IM 6.

3 Describe and discuss

relation between CDC count and
the risk of opportunistic infections

Presented by Aatisha
Roll no. 3
 How it started….

AIDS was first recognized in the United States when the U.S. Centers for Disease Control and
Prevention (CDC) reported the unexplained occurrence of Pneumocystis jirovecii pneumonia in five
previously healthy homosexual men and of Kaposi’s sarcoma (KS) with or without P. jirovecii
pneumonia and other opportunistic infections in 26 previously healthy homosexual men

In 1983, human immunodeficiency virus (HIV) was isolated from a patient with lymphadenopathy,
and by 1984 it was demonstrated clearly to be the causative agent of AIDS

-
HPV

MAC
-
MA M .
intracellular
#

&

1140-8

iCNS
Lympho .

JC virus
J
a
The current CDC classification system for HIV infection and AIDS categorizes patients
based on clinical conditions associated with HIV infection together with the level of the
①
-

CD4+ T lymphocyte count.

-

-
A confirmed HIV case can be classified in one of five HIV infection stages (0, 1, 2, 3, or
-

unknown)
--

(If there was a negative HIV test within 6 months of the

- >
*
first HIV infection diagnosis, the stage is 0 and remains 0
until 6 months after diagnosisC
-

- - E
A 6
<
/y 1 -6-adult

6
5y
-

!
-)1500 >1000-500
& 6
750 -

1499500-999 200 -

499

O
1
-

3
1140
< 500 200 · 6
& =
O 0
> -
- -

D
Advanced HIV disease (AIDS) is classified as stage 3 if one or more specific opportunistic illness has been
-

diagnosed
-
intere
 &

ADVANCED HIV DISEASE

G
*

I
-
- -

· In untreated patients or in patients in whom ①

CY I

therapy has not adequately controlled virus

replication, after a variable period, usually -

measured in years, the CD4+ T-cell count

&

falls below a critical level

-

&
(<200/μL) and the patient becomes highly

3
-
susceptible to opportunistic diseases
-

&
Viraluad
CD
·

⑤
L
·
For this reason, the CDC case definition of stage 3 (AIDS) includes all HIV-infected individuals >5 years of
-

#200/MD)
age with CD4+ T-cell counts below this level
-
·
Patients may experience constitutional signs and symptoms or may develop an opportunistic disease
abruptly without any prior symptoms.

·
untreated patients who progress to this severest form of immunodeficiency usually get opportunistic
infections or neoplasms
v -

- -

- -

- -

V
--

-
&

-
-

- -

-
-

- -

- -

-
 DY-B , Kaposi
collidiomycos
1

< 250
-
Hir
-
-
&
- Kaposi < 200
- P jirovecii all candida
.
,
- - -

>
--
< 150- Histoph cap
. ·

.
crypto
-

-
< 100
-
JC , 1Sr ,
A
gordi.
-

<50 Toxoplasma
-
-
-

MAC
-
*

-
-
CMU
&
=
- >

-
-

-
-

-
-

msympos
pathy
-
arrhea
Sprea
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① Q ③

cause
TB,
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Lymphoma,Ace Retroviral syndo,,
is

ofsweats
high .
Diseases of the Respiratory System
Acute bronchitis and sinusitis are prevalent during all stages of HIV infection.
- -

The most severe cases tend to occur in patients with lower CD4+ T-cell counts.
Sinusitis presents as fever, nasal congestion, and headache.
The diagnosis is made by CT or MRI (maxillary sinuses are most commonly involved)

Pulmonary disease is one of the most frequent complications of HIV infection.

The most common manifestation of pulmonary disease is pneumonia. &

Three of the 10 most common AIDS-defining illnesses are

recurrent bacterial pneumonia,
-

tuberculosis,
-

pneumonia due to the unicellular fungus P. jirovecii.

- -

Mycobacterium tuberculosis:
Following infection with Mycobacterium tuberculosis, the bacilli can persist for years, referred to as latent TB infection (LTBI).

