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Flashcards in HIV symposium Deck (42)
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1

Where did HIV come from?

Origins traced back to chimpanzees (HIV-1) & sooty mangabeys (HIV-2)
‘Bushmeat practices’ - cross species transmission during killing or butchering
Transfer to humans beginning of 20th century in central & W. Africa
Social changes / migratory routes / urbanisation

2

How did HIV cross from Africa to the west?

Stored specimens test positive early as 1959
Introduced to Haiti by individuals working in the DR Congo ~ 1966 – outbreak followed
Transferred to US ~ 1969-72
Increase in international travel / transfusion / blood products / IVDU
Rapid spread within gay community
1st clinical cases 1981

3

Early 1980s

HIV discovered
- Institut Pasteur 1983
- Robert Gallo 1984

Increasing reports of Pneumocystis & KS
- developed world, gay men
- IVDUs, haemophiliacs
- developing world

Antibody test in 1985

Management
- treatment of infections
- palliative care

4

Late 1980s

AZT - zidovudine (monotherapy)
- first manufactured in 1964

Patient activism

Management:
- prevention opportunistic infections
- nebulised pentamidine 1989
- palliative care

Widespread prevention campaigns
- reduction in STIs
- needle exchange

5

1991-1992

More HIV tests than any other time
- Mark Fowler diagnosed with HIV on East Enders
- Freddy Mercury died
- Arthur Ashe, Kenny Everett, Holly Johnson all HIV +

Resistance to AZT documented in people who had never taken AZT

6

1993-1994

Concorde - AZT monotherapy ineffective
Dual therapy (addition of ddC) ineffective
Therapeutic nihilism
Treatment limited to treatment and prophylaxis of OIs
Reduction in HIV testing

7

1994

ACTG 076
- antenatal & intrapartum AZT
- post partum AZT to neonate
- decreased transmission 25% -> 8%

Current practice
- combination therapy (3 drugs)
- normal vaginal delivery if VL <40
- transmission rates <1%

8

1994-1996

More ARVs approved +++

1994/5: dual therapy works (Delta)

1996: everything changes ……

9

1996/7

Protease inhibitors
Triple therapy
Nevirapine, ritonavir, indinavir
Vancouver AIDS conference (July)
"Lazarus Syndrome” - ward closures
Viral load testing

10

HAART (highly active anti-retroviral therapy)

HAART = ART = combination therapy = ‘triple’ therapy = usually at least 3 anti-retroviral drugs (ARVs)
Aim to reduce viral load to ‘undetectable’ levels - allowing immune system to partially recover
Need to take all the drugs, on time
Need to think about food restrictions, drug interactions

11

1997-2000: ART side effects

lipodystrophy
hyperlipidaemia and CVD
Glucose intolerance / diabetes
Loss bone mineral density
Gastrointestinal – N&V, diarrhoea
Peripheral neuropathy, CNS side effects
Hepatotoxicity
Renal – nephrolithiasis, proteinuria
Skin rash / hypersensitivity

12

2000-2016

Improvement in tolerability of ART

Improvement of toxicity of ART

Improvement of formulation of ART
Reduced daily dosing
Co-formulation

Shift towards earlier treatment

13

HIV lifecycle

1) binding, 2) fusion, 3) reverse transcription, 4) integration, 5) replication, 6) assembly, and 7) budding.

14

Viral dynamics and resistance

10 billion viruses produced/person/day
10,000 bases in viral genome
Mutations every 10,000 bases
Every mutation likely to occur each day
Just one mutation can cause resistance
Pools of resistant virus exists before exposure to drug therapy
Combination antivirals essential

15

Viral load


• Lower the better
• Higher viral load associated with more rapid disease progression
• Very high levels in early infection (>10,000,000 copies/ml)
• Viral load marker of treatment success: aim for “undetectable” (<40)

16

CD4 Count

Measure of immune function
Higher the better
Decreasing count associated with increasing risk of disease progression
Normal values >500
Significant risk of morbidity/ mortality if CD4 count < 200

17

Aims of treatment of HIV

To start as soon as possible
To reduce HIV transmission
To prevent further damage to the immune system ( ‘CD4 count’)
Reduce risk of opportunistic infections, tumours, direct effects e.g. HIV neurocognitive impairment
Prolong healthy life

18

Untreated HIV infection

Seroconversion

Then later on TB, Kaposi's Sarcoma, shingles, oral thrush, seborrhoeic dermatitis

Then later on Pneumocystis pneumonia, toxoplasmosis, lymphoma

Then MAC, CMV, PML, CNS lymphoma

19

HIV treatment effect

Reduced morbidity and mortality
HIV patients now living very long
As long as have no comorbidities

20

Global statistics

In 2017:

36.9 million globally were living with HIV
New HIV infections have fallen by 35% since 2000
1.8 million became newly infected with HIV
AIDS-related deaths have fallen by 48% since the peak in 2005
940,000 died from AIDS-related illnesses

21

Global ARV rollout

Made possible by generic drug production
£60 per year vs £10,000
‘3 by 5’ target - 3 million on ARVs by 2005
‘15 by 15’ target - 15 million people taking ARVs by 2015 was reached in June 15
21.7 million accessing ARVs (2017)
Clinical response similar in all settings
Next target 90:90:90 by 2020

22

What is the 2020 90-90-90 target?

By 2020, 90% of all people living with HIV will know their HIV status. By 2020, 90% of all people with diagnosed HIV infection will receive sustained antiretroviral therapy. By 2020, 90% of all people receiving antiretroviral therapy will have viral suppression.

23

by 2020 and by 2030...

Fewer than 500 000 people newly infected with HIV (currently 1.8m)

Fewer than 500 000 people dying from AIDS-related causes (currently ~1m)

Elimination of HIV-related discrimination

75:79:81 globally

48% of all PLWH have supressed virus

Reduce the number of new HIV infections by 89% by 2030 and the number of AIDS-related deaths by 81%

24

Combination prevention

Treatment as prevention - TasP
Pre-exposure prophylaxis- PrEP
Expansion of HIV testing
Condoms wherever possible

25

What is U=U

Undetectable=Untransmittable

ART is now so effective that those who are treated and have an undetectable viral load (<200 copies) have levels of virus that are untransmissible, even if having sex without condoms. This is sometimes referred to as U=U.

The Swiss Statement 2008

Partner study - zero transmissions after >58,000 episodes sex without condoms when viral load was undetectable <200

26

Test and treat programmes

Aim for 90% of new diagnoses to be taking ARVs by 90 daysAim for 98-100% PLWH to be taking effective treatmentAim for 100% PLWH have undetectable viral loads

27

What is PrEP?

Pre-exposure prophylaxis (or PrEP) is when people at very high risk of HIV take daily HIV medicines to reduce the chances of getting infected

It works – trials showed 86% effective, but actually 100% for those who took it

Historical lack of availability on NHS…

Truvada (tenofovir/emtricitabine)

28

PrEP impact trial

10,000 patients (then 13,000, now 26,000)
3 years
Generic Truvada – daily or event based
GUM clinics across UK
Open for recruitment

29

Other Prevention strategies

HIV testing
Sexually transmitted infection treatment - 40% reduction (1)
Circumcision - South Africa, Kenya, Uganda - 58% reduction

30

What kind of surfaces are the best for HIV entry

Most of the pathogens that cause the deaths of large numbers of people are those of mucosal surfaces or enter the body through these routes. The genitourinary, rectal and oral mucosa are the mucosal HIV transmission routes. An effective vaccine that can induce both systemic and local mucosal immunity is generally accepted as a major means of protection against mucosal HIV transmission and AIDS.