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HIV

From Mediwikis

Identified in 1981, over 33 million people are infected with Human Immunodeficiency Virus, primarily in Africa.

Virology

This retrovirus, belonging to the lentivirus family, has two types:

  • HIV-1 is the most common worldwide
  • HIV-2 is confined to West Africa, and while it has a more indolent course, many of the HIV-1 drugs are ineffective against HIV-2.

Pathogenesis

The virus targets CD4 T lymphocytes:

  1. Binding- To CD4 receptors, via the glycoprotein gp 120, and coreceptors CCR5 and CXCR4.
  2. Fusion- between gp 41 and the cell membrane
  3. Reverse Transcription- RNA is uncoated, DNA copies are made, and dsDNA is formed by DNA Polymerase.
  4. Integration- This viral DNA is integrated into the host's genome
  5. Transcription & Translation- DNA is replicated to form Viral RNA, and Viral mRNA, which forms structural proteins.
  6. Budding- the virus is assembled from the RNA and proteins, and released from the host cell.

Transmission

  • Sexual Intercourse- higher risk between homosexual men, and higher risk of transmission for receiving partner in hetero- and homosexual intercourse.
  • Vertical- HIV can be passed through the placenta, perinatally, or via breast feeding, especially if the mother's disease is advanced. Antiretrovirals and discouraging breast feeding both reduce the risk of transmission.
  • Contaminated blood and organ donations- although Europe and the US now screen both.
  • Contaminated sharps- for example in IV drug users who share needles

Symptoms

Initial infection may display flu-like symptoms, but after a period of latency (a number of years) symptoms include:

  1. Neurological- Sensory polyneuropathy, autonomic neuropathy
  2. Visual- Cytomegalovirus Retinitis, anterior uveitis
  3. Dermatological-Pruritis, dry, itching, flaking skin, thinning of hair, folliculitis,
  4. Haematological- Lymphopenia, Neutropenia, Anaemia (normocytic, normochromic), Thrombocytopenia or Pancytopenia.
  5. Gastrointestinal- Weight loss, diarrhoea, enteric infections
  6. Respiratory- Lots of respiratory infections which respond well to antibiotics

Investigation

Specialist referral should be within 2 weeks, and a baseline assessment performed including:

  • FBC, LFT, U&E
  • Urinalysis
  • Virology- Hepatides, HIV antibody and viral load

Management

While there is currently no cure for HIV, management has moved towards suppressing the disease, with Anti-Retroviral therapy. Other roles needed for MDT management of HIV are vaccination, recreational drug use behaviour change, sexual advice, and counseling- depression is common in those with HIV, and should be monitored regularly.

Antiretrovirals

Spotted on MCQs by them containing "vir", each of these targets a section of the lifecycle detailed above:

  • Reverse Transcriptase Inhibitors- Tenofovir, abacavir, Efavirenz, Etravirine
    • Nucleoside Reverse Transcriptase Inhibitors (NRTIs)- azidothymidine (AZT), zalcitabine (DDC)
    • Nonucleoside Reverse Transcritase Inhibitors (NNRTIs)- efavirenz
  • Integrase inhibitors- Raltegravir
  • Protease inhibitors- Fosamprenavir, Atazanavir, Daraunavir, Lopinavir, Saquinavir
  • CCR5 inhibitors- Maraviroc
  • Fusion inhibitors- Enfuvirtide

Therapy

HIV Patients are commonly given three drugs:

  • 2 NRTIs and a Protease inhibitor
  • 2 NRTIs and an NNRTI

Adherence must be >95% to effectively treat HIV

Prognosis

If untreated, the life expectancy is around 10 years post-infection. The earlier the disease is treated, the better the outcome is for the patient- with prompt treatment giving a 40-50 year lifespan, making HIV more of a chronic disease. The majority of deaths from HIV are due to opportunistic infections in the immunosuppressed patient (particularly Tuberculosis), along with cancer.

How well a patient is coping with HIV management can be measured in two ways. Primarily, a viral load is investigated. A result of <20 (or undetectable) signifies good control of HIV infection. Secondly, CD4+ count is identified. A CD4 count of over 300 indicates good control, whilst at under 200-300 CD4+ count, there is an increased likelihood of opportunistic infections such as HHV8 or EBV. Poor HIV control is overwhelmingly caused by non-compliance to HAART therapy.

It must be noted that there is an increased cardiovascular risk associated with HIV (around 60% increase in risk), whilst cardiovascular risk can be known to double for patients on HAART therapy. Therefore a patients cholesterol, blood pressure and HbA1c should be regularly noted.