Worldwide, approximately one-third of all AIDS-related deaths are associated with TB,
-
Symptoms include fatigue, weakness, weight loss, and fever. Pulmonary tuberculosis features chronic cough and spitting of blood
- - - - -

Disseminated bloodstream infections lead to lesions in many organs (miliary tuberculosis) and are associated with a high mortality rate.
&

Interferon-gamma release assays (IGRA) are FDA approved, consistent, and have higher specificity (92 to 97%) compared to (56 to 95%) for TST.
-
-

An incidental finding of fibrotic lesions on chest x-ray should prompt further diagnostic testing for LTBI and active infection.
-
Sputum samples for AFB smear and culture must be obtained, including from asymptomatic patients.
-

In HIV positive individuals whose CD4+ counts are less than 200 cells/mm^3, the presence of fibrotic lesions on chest x-ray which are highly suggestive of TB infection
- -
-
- - -

Drug-susceptible TB infection is treated for 6 months using a combination of isoniazid (INH), pyrazinamide (PZA), rifampin (RIF) or rifabutin, and ethambutol (EMB) for 2 months by directly observed therapy
(DOT), followed by INH and RIF for 4 months.
In patients with cavitary disease noted on chest X-ray or those with positive cultures, the treatment should be for a total of 9 months with an additional 3 more months of INH and RIF. All patients receiving INH
therapy must be prescribed pyridoxine supplements. Extrapulmonary TB except for CNS disease, bone, and joint involvement, should be treated for 6 to 9 months
MAC infection is a late complication of HIV infection, occurring predominantly in patients with CD4+ T-cell counts of <50/μL.
&

common presentation is disseminated disease with fever, weight loss, and night sweats,endobronchial lesions, abdominal
-

& -

pain, diarrhea, and lymphadenopathy, Anemia and elevated liver alkaline phosphatase -

DIAGNOSIS- made by the culture of blood or involved tissue. The finding of two consecutive sputum samples positive for
-
MAC is highly suggestive of pulmonary infection. Cultures may take 2 weeks to turn positive. Therapy consists of a mac-
rolide, usually6
-
clarithromycin, with ethambutol.
&

Therapy is continued until resolution of clinical signs and symptoms, negative cultures, and CD4+ T-cell counts >100/μL for
3–6 months in the setting of ART.

Neoplastic diseases of the lung including Kaposi sarcoma and lymphoma

- -
-

Fungal infections of the lung can be seen in patients with AIDS.

&

Patients with pulmonary cryptococcal disease present with fever, cough, dyspnea, and, in some cases,
-
-
hemoptysis.
&

A focal or diffuse interstitial infiltrate is seen on chest x-ray in >90% of patients

Other,
Coccidioides immitis
Aspergillosis
&

Histoplasmosis
&
Pneumocystis pneumonia (PCP)
-

Giv
caused by the fungus P. jirovecii and was once the hallmark of AIDS. It has dramatically declined in incidence following the
development of effective prophylactic regimens and the widespread use of ART.
can be identified as a likely etiologic agent in 25% of cases of pneumonia in patients with HIV infection

CD4+ T-cell counts of <200/μL

-
- -
-

Recurrent fever, night sweats, thrush, and unexplained weight loss are associated
=> -

Otic involvement may be seen as a primary infection, presenting as a polypoid mass involving the external auditory canal.
> -
ophthalmic lesions of the choroid, a necrotizing vasculitis
-

- -

Patients with PCP generally present with -

fever and a cough that is usually nonproductive or productive of only scant amounts
-
-

of white sputum. They may complain of a characteristic - retrosternal chest pain that is worse on inspiration and is described as
sharp or burning.
&

#
- -
Chest x-ray is either a normal film, if the disease is suspected early, or a faint bilateral interstitial infiltrate.
-

Thin-section CT may demonstrate a patchy ground-glass appearance. &

-

①
&

Elevation of lactate dehydrogenase is common.(due to lymphocytic infiltration) Arterial blood-gases may indicate hypoxemia
&
-- &
-

L &

08 -
Hilar
&
-
- -
-

-
=
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*

-
moxazole
com
-
- -
-
-
&

-
Diseases of the Cardiovascular System Heart disease
relatively common postmortem finding in HIV-infected patients

The most common form of heart disease is coronary heart disease.

-

Exposure to HIV protease inhibitors and certain reverse transcriptase inhibitors has been associated with
increases in total cholesterol and/ or risk of MI.
Any increases in the risk of death from MI resulting from the use of certain antiretrovirals must be balanced

Dilated cardiomyopathy associated with congestive heart failure (CHF) referred to as HIV-associated
-

cardiomyopathy. This generally occurs as a late complication of HIV infection treated with IV immunoglobulin
(IVIg).

Pericardial effusions may be seen in the setting of advanced HIV infection.

-

Predisposing factors include TB, CHF, mycobacterial infection, cryptococcal infection, pulmonary infection
Diseases of the Oropharynx and Gastrointestinal System

O o
Oral lesions, including thrush, hairy leukoplakia, and aphthous ulcers

Thrush, due to-

-
Candida infection,
- white, cheesy
- exudate, often on-
an erythematous mucosa in the posterior
oropharynx.

