1. Human immunodeficiency virus By: Mayada Elnegouly

2. INTRODUCTION 
The human immunodeficiency virus (HIV) pandemic has spread to every country in the world and has infected 59 million persons worldwide, including 20 million who have already died.

3. since the original description in 1981 of an unusual cluster of cases of Pneumocystis carinii pneumonia and Kaposi's sarcoma in previously healthy homosexual males, we achieved understanding of the acquired immune deficiency syndrome (AIDS).
The identification of a cytopathic retrovirus in 1983 and development of a diagnostic serologic test for HIV-1 in 1985 have served as the basis for developing improvements in diagnosis.

4. Retrovirus.
Single stranded, +ss RNA virus.
Enveloped virus (lipid envelope), containing envelope glycoproteins gp120 and gp41.
Reverse transcriptase enzyme is responsible for viral replication
Two types of HIV virus are identified; HIV-1 accounts for most cases in the global pandemic and HIV-2 found mainly in West Africa.
HIV-2 is less transmissible, associated with lesser rate of CD4 declines and clinical decline.

5. HIV STRUCTURE

6. REPLICATION

7. HIV STAGES Viral transmission.
Primary HIV infection (also called acute HIV infection or acute seroconversion syndrome).
Seroconversion
Clinical latent period with or without persistent generalized lymphadenopathy (PGL).
Early symptomatic HIV infection (previously known as "AIDS-related complex" or ARC and more recently referred to as Class B according to the 1993 CDC classification).
AIDS (AIDS indicator condition according to the 1987 CDC criteria and revised 1993 CDC criteria that include a CD4 cell count below 200/mm3 regardless of the presence or absence of symptoms).
Advanced HIV infection characterized by a CD4 cell count below 50/mm3

8. TRANSMISSION

10. Mechanisms of viral escape from immune response

11. !- Formation of stable pool of latently infected HIV infected CD4 cells containing the virus capable of replication.
This occurs early even before the appearance of immune response.
Pool of latency contains replication competent HIIV 1 provirus DNA, which can be detected 2 years after treatment.
In this reservoir the virus is shielded from host immune response and HAART
Decay of this reservoir is very slow and not affected by treatment.

12. How HIV persists? Persistence of latently infected cells
Ongoing viral replication
at low levels

13. 2- High antigenic variability.
Very rapid mutation.
Early and during chronic course.
3-Trapping of the virus on surface of follicular dendritic cells in lymphoid tissue in germinal centers
4- targeting during the acute infection a broad spectrum of effectors' components of antiviral immune responses.

14. Where HIV Persists During Antiviral Therapy?
At the anatomical level: Potential “hiding places” for HIV:
Brain
Lymph nodes
Peripheral blood
Gut
Bone marrow
At the cellular level: A small pool of cells harbor viral DNA integrated within the genome of the host. The frequency of these “reservoir cells” is very low (less than 1 in a million)
HIV can hide “dormant” for the lifetime of the cell

15. IMMUNOLOGICAL FACTORS OF HIV ESCAPE MECHANISMS
interference with the antigen presenting functions (monocye-macrophage-dendretic cell line)
Deletion of CD4 HIV specific T cell clone.
Deletion or exhaustion of cytotoxic T lymphocytes.
Interference with the humoral immunity.
Generation of virus escape mutants.

16. MODE OF ACQUISITION
Infectious body fluids: blood, serous effusions, CSF, semen, vaginal fluid and breast milk.
- Non-infectious body fluid: urine, vomitus and saliva (unless contaminated with blood).
Virus survives poorly in the environment: no environmental transmission recorded

17. The main routes of HIV transmission:
1-Unprotected sexual intercourse (heterosexual and homosexual).
2-Mother to child transmission: perinatal (highest risk), during pregnancy and with breast feeding (increase the risk to 45%).
3- Intravenous drug users.
4- Recipients of blood and blood products.
5- Patients on haemodyalisis.
6- Health care workers and laboratory workers.

18. VIRAL DYNAMICS

20. WHO STAGING

21. DIAGNOSIS 1- In adult and children >18months:
Diagnostic tests (Abs) for HIV infection should never be considered as positive and the patient informed until they have been confirmed by a second assay.
The first screening test (ELISA or a rapid test) should have a high sensitivity to avoid false negative.
The second confirmatory test (second ELISA or a second rapid test or a western blot) should have a high specificity to avoid false positive.
Two separate blood sample should be used.

22. 2- In children <18months:
Positive virological test for HIV (HIV RNA or HIV DNA or ultrasensitive HIV p24 antigen) confirmed by a second virological test.
Positive Abs are not recommended for definitive or confirmatory diagnosis of HIV.

