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1. HIV - I RICHA PANDEY

2. INTRODUCTION HIV belongs to retroviridae class of viruses. First recognized in US in 1981,when CDC reported unexplained occurrence of Pneumocystis jiroveci pneumonia and Kaposi's sarcoma in previously healthy homosexual men .

3. Soon recognized in male and female injection drug users ,hemophiliacs and blood transfusion recipients , among female sexual partners of men with AIDS; and among infants born to mothers with AIDS or with history of injection drug use In 1983,human immunodeficiency virus(HIV) isolated from a patient with lymphadenopathy In 1984,demonstrated to be the causative agent of AIDS

4. MORPHOLOGY OF HIV The HIV virion is an icosahedral structure containing numerous external spikes formed by the two major envelope proteins , the external gp120 and the transmembrane gp41. Virions bud from the surface of infected cell , incorporating a variety of host proteins, including major histocompatibility complex (MHC) class I and II antigens into its lipid bilayer .

5. The capsid is made of p 24 capsular proteins

6. HIV GENOME HIV -1 has genes that encode the structural proteins of the virus: 1. g a g encodes the proteins that form the core of the virion (including p24 antigen); 2 . p o l encodes the enzymes responsible for protease processing of viral proteins, reverse transcription, and integration; 3. e n v encodes the envelope glycoproteins .

7. TRANSMISSION HIV is transmitted primarily by sexual contact (both heterosexual and male to male); by blood and blood products; and by infected mothers to infants intrapartum , perinatally , or via breast milk Although a wide variety of factors including viral load and the presence of ulcerative genital diseases influence the efficiency of heterosexual transmission of HIV , such transmission is generally inefficient

8. In high-income countries the estimated per-act rate is 0.04% for female-to-male transmission and 0.08% for male-to-female transmission Rates for low-income-country female-to-male and male-to-female transmission were higher in this analysis ( 0.38% per act and 0.30% per act, respectively

9. TRANSMISSION VIA BLOOD The risk of HIV transmission following skin puncture from a needle or a sharp object contaminated with blood from a person with documented HI V infection is 0.3% and after a mucous membrane exposure it is 0.09% >90% of individuals exposed to HIV -contaminated blood products become infected following a blood transmission

10. MOTHER TO CHILD TRANSMISSION The relative risk of mother-to-child transmission from a seropositive mother to her child is 23–30% before birth ( intranatally ), 50–65% during birth ( perinatally ), and 12–20% via breast-feeding. The overall risk is 15 -25 % in developed countries and 25 – 35 % in developing countries that is further reduced by adequate ART prophylaxis during pregnancy, childbirth ,postpartum and to infant after birth.

11. PATHOGENESIS

12. CLINICAL MANIFESTATIONS The clinical consequences of HIV infection encompass a spectrum ranging from an acute syndrome associated with primary infection to a prolonged asymptomatic state to advanced disease .It is best to regard HIV disease as beginning at the time of primary infection and progressing through various stages

13. DEFINITION The current CDC classification system for HIV infected adults categorizes persons on the basis of clinical conditions associated with HIV infection B. CD4+ T lymphocyte counts.

14. Any HIV -infected individual with a CD4+ T cell count of <200/µL has AIDS by definition, regardless of the presence of symptoms.

15. WHO STAGING 2010 Clinical Stage 1 Asymptomatic PGL Clinical Stage 2 Moderate weight loss (<10% of body weight) Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis media, pharyngitis ) Herpes zoster Angular Cheilitis Recurrent oral ulceration Papular pruritic eruptions Seborrhoeic dermatitis Fungal nail infections

16. CLINICAL STAGE 3 Unexplained severe weight loss (>10% of body weight) / chronic diarrhoea >1 month / persistent fever ( > 37.5 C for > 1 month) Persistent oral candidiais Pulmonary tuberculosis Severe bacterial infections (e.g. pneumonia, empyema , bone or joint infection, meningitis, bacteraemia ) Acute necrotizing ulcerative stomatitis / gingivitis Unexplained anaemia (<8 g/dl), neutropenia (<0.5 x 10 *9/l) and /or chronic thrombocytopenia (<50 x 10 *9/l )

17. Clinical stage 4 HIV wasting syndrome Pneumocystis pneumonia Chronic herpes simplex Oesophageal candidiasis (or of trachea, bronchi or lungs) Extrapulmonary tuberculosis Kaposi sarcoma Cytomegalovirus infection CNS toxoplasmosis HIV encephalopathy