E
&

Oral hairy leukoplakia, presumed due

-

to
- -
EBV, white, frondlike lesions,
generally along the lateral borders
&

of the tongue and sometimes on

-

the adjacent buccal mucosa

Usually indicative of fairly advanced

immunologic decline; they generally
occur in patients with
CD4+ T-cell counts of <300/μL.
- - -

- - -

&
--- -
-

- -

-
 Doc
cotrimoxazol
Cryptosporidia, microsporidia, and Isospora belli are the most common opportunistic protozoa that infect
- - -

the GI tract and cause diarrhea in HIV-infected patients.

&
-

Disease caused by specific secondary infections, patients with HIV infection may also experience a chronic
diarrheal syndrome for which no etiologic agent other than HIV can be identified. This entity is referred to as
AIDS enteropathy or HIV enteropathy.

It is most likely a direct result of HIV infection in the GI tract and improves with ART. Histologic examination of
- ---

the small bowel in these patients reveals low-grade mucosal atrophy

&
Diseases of the hepatobiliary system -

Are major problem in patients with HIV infection.

Approximately 15% of the deaths of patients with HIV infection are related to liver disease co-infection with
hepatitis B or C, Among IV drug users with HIV infection, rates of HCV infection range from 70 to 95%. impact of
HIV on HBV infection, four- to tenfold increases in liver-related mortality rates have been noted in patients with
HIV and active HBV infection compared to rates in patients with either infection alone.
Lamivudine, emtricitabine, adefovir/tenofovir/entecavir, and telbivu- dine alone or in combination are useful in
the treatment of hepatitis B in patients with HIV infection

HIV and HCV co-infection, levels of HCV are approximately tenfold higher than in the HIV-negative patient with
HCV infection. There is a 50% higher overall mortality rate with a five-fold increased risk of death due to liver
disease in patients
Granulomatous hepatitis may be seen as a consequence of mycobacterial or fungal infections, particularly MAC
infection. Hepatic masses may be seen in the context of TB, peliosis hepatis, or fungal infection. Among the fungal
opportunistic infections, C. immitis and Histoplasma cap- sulatum are those most likely to involve the liver. Biliary
tract disease in the form of papillary stenosis or sclerosing cholangitis has been reported in the context of
cryptosporidiosis, CMV infection, and KS. When no diagnosis can be made, the term AIDS cholangiopathy is used

Pancreatic injury is most commonly a consequence of drug toxicity,

Diseases of the Kidney and Genitourinary Tract
may be a direct consequence of HIV infection, due to an opportunistic infection or neoplasm, or related to
drug toxicity.

presence of microalbuminuria has been associated with an increase in all-cause mortality.

HIV-associated nephropathy (HIVAN) is a true direct complication of HIV infection.
Although most patients with this condition have CD4+ T-cell counts <200/μL, HIV-associated nephropathy can
be an early manifestation of HIV infection and is also seen in children

Ultrasound examination reveals enlarged, hyper- echogenic kidneys. A definitive diagnosis is obtained through
renal biopsy.

Genitourinary tract infections are seen with a high frequency in patients with HIV infection; they present with
dysuria, hematuria, and/or pyuria and are managed in the same fashion as in patients without HIV infection

In HIV-negative individuals, genital syphilitic ulcers as well as the ulcers of chancroid are major predisposing
factors ' for heterosexual transmission of HIV infection.

Vulvovaginal candidiasis is a common problem in women with HIV infection. Symptoms include pruritus,
discomfort, dyspareunia, and dysuria. I

um
 Diseases of the Endocrine System and Metabolic Disorders
A variety of endocrine and metabolic disorders are seen in the context of HIV infection. These may be a direct
consequence of HIV infection, secondary to opportunistic infections or neoplasms, or related to med- ication
side effects.
lipodystrophy, consisting of elevations in plasma triglycerides, total cholesterol, and apolipoprotein B, as well as
&

' hyperinsulinemia and hyperglycemia.

