AIDS/HIV

ACQUIRED IMMUNE DEFICIENCY SYNDROME

1. ACQUIRED IMMUNE DEFICIENCY SYNDROME SUDESHNA BANERJEE M.SC(N) 2 ND YEAR HFCON

2. Definition: Acquired immunodeficiency syndrome (AIDS) is defined as the occurrence of life threatening opportunistic infections, malignancies, neurological diseases and other specific illnesses in patients with HIV infection and CD4 counts <200 cells/mm3 or <14% CD4.

3. Human Immunodeficiency Virus AIDS was first described in 1981. HIV-1 was isolated in 1984, and HIV-2 in 1986. Belongs to the lentivirus subfamily of the retroviridae (Retrovirus). Enveloped RNA virus, 120nm in diameter.

4. Structure of HIV :

5. Transmission

6. HIV in Body Fluids

7. Pathophysiology Due to etiological factors HIV virus binds to CD4 receptors on surface of T cells RNA enters the human cell RNA transcribes DNA by enzyme Reverse Transcriptase Integrase inserts viral DNA into Host DNA

8. Viral DNA is transcribed into mRNA mRNA is translated into protein – polyprotein Polyprotein converts into genome and becomes permanent part of cell’s genetic structure Host cell is killed as viruses are released and budding process starts Destruction of T- helper cells and immune response declines causing signs & symptoms

9. Immune defects in AIDS

10. Clinical patterns Rapid progressors or rapid disease course (15–25 %): Onset of AIDS occurs within the first few months of life Median survival time-6–9 months (if left untreated) Opportunistic infections and neurological manifestations are common In resource-poor countries, most of HIV infected newborns will have this rapidly progressing disease

11. Short-term progressors or slower progression(60–80 %) Median survival time-6 years Slower progression HIV related illnesses develop by 3–4 years progressing to AIDS by 6–7 years Present clinically with  Recurrent bacterial infections  Failure to thrive  Lymphoid interstitial pneumonitis (LIP ).

12. Long-term progressors or long-term survivors(<5 %): No clinical or immunological progression despite long duration of infection Normal CD4 and very low viral loads Possible mechanisms for this delay in disease manifestations include effective humoral immunity and/or cytotoxic T lymphocytic responses, host genetic factors, and infection with defective virus.

13. WHO clinical staging

14. Cont … Clinical stage 1 Clinical stage 2 Clinical stage 3 Clinical stage 4 Asymptomatic Persistent generalised lymphadenopathy • Unexplained persistent hepatosplenomegaly • Papular pruritic eruptions • Fungal nail infections • Angular chelitis • Extensive molluscum contagiosum • Recurrent oral ulcerations • Herpes zoster • Chronic URTI • Unexplained moderate malnutrition • Unexplained persistent diarrhea • Unexplained persistent fever (>37.5C for more than 1 month) • Persistent oral candidiasis • Oral hairy leukoplakia • Pulmonary TB • Severe recurrent bacterial pneumonia Extrapulmonary TB • Kaposi sarcoma • CNS toxoplasmosis • HIV encephalopathy • CMV retinitis • Symptomatic HIV-associated nephropathy or HIV-associated cardiomyopathy.

15. Diagnostic tests for HIV Enzyme-linked immune-sorbent assay (ELISA): Primary screening test Western blot Indirect Immunofluorescence assay: Confirms the presence of HIV antibodies. Detection of viral antigens; p24 antigen: Used to evaluate acute symptomatic HIV disease & as a screening test in blood donors to reduce the “window period”

16. Viral nucleic acid detection: PCR & branched-chain DNA assays: Monitor HIV progression & effectiveness of antiretroviral therapy . OraSure oral test: The patient places collection pad between cheek and gum. A health care professional then places pad in preservative solution and mails to a central laboratory. Initial studies reports a sensitivity and specificity >99 %. Calypte urine testing: Alternative to blood drawing. Lower sensitivity and specificity than oral mucosal transudate testing .

17. Diagnosis of TB in HIV: • Frequently negative sputum smears • Atypical radiographic findings • Resemblance to other opportunistic pulmonary infections like pneumonia In a person infected with HIV, the presence of other infections, including TB, allows HIV to multiply more quickly. This may result in more rapid progression of HIV infection. HIV infected persons have approximately an 8 ‐ times greater risk of TB than persons without HIV infection.

18. HIV Testing Who to test When to test Pregnant women and male partners At first antenatal care visit Re-test in third trimester or peripartum Offer partner testing Infants and children <18 months old At 4–6 weeks for all whose mothers are HIV Positive or status uncertain; Final status after 18 months and/or when breastfeeding ends Children Establish HIV status for all health contacts Tell their HIV status & parents or caregiver’s status Adolescents Integrate into all health care encounters. Annually if sexually active; with new sexual partners

19. Management of HIV Prophylaxis to prevent First episode of Opportunistic disease among adults infected with HIV: Pneumocystis jiroveci : Trimethoprim-sulfamethoxazole ; 1 double strength tablet by mouth, daily or TMP-SMZ 1 single strength tablet by mouth daily . Mycobacterium tuberculosis: Isoniazid , 300 mg by mouth plus pyridoxine Toxoplasma gondii : TMP-SMZ , 1 double strength orally daily .