18. Disseminated cryptococcosis Disseminated mycosis ( histoplasmosis , coccidiomycosis ) Recurrent septicaemia Lymphoma (cerebral or B cell non Hodgkin) Invasive cervical carcinoma Disseminated leishmaniasis Symptomatic HIV-associated nephropathy or symptomatic HIV – associated cardiomyopathy

19. DISEASES OF ORAL CAVITY AND GIT Mostly due to secondary infections. Also with KS and lymphoma. Oral lesions, including thrush, leukoplakia , and aphthous ulcers , are particularly common. Thrush, due to Candida infection ,and oral hairy leukoplakia due to EBV are indicative of fairly advanced immunologic decline

20. Infections of small and large intestine leading to diarrhea ,abdominal pain and fever are most significant GI problems. Infections of bacteria ,protozoa and viruses. Salmonella , Shigella and Campylobacter are common, more severe and apt to relapse. Untreated HIV have 20-fold increased risk of infection with S. typhimurium

21. Cryptosporidia , microsporidia and Isospora belli are most common opportunistic protozoa causing diarrhea. Cryptosporidial infection presents in a variety of ways, from a self-limited intermittent diarrheal illness in early stage of HIV to a severe life-threatening diarrhea in severely immunodeficient individuals.

22. THRUSH IN ORAL CAVITY

23. APHTHOUS ULCER

24. HEPATOBILIARY DISEASES One-third deaths of patients with HIV are related to liver disease. Predominantly in the setting of co-infection with hepatitis B or C Also a reflection of hepatic injury ,ranging from hepatic steatosis to hypersensitivity reactions to immune reconstitution ,seen in context of ART

25. Granulomatous hepatitis seen in mycobacterial or fungal infections, specially MAC. Hepatic masses seen in TB, or fungal infection. Biliary tract disease eg sclerosing cholangitis seen in cryptosporidiosis, CMV and KS.

26. Many drugs used to treat HIV infection metabolized by liver. Fatal hepatic reactions have been reported with ARTs including NRTI,NNRTI , and protease inhibitors.

27. DISEASES OF THE KIDNEY AND GENITOURINAR Y TRACT Diseases of the kidney or genitourinary tract may be - a. direct consequence of HIV infection b. due to an opportunistic infection c. Neoplasm

28. d. related to drug toxicity Microalbuminuria seen in 20% of untreated HIV-infected patients

29. HIV - II RICHA PANDEY

30. Disinfection & Inactivation HIV is completely inactivated (10 5 units of infectivity) by treatment for 10 minutes at room temperature with any of the following: 10 % household bleach, 50 % ethanol, 35 % isopropanol, 1 % Nonidet P40, 0.5 % Lysol, 0.5 % paraformaldehyde, or 0.3 % hydrogen peroxide. When HIV is present in clotted or unclotted blood in a needle or syringe, exposure to undiluted bleach for at least 30 seconds is necessary for inactivation.

31. Immunity HIV-infected persons develop both humoral and cell-mediated responses against HIV-related antigens . The neutralizing antibodies can be measured in vitro by inhibiting HIV infection of susceptible lymphocyte cell lines. Viral infection is quantified by ( 1) reverse transcriptase assay, which measures the enzyme activity of released HIV particles; ( 2) indirect immunofluorescence assay, which measures the percentage of infected cells; and ( 3) reverse transcriptase-polymerase chain reaction (RT-PCR) or branched-chain DNA ( bDNA ) amplification assays that measure HIV nucleic acids.

32. LAB DIAGNOSIS diagnosis of infection acute, recent, established or late stage disease prognostic markers monitoring of ARV therapies immunological and virological markers toxicities diagnosis of opportunistic infections drug resistance testing

33. Evidence of infection by HIV can be detected in three ways: ( 1) virus isolation; ( 2) serologic determination of antiviral antibodies; and ( 3) measurement of viral nucleic acid or antigens.

34. virus isolation HIV can be cultured from lymphocytes in peripheral blood (and occasionally from specimens from other sites). Primary isolates of HIV grow very slowly compared with laboratory-adapted strains. Viral growth is detected by testing culture supernatant fluids after about 7–14 days for viral reverse transcriptase activity or for virus-specific antigens (p24).

