HIV and AIDS - HIV/AIDS notes as we don\'t get lectures on it PDF

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Summary

HIV InfectionPathophysiology Retrovirus o RNA virus  make a DNA copy before they get transcribed and translated  Surface glycoproteins o Gp41 and gp120 are signiicant o Bind to CD4 receptors on target cells (T cells)GP120 in yellow Coiled red structure = chemokine receptor Both needed to get into...

Description

HIV Infection Pathophysiology 

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Retrovirus o RNA virus  make a DNA copy before they get transcribed and translated Surface glycoproteins o Gp41 and gp120 are significant o Bind to CD4 receptors on target cells (T cells)

GP120 in yellow Coiled red structure = chemokine receptor Both needed to get into target cell

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HIV specifically infects CD4+ (T-helper cells) When those cells are activated, HIV replicates and the T-helper cells are destroyed Leads to immunosuppression and dysregulation of immune system (AIDS)  High serum antibodies of “junk” antibodies  High susceptibility to opportunistic infections and cancer

Epidemiology 

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Predominantly a sexually transmitted virus (80% cases) o Also, vertical transmission (5-10% cases) o Injecting drug users, especially Eastern Europe 100,000 people in the UK have HIV ~5000 new HIV diagnoses in the UK per year o 42% are still diagnosed late o Late diagnosis has a higher mortality rate due to patients being exposed to opportunistic infections

Presentation Can initially present as seroconversion illness

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1-6 weeks after exposure Non-specific symptoms o Fever o Pharyngitis o Mouth ulcers o Lymphadenopathy o Rash Glandular Fever-like symptoms but negative monospot Clinical manifestation: o Seroconversion illness o Can be asymptomatic o Early symptomatic (see also below):  Weight loss  Diarrhoea  Lymphadenopathy  Oral candida  Skin infections

Advanced (AIDS) 6 months, HIV is not transmitted Testing done more regularly on at-risk groups o MSM (men who have sex with men) o Immigrants from sub-Saharan Africa o IV drug users o Contacts of known cases o Antenatal screening o Patients with possible HIV-associated conditions (pneumonias, TB, lymphoma) o Routine testing in high prevalence areas If the test is positive, referral should be made to a HIV specialist within 48hrs

Management Aim is to suppress virus to undetectable levels and prevent resistance  combination therapy with different classes of antivirals.

N.B. Sanctuary sites include bone marrow and treatment doesn’t hit sanctuary sites as it targets the blood. 1. Fusion/entry inhibitors o Enfuvirtide (Fuzeon, T-20) 2. Reverse transcriptase inhibitors o Abacavir (Ziagen, ABC) o Didanosine (Videx, Videx EC, ddI) o Emtricitabine (Emtriva, FTC) o Lamivudine (Epivir, 3TC) o Stavudine (Zerit, Zerit XR, d4T) o Tenofovir DF (Viread, TDF) o Tenofovir alafenamide (TAF) o Zidovudine (Retrovir, ZDV, AZT) 3. Integrase inhibitors o Raltegravir (Isentress, RAL) o Elvitegravir o Dolutegravir o Bictegravir 4. Maturation inhibitors 5. Protease inhibitors o Atazanavir (Reyataz , ATV) o Darunavir (Prezista, DRV) o Lopinavir and ritonavir (Kaletra, LPV/r) o Ritonavir (Norvir, RTV) Therapy with one drug is usually ineffective and can cause drug resistance. 

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Triple therapy standard of care (cART) o 2 Nucleoside RT inhibitors + 1 other agent o Either PI, NNRTI or Integrase Inhibitor o These are now regimes that come in 1 tablet (with multiple drugs in). HAART = highly active antiretroviral therapy...