Microbiology
Pathogens
HIV predominantly infects which of the following cells:
Answer:
HIV mainly infects CD4+ T helper cells. Viral replication results in progressive T-cell depletion and impaired cell-mediated immunity with subsequent secondary opportunistic infections and increased risk of malignancy. B-cell function is also reduced as a result of lack of T-cell stimulation.Human Immunodeficiency Virus (HIV)
Microbiology / Pathogens / HIV
Last Updated: 6th December 2020
Epidemiology and Transmission
HIV transmission occurs:
- by inoculation via a contaminated needle, instrument, blood, or blood product; through direct exposure of mucous membranes or an open wound to infected bodily fluids; or by a human bite that breaks the skin
- sexually (in semen, preseminal fluid, rectal fluid and vaginal fluids through vaginal, anal or oral sex)
- vertically from mother to child (before or during birth, or in breast milk)
In developed countries, the main risk groups are intravenous drug users, men who have sex with men (MSM) and individuals who have a current/former partner from or themselves are from an area with high HIV prevalence.
In developing countries, HIV spread is mainly via heterosexual sexual transmission, vertical transmission and through unscreened transfusions or use of contaminated medical equipment. The majority of vertical transmission occurs during labour; appropriate antiretroviral medication and caesarean section dramatically reduces the risk.
Pathogenesis
HIV mainly infects CD4+ T helper cells. Viral replication results in progressive T-cell depletion and impaired cell-mediated immunity with subsequent secondary opportunistic infections and increased risk of malignancy. B-cell function is also reduced as a result of lack of T-cell stimulation.
Clinical Features
- Incubation period
- 2 - 4 weeks (all tests will be negative)
- Seroconversion illness (2 - 3 week duration)
- Fever, myalgia, lymphadenopathy, pharyngitis, maculopapular rash, headache (may be mistaken for glandular fever)
- Latent disease
- Duration of this varies widely between people with some progressing to AIDS within 1–2 years ('rapid progressors') and others maintaining effective immune function more than 10 years later ('slow progressors')
- Disease progression
- Development of acquired immune deficiency syndrome (AIDS)
- Defined as CD4 count < 200 cells/uL or development of AIDS-defining illness
Common secondary infections in patients with HIV or AIDS:
- Bacterial
- Mycobacterium tuberculosis (TB)
- Listeria monocytogenes
- Streptococcus pneumoniae
- Salmonella spp.
- Viral
- Herpes simplex
- Cytomegalovirus
- Varicella zoster virus (shingles)
- Measles
- Fungal
- Cryptococcus neoformans (meningitis)
- Pneumocystis jiroveci (pneumonia)
- Candida spp.
- Protozoan
- Toxoplasma gondii
- Malignancy
- Kaposi sarcoma
- Non-Hodgkin's lymphoma
Diagnosis
- Diagnosis
- Combined HIV antibody and p24 antigen test
- If the test is positive, a second sample is required for confirmation
- Monitoring
- HIV viral load (PCR) and CD4+ count
There is a window of three months after primary infection (during seroconversion) where the the intial HIV test may be negative, and any negative test should be repeated after this period.
Treatment
There is no cure for infection caused by the human immunodeficiency virus (HIV) but a number of drugs slow or halt disease progression. Antiretroviral therapy (ART) has had a huge positive impact on HIV-related morbidity and mortality, and aims to reduce viral load to undetectable levels by limiting viral replication, but is also associated with serious adverse effects. HIV mutates as it replicates so drugs are used in combinations of 3 or more to reduce drug resistance.
Treatment aims to prevent the mortality and morbidity associated with chronic HIV infection whilst minimising drug toxicity. Although it should be started before the immune system is irreversibly damaged, the need for early drug treatment should be balanced against the risk of toxicity. Commitment to treatment and strict adherence over many years are required; the regimen chosen should take into account convenience and patient tolerance. The development of drug resistance is reduced by using a combination of drugs; such combinations should have synergistic or additive activity while ensuring that their toxicity is not additive. It is recommended that viral sensitivity to antiretroviral drugs is established before starting treatment or before switching drugs if the infection is not responding.
Antiretroviral drugs are classified into 5 groups depending on how they act:
- Nucleoside/tide reverse transcriptase inhibitors (NRTIs).
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs).
- Protease inhibitors (PIs).
- Integrase inhibitors (IIs).
- Entry inhibitors (EIs).
Adverse effects of ART include:
- Hypersensitivity
- Psychiatric — nightmares, sleep disturbance, mood or behaviour changes
- Hyperlipidaemia (common)
- Lipodystrophy (changes in the distribution of body fat) and lipoatrophy (loss of subcutaneous fat)
- Type 2 diabetes mellitus
- Fanconi’s syndrome (dysfunction of the proximal tubule), ureteric colic, renal and ureteric stones
- Lactic acidosis and hepatic toxicity
- Peripheral neuropathy
- Bone marrow suppression
- Pancreatitis
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