20. Varicella-zoster virus: Varicella-zoster immune globulin (VZIG), 5 vials (1.25 ml each), IM, administered less than 96 hours after exposure, ideally in less than 48 hours. Streptococcus pneumoniae : 23-valent polysaccharide vaccine, 0.5 ml IM. Hepatitis B virus: Hepatitis B vaccine: 3 doses Mycobacterium avium complex: Azithromycin, 1200 mg by mouth weekly or clarithromycin, 500 mg by mouth twice daily .

21. HIV prevention ART drugs Reverse-transcriptase inhibitors (RTIs): Block RT's enzymatic function and prevent completion of synthesis of the double-stranded viral DNA, thus preventing HIV from multiplying. Zidovudine Stavudine Lamivudine Abacavir Tenofovir

22. Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) Nevirapine Efavirenz Integrase inhibitors Block the action of  integrase , a viral enzyme that inserts the viral genome into the DNA of the host cell . Raltegravir Elvitegravir Dolutegravir  

23. Entry/fusion inhibitors Interferes with the binding, fusion and entry of an HIV  virion  to a human cell Used in combination therapy for the treatment of HIV  infection Maraviroc Vicriviroc Cenicriviroc Ibalizumab   Enfuvirtide

24. Protease inhibitors Prevent viral replication by selectively binding to viral proteases.  Blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles. Ritonavir (RTV) Indinavir (IDV) Saquinavir (SQV) Nelfinavir (NFV)

25. Maturation Inhibitors Bevirimat Inhibits the final stage in Gag processing Conversion of capsid precursor to capsid protein Active against resistant HIV strains

26. CD4 Cell count ART Regimen ATT Regimen CD4 < 50/ mm3 Start immediately Start immediately CD4 < 250/ mm3 Start as soon as ATT tolerated (2-4 weeks) Start immediately CD4 250 -350/ mm3 Start after the initial phase (8 weeks) of TB treatment completed Start immediately CD4 >350/ mm3 Re-evaluate with repeat CD4 count after TB treatment Start immediately Treatment regimen for TB

27. ART regimens for pregnant women Combination of… Zidovudine (AZT) Lamivudine ( 3TC) Nevirapine (NVP) or Efavirenz (EFV) (EFV-based regimen should not be newly initiated during the first trimester of pregnancy)

28. Recommended regimen for pregnant women who are NOT ELIGIBLE for ART, but for preventing MTCT is … To start ART as early as 14 weeks gestation OR as soon as possible (when women present late in pregnancy, in labor or at delivery) OPTION A OPTION B For pregnant women Antepartum daily AZT Single dose NVP at onset of labor AZT+3TC during labor or delivery Twice daily AZT+ 3TC for 7 days in postpartum period For pregnant women Triple ART from 14 weeks of gestation until 1week after stopping breast feeding(now stopped) Recommended regimens include:- AZT+3TC+LPV/r AZT+ 3TC+ ABC AZT+3TC+EFV TDF+3TC+ EFV

29. Breastfeeding Important modality of transmission of HIV infection. Risk of infection highest in the early months of Breast feeding. Increase Risks: – Detectable levels of HIV in breast milk – Presence of mastitis – Low maternal CD4+ T cell count

30. Standard precautions

31. Transmission-Based precautions Airborne precautions: Place the patient in private room that has monitored negative pressure. Keep the door closed. Use respiratory protection when entering room of patient

32. Droplet Precautions: Use a private room, if available. Door may remain open. Wear a mask when working within 3 feet of the patient. Transport the patient out of the room only when necessary, and place a surgical mask on the patient if possible.

33. Contact Precautions: Place the patient in a private room available.   Change gloves after having contact with infective material. Remove gloves before leaving the patient environment, and wash hands with an antimicrobial or waterless antiseptic agent.   Wear a gown if contact with infections agent is likely or patient has diarrhea, an ileostomy, colostomy, or wound drainage not contained by a dressing. Limit movement of the patient out of the room .

34. Nursing diagnosis Disturbed thought processes related to shortened attention span, impaired memory, confusion, and disorientation associated with HIV encephalopathy . Pain related to impaired perianal skin integrity secondary to diarrhea and peripheral neuropathy . Imbalanced nutrition, less than body requirements, related to decreased oral intake . Social isolation related to stigma of the disease, withdrawal of support systems, isolation procedures, and fear of infecting others .

35. Recent advances HAART (The Highly Active Antiretroviral Therapy ): -- 2 NRTI + 1 NNRTI PI containing regimens -- 2 NRTI + PI OR NRTI + NNRTI + PI The most recent guidelines recommend that HAART to be offered to patients with a CD4 count of less than 350 cells/mm 3 or a plasma HIV-RNA (viral load) level greater than 55,000 copies/ mL. The use of HAART commonly results in an increase in CD4 count of 100-240 cells/mm 3 . This increase may return the patient’s number of cells to the normal range; this is known as immune reconstruction .

36. Pox- vector and protein vaccine combination

37. Advances Stem cell Approach

38. Advances Gene Therapy

39. Advances Shock and Kill approach