4. Hemelaar J.Trends Mol Med. 2012 Jan 11.
Tebit DM, Arts EJ. Lancet Infect Dis. 2011 Jan;11(1):45-56.
HIV came from
non-human
primates
5.
6. Global Distribution of HIV-1 Hemelaar J.Trends Mol Med. 2012 Jan 11.
The greatest diversity of HIV
sequences is seen in Central Africa
7. Natural History of HIV/AIDS
Acquired Immune Deficiency Syndrome (AIDS)
caused by Human Immunodeficiency Virus (HIV)
Disease first described in 1981
8. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men:
evidence of a new acquired cellular immunodeficiency
MS Gottlieb, R Schroff, HM Schanker, JD Weisman, PT Fan, RA Wolf, and A Saxon
Dec 10, 1981
9. Natural History of HIV/AIDS
Acquired Immune Deficiency Syndrome (AIDS)
caused by Human Immunodeficiency Virus (HIV)
Disease first described in 1981
Immune system attacked. Victim dies of
secondary infections
10. How HIV causes AIDS
HIV invades immune system cells especially helper T cells which
have a vital role in the immune system
Effector T cells attack the virus and stimulate B cells to produce
antibodies to the virus. In addition effector T cells stimulate
macrophages to ingest cells infected with the virus and killer T
cells to destroy infected cells displaying viral proteins
Virus mutates and the proteins on its outer surface (gp120 and
gp41) change. Mutant virus particles bearing new surface
proteins survive immune system attack and begin new round of
infection
Each round of infection reduces numbers of helper T cells
because they are infected by the virus and destroyed.
Furthermore, because each lineage of T cells has a limited
capacity for replication, after a finite number of rounds of
replication the body’s supply of helper T cells becomes
exhausted. The immune system eventually is overwhelmed and
collapses
11. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men:
evidence of a new acquired cellular immunodeficiency
MS Gottlieb, R Schroff, HM Schanker, JD Weisman, PT Fan, RA Wolf, and A Saxon
Dec 10, 1981
Leu3=CD4
12. Natural history of untreated HIV
infection
Pantaleo G, Graziosi C, Fauci AS. New concepts in the immunopathogenesis of
human immunodeficiency virus infection. N Engl J Med. 1993;328:327-35.
16. HIV exposure at
mucosal surface (sex)
Virus collected by
dendritic cells, carried
to lymph node
HIV replicates in
CD4 cells, released
into blood
Virus spreads to
other organs
Day 0
Day 0-2
Day 4-11
Day 11+
The HIV Infection mechanism
17. HIV– Acute HIV+
• There is a marked reduction in mucosal CD4 cells — T
cells, DCs, and macrophages
Profound Depletion of Mucosal Barrier
Brenchley JM, et al. J Exp Med. 2004;200:749-759.
18. HIV in body fluids
Sperm
11,000 Vaginal
Fluid
7,000
Blood
18,000
Amniotic
Fluid
4,000 Saliva
1
Mean number of HIV particles in 1 ml of each body fluid
19. Modes of HIV Transmission
Sharing Semen and
Vaginal Fluids
Sharing Needles
& Syringes
Through Infected Blood During Pregnancy
or Birth
Breast Feeding
Needle Stick
Injury
20. Risk of HIV Transmission with Single
Unprotected Exposure
21. Total Living with HIV 35.3 million
North America
1.3 million
[980 000 – 1.9 million]
Latin America
1.5 million
[1.2 million – 1.9 million]
Caribbean
250 000
[220 000 – 280 000]
Western &
Central Europe
860 000
[800 000 – 930 000]
Middle East & North Africa
260 000
[200 000 – 380 000]
Sub-Saharan Africa
25.0 million
[23.5 million – 26.6 million]
Eastern Europe
& Central Asia
1.3 million
[1.0 million – 1.7 million]
South & South-East Asia
3.9 million
[2.9 million – 5.2 million]
Oceania
51 000
[43 000 – 59 000]
East Asia
880 000
[650 000 – 1.2 million]
25. Timing of Initiation of Antiretroviral Drugs
during Tuberculosis Therapy: the SAPiT trial
Abdool Karim SS, N Engl J Med 2010; 362:697-706
26. TB and IRIS
Mean of 15 days after starting HAART
Risk factors:
• Starting ARV’s within 6 weeks of TB treatment
• Disseminated, extra-pulmonary disease
• Low base line CD4 count
• Rise in CD4 %
• Fall in viral load
27. Natural History of HIV/AIDS
Acquired Immune Deficiency Syndrome (AIDS)
caused by Human Immunodeficiency Virus (HIV)
Disease first described in 1981
Immune system attacked. Victim dies of
secondary infections
Increased inflammation also in patients with
controlled infection by the therapy
28. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men:
evidence of a new acquired cellular immunodeficiency
MS Gottlieb, R Schroff, HM Schanker, JD Weisman, PT Fan, RA Wolf, and A Saxon
Dec 10, 1981
T10=CD38
Leu3=CD4
29. Inflammation
↑ Monocyte activation
↑ T cell activation
Dyslipidemia
Hypercoagulation
Microbial
translocation
HIV-associated fat
Metabolic syndrome
HIV production
HIV replication
CMV
Excess pathogens
Loss of regulatory
cells
Co-morbidities
Aging
Deeks S et al Lancet 2013
30. Inflammation predicts disease in
treated HIV infection, as it does
in the general population
Mortality (Kuller, PLoS Med, 2008, Sandler JID 2011, Tien JAIDS 2011)
Cardiovascular Disease (Baker, CROI 2013)
Lymphoma (Breen, Cancer Epi Bio Prev, 2010)
Venous Thromboembolism (Musselwhite, AIDS, 2011)
Type II Diabetes (Brown, Diabetes Care, 2010)
Cognitive Dysfunction (Burdo AIDS 2012)
Frailty (Erlandson, JID 2013)
31. Weber R, et al. Arch Intern Med. 2006;166:1632-41.
Cause of Death (Incidence) in the D:A:D Study
23,441 HIV-infected persons prospectively followed for a median of 3.5 years
N = 1,246 deaths
32. Fibrinogen and CRP, independent
predictors of mortality in the FRAM study
Tien, JAIDS 2010
922 HIV-infected
participants > 85% on
cART (past or present)
70% with history of AIDS
50% HIV-RNA BLD
20% HCV+
5-year mortality risk
33. Immunological and clinical manifestations
shared by HIV+ and elderly
Immunologic
characteristics
Naïve T cells
T cell diversity
Memory cells
Differentiated,
senescent CD8+ T cells
(eg CD28-CD57+)
Telomere length
CD16+ monocytes
monocyte function
Functional immune
defects
Replicative capacity
Tumour surveillance
Pathogen protection
Chronic inflammation
Clinical
manifestations
Vaccine responses
Infections
Age-associated non
communicable diseases
(eg CVD, non-AIDS cancers,
bone/kidney disease, frailty,
neurocognitive decline)
34.
35. HIV Results in Accelerated
Age-related Conditions
Development of frailty, muscle wasting
Insulin resistance, diabetes and
cardiovascular disease
Chronic kidney disease
Bone disease
Cognitive impairment and dementia
Non AIDS-defining malignancies
Liver disease and HCC
Effros RB et al. Clin Infect Dis 2008
Editor's Notes
There are a number of immunologic and clinical features of ageing that are shared by HIV infected individuals and the elderly.There is good evidence that changes occur in T cells as we age such as the accumulation of senescent T cells and emerging evidence of changes in monocytes. These changes are juxtaposed on evidence of chronic inflammation and clinically associated withincreased risk of infection as well as non communicable diseases of ageing
