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ACQUIRED IMMUNE
DEFICIENCY
SYNDROME
SUDESHNA
BANERJEE
M.SC(N) 2ND YEAR
Definition:
â€ĸ 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.
Human Immunodeficiency Virus
AIDS was first described in 1981.
īƒŧ HIV-1 was isolated in 1984, and
HIV-2 in 1986.
īƒŧ Belongs to the lentivirus
subfamily of the retroviridae (Retrovirus).
īƒŧ Enveloped RNA virus, 120nm in diameter.
Structure of HIV:
Transmission
HIV in Body Fluids
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
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
Clinical patterns
Rapid progressors or rapid disease course
(15–25%):
Onset of AIDS occurs within the first few months of
Median survival time-6–9 months (if left untreated)
Opportunistic infections and neurological
are common
In resource-poor countries, most of HIV infected
will have this rapidly progressing disease
Short-term progressors or slower
progression(60–80%)
Median survival time-6 years
Slower progression
HIV related illnesses develop by 3–4 years progressing
AIDS by 6–7 years
Present clinically with
ī‚§ Recurrent bacterial infections
ī‚§ Failure to thrive
ī‚§ Lymphoid interstitial pneumonitis (LIP).
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
cytotoxic T lymphocytic responses, host genetic
and infection with defective virus.
WHO clinical staging
Contâ€Ļ
Clinical
stage 1
Clinical stage
2
Clinical stage
3
Clinical
stage 4
Asymptomatic
Persistent
generalised
lymphadenopa
thy
â€ĸ Unexplained persistent
hepatosplenomegaly
â€ĸ Papular pruritic
eruptions
â€ĸ Fungal nail infections
â€ĸ Angular chelitis
â€ĸ Extensive molluscum
contagiosum
â€ĸ Recurrent oral
ulcerations
â€ĸ Herpes zoster
â€ĸ Chronic URTI
â€ĸ Unexplained moderate
malnutrition
â€ĸ Unexplained persistent
diarrhea
â€ĸ Unexplained persistent
fever (>37.5C for more
than 1 month)
â€ĸ Persistent oral
candidiasis
â€ĸ Oral hairy leukoplakia
â€ĸ Pulmonary TB
â€ĸ Severe recurrent
bacterial pneumonia
Extrapulmonary TB
â€ĸ Kaposi sarcoma
â€ĸ CNS toxoplasmosis
â€ĸ HIV encephalopathy
â€ĸ CMV retinitis
â€ĸ Symptomatic HIV-
associated
nephropathy or
HIV-associated
cardiomyopathy.
Diagnostic tests for HIV
Enzyme-linked immune-sorbent assay (ELISA):
īƒŧ Primary screening test
Western blot
Indirect Immunofluorescence assay:
īƒŧ Confirms the presence of HIV antibodies.
Detection of viral antigens; p24 antigen:
īƒŧ Used to evaluate acute symptomatic HIV disease & as a screening test
in blood donors to reduce the “window period”
Viral nucleic acid detection: PCR & branched-chain DNA assays:
īž Monitor HIV progression & effectiveness of antiretroviral therapy.
OraSure oral test:
īž 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:
īž Alternative to blood drawing.
īž Lower sensitivity and specificity than oral mucosal transudate testing.
Diagnosis of TB in HIV:
â€ĸ Frequently negative sputum smears
â€ĸ Atypical radiographic findings
â€ĸ 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.
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
Management of HIV
Prophylaxis to prevent First episode of Opportunistic disease among adults
infected with HIV:
īļPneumocystis jiroveci : Trimethoprim-sulfamethoxazole;1
double strength tablet by mouth, daily or TMP-SMZ 1 single
strength tablet by mouth daily.
īļMycobacterium tuberculosis: Isoniazid, 300 mg by mouth plus
pyridoxine
īļToxoplasma gondii: TMP-SMZ, 1 double strength orally daily.
īļVaricella-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.
īļStreptococcus pneumoniae: 23-valent polysaccharide
vaccine, 0.5 ml IM.