-
-

Patients with advanced HIV disease may

develop hyponatremia due to the syndrome of
inappropriate antidiuretic hormone
(vasopressin) secretion (SIADH)
-

Thyroid function may be altered in 10–

&

15% of patients with HIV infection. Both

hypo- and hyperthyroidism may be seen
-

-
- -

-
Immunologic and rheumatologic disorders
Are common in patients with HIV infection
Range from excessive immediate-type hypersensitivity reactions to an increase in the incidence of reactive
arthritis ,conditions characterized by a diffuse infiltrative lymphocytosis.
The occurrence of these phenomena is an apparent paradox in the setting of the profound immunodeficiency
and immunosuppression that characterizes HIV infection and reflects the complex nature of the immune system

HIV-infected individuals also experience a variety of joint problems without obvious cause that are referred to
generically as HIV- or AIDS-associated arthropathy

Diseases of the Hematopoietic System Disorders

-
--
including lymphadenopathy, anemia, leukopenia, and/or thrombocytopenia are common throughout
- -
-

the course of HIV infection and may be the direct result of HIV, manifestations of secondary infections
&

and neoplasms, or side effects of therapy

Anemia is the most common hematologic abnormality in HIV-infected patients

-
-
Dermatologic problems
occur in >90% of patients with HIV infection.
prem
Seborrheic dermatitis occurs in up to 50% of patients with HIV infection.
- -

②
Folliculitis is among the most prevalent dermatologic disorders in patients with HIV infection and is seen in
-
~20% of patients. It is more common in patients with CD4+ T-cell counts <200 cells/μL.
-

Reactivation herpes zoster (shingles) is seen in 10–20% of patients with HIV infection.
-

Infection with herpes simplex virus in HIV-infected individuals is associated with recurrent orolabial, genital,
&

and perianal lesions as part of recurrent reactivation syndromes recurrent mucosal ulcers, recurrent HSV
infection in the form of herpetic whitlow
-

O
· ②
-

Herpetic whitlow in a
E & child with AIDS
Folliculitis in AIDS patient
#
J
Neurologic problems that occur in HIV-infected individuals may be either primary to the pathogenic processes of
HIV infection or secondary to opportunistic infections or neoplasms.

Opportunistic infections # R Liposomal

ART should be initiated blu 4-6
& Toxoplasmosis
wh
Amphotericin Clf-fever, madache
after => B

fungal inf undergoing

bird dropings antifungal
altered mental status (till eD > 200 (
fluconazole -
x

GRIS-immune Reactivation
&
,

& Cryptococcosis miningitis

stiffness neck
inf - skin Lesions , pulmonary
cranial no abn.
:

inflammatory syndrome .
-

mentation
Lethary , altered

Progressive multifocal leukoencephalopathy

& Cytomegalovirus Mu
Syphilis
Mycobacterium tuberculosis
HTLV-1 infection
Amoebiasis Neoplasms
Primary CNS lymphoma Kaposi’s sarcoma Galecephalitis,encphpathy
Peripheral neuropathy
Acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome)
Chronic inflammatory demyelinating polyneuropathy (CIDP)
Mononeuritis multiplex
Distal symmetric polyneuropathy Myopathy

=
serebralsynd
Global

Exopamagondii
Greseue-Cats
C
CD4 < 50

LProgressive
& Multifocal Leucoencephathy)
Sweeks -
months
white matterdisease
JCvines (DNA virus
Lfocal nurologic deficit
- -

Rx-ART
>
Ophthalmologic Diseases
occur in ~50% of patients with advanced HIV infection.
The most common abnormal findings on funduscopic examination are cotton-wool spots.
-

These are hard white spots that appear on the surface of the retina and often have an irregular edge.
- -
They represent areas of retinal ischemia
-
secondary to microvascular disease.
-

O
herpes
&
One of the most devastating consequences of HIV infection is CMV retinitis.
-

Patients at high risk of CMV retinitis (CD4+ T-cell count <100/μL) should undergo an ophthalmologic examination
#-
-
every 3–6 months. It results in painless, progressive loss of vision. Dementia ,ventriculoencephalitis
-
&

Patients may also complain of blurred vision, “floaters,”

-

The disease is usually bilateral, although typically it affects one eye more than the other.
-

Rx ganicyclovir
&

P. jirovecii can cause a lesion of the choroid

- -
J
Neoplastic Diseases
The neoplastic diseases considered to be AIDS-defining conditions are Kaposi’s sarcoma, non-Hodgkin’s
lymphoma, and invasive cervical carcinoma

Kaposi’s sarcoma is a multicentric neoplasm consisting of multiple vascular nodules appearing in the skin,
mucous membranes, and viscera.
The clinical course of KS ranges from indolent, with only minor skin or lymph node involvement, to fulminant,
with extensive cutaneous and visceral involvement. may be seen at any stage of HIV infection, even in the
presence of a normal CD4+ T-cell count. The initial lesion may be a small, raised, reddish-purple nodule on the
-
skin a discoloration on the oral mucosa

- - -
&