35. Serology Test kits are commercially available for measuring antibodies by enzyme-linked immunoassay (EIA ). A positive test in a serum sample must be confirmed by a repeat test. If the repeat EIA test is reactive, a confirmation test is performed to rule out false-positive EIA results. Antibodies to viral core protein p24 or envelope glycoproteins gp41, gp120, or gp160 are most commonly detected .

36. The decline of anti-p24 may herald the beginning of clinical signs and other immunologic markers of progression. The mean time to sero -conversion after HIV infection is 3–4 weeks. Most individuals will have detectable antibodies within 6–12 weeks after infection, whereas virtually all will be positive within 6 months.

37. Need for 4 th Generation ELISA Methods A new generation Method in ELISA Can detect both Antigen and Antibody in the same run ( in the same ELISA Plate ) Helpful to make early diagnosis at least in few cases . Determination of P 24 Antigen by ELISA

38. Confirmatory Serological Tests HIV Western Blots. Line Immunoassay ( LIA ) Immuno fluorescent Assay ( IFA ) Utility is limited due technical and economical reasons

39. Limitation of Western Blot Test If not designed for HIV 2 inclusion, we miss HIV2 infections , Can give Indeterminate results in Pregnancy After administration of Tetanus Toxoid . Autoimmune conditions.

40. Other supporting tests in AIDS Flowcytometry for Estimation of CD 4 lymphocytes CD4 count measurements help for staging the diseases. Flow cytometry has become the prominent tool in estimations of CD4 . Uses of Absolute CD4 Lymphocyte counts. Most widely used predictor of HIV progression . Risk of progression to an AIDS defining illness , opportunistic infections or malignancy is high, when the counts drop below 200/mcl

41. Molecular Methods in Diagnosis of AIDS 1. The reverse transcription polymerase chain reaction. 2. Nucleic acid sequence amplification. ( NASBA ) 3. Branched chain DNA bDNA .

42. Detection of Viral Nucleic Acid or Antigens Amplification assays such as the RT-PCR , DNA PCR, and bDNA tests are commonly used to detect viral RNA in clinical specimens. The RT-PCR assay uses an enzymatic method to amplify HIV RNA; the bDNA assay amplifies viral RNA by sequential oligonucleotide hybridization steps. The tests can be quantitative when reference standards are used; appropriate positive and negative controls must be included with each test.

43. HIV Viral Load tests. The tests measure the amount of actively replicating HIV virus. Correlates with response to antiretroviral drugs Most helpful in diagnosis of HIV before Sero conversion. False positives should be possible with low viremia < 500 copies

44. DIAGNOSIS OF HIV For symptomatic persons: the sample should be reactive with two different kits. For asymptomatic persons: the sample should be reactive with three different kits

45. Types of HIV Assays Virus Detection & Quantification DIAGNOSIS MANAGEMENT EIA Simple, rapid tests Immunoblots Incident assays DNA (RNA) RNA modified Ag Viral Culture, phenotyping CD4+ ARV Resistance – genotyping ARV Sensitivity

46. Screening Tests for HIV/AIDS Detection A screening test posses high Sensitivity We rarely miss the Diagnosis in Infected patients. Done as mass screening procedure. Economical . Developing countries depend on these tests even for Diagnosis.

47. Confirmatory Tests in AIDS It is important to confirm all screening tests with Confirmatory tests, or we brand some one without infection as infected, Confirmatory tests differentiates false reactive tests. and identifies truly infected or not.

48. Before you declare a person infected with HIV / AIDS you should perform both methods . Faulty testing methods can lead to catastrophic consequences, and legal litigations .

49. MANAGEMENT Assessment of CD 4 Count

50. WHO Test Strategies Strategy I: Test all samples with one EIA Strategy II: Strategy I with all reactives retested in a more specific test with different principle and/or antigen. Strategy III: Strategy II with reactives tested in a third test differing from the first two tests. Transfusion Safety Strategy I Surveillance >10 % Strategy I, < 10% Strategy II Diagnosis >10 % Strategy II, < 10% Strategy III

51. AIMS OF ART Clinical goals : Prolongation of life and improvement in quality of life Virological goals : Greatest possible reduction in viral load for as long as possible Immunological goals : Immune reconstitution that is both quantitative and qualitative Therapeutic goals : Rational sequencing of drugs in a fashion that achieves clinical, virological and immunological goals while maintaining treatment options, limiting drug toxicity and facilitating adherence Reduction of HIV transmission in individuals : Reduction of HIV transmission by suppression of viral load