īļHepatitis B virus: Hepatitis B vaccine: 3 doses
īļMycobacterium avium complex: Azithromycin, 1200 mg by
mouth weekly or clarithromycin, 500 mg by mouth twice
daily.
HIV prevention ART drugs
īąReverse-transcriptase inhibitors (RTIs):
Block RT's enzymatic function and prevent completion of
synthesis of the double-stranded viral DNA, thus preventing
HIV from multiplying.
īƒ˜ Zidovudine
īƒ˜ Stavudine
īƒ˜ Lamivudine
īƒ˜ Abacavir
īƒ˜ Tenofovir
īąNon-nucleoside reverse-transcriptase inhibitors (NNRTIs)
īƒ˜ Nevirapine
īƒ˜ Efavirenz
īą Integrase inhibitors
Block the action of integrase, a viral enzyme that inserts the
viral genome into the DNA of the host cell.
īƒ˜ Raltegravir
īƒ˜ Elvitegravir
īƒ˜ Dolutegravir
â€ĸ
īą Entry/fusion inhibitors
īƒŧ Interferes with the binding, fusion and entry of an
HIV virion to a human cell
īƒŧ Used in combination therapy for the treatment
of HIV infection
īƒ˜ Maraviroc
īƒ˜ Vicriviroc
īƒ˜ Cenicriviroc
īƒ˜ Ibalizumab
īƒ˜ Enfuvirtide
īąProtease inhibitors
īƒŧ Prevent viral replication by selectively binding to
viral proteases.
īƒŧ Blocking proteolytic cleavage of protein precursors that are
necessary for the production of infectious viral particles.
īƒ˜ Ritonavir (RTV)
īƒ˜ Indinavir (IDV)
īƒ˜ Saquinavir (SQV)
īƒ˜ Nelfinavir (NFV)
īąMaturation Inhibitors
īƒ˜ Bevirimat
īƒŧ Inhibits the final stage in Gag processing
o Conversion of capsid precursor to capsid protein
īƒŧ Active against resistant HIV strains
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
ART regimens for pregnant
women
Combination ofâ€Ļ
īƒ˜Zidovudine (AZT)
īƒ˜Lamivudine (3TC)
īƒ˜Nevirapine (NVP) or Efavirenz (EFV) (EFV-based
regimen should not be newly initiated during the
first trimester of pregnancy)
Recommended regimen for pregnant women
who are NOT ELIGIBLE for ART, but for
preventing MTCT isâ€Ļ
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
Breastfeeding
īƒŧ Important modality of transmission of HIV infection.
īƒŧ Risk of infection highest in the early months of Breast
feeding.
â€ĸ Increase Risks:
– Detectable levels of HIV in breast milk
– Presence of mastitis
– Low maternal CD4+ T cell count
Standard precautions
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
Droplet Precautions:
īƒŧ Use a private room, if available. Door may remain open.
īƒŧ Wear a mask when working within 3 feet of the patient.
īƒŧ Transport the patient out of the room only when necessary,
and place a surgical mask on the patient if possible.
Contact Precautions:
īƒŧ Place the patient in a private room available.
īƒŧ 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.
īƒŧ 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.
īƒŧ Limit movement of the patient out of the room.
Nursing diagnosis
īƒ˜ Disturbed thought processes related to shortened attention span,
impaired memory, confusion, and disorientation associated with HIV
encephalopathy.
īƒ˜ Pain related to impaired perianal skin integrity secondary to diarrhea
and peripheral neuropathy.
īƒ˜ Imbalanced nutrition, less than body requirements, related to
decreased oral intake.
īƒ˜ Social isolation related to stigma of the disease, withdrawal of
support systems, isolation procedures, and fear of infecting others.
Recent advances
HAART (The Highly Active Antiretroviral
Therapy):
-- 2 NRTI + 1 NNRTI
PI containing regimens
-- 2 NRTI + PI OR NRTI + NNRTI + PI
īļ The most recent guidelines recommend that HAART to be offered to
patients with a CD4 count of less than 350 cells/mm3 or a plasma HIV-RNA
(viral load) level greater than 55,000 copies/mL.
