HIV AIDS

HIV lecture based on harrison textbook of medicine 20th edition

1. HIV 26 August 2021 based on Harrison textbook of medicine 20 th edition Dr. Chirantan Mandal SenioResident Medicine AIIMS Kalyani

2. epidemiology first recognized in US in 1981 among IVDU, transfusion recipients By 1985 with advent of ELISA the extent of epidemic became clear MNOP 4 groups in HIV1 and A to H 8 groups in HIV2 most common cause of HIV pandemic is HIV-1 M group viruses.

3. icosahedral SSRNA virus binding of HIV gp120 to host cell surface CD4 gp120 facilitates binding to 2 co-receptors occurs via gp41 molecule RNA to pro HIV viral DNA preintegration complex traverses the cytoplasm to reach nucleus duration of the HIV-1 replication cycle is 2 days

4. formation of proHIV dsDNA . HIV mRNA is translated into proteins,viral particle is formed by the assembly of HIV proteins

5. P athophysiology HIV cross through microscopic disruptions across rectal & vaginal mucosal seeking CD4Tcells (serve as early HIV amplifiers) progressive decline of CD4Tcell <200 ( high risk opportunistic infections) (profound immunodeficiency) since CD4Tcells are very widely spread out in mucosa (obstacle to infection) hence sexual transmission of HIV is very inefficient Once infection is established, the HIV replicates in lymphoid cells in the mucosa, submucosa, & lymphoreticular tissues that drain the gut or genitals

6. Immune response to HIV Novice antibodies against envelope proteins gp120 and gp41 of HIV usually appear within 12 weeks of primary infection these novice antibodies both protective, also contributing to the pathogenesis of HIV (antigp120 antibodies can kill any CD4Tcells containing HIV like a bystander effect) The first protective neutralizing antibodies preventing spread of infection appear after approx 24 weeks of infection. Due to its high rate of mutation the HIV virus has already quickly escaped these (and subsequent) neutralizing antibodies. MHC class I–restricted CD8Tcells through their HIV-specific antigen receptors, bind to and cause the lytic destruction of target cells

7. Immune escape sustained persistent viral replication & regular mutation causes overwhelming immune activation & immune exhaustion downregulated HLA-class1 on surface of HIV-infected cells, resulting in the lack of ability of CD8Tcells & antibody to identify & kill infected cells humoral immune system doesn’t produce classic neutralizing antibodies against HIV envelope until years after infection is firmly established envelope gp120/gp41 hypervariability by continually mutation Latently infected CD4Tcells may serve as persistent reservoir of HIV which can infect other CD4Tcells. It may take several years for this pool of latently infected CD4Tcells to be completely eliminated

8. phases of HIV Acute HIV infection Chronic HIV infection asymptomatic (clinical latency ) symptomatic (AID related complex) AIDS (CD4 < 200) advanced HIV (CD4 < 50)

9. Phases of HIV infection First few days, HIV remains undetectable in plasma ECLIPSE PHASE more virus produced within 2 to 4 weeks, HIV is disseminated to draining lymph nodes (easy access to high quantity of CD4+Tcell) allowing for a easily detectable burst of high-level viremia ACUTE HIV VIREMIA (very rarely acute flu like symptom due to profuse viremia ) 40–70% of all CD4+T cells in the GALT are eliminated during acute phase. viremia during primary acute infection, contributes to virus dissemination throughout the lymphoid tissue, even though commonly asymptomatic initial severe viremia in primary HIV does not necessarily determine the rate of disease progression once infection has been established the HIV succeeds in escaping complete immune-mediated clearance, paradoxically thrives on immune activation, and is never eliminated completely from body. CHRONIC INFECTION develops, persists in untreated patient for 10 years before patient becomes clinically ill

10. ACUTE HIV VIREMIA

11. ACUTE HIV VIREMIA

12. Clinical latency Asymptomatic stage clinical latency is asymptomatic but progressive decline in CD4Tcells level in untreated, due to significant spike in viremia LT nonprogressors (5–15% of HIV-infected) infected ≥10 years, stable without treatment , normal CD4 count Elite controllers (1% of HIV-infected) (HLA-B57-01/05) almost undetectable (<50 HIV RNA/ml) viremia + normal CD4 counts This happens because HIV coudnt escape CD8Tells in these patients CD8Tcell successfully kills HIV & suppress HIV for very long

