This document discusses HIV/AIDS, including its definition, epidemiology, transmission, diagnosis, clinical staging, opportunistic infections, and impact on tuberculosis. HIV is a retrovirus that targets CD4+ T cells and causes AIDS by destroying the immune system. It is most commonly transmitted through unprotected sexual contact and blood exposure. Diagnosis involves antibody and viral load testing. Disease progression involves clinical stages from asymptomatic to severe AIDS. Common opportunistic infections increase with lower CD4 counts, and tuberculosis is particularly impacted by HIV co-infection.

1. Middle School Grade: 6 - 8 CCSS, NGSS
HIV/AIDS

2. Outline
 Definition
 Epidemiology
 Classification
 Transmission
 Diagnosis
 Common OIs
 Principles of HAART
 Treatment monitoring
 IRIS

3. HIV disease is a spectrum of conditions ranging from
primary infection to advanced stages associated with
opportunistic diseases.
A lifelong, potentially life-threatening disease caused by
the HIV.

4.  AIDS was first recognized in US in 1981, when
the CDC reported the unexplained occurrence
of PCP and KS in homosexuals.
 In 1983, HIV was isolated from a patient with
LAP.
Epidemiology of
HIV/AIDS

5.  In 1984, HIV was demonstrated clearly to be the
causative agent of AIDS.
 In 1985, ELISA was developed.
 In Ethiopia ,HIV infection 1st evidenced in 1984.

7. Retroviruses
• Midsized viruses with an enveloped capsid containing
two copies of a ss (+) RNA genome, tRNA, RT integrase,
and PR.
1. All RV genomes contain three genes— Each gene encodes a
polyprotein, which is cleaved to yield the final gene products.
gag → nucleocapsid protein(p7,17&24)
pol → enzymes (ЯT, integrase, & protease)
env → envelope gp(gp41,120)
)

9. HIV
HIV1
Highly transmissible
worldwide distribution
M(90%)
A-K clads
C -common
in Ethiopia
N O P
HIV2
W/Africa

10. CD4+ Cells?
CD4+ T lymphocytes – the primary cells
Myeloid lineage cells such as monocytes and MØs
Langerhans cells,DCs, & microglial cells-express low
level of CD4
 MØs and DCs are resistant to the cytolytic effects of the
HIV(unlike CD4+ T cells)→reservoirs of the virus
Are cells which express CD4 as their surface marker.
These are:-
 Are target cells of HIV

11. Normal count 700-1200 cells/μL
 Recognition of Ags in association with MHC-II
proteins.
 Activation of macrophages via release of IFN-γ.
 Clonal expansion of CD4 T cells via release of IL-2.
 Activation CD8 cytotoxic T cells via release of IL-2.
 Activation and differentiation of B cells.
 Induction of NK cells.
CD4 T cell functions

12.  infect only activated T cell lines.
 Use CXCR4 (expressed only on T cells) as coreceptor.
 Later,R5 strain→→X4 strain(due to mutations in genes that
encode gp120).
There are two strains of HIV
B.T-cell tropic (X4 virus) strains
A.Macrophage- tropic (R5 virus) strains
infect both monocytes,møs and T cells.
Use CCR5 (expressed on both monocytes and T cells) as their
coreceptor.
Initial infections are by R5 strains ≈ 90%

14. Replication of HIV

15. Route of transmission
It enters thru mucosal abrasions by:
Direct entry of virus into the blood vessels or
Entry into the mucosal DCs.
The presence of any other concomitant STDs ↑ HIV trans…thru
 Genital ulcerations
 By increasing the seminal fluid content of inflammatory cells
carrying HIV
1.Sexual contact

16.  IVD abusers :thru shared needles, syringes etc.
 Patients receiving blood or blood components
 Infected patient to the physician thru needle stick injury:
 Blood transfusion of infected blood (90-95% chance)
2. Parenteral inoculation

