HIV symposium Flashcards
origin of HIV
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 it get to the west from Africa
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 therapies for HIV
AZT - zidovudine (monotherapy)
first manufactured in 1964
but people started resisting drug although never taking it
1993-4
Concorde - AZT monotherapy ineffective
Dual therapy (addition of ddC) ineffective
Therapeutic nihilism
Treatment limited to treatment and prophylaxis of OIs
Reduction in HIV testing
how to protect baby from getting HIV
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%
what happened in 1996-7
Protease inhibitors
Triple therapy
Nevirapine, ritonavir, indinavir
Vancouver AIDS conference
(July)
“Lazarus Syndrome” - ward closures
Viral load testing
what is HAART
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
side effects of HART
Lipodystrophy
hyperlipidaemia
CVD
Glucose intolerance /
diabetes
Loss bone mineral density
Gastrointestinal – N&V, diarrhoea
Peripheral neuropathy, CNS side effects
Hepatotoxicity
Renal – nephrolithiasis, proteinuria
Skin rash / hypersensitivity
what occurred between 2000-6
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 replication
view slide 32
HIV rep examples
Anti-retroviral classes Examples Fusion inhibitors T20 (enfurvitide) CCR5 receptor inhibitors Maraviroc Nucleoside reverse transcriptase inhibitors (NRTIs) Tenofovir, abacavir, lamivudine, emtricitabine Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Efavirenz, rilpivirine, etravirine Integrase inhibitors Dolutegravir, raltegravir Protease inhibitors (PIs) Darunavir, atazanavir
HIV dynamic
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
what is the viral load
Measure of viral replication
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)
what is the 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
aim for viral load
Aim to suppress virus replication (reduce ‘viral load’ to less than 40 copies/ml)
stats
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
