HIV and AIDS

Question 1

What does HIV stand for?

Answer 1

Human Immunodeficiency Virus

Question 2

What does AIDS stand for?

Answer 2

Acquired Immune Deficiency Syndrome

Question 3

Why type of virus is HIV?

Answer 3

Lentivirus (slow)

-HIV and AIDS both retroviruses

Question 4

HIV transmission

Answer 4

Sexual contact
Blood
-blood contact
-IVDU
Infected blood products
In utero
Breast milk

Question 5

Major route of HIV infection in developed countries

Answer 5

Male - homo/bisexual

Question 6

Major route of HIV infection in developing countries

Answer 6

Male and female - heterosexual

Child - infected via in utero transmission

Question 7

HIV types

Answer 7

HIV 1 - most common

HIV 2 - less easily transmitted and less pathogenic

Question 8

Main groups of HIV 1

Answer 8

Main (M) - pandemic strains
New (N)
Outlier (O) - confined to Cameroon area
Many subtypes

Question 9

HIV mutates readily

Answer 9

Reverse Transcriptase does not proofread

• ***** diagram
• infected individuals contain a heterogenous viral population

Question 10

HIV evolution and origins

Answer 10

Likely chimp co-infection with 2 SIV strains
-viral crossover creates new strain
-how did it transfer to humans?
Origin of HIB-1 in Cameroonian Chimps –> Congo in 1920s –> urbanisation –> diamonds –> rail travel –> indipendence 1960s
HIV-2 confined to west Africa

Question 11

HIV shape (DIAGRAM)

Answer 11

Lipid membrane of envelope, envelope glycoproteins, host proteins
Matrix protein
Major structural (core) protein
Single-stranded RNA, p7^gag, p9^gag, reverse transcriptase

Question 12

Infection of CD4 positive cells (DIAGRAM)

Answer 12

E.g. Th-cell, gp120

• initial attachment via gp120 binding to CD4
• followed by co-receptor (CCR5/ CXCR4) binding
• attachment followed by membrane fusion and internalisation (gp41 dependent)
• when cells are activated viral proteins are produced and 1000s of new virus progeny synthesised

Question 13

Resistance to co-receptor binding

Answer 13

People with CCR5 mutations are resistant

• occurs in 2-14% of Europeans (caucasian), and 15% of Icelandic
• heterozygous: < susceptibility to infection
• homozygous: resistance

Question 14

Why so much resistance in Caucasian Europe?

Answer 14

Mutation is 3000 years old
Evidence suggests not selection pressure
Unlikely that it was Vikings
Maybe Founder effect
-spread from smaller population in which high frequency occurred

Question 15

Virus variation during HIV infection

Answer 15

Isolates from early infection - CCR5 (M)
-macrophage tropic and low cytopathic effect
-more transmissable
Isolates from late infection - CXCR4 (T)
-high cytopathic ability 
-less transmissable

Question 16

Infection and dissemination

Answer 16

Blood stream –> macrophage

1. –> virus reservoir and transport –> dysfunction, virus release, cytokine release and dysregulation of immune functions
2. –> CD4 cell, T cell –lymph node (increased viral load in blood–> CD4 cell cytolysis –> AIDS, dementia, immunodeficiency, loss of B-cell control (lymphadenopathy and hypergammaglobulinaemia), loss of DTH function (cutaneous infections, intracellular pathogens) –> loss of T-cell function –> severe systemic opportunistic infections, Kaposi’s sarcoma, lymphoma

Question 17

Disease progression

Answer 17

Primary infection - 1000 CD$+ cells/ μl
3-6 weeks: acute HIV syndrome
-dissemination of virus
Clinical latency 12 weeks - 10 years
10 years: constitutional symtpoms, opportunistic infections
11 years: death

Question 18

Opportunistic bacterial infections and AIDS

Answer 18

Mycobacterium tuberculosis
Salmonella
Haemophilus, Streptococcus, Pneumococcus- Pyogenic infections (pus formers)
-recurrent

Question 19

Opportunistic protozoal infections and AIDS

Answer 19

AIDS-defining:

• Cryptosporidium (chronic diarrhoea)
• Toxoplasma gondii (disseminated, including CNS - from cats)

Question 20

Opportunistic fungal infections and AIDS

Answer 20

Aspergillus - pneumonia
AIDS-defining
-Candida - oral presentation
-Crytococcus neoformans - CNS
-Pneumocystis jiroveci/ carinii - pneumonia

Question 21

Opportunistic viral infections and AIDS

Answer 21

AIDS-defining:

