1. AIDS Dr. Gerrard Uy

2. AIDS Definition: – According to the CDC classification system, any HIV infected individual with a CD4 T cell count of <200/uL has AIDS, regardless of the presence of symptoms or opportunistic diseases

3. AIDS Etiologic agent: – HIV (Human Immunodeficiency Virus) – 2 types: HIV 1 and HIV 2 – Most common cause: HIV 1 – Both HIV1 and HIV2 are zoonotic infection

4. Classification categorizes persons on the basis of clinical conditions associated with HIV infection and CD4+ T lymphocyte counts

5. Replication and CD-4 involvement

6. Classification Category A – Asymptomatic HIV infection – Persistent generalized lymphadenopathy – Acute (primary) HIV infection with accompanying illness or history of acute HIV infection

7. Category B – Bacillary angiomatosis Candidiasis, – oropharyngeal (thrush) – Candidiasis, vulvovaginal; persistent, frequent, or poorly responsive to therapy – Cervical dysplasia – Constitutional symptoms >1 month – Hairy leukoplakia – oral Herpes zoster (shingles), involving at least two distinct episodes or more than one dermatome – Idiopathic thrombocytopenic purpura – Listeriosis – Pelvic inflammatory disease, particularly if complicated by tuboovarian abscess – Peripheral neuropathy

8. Category C: Conditions listed in the AIDS surveillance case definition. – Candidiasis of the bronchi, trachea, or lungs – Invasive cervical cancer – Coccidoidomycosis – CMV retinitis – HIV encephalopathy – Histoplasmosis – Kaposi’s sarcoma – Lymphoma, Burkitts – Mycobacterium avium complex infection – Mycobacterium tuberculosis – Pneumocystis jiroveci – Recurrent pneumonia

9. Transmission transmitted by both homosexual and heterosexual contact; by blood and blood products; and by infected mothers to infants either intrapartum, perinatally, or via breast milk

10. Sexual Transmission HIV infection is predominantly a sexually transmitted disease (STD) worldwide Mostly male to male contact in US heterosexual is more common in developing countries male circumcision is associated with a lower risk of HIV infection among men

11. Sexual Transmission concentrate in the seminal fluid, esp. in genital inflammatory states such as urethritis and epididymitis, conditions closely associated with other STD cervical smears and vaginal fluid strong association of HIV transmission with receptive anal intercourse More male to female than female to male

12. Other sexual issues Studies have found that male to female HIV transmission is usually more efficient than the opposite Oral sex is a much less efficient mode of transmission of HIV than is receptive anal intercourse association of alcohol consumption and illicit drug use with unsafe sexual behavior leads to an increased risk of sexual transmission of HIV

13. Transmission by blood and blood products receive HIV-tainted blood transfusions transplanted tissue sharing injection paraphernalia such as needles, syringes, the water in which drugs are mixed Do not require IV (intravenous pucture), even SC and IM can transmit Among IDUs, infection increases with duration, frequency, and the number of partners

14. Transmission by blood and blood products The risk for HIV infection in the US is 1 in 1.5M donations Despite the best efforts in science one cannot completely eliminate the risk of transufion related transmission of HIV since current technology cannot detect HIV RNA for the first 1-2 weeks following infection

15. Occupational Transmission: Health workers small, but definite, occupational risk 600,000–800,000 health care workers are stuck with needles in the US risk of HIV transmission following skin puncture from a needle or a sharp object that was contaminated with blood from a person with documented HIV infection is ~0.3% and after a mucous membrane exposure it is 0.09%

16. Occupational Transmission: Health workers The following fluids are also potentially infectious: – CSF, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, amniotic fluid Not considered infectious: – Feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomitus (unless they are visibly bloody)

17. Maternal-Fetal/Infant Transmission during pregnancy, during delivery, or by breast-feeding HIV can be transmitted to the fetus as early as the first and second trimester most commonly in the perinatal period risk of HIV infection via breast-feeding is highest in the early months of breast-feeding

18. Maternal-Fetal/Infant Transmission Factors involved in increasing risk of transmission: – Low maternal CD4 count – Prolonged interval between membrane rupture and delivery – Presence of chorioamnionitis during delivery – STD during pregnancy – Cigarette smoking – Obstetrical procedures

19. Diagnosis of HIV Infection Depends on the demonstration of antibodies to HIV and/or direct detection of HIV or one of its components Antibodies to HIV generally appear in the circulation 2-12 weeks following infection ELISA – standard blood screening test – Sensitive but not specific – Factors associated with false positive results: Autoantibodies, hepatic disease, recent influenza vaccination, and acute viral infections

20. Diagnosis of HIV Infection Western blot – most commonly used confirmatory test – Compares specific antigens and their molecular weights to detect HIV gene products While Western blot is an excellent confirmatory test, it is a poor screening test Once HIV is confirmed, next step is to do a CD4 T cell count

21. Diagnosis of HIV Infection CD4 T cell count is the laboratory test accepted as the best indicator of the immediate state of immunologic competence CD4 < 200/uL = high risk of disease from P. jiroveci CD4 <50/uL = high risk of disease from CMV, MAC, T. gondii Patients with HIV should have their CD4 counts monitored every 3-6 months CD4 < 350/uL is and indication for consideration of initiating ARV therapy

22. Clinical Manifestations Acute HIV Syndrome (50-70%) – 3–6 weeks after primary infection – fever, skin rash, pharyngitis, and myalgia – usually persist for one to several weeks and gradually subside

23. Clinical Manifestations The Asymptomatic Stage—Clinical Latency – median time for untreated patients is ~10 years – active virus replication is ongoing and progressive – Ave. rate of CD4+ T cell decline is ~50/uL per year – <200/uL – level at which risk for opportunistic infections is high

24. Clinical Manifestations Symptomatic Disease – can appear at any time – diagnosis of AIDS is made in anyone with HIV infection and a CD4+ T cell count <200/uL – anyone with HIV infection who develops one of the HIV-associated diseases considered to be indicative of a severe defect in cell-mediated immunity

25. AIDS - symptomatic Pneumocystis jiroveci – pneumonia MTB Toxoplasmosis – Varicella Cryptococcus neoformans – cryptococcosis Histoplasma capsulatum

27. Management Combination antiretroviral therapy (ART), or highly active antiretroviral therapy (HAART), is the cornerstone of management of patients Reverse Transcriptase Inhibitors (Ziduvudine) Protease Inhibitors (Saquinavir) Entry Inhibitors Suppression of HIV replication is an important component in prolonging life