HIV

1. HIV

2. INTRODUCTION • A – acquired • I – immuno • D – deficiency • S – syndrome • Devastating fatal disease caused by the retrovirus : human immuno-deficiency virus • Characterized by profound immuno-suppression that leads to opportunistic infections, secondary neoplasms and neurologic manifestations.

3. Two genetically distinct population of viruses are known to cause AIDS: • HIV-1 : most common in central Africa and rest of the world • HIV-2 : West Africa and India.

4. EPIDEMIOLOGY • According to Joint United Nation Programme on HIV/AIDS ( UNAIDS) and WHO , approximately 38.6 million people are living with HIV infection. • “India is the second largest country in the world with HIV/AIDS population after South Africa” High prevalence: A.P, Karnataka, Maharashtra, Manipur, Nagaland, TamilNadu Moderate prevalence: Gujarat, Goa, Union Territory of Pondicherry

5. PATHOGENESIS • 2 main targets for HIV infection: immune system and CNS • Profound immune deficiency, primarily affecting cell-mediated immunity is the hallmark of AIDS • HIV has affinity for CD4 + cells • CD4 + T cells • macrophages • dendritic cells • Cells should have • Receptori.e CD4 • Coreceptor : cell surface chemokine receptors CCR5 (macrophages) or CXCR4 ( T cells)

6. LIFE CYCLE OF HIV • Infection of cells • Integration of provirus into host cell genome. • Activation of viral replication • Production & release of infectious virus

9. Mechanism of loss of CD4+ cell

10. Modes Of Transmission • Blood, semen, vaginal fluids, and breast milk • Small amounts in the saliva and tears

11. Progression of HIV infection • 3 phases: • Acute phase • Chronic phase • Crisis phase

12. ACUTE PHASE: • 1° infection , virus dissemination, acute retroviral syndrome • Initial spread of virus & host response • Clinically : self limited acute illness with non-specific symptoms: • Sore throat • Myalgia • Fever • Weight loss • Fatigue • Diarrhea • Vomiting

13. Primary infection of cells in mucosal lymphoid tissue Drainage to lymph nodes Infection established in lymphoid tissue Acute HIV syndrome, spread of infection throughout the body viremia Immune response Partial control of viral replication Drop in viremia to low but detectible levels by abt 12 weeks

14. 2. CHRONIC PHASE: • Lymph nodes & spleen - sites of continuous HIV replication & cell destruction. • Immune system remains competent –few or no clinical manifestations : ‘clinical latency period’. • Majority of peripheral blood T cells do not harbour virus --- but destruction of T cells in lymphoid tissue continues • Either asymptomatic or minor opportunistic infections – oral/vaginal candidiasis, herpes zoster etc

15. Over period of years – continuous cycle of infection + cell death + new infection = steady decline of no. of CD4 T cells in lymphoid tissue & circulation • Host defense begins to waver • Proportion of surviving CD4+ cells infected with HIV • Viral burden per CD4 cell

16. 3) CRISIS PHASE • Full blown AIDS, characterized by • Catastrophic breakdown of host defense : CD4+ T cells ˂200 cells/ɥL • Marked viremia • Long standing fever ˃ 1 month • Fatigue • Weight loss • diarrhea • After a period : • Serious opportunistic infections • 2° neoplasms AIDS indicator • Neurologic symptoms diseases

18. In the absence of treatment most, but not all, pts with HIV infection progress to AIDS after chronic phase lasting from 7-10 years. • Exceptions: • Rapid progressors– chronic phase 2-3 yrs • Long term non-progressors- untreated HIV-1 infected persons – asymptomatic for 10 yrs or more with stable CD4+ T cell count & low level plasma viremia • Average survival rate after full blown AIDS – 18-24 months

19. AIDS classification system Centre For Disease Control And Prevention (CDC) • According to CD4+ count & their development of symptoms in various categories:

20. According to clinical course or natural history of disease: • Group 1- Acute HIV infection • Group 2- Asymptomatic infection • Group 3- persistent generalized lymphadenopathy • Group 4 : other diseases • Subgroup A- constitutional disease • Subgroup B- Neurological diseases • Subgroup C- secondary opportunistic infections • Subgroup D- secondary cancers , kaposis sarcoma, lymphomas • Subgroup E- ˂200 CD4 T lymphocytes/ɥL, pulmonary TB, recurrent pneumonia

21. WHO clinical staging of established HIV infection

22. ORAL LESIONS • Certain oral lesions provide a strong indication of the presence of HIV infection. • Oral lesions are useful markers of disease progression & immunosuppression. • Strongly associated with immunosuppression, as measured by CD4 cell counts.

