to the reverse transcriptase enzyme and change its shape so it can't function. Examples: efavirenz, rilpivirine. Unlike NRTIs, they don't mimic nucleosides.
• Protease inhibitors (PIs): Block the protease enzyme, which normally cleaves viral polyproteins into functional pieces. Without this cleavage, new viral particles are immature and non-infectious. Examples: darunavir, atazanavir.
• Integrase strand transfer inhibitors (INSTIs): Block the integrase enzyme, preventing viral DNA from inserting into the host genome. Examples: dolutegravir, bictegravir. INSTIs are now preferred in many first-line regimens due to high efficacy and tolerability.
• Entry inhibitors: Prevent HIV from entering the cell in the first place. CCR5 antagonists (maraviroc) block the CCR5 co-receptor; fusion inhibitors (enfuvirtide) block the physical merging of viral and cell membranes.

Side effects of antiretrovirals

• NRTIs: Lactic acidosis, hepatic steatosis (fatty liver), bone marrow suppression, renal toxicity (especially tenofovir disoproxil fumarate)
• NNRTIs: Rash (can be severe with nevirapine), hepatotoxicity, neuropsychiatric symptoms (vivid dreams, dizziness with efavirenz), lipid abnormalities
• PIs: GI intolerance (nausea, diarrhea), lipodystrophy (fat redistribution), metabolic abnormalities (hyperglycemia, hyperlipidemia), significant drug interactions due to CYP450 inhibition
• INSTIs: Generally the best-tolerated class. Potential for weight gain; dolutegravir has been associated with neural tube defects if taken around the time of conception

Nursing Considerations and Patient Education

Nursing considerations for HIV medications

Before and during ART, nurses play a critical role in safety monitoring and adherence support:

• Before starting: Assess for drug allergies, contraindications, current medications (check for interactions), and baseline labs (liver function, renal function, CBC, CD4+ count, viral load).
• Ongoing monitoring: Track labs regularly to catch adverse effects early. Watch for signs of lactic acidosis (NRTIs), rash (NNRTIs), hepatotoxicity, and renal impairment.
• Administration: Verify correct dose, route, and timing. Some antiretrovirals must be taken with food; others on an empty stomach. Confirm the patient understands their specific regimen.
• Adherence support: This is arguably the most important nursing role. Even small gaps in adherence can allow the virus to replicate and develop resistance. Help patients develop practical strategies like pill organizers, phone alarms, or linking doses to daily routines.
• Confidentiality and emotional support: HIV still carries stigma. Maintain strict confidentiality and provide nonjudgmental care.

Patient education for antiretroviral therapy

• Adherence is everything. Missing doses allows the virus to replicate and mutate, which can lead to drug resistance and treatment failure. Patients need to understand that ART doesn't cure HIV; it suppresses the virus, and that suppression depends on consistent dosing.
• Side effect management: Teach patients which side effects are common and expected (mild GI upset, headache) versus which require immediate medical attention (severe rash, signs of lactic acidosis like muscle pain and rapid breathing, jaundice).
• Storage and handling: Some medications require refrigeration; others should be kept at room temperature away from moisture.
• Transmission prevention: Even on effective ART, patients should practice safe sex (consistent condom use) and never share needles. That said, patients with a consistently undetectable viral load have effectively no risk of sexually transmitting HIV (the "Undetectable = Untransmittable" or U=U concept).
• Pregnancy considerations: Patients who are pregnant or planning pregnancy should consult their provider, as some antiretrovirals (particularly dolutegravir around conception) carry specific risks. ART during pregnancy is still essential to prevent perinatal transmission.
• Follow-up: Regular appointments for viral load and CD4+ monitoring are necessary to confirm the regimen is working and to detect problems early.
• Support resources: Connect patients with mental health services, substance use treatment if applicable, peer support groups, and case management services.