• HSV: chronic oral infection
• EBV: hairy leukoplakia and B-cell lymphomas
• HHV-8: Kaposis sarcoma

Question 22

Some oral manifestations of HIV infection

Answer 22

Thrush
Erythematous candidosis
Gingival erythema
Hairy leukoplakia

Question 23

Progression to AIDS - untreated

Answer 23

10% of HIV-infected subjects progress within 2-3 years
5-10% clinically asymptomatic after 10 years
Remaining subjects progress to AIDS within 10 years - DEATH
Situation drastically improved by antiretroviral therapy
-low rates of AIDS and death compared to diagnoses in ART area

Question 24

The AIDS epidemic

Answer 24

In UK most new infections among homosexual community (57.5%)
-39% hetero
-3% IVDU
-0.5% mother-child
Asian and African epidemic more heterosexual
-may be due to associated high level of STDs - ulceration

Question 25

Global estimates 1. people living with HIV 2016 2. AIDS related deaths 2016 3. No. new HIV infections per day

Answer 25

1. 36.7 million - numbers going up per year 2. 1 million - numbers going down 3. 5000 - 64% sub-Saharan Africa

Question 26

2011 World AIDS day aims

Answer 26

1. Focused interventions for key populations at higher risk 2. Elimination of new HIV infections among children 3. Behaviour change programmes 4. Condom promotion and distribution 5. Treatment, care and support 6. Voluntary medical male circumcision in countries with high HIV - improves hygiene - lwoers underlying STDs

Question 27

Ending AIDS targets by 2020

Answer 27

90% of people living with HIV know their status 90% of people living with HIV who know their status are on treatment 90% of people on treatment are virally suppressed

Question 28

Stigma

Answer 28

Discrimination in health-care settings, eastern Europe

Question 29

Botswana

Answer 29

Recent success Number of new infections dramatically lowered to 10,000 Treatment coverage increased to around 90% Almost at 90 90 90 targets

Question 30

HIV drug targets

Answer 30

``` Fusion inhibitors *NRTIs (nucleoside reverse transcriptase inhibitor)* NNRTI (non-) Integrase inhibitors PI (Protease inhibitors) CCR5 entry inhibitors ```

Question 31

NRTI mechanism (DIAGRAM)

Answer 31

Nucleotide analogues cause chain termination when RT builds DNA from RNA

Question 32

Treatment

Answer 32

Highly Active Anti-Retroviral Therapy First line regimen -2NRTIs (side-effects must be managed) -e.g. zidovudine (AZT), lamivudine (3TC), embricatabaine (FTC), stavudine (d4T) -1NNRTI - inactive against HIV-2 -e.g. Efaviren, Nevirapine OR Protease inhibitor (PI): high turnover in body = many pills -boosted with Ritonavir to improve efficacy -e.g. Indinavir (IDV), Fos-amprenavir (FPV) OR Integrase inhibitor

Question 33

Side-effects of NRTIs

Answer 33

AZT- headaches and nausea, anaemia, neutropenia Stavudine-lactic acidosis, lipoatrophy (loss from face and limbs – gain to neck and tummy) and peripheral neuropathy- possibly via mitochondrial toxicity Rashes

Question 34

Side-effects of NNRTIs

Answer 34

Stevens Johnson Syndrome: a severe disorder of mucous membranes Teratogenecity

Question 35

Side effects of PIs

Answer 35

Lipodystrophy - fat loss from legs - fat gain - pot belly

Question 36

Resistance to HIV drugs

Answer 36

Increasing problem Drug holidays -ineffective -compliance also an issue

Question 37

Alterative first line

Answer 37

DTG or dolutegravir used with tenofovir disoproxil fumarate (NtRTI) & lamivudine (NRTI) DTG – Integrase inhibitor, first used in 2014 but becoming more and more widely used

Question 38

Vaccine prospects

Answer 38

Still some way off -mutation rates high But best prospect for eradication?

Question 39

Dental transmission control

Answer 39

Very low risk, even with risk contact only 1/300 chance of infection Normal infectious control procedures -gloves -sterilise instruments -dispose of sharps -suction -care if blood spillage If at risk: contact Occy health physician for prophylactic HAART and HIV testing If needlestick with HIV+ pt - PEP administration ASAP within 72hrs -no NHS emplyee infected in last 10y

Question 40

HIV testing

Answer 40

ELISA based blood test -detects HIV antibodies in blood Antibody takes 6-12 weeks to develop Most reliable testing at 3 months (re-test at 6 months) Babies may test positive from maternal antibody - PCR test Home test kits exist but blood test most reliable