HIV is an infectious disease that 37.7 million+ people are living with (1.5 million new cases annually). Most cases are acquired through sexual contact, prenatally, intrapartum, postnatally (breastfeeding) or through contaminated needle/syringe sharing.
It is a retrovirus affecting CD4+ T-cells and macrophages. It can be transmitted through blood, sexual fluids, breast milk. The most common form of transmission is sexual intercourse, however, the risk of transmission per exposure is about 0.1%. This number varies if you have concurrent STIs, a high HIV viral load and lack of antiretroviral therapy.
These are viruses containing the enzyme reverse transcriptase which is able to make a DNA copy from the viral RNA.
Pathphysiology
The HIV virus gains entry by attaching to the CD4 receptor and co-receptor (CCR5 or CXCR4) with its gp120 and gp41 glycoproteins as well. As it uncoats, reverse transcriptase generates cDNA which integrates into the host DNA. The cDNA is then transcribed and translated to allow for replication of the virus. The virus then destroys the CD4+ T-cell and when destroyed, the infectious reservoir is released.
HIV can lead to AIDS as the CD-4 count progressively declines → AIDS-defining illnesses.
🔢 Classification
- HIV type 1 - this is the more dangerous virus that is responsible for the pandemic. It has 3 main groups M,N and O.
- HIV type 2 - less pathogenic and predominantly found in West Africa.
⚠️ Risk factors
- Needle sharing and IV drug use
- Unprotected intercourse
- Healthcare workers (needle stick injury)
- High maternal viral load (mother-child transmission)
😷 Presentation
Most people present with flu-like illness 2-6 weeks after infection.
It can range from a glandular fever presentation of fever, lymphadenopathy, sore throat all the way up to a presentation with meningoencephalitis (rarely).
- ⭐️ Fever
- ⭐️ Lymphadenopathy
- Maculopapular rash - upper chest commonly.
- Mucosal ulcers angular stomatitis oral thrush or oral hairy leukoplakia.
- Weight loss and wasting
- Diarrhoea - potentially due opportunistic infections such as cryptosporidium (+ other protozoa) and mycobacterium avium intracellulare.
- Myalgia
- Arthralgia
- Fatigue
- Depression
- Tuberculosis
- Kaposi’s sarcoma - more on this later.
- Asymptomatic
Onset of symptoms within 3 weeks that lasts longer than 2 weeks, especially involving the CNS is associated with a rapid progression to AIDS.
🔍 Investigations
HIV seroconversion refers to the development of antibodies towards the HIV virus. This usually occurs between 3-12 weeks after infection and can be useful for diagnosis.
- HIV antibodies - 99% of patients develop antibodies by 12 weeks.
- 🥇 ELISA - used as first-line but is not confirmatory.
- 🏆 Western Blot Assay - used for confirmation.
- HIV rapid test - may also be done. A secondary rapid test is used for confirmation.
- p24 antigen test - p24 is a protein making up the HIV core. Its levels are highest during viral replication and therefore it is detectable during acute infection and once again in late stages of infection. As this window may be relatively narrow, it is a supplementary test.
- PCR - mainly used in infants.
- CD4 count
- >500cells/mL - patient is usually asymptomatic
- <350cells/mL - substantial immune suppression
- <200cells/mL - AIDS
Other tests that should be done are: viral load testing pregnancy test, Mantoux test hepatitis screening STI screening (gonorrhoea, chlamydia, syphilis), kidney function liver function glucose, lipids.
🧰 Management
Antiretroviral therapy (ART) involves the use of 3 drugs - 2 nucleoside reverse transcriptase inhibitors (NRTIs) and a protease inhibitor (PI)/non-nucleoside reverse transcriptase inhibitor (nNRTI). The use of 3 drugs reduces viral replication and also reduces risk of resistance.
Patients are to be started on ART as soon as diagnosis is made. Previously ART was started when patients reached a threshold for CD4 count.
Let’s quickly recap the types of antiretroviral treatments we have:
- Viral entry inhibitors - these prevent HIV-1 from entering the CD4+ cells. The mechanism of entry (as described above) is antagonised.
- Maraviroc - a CCR5 inhibitor that prevents binding to gp41.
- Enfuvirtide - a gp41 inhibitor that prevents fusion.
- Nucleoside reverse transcriptase inhibitors (NRTI) - nucleosides are essentially nucleotides without the phosphate group (solely the nitrogenous base and sugar group). They inhibit nucleic acid synthesis and thus DNA synthesis and protein synthesis.
- Zidovudine - a thymidine analogue. May cause anaemia, myopathy, black nails.
- Lamivudine - a cytidine analogue.
- Stavudine
- Emtricitabine
- Zalcitabine
- Tenofovir - may cause renal impairment and osteoporosis.
- Didanosine - may cause pancreatitis.
- Non-nucleoside reverse transcriptase inhibitors (nNRTI) - also inhibit reverse transcriptase and prevent nucleic acid synthesis.
- Nevirapine
- Efavirenz
- Protease inhibitor (PI) - viral protease cleaves a large viral polypeptide into smaller functional units. By inhibiting this action, we prevent functional units to be formed.
- Ritonavir - a potent CYP450 inhibitor.
- Saquinavir
- -navir
- Integrase inhibitors - prevent integration of viral DNA into the host DNA.
