Comprehensive information about HIV AIDS in. also includes latest protocols and guidelines

1. HIV-AIDS
-Dr Manish Deshmukh
Junior Resident (Gen Medicine)
GMC Nagpur

2. HISTORY
 1st case came from US in 1981
 HIV isolated in 1983
 Initial reporting symptom on presentation were
P.Jiroveci Pneumonia & Kaposi’s Sarcoma
 In INDIA 1st HIV Positive case detected in CSW in
Tamilnadu (1986)

3. EPIDEMIOLOGY
 Approx. 38 million in world are infected with HIV in
2019
 At the end of June 2020,26 million people were
accessing ART
 India is 3rd largest epidemic in world,2.35 million
people living with HIV out of 1.345 million receiving
ART

4. DEFINITION
 2006 WHO Definitions
 Advanced HIV infection (most relevant for
patient management)
• WHO Clinical Stage 3 or 4
OR
• CD4 count < 350cells/mm3
 AIDS
• WHO Clinical Stage 4
OR
• CD4 Count < 200cells/mm3

5.  In INDIA for Person >12 yrs AIDS is Defined as,
1. Two +ve test for HIV Infection by ERS (ELISA,RAPID,SIMPLE)
AND
2. Any one of the following
a. significant weight loss(>10% of body wt) within 1 month (cause other
than
HIV not known)
And
Chronic Diarrhoea >1 month or prolonged fever >1 month
b. TB – extensive PTB, Disseminated, Miliary, Extrapulmnary TB
c. Neurological Impairment (cause other than HIV not known)
d. Oesophageal Candidiasis
e. Life threatening Recurrent Pneumonia
f. Kaposi's Sarcoma
g. Other Condition : Cryptococcal Meningitis, Toxoplasmosis,CMV
retinitis

6. CHARACTERISTICS
 HIV is ssRNA Human Retrovirus possesses RNA dependent
DNA Polymerase
 m/c cause of HIV in World – HIV 1 but HIV 2 is m/c in west
Africa
 Causes infection & depletion of CD4+T cells
 Sev. Immunosuppression leads to Opportunistic infection,
Sec. Neoplasm, Neurologic Manifestation

7. MORPHOLOGY & STRUCTURE
 Spherical, enveloped RNA retrovirus of 90-120mm in diameter
 Envelop:- main component for binding to CD4+ T cells principal
antigen – gp41, gp120
 Nuclocapsid:-
• Outer Icosahedral shell :- principal antigen is p18
• Inner Icosahedral shell :- core antigen p24
(Antigens and Antibodies against p24 are used in diagnosis by ELISA )
 RNA:- constitutes the genome
• Polymerase antigen- p31, p51, p66

9. TRANSMISSION
1. Sexual Transmission
• m/c mode of transmission(Heterosexual>Homosexual)
• Increased transmission with coexisting STDs (Syphilis,
Chancroid & Herpes)
• Virus present in vaginal and cervical secretions in females &
semen in Men
• Transmission depends upon integrity of exposed site ,type&
Volume of fluid, level of viremia
2. Parenteral Transmission
• IV Drug Abusers
• Transfusion of Blood & Blood Products
• Splash Of Blood Products on Mucosa

10. 3. Fetal Transmission
• Transmission occurs at various stages
4. Health Care worker Transmission
• Extremely rare
• Occurs after accidental needle stick injury or exposure of nonintact skin to
blood products
During Pregnancy Perinatal Period Breast Feeding
20-30% of Cases m/c period (50-60%) 10-20%
Can occur as early as
1st & 2nd Trimester

11. Mode of Transmission Risk of Transmission Contribution to total
no. of cases
Sexual Transmission 0.01-1.0% >80%
Mother to child
Transmission
30% 1%
Blood Transmission 90% 3-5%
HCW Transmission 0.01-1.0% 5-10%
Highest Risk Potentially Infectious Not Infectious
Blood & visible bloody
body Fluids
CSF, Synovial Fluid,
Pleural Fluid,
Pericardial Fluid,
Amniotic Fluid
Faeces, Urine, Saliva,
Sputum, Sweat, Nasal
Secretion, Tears,
Vomitus

12. HETEROSEXUAL
Blood & Blood
Products
Infected Needles &
Syringes
Homosexual
Parent to child
Not Specified

13. PATHOGENESIS
• From exposure site virus enters into blood or tissues of an
Individual.
• Virus is transported by Dendritic cells from exposure site to
regional LN where Permanent infection establishes
• This is then f/b viremia & dissemination to Lymphoid Organ
which are the main site of viral replication
• Major Targets of HIV :- Immune system & Nervous System

18. CDC CATEGORIES
Category – A
• Asymptomatic
• Primary HIV Infection
• PGL
Category – B
• Constitutional symptom: Fever (38.5 °C) or Diarrhoea > 1 month
• Bacillary angiomatosis
• Oropharyngeal candidiasis (thrush)
• Vulvovaginal candidiasis, persistent or resistant
• Pelvic inflammatory disease (PID)
• Cervical dysplasia (moderate or severe)/cervical carcinoma in situ
• Oral hairy leukoplakia
• Idiopathic thrombocytopenic purpura
• Peripheral neuropathy
• Herpes zoster (shingles), involving 2 or more episodes or 1 or more dermatomes
Category – C
• Same as WHO stage 4 with following modification
- PTB included
- Recurrent Salmonella Septicaemia