īļ The use of HAART commonly results in an increase in CD4 count of 100-240
cells/mm3. This increase may return the patient’s number of cells to the
normal range; this is known as immune reconstruction.
Pox- vector
and protein
vaccine
combination
Advances Stem cell
Approach
Advances Gene Therapy
Advances Shock and Kill approach
AIDS/HIV

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AIDS/HIV

  • 2. Definition: â€ĸ 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. īƒŧ HIV-1 was isolated in 1984, and HIV-2 in 1986. īƒŧ Belongs to the lentivirus subfamily of the retroviridae (Retrovirus). īƒŧ Enveloped RNA virus, 120nm in diameter.
  • 6. HIV in Body Fluids
  • 7.
  • 8. 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
  • 9. 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
  • 10.
  • 11. Clinical patterns Rapid progressors or rapid disease course (15–25%): Onset of AIDS occurs within the first few months of Median survival time-6–9 months (if left untreated) Opportunistic infections and neurological are common In resource-poor countries, most of HIV infected will have this rapidly progressing disease
  • 12. Short-term progressors or slower progression(60–80%) Median survival time-6 years Slower progression HIV related illnesses develop by 3–4 years progressing AIDS by 6–7 years Present clinically with ī‚§ Recurrent bacterial infections ī‚§ Failure to thrive ī‚§ Lymphoid interstitial pneumonitis (LIP).
  • 13. 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 cytotoxic T lymphocytic responses, host genetic and infection with defective virus.
  • 15. Contâ€Ļ Clinical stage 1 Clinical stage 2 Clinical stage 3 Clinical stage 4 Asymptomatic Persistent generalised lymphadenopa thy â€ĸ Unexplained persistent hepatosplenomegaly â€ĸ Papular pruritic eruptions â€ĸ Fungal nail infections â€ĸ Angular chelitis â€ĸ Extensive molluscum contagiosum â€ĸ Recurrent oral ulcerations â€ĸ Herpes zoster â€ĸ Chronic URTI â€ĸ Unexplained moderate malnutrition â€ĸ Unexplained persistent diarrhea â€ĸ Unexplained persistent fever (>37.5C for more than 1 month) â€ĸ Persistent oral candidiasis â€ĸ Oral hairy leukoplakia â€ĸ Pulmonary TB â€ĸ Severe recurrent bacterial pneumonia Extrapulmonary TB â€ĸ Kaposi sarcoma â€ĸ CNS toxoplasmosis â€ĸ HIV encephalopathy â€ĸ CMV retinitis â€ĸ Symptomatic HIV- associated nephropathy or HIV-associated cardiomyopathy.
  • 16. Diagnostic tests for HIV Enzyme-linked immune-sorbent assay (ELISA): īƒŧ Primary screening test Western blot Indirect Immunofluorescence assay: īƒŧ Confirms the presence of HIV antibodies. Detection of viral antigens; p24 antigen: īƒŧ Used to evaluate acute symptomatic HIV disease & as a screening test in blood donors to reduce the “window period”
  • 17. Viral nucleic acid detection: PCR & branched-chain DNA assays: īž Monitor HIV progression & effectiveness of antiretroviral therapy. OraSure oral test: īž 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: īž Alternative to blood drawing. īž Lower sensitivity and specificity than oral mucosal transudate testing.
  • 18. Diagnosis of TB in HIV: â€ĸ Frequently negative sputum smears â€ĸ Atypical radiographic findings â€ĸ 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.
  • 19. 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
  • 20.
  • 21. Management of HIV Prophylaxis to prevent First episode of Opportunistic disease among adults infected with HIV: īļPneumocystis jiroveci : Trimethoprim-sulfamethoxazole;1 double strength tablet by mouth, daily or TMP-SMZ 1 single strength tablet by mouth daily. īļMycobacterium tuberculosis: Isoniazid, 300 mg by mouth plus pyridoxine īļToxoplasma gondii: TMP-SMZ, 1 double strength orally daily.
  • 22. īļVaricella-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. īļStreptococcus pneumoniae: 23-valent polysaccharide vaccine, 0.5 ml IM. īļHepatitis B virus: Hepatitis B vaccine: 3 doses īļMycobacterium avium complex: Azithromycin, 1200 mg by mouth weekly or clarithromycin, 500 mg by mouth twice daily.