13. Symptomatic Stage chronic

14. Direct end organ damage by HIV HIVAN HIV associated nephropathy HAND HIV associated neurocognitive disorder HIV enteropathy HIV cholangiopathy HIV cardiomyopathy

15. confirmed HIV, classified in 1 of 5 HIV infection stages (0, 1, 2, 3, unknown) negative HIV test within 6 months first positive HIV test is called stage is 0 Advanced HIV disease (AIDS) is classified as stage 3 ( anyopportunistic illness)

16. Diagnosis of HIV HIV antibodies to appear by 12 weeks postinfection standard ELISA/EIA blood screening tests are based on detection of antibodies sensitivity of >99.5%. 4 th generation EIA tests detects both antibodies to HIV & p24 antigen of HIV1&2. false-positive EIA tests are antibodies to class II antigens (such as may be seen following pregnancy, blood transfusion, or transplantation), autoantibodies, hepatic disease, recent influenza vaccination, and acute viral infections. For these reasons, anyone suspected inconclusive 4 th generation EIA should have the result confirmed with a more HIV-1- or HIV-2-specific antibody immunoassay / western blot / plasma HIV RNA level negative EIA does not indicate clearing of infection; rather, it signifies levels of ongoing exposure to virus or viral proteins insufficient to maintain a measurable antibody response. If these individuals have discontinued therapy, viruses and antibodies have reappeared.

17. LAB MONITORING OF PLHIV ( patientslivingwithHIV ) CD4+Tcell count is accepted as the best indicator of the immediate state of immunologic competence of PLHIV CD4+Tcell<200/ μL are at high risk of P . jirovecii primary prophylaxis is indicated CD4+Tcell<50/ μL are at high risk of disease from CMV, mycobacteria of the M. avium complex, or T. gondii primary prophylaxis is indicated

18. HIV RNA Determinations  precise quantitation of HIVRNA using RT-PCR assay HIV RNA below cut-offs wrongfully told “undetectable ,” should be avoided as it is imprecise and leaves the false impression that the level of virus is zero changes in HIV RNA levels over time delineates viremia, disease progression, viral turnover rate, immune activation and replication. HIVRNA levels should never be made on a single determination Measurements of plasma HIVRNA levels should be made at the time of HIV diagnosis and every 3–6 months thereafter in the untreated patient Following the initiation of therapy or any change in therapy, plasma HIVRNA levels should be monitored approximately every 4 weeks until is effective effective ART means plasma HIVRNA will drop to <50 copies/mL within 6 months of the initiation. During therapy, levels of HIV RNA should be monitored every 3–6 months to evaluate the continuing effectiveness of therapy.

19. Treatment opportunistic infection

20. lab checkup before ART anti retroviral

21. Treatment HIV

22. Protease inhibitors

23. When to start ART when not to ART should not be started in the presence of an active OI In general, OIs should be treated or stabilized before commencing ART Mycobacterium Avium Complex (MAC) and Progressive Multifocal Leukoencephalopathy (PML) are exceptions in which commencing ART may be the preferred treatment

24. whom to give ART current recommendation is to TREAT ALL, regardless of the clinical stage or CD4 count All persons diagnosed with HIV infection should be initiated on ART regardless of the CD4 count or WHO Clinical Staging or age group or population sub-groups

25. first-line ARV Regimen India (2018)

26. Second line ART India (2018)

27. IRIS worsening of signs symptoms due to known /occult infections within 6 weeks to 6 months after initiating ART, with an increase in CD4 count.

28. IRIS types IRIS is generally self-limiting, and interruption of ART is rarely indicated, but people may need to be reassured in the face of protracted symptoms to prevent discontinuation of ART

29. Prophylactic treatment

30. Pregnant HIV

31. lifelong ART for all pregnant and breastfeeding women PLHIV in which all pregnant women living with HIV receive a “single-pill” triple-drug ART regimen (TDF +3TC + EFV) regardless of CD4 count or clinical stage Pregnant HIV

32. TB + HIV

33. Needlestick injury Postexposure prophylaxis for doctors first dose of PEP should be administered ideally within 2 hours (certainly within first 72 hours) baseline rapid HIV testing of the source of the exposed should be done before starting PEP. Initiation of PEP should not be delayed while waiting for the results of HIV testing of the source

34. Thank you