HIV symposium Flashcards
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
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
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
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
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
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
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%
1994-1996
More ARVs approved +++
1994/5: dual therapy works (Delta)
1996: everything changes ……
1996/7
Protease inhibitors Triple therapy Nevirapine, ritonavir, indinavir Vancouver AIDS conference (July) "Lazarus Syndrome” - ward closures Viral load testing
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
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
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
HIV lifecycle
1) binding, 2) fusion, 3) reverse transcription, 4) integration, 5) replication, 6) assembly, and 7) budding.
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
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)
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
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
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
HIV treatment effect
Reduced morbidity and mortality
HIV patients now living very long
As long as have no comorbidities
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
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
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 sustainedantiretroviral therapy. By 2020, 90% of all people receiving antiretroviral therapy will have viral suppression.
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%
Combination prevention
Treatment as prevention - TasP
Pre-exposure prophylaxis- PrEP
Expansion of HIV testing
Condoms wherever possible