23. Classification Of Oral Lesions • EC clearinghouse classification (1993) [1993 Clearinghouse classification of oral lesions associated with adult HIV infection] • Presumptive criteria : relate to the initial clinical appearance of the lesion. • Definitive criteria : they are the result of special investigations for absolute diagnosis. • These two added give the diagnostic criteria of the oral manifestation of HIV infection.

25. Pindborg’s classification (1988) • Fungal infection • Bacterial infection • Viral infection • Neoplasms • Neurologic disturbances • Unknown causes PindborgJJ.Classification of oral lesions associated with HIV infection. Oral Surg Oral Med Oral Pathol 1989;67:292-5

26. Classification of oral lesions associated with HIV infection based on intensity & features Group 1 : seven cardinal lesions strongly associated with HIV infection. 1)Oral candidiasis 2)Hairy leukoplakia 3)Kaposi sarcoma 4)Linear gingival erythema 5)NUG 6)NUP 7)Non hodgkins lymphoma Group 2 : 1)Atypical ulcers 2)Salivary gland diseases 3) Viral inf : CMV, HSV,HPV,HZV Group 3: Lesions rarer than those of group 1 & 2. 1)Diffuse OML 2)SCC CooganMM,GreenspanJ,Challacombe SJ .Oral lesions in infection with immunodeficiency virus. Bull World Health Organ.,2005;83: 700-70

27. Classification of Oral Conditions by Degree of Immune Suppression (ODHIS) < 500 CD4+ count< 200 CD4+ count • Erythematouscandidiasis - Hyperplasticcandidiasis • Oral Hairy Leukoplakia - Major aphthous ulcers • Hyposalivation -Chronic HSV • Linear gingival -Necrotizing ulcerative erythema (LGE) periodontitis (NUP) • Human papilloma - Histoplasmosis virus (HPV)

28. CANDIAISIS • Most common intra-oral manifestation • Caused predominantly by Candida albicans, others eg. C. tropicalis, C. glabrata, C. krusei

29. Significance: • Often presenting sign--- leads to initial diagnosis • Been reported that oral/pharyngeal candidiasis in HIV infected persons--- may herald development of full blown AIDS within 2 years • More than 90 % of pts with AIDS develop oral candidiasis, during disease course.

30. Four clinical patterns: • Psudomembraneouscandidiasis: • White to yellowish white plaques • Easily scraped off, exposing red areas. • Seen usually when CD4 count˂200 cells/cu.mm

31. Usually extensive involving more than 1 site. • May involve oropharynx & oesophagus. • May be associated with symptoms of soreness and pain. • Plaques are composed of dense aggregates of hyphal forms of candida containing desquamated epithelial & inflammatory cells • Mucosal epithelium to which they are attached is usually atrophic.

32. 2) Erythematouscandidiasis: • Begin to appear as CD4 count drops below 400 cells/cu.mm • Red lesions commonly located on the dorsum of the tongue, palate & buccal mucosa.

33. Clearest clinical sign of EC usually appears on tongue in the form of diffuse erythema & atrophy of filliform papillae • Tongue lesions are referred to as central papillary atrophy. • Lesions may be asymptomatic or associated with soreness or burning symptoms. • Biopsy specimens show : epithelial atrophy & fairly intense inflammation but hyphae rarely seen. • Association with candidaconfirmed by culture & resolution of lesion after anti-fungal therapy.

34. Hyperplasticcandidiasis : • White plaques which cannot be removed by scrapping. • Diagnosis is through biopsy & response to anti fungal treatment

35. Biopsy: epithelial hypertrophy & hyperkeratosis • Special stains will reveal candidalhyphae invading superficial layers of epithelium. • Presence of candida in these lesions may represent opportunistic infection of an abnormal mucosal surface, such as that occurring in HL, rather than the effect of candidal infection alone.