17. N.B. HIV is most efficaciously transmitted by conta blood
transfusion and least efficaciously by sexual contact.
However, MC mode of spread of is sexual contact.
15–40% w/o ARV
 Trans placental spread
 Infected birth canal during normal vaginal delivery: the MC route
for MTCT.
 Ingestion of breast milk
Can be ↓ by the use of elective c-s and ARVs like NVP and AZT.
3. MTCT

19. TEST USE COMMENTS
ELISA Screening test  Detects anti-gp120 Abs
 +ve within 3–5 weeks; all in 3 months .
 Detect Abs for HIV-1, HIV-2, and p24 Ag
Western blot and
nucleic acid assays
confirmatory tests  Used if ELISA is +ve or indeterminate.
 Positive test : presence of p24 Ag and gp41 Abs, and
either gp120 or gp160 Abs.
p24 Ag Indicator of active viral replication
Present before anti-gp120 Abs.
 Positive before seroconversion and when AIDS is
diagnosed (two distinct peaks)
 Used by blood banks to screen for HIV;
 ↓ed the chance for contracting HIV by blood
transfusion
 For early infant dx
CD4 T-cell count Monitoring immune status  Useful in determining when to initiate HIV treatment
and when to administer prophylaxis against OIs
HIV viral load Detection of actively dividing virus
Marker of disease progression
 Most sensitive test for dx of acute HIV before
seroconversion.
Laboratory Tests for HIV Diagnosis

20. HIV test algorithms
Initial test →highly
sensitive(KHB)
Confirmatory test (Stat
pack)→highly specific
Tiebreaker(Uni-gold)
→highly sensitive+specific

21. Immuno-pathogenesis
HIV target cell having CD4+ marker, which is highly expressed on T helper cell, and
have significant effect on them. other like
 monocyte/macrophage lineage
 DCs
 Epidermal Langerhans
 FDCs, and B cells,
 Thymus
 epithelial cell
T helper cells have important role in the immune system, they help the
activity of other immune cell by releasing cytokines.
Central for both cell mediated and humeral immune arms

23. Escape of HIV from Immune System Control
 Exhaustion of HIV-specific CD8+ T cells
 Down regulation of HLA class I molecules on the surface of
HIV-infected cells by the viral proteins Nef, Tat, and Vpu,
 Hypervariability in the primary sequence of the envelope,
extensive glycosylation of the envelope, and
conformational masking of neutralizing epitopes
 HIV preferentially infects activated CD4+ T cells

24. Chronic and persistent inflammation
Chronic and persistent inflammation is hall mark of HIV virus
 Activation of immune system has been shown to increase the HIV viral load
(Tuberculosis and Malaria infection has been shown to result significant
increase burden of the viral load)
 Functional exhaustion of virus-specific T cells result in immune dysfunction
 Multiorgan damage (Accelerated aging syndrome ,Bone
fragility,Cancers,Cardiovascular,Diabetes,Kidney ,Liver diseases and
Neurocognitive dysfunction)

25. Natural history of HIV/AIDS
 The course of HIV/AIDS in untreated individual range from early Acute retroviral syndrome ,
prolonged period of clinical latency to AIDS phase.

27. Acute retroviral infection
It is estimated that 50–70% of individuals with HIV infection experience
an acute clinical syndrome ~3–6 weeks after primary infection
 Symptoms usually persist for one to several weeks and gradually
subside as an immune response to HIV develops and the levels of
plasma viremia decrease.
 In many patients, the illness is mild and only identified on
retrospective enquiry at later presentation

29.  SEROCONVERSION — Most patients seroconvert to positive HIV
serology within 4 to 10 weeks after exposure and ≥95 percent
seroconvert within six months.
 Viral set point: The level of HIV viremia early in the course of HIV where
the viral load plateaus
(very low viral load and high viral load)

30. Clinical latency
Period of continued viral replication and gradual decline in CD4 +
cells
Clinical latency should not be confused with microbiologic latency
• (HSV , HBV and HCV )
 CCR5 (delta) 32
 HLA-class I alleles

31. AIDS
 The spectrum of illnesses that one observes changes as the
CD4+ T cell count declines. The more severe and life-
threatening complications of HIV infection occur in patients
with CD4+ T cell counts <200/um