- Raltegravir
- Dolutegravir
- -gravir
Adverse effects of all NRTIs are: peripheral neuropathy.
Adverse effects: CYP450 interactions, rashes.
Adverse effects: diabetes, hyperlipidaemia, buffalo hump, central obesity, CYP450 inhibitor.
The regimen of choice contains a backbone of 2 NRTIs:
- Emtricitabine
- Tenofovir disproxil/tenofovir alafenamide
The third drug is either an:
- Integrase inhibitor (-gravir)
- nNRTI - efavirenz
- Protease inhibitor (-navir)
All patients with a CD4 count <200 should receive co-trimoaxazole prophylaxis (jirovecii prophylaxis). it is given daily or on alternate days (3 times a week).
Verticle transmission is possible with HIV. As a result we need to treat HIV positive women during pregnancy to minimise this transmission.
We can minimise transmission likelihood from 25-30% all the way down to 2%.
Some factors which can reduce vertical transmission include:
- Maternal antiretroviral treatment
- C-section - however, if the viral load is <50 copies/ml at 36 weeks then vaginal delivery is recommended.
- Neonatal antiretroviral treatment -
- Zidovudine is administered orally if viral load is <50 copies/ml.
- Triple ART - is given if maternal viral load is >50 copies/ml.
- Bottle feeding - breastfeeding is not recommended.
The presence of AIDS-defining illnesses alongside the presence.
Tuberculosis Kaposi’s sarcoma
Kaposi’s sarcoma is the most common neoplasm associated with HIV.
🦠 - It occurs as a result of HHV-8 (human herpesvirus 8).
😷 - It presents as purple papules/plaques on the skin or on mucosal surfaces (such as in the respiratory tract or gastrointestinal tract). These may later on become ulcerated.
🚨 - If there is respiratory involvement it may cause massive haemoptysis and pleural effusion.
🧰 - Management includes:
- Radiotherapy
- Resection
Pneumocystis jiroveci pneumonia
🦠 Pneumocystis jiroveci (formerly known as pneumocystis carinii) is a unicellular eukaryote (most classify it as a fungus but some consider it a protozoa). It causes the most common opportunistic infection in AIDS, being pneumocystis jiroveci/carinii pneumonia (PCP).
😷- It presents with:
- Dyspnoea
- Dry cough
- Fever
- Few chest signs
Extrapulmonary symptoms include:
- Hepatosplenomegaly
- Lymphadenopathy
- Choroiditis
🚨- It may become complicated, causing a pneumothorax.
🧰 - Management includes:
- 🥇 Co-trimoxazole - it is given daily or on alternate days (3 times a week).
- Adjuvant corticosteroids if pO2 <9.3kPa. It has reduced deaths by 1/3rd and respiratory failure by 1/2.
- CXR - bilateral interstitial pulmonary infiltrates is typical. However it may even be normal or present with other findings.
- Exercise-induced desaturation
- 🏆 Bronchoalveolar lavage (BAL) - induces sputum samples which are stained with Grocott’s silver stain and show a characteristic Mexican hat appearance.
Neurocomplications
Toxoplasmosis
Makes up 50% of cerebral lesion in HIV patients.
Presents with: headache, confusion, drowsiness.
Identified on CT as single/multiple ring enhancing lesions.
Management includes: sulfadiazine and pyrimethamine.
Primary CNS lymphoma
Makes up about 30% of cerebral lesions in HIV patients.
It is caused by/associated with Epstein-Barr virus.
Identified on CT as single/multiple homogenous enhancing lesions.
Management includes: steroids, chemotherapy and surgical resection if a low-grade tumour.
Toxoplasmosis | CNS lymphoma |
Usually multiple lesions | Single lesion |
Ring enhancement | Solid/homogenous enhancement |
Thallium SPECT negative | Thallium SPECT positive |
Cryptococcus
Cryptococcus is the most common fungal infection of the CNS.
It presents with headache, fever, malaise, nausea/vomiting, seizures.
Meningitis is the typical presentation.
On CT it may present with meningeal enhancement and cerebral oedema. ➡️
Encephalitis
Due to CMV or even HIV itself. HSV may also cause it but it is relatively rare.
CT presents with an oedematous brain.
Progressive multifocal leukoencephalopathy
This is an infection of oligodendrocytes by JC virus. It causes widespread demyelination.
It presents with subacute onset and behavioural changes, speech/motor/visual impairment.
On CT it presents with single/multiple lesions that are not enhancing. MRI is a better modality for the white-matter lesions.
Oesophageal candidiasis
Most common cause of oesophagitis in patients with HIV. Usually seen in patients with CD4 <100. Symptoms include dysphagia and odynophagia.
Management is with fluconazole/itraconazole.
- Oral thrush - due to Candida albicans
- Shingles - due to herpes zoster
- Hairy leukoplakia - due to EBV
- Kaposi’s sarcoma - due to HHV-8
- Cryptosporidiosis
- Toxoplasmosis
- Progressive multifocal leukoencephalopathy
- Pneumocystis jirovecii pneumonia
- HIV dementia
- Aspergillosis - due to aspergillus fumigatus
- Oesophageal candidiasis - due to candida albicans
- Cryptococcal meningitis
- Primary CNS lymphoma - due to EBV
- CMV retinitis
- Mycobacterium avium intracellulare