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Introduction. Human immunodeficiency virusCharacterized by opportunistic infections and malignanciesChanging in the clinical spectrum of the diseaseRelated to multiple factors. HIV virus. HAART. Protease therapyDecline in morbidity and mortality1997 StudyPre-HAART and HAART erasReduced viral loads and increased CD4 cells .
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1. Clinical manifestations of HIV Emerging trends Garfield Forbes
2. Introduction Human immunodeficiency virus
Characterized by opportunistic infections and malignancies
Changing in the clinical spectrum of the disease
Related to multiple factors
3. HIV virus
4. HAART Protease therapy
Decline in morbidity and mortality
1997 Study
Pre-HAART and HAART eras
Reduced viral loads and increased CD4+ cells
5. Evolving epidemiological trends Reduced rate of mortality decline
Viral resistance
Compliance
Side effects linked to HAART
6. Pathogenesis of the trends Drug toxicity
Prolonged exposure to HIV
Cytokine mediated
Immune changes accompanying viral suppression
7. HAART toxicity Mitochondrial metabolism
Lactic acidosis
Pancreatitis
Pregnant females –Stavudine/ ddI
8. Lactic acidosis Abdominal pains
Vomiting
Nausea
Hepatic steatosis
Abnormal LFTS
Peripheral lipoatrophy
9. HAMMAS HIV- associated metabolic and morphologic abnormality syndrome
Insulin resistance- GLUT-4
Dyslipidemia
? PI
Documented prior to HAART
10. Skeletal changes Osteopenia
Cytokine mediated
IL-2, TNF
HAART increases level of TNF
Interventions in high risk groups
11. TNF
12. TNF mechanisms
13. Cardiovascular changes Accelerated atherosclerosis
Myocardial infarction- markedly increased risk
Hypercoaguable state
Vasculitis
Increased VLDL/ Cholesterol
Indinavir
Switching therapy
14. Haematologic changes Cytopenias
Immune thrombocytopenic purpura
TTP
15. Malignancies Kaposi sarcoma- declining incidence
Non-Hodgkins lymphoma-mixed
16. Opportunistic infections Reduced incidence worldwide
Reporting bias
PCP
CMV
Bacterial pneumonias
Toxoplasmosis
Cryptococcosis
17. Pathogenesis of OIs Co-pathogenesis
Up regulation of HIV replication
Latently infected CD4+ cells activated
Increased susceptibility to de novo infections
Cellular signaling by cytokines IL-6 and TNF
18. OIs Prophylaxis Trial following Increased CD4+ cells and reducing viral loads
Antigen specific immunity lost
19. Immune reconstitution syndromes Early in therapy
Inflammatory manifestations
Low CD4+ count a high risk factor
MAC
Tb- Cavitary lung lesions
HHV-8, CMV
Fever, lymphadenitis
Steroids and antimicrobials
20. Tuberculosis Higher prevalence
Often precedes diagnosis of HIV infection
Extra-pulmonary and miliary forms more common
21. Pulmonary Tb
22. Syphilis Ocular
Neurosyphilis
CSF pleocytosis
VDRL- Positive in 2/3
23. Herpes viruses HHV-8
GBV-Type C
24. Increasing viral resistance Multiple resistant strains
Implications for public health
25. Acute HIV infection Transient symptomatic illness
Mononucleosis type symptoms
Rapid viral replication
Aggressive immune response
Index of suspicion
26. Acute HIV infection
27. Acute intervention in Acute HIV infection Early diagnosis
Triple therapy
Reduction in reservoirs
28. Acute HIV intervention
29. Acute HIV infection
30. Acute infection
31. Progressive multifocal leucoencephalopathy
32. PML Reactivation of JC virus
Progressive neurological deterioration
Defective oligodendrocyte and myelin maintenance
PI response
33. The wasting syndrome Tumor necrosis factor – alpha
Alteration of gut permeability
GI immunologic changes
34. Conclusion Important in Diagnosis and early targeted interventions
Public Health importance
Research
35. Thank you
36. Thank You