32. Clinical Staging of HIV/AIDS
There are different types of staging systems.
The commonly used are:
 The WHO clinical staging system
 The CDC staging system
WHO classification does not require CD4 count and hence is
more appropriate to use in resource limited settings with high
HIV prevalence

33. Clinical Stage 1
 Asymptomatic infection
 Persistent generalized lymphadenopathy (PGL)

34. Clinical stage 2
 Unexplained moderate weight loss ( < 10 % of body weight
)
 Recurrent upper respiratory tract infections
 Minor mucocutaneous manifestations
 Herpes zoster current or in last 2 years

35. Clinical stage 3
 Unexplained chronic diarrhea longer than 1 month
 Unexplained prolonged fever > 1 month
 Pulmonary tuberculosis
 Persistent Oral candidiasis (thrush)
 Oral hairy leukoplakia

36.  Recurrent vaginal candidiasis
 Severe bacterial infection
 Acute necrotizing ulcerative stomatitis, gingivitis, or
periodontitis
 Unexplained anemia ,neutropenia,and chronic
thrombocytopenia for more than one month

37. Clinical stage 4
 HIV wasting syndrome - Weight loss > 10% plus -
Unexplained chronic diarrhoea > 1 month OR -
Unexplained prolonged fever > 1 month
 Extrapulmonary tuberculosis
 Pneumocystis pneumonia ( PCP)
 CNS toxoplasmosis

38.  Cryptococcal meningitis (or other extra pulmonary crypto)
 Kaposi's sarcoma
 Visceral Leishmaniasis,
 Candidiasis of esophagus, trachea, bronchi, or lung

39.  Recurrent severe bacterial pneumonia
 Visceral Herpes simplex
 Chronic herpes simplex infection- orolabial, genital, or
anorectal
 Cytomegalovirus infection (other than liver, spleen, LN)

40.  Lymphoma (cerebral or B-cell non-Hodgkin)
 Any disseminated endemic mycosis
 Invasive cervical carcinoma
 Cryptosporidiosis, Isosporiasis
 Disseminated Mycobacterial diseases other than
tuberculosis
 Recurrent non-typhoidal salmonella septicaemia (2 or
>episodes in one year)
 Progressive multifocal leukoencephalopathy (PML)

41.  HIV encephalopathy
 HIVAN
 HIV Enteropathy

42. Clinical manifestations and Common OI
 The clinical consequences of HIV infection encompass a
spectrum ranging from an acute syndrome associated with
primary infection to a prolonged asymptomatic state to
advanced disease.
 In general, we classify the manifestations
I. Primary infections (directly caused by HIV)
II. Secondary infections (opportunistic infections)

43. When do we say someone has AIDS?
A diagnosis of AIDS is made in any individual age 6
years and older with HIV infection and a CD4+ T cell
count<200/μL or presence of AIDS defining illnesses
regardless of CD4 count.
AIDS defining illnesses are opportunistic infections ,
malignancies & conditions associated with HIV directly.

44.  Most common OIs are both preventable &
treatable.
• General strategies to prevent opportunistic infections are:
– Reduction of exposure
– Chemoprophylaxis(primary/secondary)
– Immunization and
– Starting HAART

45. Chemoprophylaxis(primary/secondary)
• The 3 OI prophylaxis therapy practiced in Ethiopia are:

46. Dosage OI’s used against Indications for
starting
Criteria for
discontinuation
Cotrimoxazol
e Preventive
Therapy (CPT)
960mg
po/d
Bacterial infections,
20PCP
,Toxoplasmos
is,
Isospora belli,
cyclospora,Malaria
-Any who stage
and CD4 <350
-WHO stage 3
& 4 regardless
of CD4
-Never or when
CD4 ≥350 cells
after 6 months of
ART
-C/Is to CPT severe
allergy to sulfa
drugs;
Isoniazid
Prophylaxis
Therapy (IPT)
INH 300 mg x
6 month
reduces active TB
in HIV patients
ALL HIV
infected
patients without
active TB
C/Is: Active
hepatitis alcohol
intake
regular/heavy ,peri
pheral neuropathy
Fluconazole 200mg Po
daily
After
completing
treatment for
Cryptococcal
meningitis

