L.20. HIV and AIDS

describe the original HIV case spread

originally seen in young gay men

death sentence- dying of things they normally shouldn’t e.g. pneumonia and cancer

describe a retrovirus

RNA genome, turns into DNA and then transcribed into genome of host cell nucleus

where did HIV originate

cameroon

zoonotic disease from soldiers eating hunted chimpanzee meat

how did HIV spread from cameroon to other african countries

colonialisation

urbanisation

sex work

off books medical treatment

social change

how did HIV spread globally

exchange of medical workers between Kinshasa in DRC and Haiti helped spread disease, then from Haiti to USA

describe basic transmission of HIV

• sexually transmitted- homosexual AND heterosexual transmission

• contaminated blood products

• mothers milk

• perinatal transmission during birth

describe HIV epithelia crossover- damage

HIV needs to cross epithelia to integrate. skin abrasions are a common way the virus can cross this barrier. HIV is particularly easily spread during anal sex as the anus epithelia has limited flexibility and thickness so is susceptible to damage e.g. micro-abrasions and extended physical damage. STIs can also cause micro-abrasions and inflammation, leading to recruitment of immune cells to damaged/inflamed sites

describe HIV transcytosis

• virus binds to epithelial cells and enters via endosomal/lysosomal system

• at some point the virus is detected by APCs e.g. macrophages, dendritic cells

• initiates classic antigen presentation response of antigens to the lymph nodes

• T cells in the lymph nodes then facilitate virus replication, which is why in acute infection swollen lymph nodes are often observed.

describe HIV binding to immune cells

infects CD4+ lymphocytes and macrophages

CD4+ are helper T cells, if virus replicates in helper T cells then drives cell death and loss of T cell

HIV binds dendritic cells, these DCs are coated in material facilitating binding

why might HIV positive diagnosis be more prevalent in gay men

more engaged in regular testing

describe clinical course of first few weeks of infection e.g. symptoms

patient ill but unclear what illness may be- commonly assumed to be a flu or covid etc

what are the three types of clinical manifestation of HIV

• acute primary infection syndrome

• asymptomatic disease

• symptomatic HIV infection and AIDS

describe acute primary infection syndrome

flu like illness with high levels of viral replication until infection brought under immune control

manifests as lymphadenopathy

describe HIV asymptomatic infection

no outward sign of disease, but a slow CD4+ count decline and very active viral replication

stage can persist for 10+ years

describe symptomatic HIV infection and AIDS

immune system ceases to function and disease progresses, resulting in death

name 5 common opportunistic infections affecting AIDS patients

• tuberculosis

• candida- throat, mouth, genitals

• herpes, HPV- genital warts/cancers

• kaposi’s sarcoma (skin cancer)

• cytomegalovirus- infected liver

what is the testing route for HIV diagnosis

ELISA: screening test

western: blot confirmation test

quantitative PCR (qPCR): assesses stage/monitor and course of therapy

describe elisa

enzyme linked immunosorbent assay

antigen coated plate

patient serum sample added

patient antibodies bind the antigen on plate

if patient HIV antibodies are detected, more specific testing is required for definitive diagnosis

describe western blot

voltage passed through antigens samples loaded on gel

smaller proteins move further

antiviral therapy for HIV entry stage

entry inhibitors

• attachment inhibitor

• post attachment inhibitor

• coreceptor antagonist

• fusion inhibitor

antiviral therapy for HIV reverse transcription stage

NRTI- nucleosidic reverse transcriptase inhibitors

NNRTI- non nucleosidic reverse transcriptase inhibitors

antiviral therapy for HIV integration stage

integrase inhibitors

antiviral therapy for HIV assembly/maturation stage

protease inhibitors

describe HIV therapy methods and outcomes

combination pills

injectable therapies

if put onto drug immediately then better cytotoxic T cell response, less likely to transmit if treated quickly

why is there no HIV vaccine

virus is too variable

outline pre-exposure prophylaxis

HIV prevention pill taken daily (before potential exposure) by individuals who are HIV negative but at substantial risk, e.g. sex workers or drug users

commonly reverse transcriptase inhibitors

reduce infection risk by up to 92%

describe once year prep that is in development

lencapavir- capsid inhibitor given as a once a year injection

how is male circumcision a preventative measure for HIV

randomised trials found circumcision reduces HIV risk in males by up to 50-60%

unclean foreskin can contain a microbiome that hosts low level infections like HIV virus