19. CLINICAL MANIFESTATION
 Acute HIV Syndrome :
• Seen in 50-60%
• Occurs after 3-6 weeks of infection and resolves spontaneously in 2-
4 weeks
• During this period, uncontrolled viral replication occurs & results in
high level of HIV (High Plasma Viremia)
• At this period patient is highly infectious
• Typical viral illness: fever, malaise, myalgia, arthralgia
• Seroconversion occurs (antibody positive by 3-7 weeks after
infection)
• Virus dissemination to lymphoid organ occurs

20.  Middle Latent Phase:
• Median time for untreated patient is 7-10years
 Symptomatic Disease/Final Crisis Phase:
1. CD4 + Count 200-500:
a. Pneumococcal pneumonia b. PTB
c. Herpes Zoster d. Kaposi's Sarcoma
e. Cryptosporidium f. Oral thrush
g. Oral Hairy Leucoplakia

23. 2. CD4 + Count <200:
a. PCP b. Candida Esophagitis
c. Toxoplasma d. Histoplasma
e. Coccidiomycosis f. Extra pulmonary TB
g. Recurrent/Disseminated Viral Herpes Simplex
h. PMLE
3. CD4 + Count <50:
a. CMV b. MAC
c. Primary CNS lymphoma

25. DISEASES IN VARIOUS SYSTEMS
 Respiratory System
 Infections :-

26.  Non-Infectious:-

27. IMPORTANT MANIFESTATION OF HIV
 m/c is manifestation is Pneumonia(m/c cause-Pneumococcal)
 m/c Opportunistic infection is TB
 Pneumocystis Jiroveci:-
• Occurs when CD4+ T cell count < 200
• Binds & damage type 1 Pneumocytes,hypertrophy of type 2
Pneumocytes
• Remains Extracellular

29.  Diagnosis:
 Treatment:
•
• (if pO2 <70mmHg;
• Add steroids)

30.  Tuberculosis:-

34.  In case where patient needs TB & HIV treatment
concurrently 1st line treatment option includes: ZDV/3TC
or d4T(stavudine)/3TC + either an NNRTI or Abacavir

36.  Cardiovascular System:-
1. DCMP
2. Pericarditis
3. Myocarditis
4. Endocarditis
5. Others
• Primary Pulmonary Hypertension
• LV Dysfunction
• Vascular Lesion

37.  Neurological Diseases:-
• Neurologic problems occur throughout the course of disease
irrespective of the immune status
• The Brain infected as early as first few weeks, low grade
inflammation continues
• Virtually all HIV infected patients have some degree of CNS
involvement :- evidence ~90% CSF abnormality even during
asymptomatic phase.
• Affects all levels of the neuraxis
• Overall,20 disease of CNS occur in ~1/3 of patients with AIDS.
But this frequency is considerably less in patients receiving ART.
• Nature of problem:-inflammatory-demyelinating-degenerative

38.  Cryptococcal meningitis :-
• m/c cause of meningitis in pts with AIDS ( CD4 < 100/mm3
• C/P:
Subacute meningoencephalitis: Headache, fever, n & v,
photophobia, stiff neck (meningeal signs absent in 50%),
Personality changes, cognitive impairment, altered mentation and
coma.
• Diagnosis:
• CSF : Culture +ve in > 95%( gold standard) Indian ink +ve in 60-80%
• Treatment:
• Amp B + 5 FC x 2 wks f/b Fluconazole 400mg daily x 8 wks /until CSF
sterile

39.  Cerebral toxoplasmosis:-
• m/c cause for
1. ICSOL
2. ENCEPHALITIS
3. FND
• Occurs when CD4+ count <200
• m/c site of lesion – Brain Stem
• Clinical feature:
• typically present with headache, Focal neurologic deficits & seizure
• Diagnosis: Demonstration of IgG & IgM
• MRI – Ring enhancing lesion
• Treatment:
Two choices-
1- Pyrimethamine(200mg-L/75C) + sulfadiazine(6-8g/d -4d/d)
2- Pyrimethamine+Clindamycine(600mg q6h)

41.  Progressive Multifocal Leukoencephalopathy:-
• Etiology: JC virus, reactivation of prior infection
• Lesions are usually bilateral, asymmetric, & localized preferentially to
periventricular areas & subcortical white matter .
• Clinical feature:
• Protracted course +/- Change in mental state,
• Multifocal deficit: hemiparesis, aphasia, sensory deficit
• Ataxia & visual field defect.
Diagnosis:
CT : patchy or confluent hypodense lesions of white matter
MRI: multiple non enhancing white matter lesion (predilection for occipital or parietal
lobes).
Confirmation : PCR for JC :- specific, if +ve decrease need for biopsy