47.  CVS manifestations;
coronary heart disease
 Renal and GU
manifestations of HIV
HIVAN
 Neoplastic Diseases
AIDS-defining conditions are
Kaposi’s sarcoma,NHL, and
invasive cervical carcinoma.
Non-AIDS-defining HL; multiple
myeloma; leukemia; melanoma;
 Diseases of the
Hematopoietic System;
Lymphadenopathy, anemia,
Thrombocytopenia
 Neurologic manifestations
 GI manifestations
Oral : candidiasis, OHL
Esophagus: esophagitis
Diarrehal diseases;multicause
-(HIVAE)
Rectal lesions
Hepatobiliary Diseases

48. CD4 count and risk of common HIV-associated
infections

49. Tuberculosis
M. tuberculosis obligate aerobic, rod-shaped, non
spore-forming, AFB positive bacterium.
TB is the most common OI in Ethiopia.
Can occur at any CD4 count.
• TB is responsible for an estimated 24% of all HIV-
related mortality
 Saw a worldwide resurgence associated with the HIV
epidemic.
 1/3 of HIV related deaths
 100 X increased risk of Tb after HIV
 7-10% risk of annual Tb reactivation
49

50. Impact of HIV on TB
 Increases rate of TB re-activation,
progression and active TB
 Increases TB morbidity and
mortality (5-14 fold)
 Alters clinical manifestations of TB
 Creates diagnostic challenges
 Complicates treatment
Impact of TB on HIV
• TB infection activates T-cells,
indirectly supporting HIV
replication
• Accelerates HIV disease
progression.
– Active TB is associated with
increased HIV-1 viral load,
progression to AIDS, high
mortality
• HIV viral load decreases with
successful TB therapy
• TB therapy when combined with
ARV has potential for drug-drug
interactions and side effects

51. Clinical manifestations
In early HIV – TB presents in the typical pattern of pulmonary
reactivation occurs;
•Cough > 2 weeks
•Constitutional Sx (fever, dyspnea on exertion,weight loss, night sweats)
•CXR suggestive of pulmonary TB revealing cavitary apical disease of
the upper lobes

52. -In late stages of HIV, when CD4 is <200, a primary TB–like
pattern with atypical clinical & CXR findings are common
-Clinical manifestations become more atypical as immune function
deteriorates

53. Extra-pulmonary and disseminated disease is more likely, reported in up to
70%, more common with lower CD4 counts

54. TB Diagnosis
 Need to screen all Tb pts for HIV and the vise versa
 Gene Xpert MTB/RIF is the preferred initial diagnostic test
• Microscopic examination of sputum smears - specific,
readily available, and most important test.2or3 early morning
specimens Acid-fast bacillus smear
• Radiologic examination (CXR)
 Early HIV : typical adult TB features (with upper-lobe
infiltrates/cavitation , no significant LAP or pleural effusion )
 Late HIV: Atypical clinical & CXR findings are
common,Lower/middle lobe opacity, little or no cavitation ,
interstitial / milliary pattern, adenopathy (hilar,
paratracheal), Pleural/ Pericardial effusion may also be
normal
 Histo-pathological examination
 Culture is the gold standard a definitive diagnosis.
54

55. TB and HIV management
 Timing of starting ART in all TB patients, irrespective of CD4
count Anti TB should be initiated first, followed by ART as soon as
possible within the first 8 weeks of treatment, for those with CD4
< 50 cells should receive ART immediately within the first 2 weeks
of anti TB.
 Potential disadvantages of delaying ART:
 Reduced pill burden and better drug adherence
 Less chance of drug interactions and toxicity
 Reduced chance of IRIS
 Potential disadvantages of delaying ART:
 Patient may die from a different OI that could have been
prevented by improving immune status with ART
 TB disease may progress faster without ART
55

