EMmedonline

• The etiological agent of AIDS is HIV, which belongs to the family of human retroviruses & subfamily of lentiviruses.

• Four recognised human retroviruses belongs to two group

  • Human T lymphotropic viruses (HTLV-1,2)

  • Human immundeficiency virus (HIV-1,2)

MODES OF TRANSMISSION

• Sexual >75% : Homosexual, heterosexual

• Parenteral – blood, blood product transfusion

• Vertical Transmission : Mother to child

• Injection drug use

• The transmission risk after exposure is over 90% for blood or blood product, 15 – 40% for vertical route, 0.5 – 1.0% for injection drug use, 0.2 -0.5% for genital mucous membrane.

CLINICAL MANIFESTATION

• 50-70% of individuals experience an acute clinical syndrome 3-6 weeks after primary infection.
  

  General	Fever Pharyngitis Lymphadenopathy Headache/retro orbital pain Athralgia/myalgia Lethargy/ malaise Anorexia/weight loss
  Neurologic	Meningitis Encephalitis Peripheral neuropathy Myelopathy
  Dermatologic	Erythematous maculopapular rash Mucocutaneous ulceration

  
  

The asymptomatic stage – Clinical latency

• The length of time from initial infection to the development of clinical disease varies greatly, the median time for untreated patients is approx 10yrs.

• Individuals remain well during this period with no evidence of disease except for the possible presence of persistent generalised lymphadenopathy. (Defined as enlarged glands at 2 or more extra inguinal sites)

• Long term non progressors: They have low levels of HIV RNA , decline in CD4 cells takes over a period of time.

• Persons with high levels of RNA progress to symptomatic disease faster than do patients with low levels of HIV RNA.

• Some patients remain asymptomatic despite progressive decline CD4 counts , in these patients appearance of an opportunistic disease may be the first manifestation of HIV.

AIDS

• A diagnosis of AIDS is made in anyone with HIV infection & a CD4+ T cell count <200/μL & in anyone with HIV infection who develop one of the HIV associated disease considered to be indicative of a severe defect in cell mediated immunity.

AIDS DEFINING DISEASE

• Oesophageal candidiasis

• Pulmonary/Extrapulmonary TB

• Invasive cervical cancer, kaposi's sarcoma

• Disseminated mycobacterium avium infection

• Pneumocystis jiroveci pneumonia

• Cryptosporidial diarrhea

• Extrapulmonary histoplasmosis/ coccidodomycosis

• Cerebral toxoplasmosis

• CNS lymphoma

• HIV dementia

• Cryptococcal meningitis

• CMV retinitis

• Progressive multifocal leucoencephalopathy

DIAGNOSIS

• The diagnosis of HIV infection depends on demonstration of antibodies to HIV & or the direct detection of HIV or one of its components.

• Antibodies to HIV generally appear in the circulation 3-12 weeks following infection.

P24 antigen capture assay:

• They detect viral protein p24 in the blood of HIV infected individuals where it exists as free antigen or complexed to anti-p 24 antibodies.

• During the first week of infection there is a brisk rise in p24 antigen levels. Once the antibodies develop they decline.

ELISA

• Standard screening test for HIV is ELISA (Sensitivity of >99.5%.).

• ELISA is an extremely sensitive test, it is not optimal with regard to specificity.

• Factors associated with false positive test are antibodies to class II antigens (such as may be seen following pregnancy, blood transfusion or transplantation, auto antibodies, hepatic disease, acute viral infection, recent influenza vaccination).

• These people must be subjected to confirmatory test by western blot.

WETERN BLOT

• Western blot is based on the fact that multiple HIV antigen of different, well characterized molecular weight elicit the production of specific antibodies,& they can be separated based on molecular weight. The antibodies to each component can be detected as discrete bands on the western blot.

• Western blot is considered positive if antibodies exist to two of the three HIV proteins: p24, gp41 & gp 120/160.

Graph showing the relationship between CD4 counts and viral load during the course of disease

Attribute : "Hiv-timecourse" by Jurema Oliveira - Based on Figure 1 in Pantaleo, G et al. (February 1993). "New concepts in the immunopathogenesis of human immunodeficiency virus infection". New England Journal of Medicine 328 (5): 327-335. PMID 8093551.Also available via Figure 4 in The relationship between the human immunodeficiency virus and the acquired immunodeficiency syndrome. US National Institute of Allergy and Infectious Diseases Retrieved on November 3, 2009.Supporting data for this disease course is available in Piutak, M et al. (March 1993). "High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR". Science 259 (510): 1749-54. PMID 8096089.. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Hiv-timecourse.png#mediaviewer/File:Hiv-timecourse.png

CD4+ T CELL COUNTS

• They are generally accepted as the best indicator of immediate state of immunologic competence of patient with HIV infection.

• Persons with CD4+ T cell counts <200/μL are at high risk of developing P. jiroveci.

• Persons with CD4+ Tcells count <50/μL are at high risk for CMV, Mycobacterium avium complex, T. gondii.

• CD4+ T cell counts should be measured at the time of diagnosis & then every 3-6 months.

• If CD4+ T cell count is <200/μL prophylaxis for P. jiroveci should be started.

• If CD4+ Tcell count is <50//μL primary prophylaxis for MAC is indicated.

• A CD4+ T cell percent of 15 is comparable to CD4+ T cell count of 200//μL

• In persons with hypersplenism or splenectomy & in patients on bone marrow suppressing drugs, THE CD4+ T cell percentage may be a more reliable indication of immune function.

Viral Load

• It is used a prognostic marker & for starting the HAART.

• Optimal viral suppression is defined as a viral load persistently below the level of detection < 20 -75 copies/ml.

• Plasma viral load is measured before initiation of therapy and preferably within 2-4 weeks after treatment initiation or modification.

• In patients with stable ART viral load is checked every 3-4 months.

INITIAL EVALUATION OF THE PATIENT WITH HIV INFECTION

• History & physical examination

• Routine chemistry & hematology

• AST, ALT , direct & indirect bilirubin

• Lipid profile & fasting glucose

• CD4+T COUNTS

• Two plasma HIV RNA level

• HIV resistance checking

• HLA-B5701 screening

• VDRL test

• Anti toxoplasma antibody titer

• PPD skin test

• Mini mental status examination

• Serologies for hepatitis A,B &C

• Immunisation with pneumococcal polysaccharide, influenza as indicated

• Immunization with hepatitis A &B if negative

• Counseling regarding natural history & transmission

• Help contacting others who might be infected.

ANTIRETROVIRAL THERAPY

INDICATIONS

• All patients with AIDS defining illness

• All patients with CD4 <200 cells/mm³.

• CD4 200 to 350 cells/mm³ should be offered HAART

• HIV RNA >10000 copies/ml

• Pregnancy

HAART REGIMEN

• NNRTI BASED REGIMEN (1NNRTI + 2 NRTI)

• Efavirenz 600mg HS + Tenofovir 300mg + Emtricitabin 200mg (Single Tab HS)

• Efavirenz 600mg HS (after 2 hrs of food) + Lamivudine 150mg BD + Zidovudine 300mg BD. (T. Lazid E, T. Duovir E) or Stavudine/didanosine

• Nevirapine 200mg OD for 1^st 14 days, then 200mg BD + Lamivudine+ Zidovudine 300mg BD or stavudine/didanosine

• PI BASED REGIMEN

  • Single PI or Ritonavir boosted PI regime + 2NRTI is used

Updated on 1/1/2015

Reference

• Harrison 18^th edition

• Davidson