23. Western Blot Assay

24. TREATMENT WHEN TO TREAT. DURATION OF TREATMENT. REGIMEN.
TREATMENT OSF SPECIAL SITUATIONS.
TREATMENT OF OPPORTUNITIC INFECTIONS.

25. ANTIRETROVIRAL THERAPY: HHS GUIDELINES
HHS Antiretroviral Therapy Guidelines: March 2012 Initiating Therapy in Treatment-Naïve Patients
Recommend: Moderate (BIII)
500
Recommend: Strong (AII)
350
Recommend: Strong (AII)
Source: 2012 HHS Antiretroviral Therapy Guidelines. AIDS Info (

26. ANTIRETROVIRAL THERAPY: HHS GUIDELINES
Initiating Antiretroviral Therapy in Treatment-Naïve Patients Change in CD4 Threshold in HHS Guidelines
2012
2009
500
2007
350
2003
200

27. WHEN TO START

28. ANTIRETROVIRAL THERAPY: HHS GUIDELINES
HHS Antiretroviral Therapy Guidelines: March Initiating Therapy in Treatment-Naïve Patients
Earlier Therapy
Later Therapy

29. INITIATING ANTIRETROVIRAL THERAPY
Why are we treating earlier with antiretroviral therapy?

30. ANTIRETROVIRAL THERAPY: HHS GUIDELINES
HHS Antiretroviral Therapy Guidelines: March Factors Affecting Decision on When to Initiate Therapy
More effective regimens
More convenient regimens
Better tolerated therapy
Less long-term toxicity
Better immune recovery
Lower rates of resistance
More treatment options
Concerns for uncontrolled viremia
Decrease HIV transmission
Lack of RCT data supporting early Rx
Potential drug toxicity
Drug and monitoring cost
Potential negative impact on QOL
Later Therapy
Earlier Therapy

31. Once treatment is initiated, ART is continued indefinitely.
DURATION OF TREATMENT
Once treatment is initiated, ART is continued indefinitely.

32. DRUG CLASSES NON NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS.
NUCLEOSIE & NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIS)
NON NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS.
PROTESE INHIBITORS. INTEGRASE STRAND TRANSFER INHIBITORS.

33. DRUG CLASSES

34. DRUG CLASSES

35. DRUG CLASSES

36. DRUG CLASSES

37. DRUG CLASSES

38. DRUG CLASSES

39. DHHS Antiretroviral Therapy Guidelines: October Preferred Regimens for ARV-Naïve Patients: Pill Burden
Class
Therapy
Pill Burden
NNRTI-Based
Efavirenz-Tenofovir-Emtricitabine
PI-Based
Ritonavir + Atazanavir + Tenofovir-Emtricitabine
Darunavir + Ritonavir + Tenofovir-Emtricitabine
INSTI-Based
Raltegravir + Tenofovir-Emtricitabine
Source: 2011 DHHS Antiretroviral Therapy Guidelines. AIDS Info (

40. ANTIRETROVIRAL THERAPY: HHS GUIDELINES
TREATMENT REGIMENS

41. TREATMENT OSPECIAL SITUATIONS

42. TREATMENT OF SPECIAL SITUATIONS (cont.)

43. REATMENT OF SPECIAL SITUATIONS (cont.)

44. IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME

45. Source Infection Status
Recommended HIV PEP after Percutaneous Exposure Known Source HIV Status
Percutaneous Exposure Type
Source Infection Status
HIV+ Class 1*
HIV+ Class 2^
Less Severe¶
Recommend Basic 2-drug PEP
Recommend Expanded > 3-drug PEP
More Severe#
Recommend Expanded 3-drug PEP
¶ Less Severe: e.g., solid needle or superficial injury
# More Severe: e.g., large-bore hollow needle, deep puncture, visible blood on device, or needle used in patient’s artery or vein
*HV+ Class 1: Asymptomatic HIV infection or low viral load (e.g., <1,500 copies/mL)
^HIV+ Class 2: Symptomatic HIV, AIDS, acute seroconversion, or known high viral load
Source: CDC and Prevention. MMWR Morb Mortal Weekly Rep. 2005;54(RR-9):1-17.

46. Huge Breakthrough In HIV Research Brings Us Closer To A Vaccine, January 2013
“What we did was give instructions to the immune system so it could learn to destroy the virus, which it does not do naturally,” said Felipe Garcia, one of the scientists in the team at Barcelona University’s Hospital Clinic.
The therapeutic vaccine, a shot that treats an existing disease rather than preventing it, was safe and led to a dramatic drop in the amount of HIV virus detected in some patients, said the study, published Wednesday in Science Translation Medicine.
The vaccine allowed patients temporarily to live without taking multiple medicines on a daily basis