56. Pneumocystis pneumonia (PCP)
 Causative organism is yeast like fungus called P
. jirovecii
 Developmental stage: Trophozoite - Precyst - Cyst
Transmission:
-Reactivation of latent infection acquired during childhood
-De novo infection from environmental sources
-Person to person(Airborne transmission)
 Host predisposing factors immunocompromisation:-
Common in PLWHA with CD4 < 200/μL, not on CPT, previous Hx of PCP
 Diagnosis is mostly by clinical presentation and chest X-ray
Clinical presentation:- Indolent course
- Fever, Dry cough ,retrosternal chest pain ,dyspnea, tachypnea,
unexplained weight loss, Minor auscultatory findings
- Can have extra pulmonary manifestations(ear, eye, liver, spleen…)

57. Diagnosis
 Chest x-ray findings:-
-Either a normal film OR faint bilateral interstitial infiltrate
-less commonly lobar infiltrates and pleural effusions, of upper lobe cavitary
disease
 Arterial blood gas may indicate hypoxemia with a decline in Pao2
and an increase in the arterial-alveolar (a–a) gradient.
 Lactate dehydrogenase Elevated
 HRCT may demonstrate a patchy ground-glass appearance
 Definitive diagnosis of PCP is done by histological identification of
the of the causative organism in a clinical specimen.

58. Faint bilateral interstitial infiltrates
beginning in the perihilar regions
X-ray showing cysts in PCP
HRCT showing patchy
ground glass
attenuation with a
background of
interlobular septal
thickening

59. A definitive diagnosis requires demonstration of the
organism in clinical specimens
 Specimen collection:-
Induced sputum, BAL,Transbronchial and Open lung
biopsy
 Histopathologic staining:-
Methenamine silver stain, Toluidine blue stain,
Wright- Giemsa stain
 Immunofluorescent staining with monoclonal
 PCR used to detect specific DNA sequences for P.
jirovecii
59

60. Cerebral Toxoplasmosis
 Life cycle of toxoplasmosis ; causative organism T.gondii

61. Clinical features
 Cerebral toxoplasmosis is caused by reactivation of residual
tissue cysts from past infection, which results in the
development of space-occupying lesions.(10x more common
in the seropositive)
 Clinical presentations
 fever, headache, and focal neurologic deficits.
 Cerebral edema may cause confusion, dementia, and lethargy,
which can progression to coma.

62. Diagnosis
 MRI :-characteristic findings on imaging are multiple space-
occupying lesions with ring enhancement on contrast and
surrounding oedema
 double-dose contrast CT
 Serology:-evidence of previous exposure (Ig)G antibodies);
sensitive but not specific
 Definitive diagnosis is by brain biopsy but this is seldom necessary

63. MRI showing multiple ring enhancing
lesions with surrounding edema.

64. Cryptococcal meningitis
 Cryptococcosis is a systemic mycosis caused by two
environmental yeast species, Cr.gattii & Cr.neoformans
(common in PLWHA).
 Source of infection pigeons droplet. (inhalation of yeasts)
 subacute meningoencephalitis with fever, nausea, vomiting,
altered mental status, headache, and meningeal signs.
 may also develop cryptococ-comas and cranial nerve
involvement. one-third of patients also have pulmonary
disease
64

65. Diagnosis
 Lumbar puncture:-The CSF profile may be normal or may show
 modest elevations in WBC or protein levels (variable)
 decreases in glucose.
 The opening pressure in the CSF is usually elevated.
Indian Ink: typical round encapsulated yeast consistent with
cryptococcus…seen in > 75 %
 Cryptococcal Ag test:-detected in serum and CSF(high
sensitivity and specificity)
 Blood cultures for fungus are often positive
 The definitive diagnosis is made by culture of CSF.