36. 4)Angular chelitis: • Erythema/ fissuring/scaling of angles of the mouth. • It can be due to : • candidaalbicans& staphylococcus aureus • staphylococcus aureus or candidaalbicansalone. • Usually bilaterally

37. Diagnosis: • Clinical appearance • Smears from lesion PAS staining for • Biopsy hyphae • Culture on Sabouraud’s agar

38. Treatment: • Topical anti-fungal agents: nystatin, clotrimazole • Systemic anti-fungal agents: fluconazole, ketaconzole

39. ORAL HAIRY LEUKOPLAKIA • 1st reported by Greenspan & co-workers in 1984. • Most common EBV related lesion in patients with AIDS. • Term given due to corrugated surface of epithelium.

40. Increased prevalence - Associated with CD4 count <200cells/mm3 & higher HIV viral load • Hypothesized that : • Basal epithelial cells of lateral margin of tongue normally harbors latent EBV & significant diminution of Langerhans cells by HIV, in affected sites === reactivation of EBV with subsequent epithelial hyperplasia.

41. Clinically • Presents as white mucosal plaque • Does not rub off • Lateral border of tongue. • App : faint white vertical streaks to thickened & furrowed areas of leukoplakia , exhibiting shaggy keratotic surface. • Infrequently may become extensive & cover entire dorsal & lateral surface of tongue

42. Histopathology : • Features of epithelial hyperplasia with acanthosis & hyperkeratosis, which produces surface corrugations.

43. Band like zone of lightly stained cells with abundant cytoplasm (“balloon cells”) in the upper spinous layer. • Superficial epithelium reveals scattered cells with nuclear clearing & a characteristic peripheral margination of chromatin seen as nuclear beading. ( due to extensive EBV replication ,that displaces chromatin to nuclear margin) • Heavy candidal infestation of parakeratin layer typical • Normal inflammatory reaction to fungus usually absent.

44. Diagnosis: • Presumptive diagnosis: clinical features sufficient. • Definitive diagnosis: demonstration of EBV within lesion--- PCR, in situ hybridization, IHC, Southern blottting or EM. Treatment: • Usually not required • Discomfort and esthetic concerns may necessitate therapy. • Antiviral agents: acyclovir, ganicyclovir • Antifungal agents : nystatin, ketoconazole • Topical treatment with retinoids – temporary remission • Pts on HAART – significant reduction in prevalence of OHL

45. KAPOSI’S SARCOMA • Multifocal neoplasm of vascular endothelial cell origin --- HHV8 • Most common oral malignancy in HIV pts. • Usually arises when CD4 count˂200 cells/cu/mm • Begins with single or multiple lesions of the skin or oral mucosa. • Most commonly seen on the trunk, arms, head & neck. • Approx. 70% of individuals with HIV-related KS of skin or viscera demonstrate oral lesions. • In 20% oral cavity is initial site of involvement

46. O/M: • Hard palate, gingiva & tongue. • Can invade bone & create tooth mobility. • Begin as flat, brown or reddish purple macular lesions that do not blanch on pressure. • With time develop into plaques or nodules. • Pain, bleeding & necrosis.

47. Diagnosis: • Presumptive diagnosis: clinical presentation & history. • Definitive diagnosis: biospy. • Bacillary angiomatosis often mimics KS: diagnosis made from biopsy of lesion examined with Warthin-Starry stain.

48. Treatment: • Radiation or systemic chemotherapy, surgical excision, cryotherapy, laser ablation or electrosurgery. • Oral lesions – intralesional injection of vinblastine, sclerosing agent (sodium tetradecylsulfate).

49. NON-HODGKINS LYMPHOMA • 2nd most common malignancy of HIV-infected individuals. • Prevalence: 6o times greater than seen in normal population • Usually occurs when CD4 count ˂ 100 cells/cu.mm • Presents as high grade & aggressive disease that frequently is associated with widespread involvement & short survival time. • Lymphomas in pts with AIDS usually occurs in extra-nodal location; CNS being most common site.

50. Oral manifestations: • Oral lesions seen as soft tissue enlargement / large painful , ulcerated mass. • palate or gingiva • Intraosseous involvement resemble diffuse progressive periodontitis. • Widening of PDL & loss of lamina dura. TREATMENT: • Combined chemotherapy & radiation.