42.  Vacuolar myelopathy:
-Vacuolar changes in dorsolateral thoracic cord
-Myelin sheath - Preserves axons
-Release of cytokines or abnormal B12 utilization
 Presentation:
• Gait disturbances, leg weakness, spasticity, ataxia,
DTR, extensor plantar response, Impaired
proprioception-vibration & position-Sphincter
dysfunction following deterioration of gait
• Spares the arm
• Sensory level and back pain- unusual

43.  Haematological Condition:
- Mostly d/t Bone marrow infiltration by opportunistic infection,
neoplasm & BM suppression by Drugs

44.  Malignancies

47. CMV
 Once infected with CMV, individual carry CMV for life:
reactivation occurs with Immunosuppression i.e.
organ transplant/HIV
 In HIV,
 CMV disease other than Liver/Spleen/LN is AIDS defining
 CD4+ < 50
 RS – B/L infiltrates in Lower Lobes which spreads
centrally and superiorly
 GIT – Esophagitis, Hepatitis
 Encephalitis – Progressive Dementia,FND
 Retina – Tomato Ketchup Appearance (Perivascular h’age
& exudate)
 Diagnosis - 1. Fundus 2. CMV DNAPCR
 Treatment – Ganciclovir 5mg/kg BD X 21 Days

48. DIAGNOSIS
 Viral Antibodies
 Viral Antigens
 Viral RNA/DNA
 Culture
(Window Period:- duration between exposure to HIV to tested
positive for HIV antibodies)
a) Antibody detection – 22 Days
b) P24 detection – 16 Days
c) Nucleic Acid Testing – 12 Days

49. STEPS FOR HIV TESTING
1. Step 1
• Screen with 4th gen HIV-1/HIV-2/p24 Ag-Ab Combination Assay
Negative Positive
No further testing required Step 2

50. STEP – 2
 HIV – 1/HIV – 2 Antibody Differentiation Assay
 HIV -1 Reactive & HIV- 2 Nonreactive = HIV – 1 Ab detected
 HIV -2 Reactive & HIV- 1 Nonreactive = HIV – 2 Ab detected
 HIV -1 Reactive & HIV- 2 Reactive = HIV Ab detected
 HIV -1 Nonreactive or Indeterminate & HIV- 2 Nonreactive =
Proceed to Step 3

51. STEP –3
 Nucleic Acid Amplification Test i.e. HIV – 1 RNA Testing
 If +ve = Acute HIV - 1 Infection
 If -ve = Negative for HIV - 1 Infection

52. SEROLOGY
 Anti – HIV Ab detected within 3 – 12 Weeks after Infection.
 Routine test for Screening is by ELISA
 Confirmation by Western blot
 HIV Abs are not protective and are persist for life

53. VIROLOGY
 p24 Antigen - detected shortly after infection ad
disappears by 8-10 weeks after exposure
 Confirmation by Western blot

54. CD4+ CELL COUNT
 Done by flow cytometry
 Most useful indicator for immunosuppression by
active HIV
 Normal = >500

55. TREATMENT
 Indication
 ART should be initiated in all PLHIV, regardless of WHO
clinical stage & any CD4 cell Count
 As priority, started in Adults with WHO stage 3 or stage 4 and
CD4+ <350
 Active TB
 Co-infection HBV
 HIV positive partner
 Pregnant and breastfeeding women
 In patients with opportunistic infection: ART should be
initiated within 2 weeks
 Exception
 Cryptococcal Meningitis: ART should be initiated 5 weeks after
starting T/t Cryptococcal infection
 Tuberculosis: ART should be initiated 2-8 weeks after starting AKT

56.  Principal Of ART:
 Goal :- Reduce viral load to <50 copies/ml
 Other Goal :- Improve CD4 Count >200cells/L
Improve quality & quantity of life
 HIT HARD & HIT EARLY
 FIEST CHANCE = BEST CHANCE

57. ANTIRETROVIRAL
 Nucleoside analogue reverse-transcriptase
inhibitors(NRTI)
 Block reverse transcriptase activity by incorporating themselves into the viral
DNA & acting as chain terminators in synthesis of proviral DNA

58.  Non-nucleoside reverse-transcriptase inhibitors
(NNRTIs)
 Bind directly and non-competitively to reverse transcriptase and blocking
its activity

59.  Protease Inhibitor
 Inhibits HIV -1 protease and leads to release of structurally disorganised
and non infectious viral particle

60.  Principles for changing regimen
1. Single drug should not be added or changed to a failing
regimen, only if resistance testing s/o resistance to 1 drug
2. Cross resistance among NNRTI’s common & therefore
changing between NNRTI’s should be avoided.
3. In PI therapy,Nelfinavir should always be given 1st
4. Cross resistance between ritonavir & Indinavir is common &
therefore changing between these 2 drugs should be
avoided

61. DOLUTEGRAVIR
 Suppresses viral load in higher portion
 Higher barrier to resistance
 Fewer side effects
 Reduces need to switch regimen
 Drug Interaction
 It increases Metformin level which may cause
Hypoglycaemia
 May interact with Anticonvulsant hence use should be
avoided