66. Culture histopathological
examination(B)
MRI:-showing space
occupying lesion(A)

67. Treatment of common opportunistic
infections in adults with AIDS

69. HAART
 HAART aka cART – combination of effective
antiretroviral drugs that suppress HIV replication by
acting at different stages of the viral life cycle.
 It is not a cure.
 With careful and appropriate drug choice, >80% of
patients have undetectable viral load at 4-6
months.
 There are 6 classes of antiretroviral drugs.
1. NRTI
2. NNRTI
3. Protease inhibitors
4. Fusion inhibitors
5. Integrase inhibitors
6. CCR5 inhibitors

71. Goals of therapy
 Reduce the viral load to an undetectable level(<50
copies/ml) for as long as possible.
 Improve the CD4 count to >200 cells/ml so that
severe HIV related disease is unlikely.
 Increase life expectancy and quality of life without
unacceptable drug related side effects.
 Reduce transmission(MTCT, among partners…)

72. Principles of therapy of HIV/AIDS
 Use combination of effective drugs: 3-4 drugs
from 2-3 classes.
 Maximum suppression of viral replication
 Avoid development of drug resistance
 When resistance develops drugs should be
changed or added.
 Make an appropriate decision on drug selection.
 It is better to select a simple regimen for a better
patient compliance.
 Medication adherence is critical.
 Once treatment regimen is started, interruption
is not recommended.

73. When to start ART?
 The ideal time for ART initiation depends on:
Clinical condition &
Patient readiness for ART.
 It should be initiated in all PLHIV, regardless of WHO clinical
stage or CD4 count.
 Priority should be given for patients with advanced HIV
disease.

74. What to start?
 1st line therapy: should consist 2 NRTI + 1 INSTI/NNRTI
 Alternatives:
 AZT + 3TC + NVP
 TDF + 3TC + NVP
 TDF + FTC + EFV
 ABC + 3TC+ AZT/NVP

75.  2nd line therapy: used if 1st line is failed or caused a series
side effect.
 should consist of ritonavir boosted PI(ATZ or LPV) plus 2
unused NRTIs, one of which should be TDF or ATZ based on
what was used on 1st line therapy.

76. Treatment failure
failure Population group definition
Clinical failure Adults & adolescents • New or recurrent WHO stage 4 disease condition after 6
months of therapy.
• Certain WHO 3 conditions( pul.TB & severe bacterial
infections) after 6 months of therapy.
children • New or recurrent WHO stage 3 & 4 conditions ( except
TB) after 6 months of therapy.
Immunological
failure
Adults & adolescents • CD4 count ≤250cells/mm3 ff clinical failure.
• Persistent CD4 level <100cells/mm3.
children >5
years
• Persistent CD4 level <100cells/mm3.
<5
years
• Persistent CD4 level <200 cells/mm3.
Virological failure All population
groups
• VL >1000copies/ml in 2 consecutive measurements in 3
months, with EAS b/n the measurements.

77. ART monitoring
Goals of monitoring therapy
 Assess adherence
 Evaluate response to therapy.
 Detect drug toxicity
 Recognize treatment failure as early as possible.

78. ART monitoring cont…
 Clinical evaluation: review history and P/E at every visit.
 Laboratory tests
 For monitoring toxicities
 Hgb/Hct
 RFT
 LFT(AST, ALT)
 Lipid profile
 Blood sugar
 For monitoring response to therapy
 CD4 count
 Viral load
 Others
 screening for TB
 Screening for STI
 Pregnancy test

79. IRIS
 IRIS is a spectrum of signs and symptoms associated with an
immune recovery brought by ART.
 Occurs in 10-30% of individuals initiating a potent ART.
 Signs and symptoms include; prolonged fever, localized
lymphadenitis, raised ICP
, pulmonary infiltrates on CXR…
 Commonly occur after 4-8 weeks after initiating therapy.
 2 types:
1. Paradoxical IRIS : recurrence of previously diagnosed and treated
OI.
2. Unmasking/new IRIS: occurrence of a new symptomatic disease
from a subclinical/latent OI.

80. Diagnosis of IRIS
 Low pretreatment CD4 count.
 Positive immunological response to ART
 Clinical symptoms consistent with inflammatory process.
 Clinical course not consistent with drug toxicity or
previously/newly diagnosed OI.
 Management:
 Treat OI
 Short term corticosteroids