  • 23. HIV prevention ART drugs īąReverse-transcriptase inhibitors (RTIs): Block RT's enzymatic function and prevent completion of synthesis of the double-stranded viral DNA, thus preventing HIV from multiplying. īƒ˜ Zidovudine īƒ˜ Stavudine īƒ˜ Lamivudine īƒ˜ Abacavir īƒ˜ Tenofovir
  • 24. īąNon-nucleoside reverse-transcriptase inhibitors (NNRTIs) īƒ˜ Nevirapine īƒ˜ Efavirenz īą Integrase inhibitors Block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. īƒ˜ Raltegravir īƒ˜ Elvitegravir īƒ˜ Dolutegravir â€ĸ
  • 25. īą Entry/fusion inhibitors īƒŧ Interferes with the binding, fusion and entry of an HIV virion to a human cell īƒŧ Used in combination therapy for the treatment of HIV infection īƒ˜ Maraviroc īƒ˜ Vicriviroc īƒ˜ Cenicriviroc īƒ˜ Ibalizumab īƒ˜ Enfuvirtide
  • 26. īąProtease inhibitors īƒŧ Prevent viral replication by selectively binding to viral proteases. īƒŧ Blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles. īƒ˜ Ritonavir (RTV) īƒ˜ Indinavir (IDV) īƒ˜ Saquinavir (SQV) īƒ˜ Nelfinavir (NFV)
  • 27. īąMaturation Inhibitors īƒ˜ Bevirimat īƒŧ Inhibits the final stage in Gag processing o Conversion of capsid precursor to capsid protein īƒŧ Active against resistant HIV strains
  • 28. 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
  • 29. ART regimens for pregnant women Combination ofâ€Ļ īƒ˜Zidovudine (AZT) īƒ˜Lamivudine (3TC) īƒ˜Nevirapine (NVP) or Efavirenz (EFV) (EFV-based regimen should not be newly initiated during the first trimester of pregnancy)
  • 30. Recommended regimen for pregnant women who are NOT ELIGIBLE for ART, but for preventing MTCT isâ€Ļ 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
  • 31. Breastfeeding īƒŧ Important modality of transmission of HIV infection. īƒŧ Risk of infection highest in the early months of Breast feeding. â€ĸ Increase Risks: – Detectable levels of HIV in breast milk – Presence of mastitis – Low maternal CD4+ T cell count
  • 33. 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
  • 34. Droplet Precautions: īƒŧ Use a private room, if available. Door may remain open. īƒŧ Wear a mask when working within 3 feet of the patient. īƒŧ Transport the patient out of the room only when necessary, and place a surgical mask on the patient if possible.
  • 35. Contact Precautions: īƒŧ Place the patient in a private room available. īƒŧ 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. īƒŧ 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. īƒŧ Limit movement of the patient out of the room.
  • 36. Nursing diagnosis īƒ˜ Disturbed thought processes related to shortened attention span, impaired memory, confusion, and disorientation associated with HIV encephalopathy. īƒ˜ Pain related to impaired perianal skin integrity secondary to diarrhea and peripheral neuropathy. īƒ˜ Imbalanced nutrition, less than body requirements, related to decreased oral intake. īƒ˜ Social isolation related to stigma of the disease, withdrawal of support systems, isolation procedures, and fear of infecting others.
  • 37. Recent advances HAART (The Highly Active Antiretroviral Therapy): -- 2 NRTI + 1 NNRTI PI containing regimens -- 2 NRTI + PI OR NRTI + NNRTI + PI īļ The most recent guidelines recommend that HAART to be offered to patients with a CD4 count of less than 350 cells/mm3 or a plasma HIV-RNA (viral load) level greater than 55,000 copies/mL. īļ The use of HAART commonly results in an increase in CD4 count of 100-240 cells/mm3. This increase may return the patient’s number of cells to the normal range; this is known as immune reconstruction.
  • 38.
  • 42. Advances Shock and Kill approach