Pathophysiology / transmission

• Heterosexual, MSM (inc. sex work), mother-to-child, MSM, IVDU

Prevention

• Pre-exposure prophylaxis (PrEP): HIV-negative partner takes ART (e.g. Tenofovir [TDF]/Emtricitabine[FTC]) before sexual contact (reduced HIV infections: PROUD trial, 2016)

• Post-exposure prophylaxis (PEP): e.g. Truvada + Raltegravir, 28/7

• Microbicides for women, treatment as prevention, male circumcision, STI treatment, condoms, HIV testing, behavioural measures (ABC..)

Epidemiology

• 37 million PLHIV, 70% live in Africa. 1.8 million infections. 1 million deaths (2018)

• Highest rates: Swaziland (27.4%), Botswana (22.8%), Lesotho (23.8%), South Africa (19%), Zimbabwe (13.3%). Note in-country variation

• Absolute numbers: South Africa (7 million), Nigeria (3.4 million), India (2.1 million), Japan (28,000 PLHIV, 1,500 new infections/year)

• 90% know their status, 90% on treatment, 90% viral load suppressed (90:90:90 UNAIDS goal)

Natural course

• Acute (0-12 weeks): HIV RNA peak and decrease, CD4 blood and GIT start to decrease

• Asymptomatic (1-7 years): slow increase in RNA and decrease in CD4

• AIDS (7+ years): increase in RNA, decrease in CD4

Clinical features by stage

Acute HIV infection

• Rash, lymphadenopathy

WHO stage 1

• Persistent lymphadenopathy

WHO stage 2 (wt loss, URTI, various skin, nails...)

• Moderate unexplained weight loss >10%,

• Recurrent URTI (sinusitis, tonsillitis, otitis media, pharyngitis)

• Papular pruritic eruptions (immune dysregulation: prolonged allergic reaction to insect bites)

• Herpes zoster

• Seborrhoeic dermatitis

• Fungal nail infections

WHO stage 3 (oral, pulmonary TB...)

• Severe weight loss >10%

• Chronic diarrhoea >1 month

• Persistent fever (intermittent or constant >1 month)

• Severe bacterial infections

• Unexplained anaemia (<8 g.dl) and/or chronic thrombocytopenia (<50)

• Oral candidiasis

• Oral hairy leukoplakia (EBV-associated)

• Pulmonary TB

WHO stage 4 (oesophageal, malignancy, neuro)

• Kaposi's sarcoma

Fungal

• Oesophageal candidiasis

• Pneumocystis jirovecii pneumonia

• Cryptococcal meningitis / cryptococcosis

• Talaromycosis (penicilliosis), endemic in Asia only

• Coccidioidomycosis (America only)

• Neuro (toxo, PML, CMV, lymphoma)

Opportunistic infections by system

Respiratory

• Pneumocystis jiroveci pneumonia, herpes zoster, candidiasis

• TB

GI

• Cryptosporidium diarrhoea

Skin: umbilicated papules

• Molluscum contagiosum (Poxvirus)

• Cryptococcal disease

• Melioidosis

• Disseminated mycobacterial infection

• Bacillary angiomatosis (B. henselae, B. quintana)

• Histoplasmosis

• Talaromycosis (penicilliosis)

Neuro big 3

• TB, crypto, toxo

• Cytomegalovirus retinitis: (cheese & tomato pizza), gangcliclovir

• Cryptococcal meningitis (e.g. chronic headache, 6th nerve palsy)

Cerebral SOL in HIV

• Toxoplasmosis

• Bacterial abscess

• Cryptococcoma

• Tuberculoma

• Neoplasm: primary CNS lymphoma

• Other: Progressive Multifocal Leukoencephalopathy (PML), stroke, neurosyphlis, (cerebral) malaria

• Rx: treat the treatable....

Diagnosis

• Antibody tests: HIV-1 and 2 antibodies (3 months) e.g .ELISA, Western Blot, qualitative immunoassays/RDTs (highly specific but false positives can occur, therefore needs further confirmation)

• Antigen tests: detects the presence of the p24 antigen/protein (capsid protein) of the virus (1 month: window period approx. 16 days)

• Combined antigen/antibody tests: 4th generation ‘combined’ antibody/antigen test -

• Nucleic acid detection: (window period approx. 12 days)

A negative result on a 4th generation test performed at 4 weeks post-exposure is highly likely to exclude HIV infection. A further test at 8 weeks post-exposure need only be considered following an event assessed as carrying a high risk of infection

Sequence of testing

• HIC: ELISA + p24 antigen testing. If positive: Western blot. If positive, take blood again: ELISA + p24 antigen/Western blot/PCR

• LIC: POC tests: ELISA and p24. If positive: repeat.

EMTCT

Vaccines for HIV positive adults: annual influenza, pneumococcal, Hepatitis B, hepatitits A (for MSM). Live vaccines should not be given BCG, cholera, oral typhoid, oral polio [Sabin]. All inactivated immunisations are safe (pertussis, diphtheria, tetanus, polio [salk], typhoid, meningitis C)

Follow up: women: annual cervical smears as at more risk from HPV-related disease, including cervical cancer and warts

Prognosis

Late diagnosis of HIV (CD4,350) is associated with tenfold increased risk of dying within a year in the UK.