HARRISON’S

MAYOR HILARION
A. RAMIRO SR.
CLUB:
MEDICAL CENTER
AIDS RELATED DISEASES AND
DEPARTMENT OF OPPORTUNISTIC INFECTIONS
INTERNAL
MEDICINE PRESENTED BY: DR. LADY AIZAHLYN ANGOD
DEFINITION
q AIDS was originally defined empirically by the Centers for
Disease Control and Prevention (CDC) as “the presence of a
reliably diagnosed disease that is at least moderately
indicative of an underlying defect in cell-mediated immunity
in the absence of any known cause for such a defect.”

Following the recognition of the causative virus, HIV, and the

development of sensitive and specific tests for HIV infection, the
definition of AIDS has undergone substantial revision.
DEFINITION
q The current CDC classification system for HIV infection and
AIDS categorizes patients based on:
§ Clinical conditions associated with HIV infection
§ Level of the CD4+ T lymphocyte count.

The definition and staging criteria of AIDS are complex and

comprehensive and were established for surveillance purposes
rather than for the practical care of patients.

The clinician should not focus on whether the patient fulfills the
strict definition of AIDS, but should view HIV disease as a
spectrum ranging from primary infection, with or without the
acute syndrome, to the relatively asymptomatic stage, to
advanced stages associated with opportunistic diseases.
CONFIRMED HIV CASE
q can be classified in one of five HIV infection stages

0
1
2
3
U
CONFIRMED HIV CASE
q can be classified in one of five HIV infection stages
If there was a negative HIV test within 6 months of the first HIV
0 infection diagnosis, the stage is 0 and remains 0 until 6 months after
diagnosis.

1
2
3
U
CONFIRMED HIV CASE
q can be classified in one of five HIV infection stages

0
1
2
Advanced HIV disease (AIDS) is classified as stage 3 if one
3 or more specific opportunistic illness has been diagnosed

U
CDC STAGE 3 (AIDS) DEFINING OI IN HIV
CONFIRMED HIV CASE
q can be classified in one of five HIV infection stages

0 Otherwise, the stage is determined by CD4+ T

lymphocyte test results and immunologic criteria
1
2
3
U
CONFIRMED HIV CASE
q can be classified in one of five HIV infection stages

0
1
2
3
U
If none of these criteria apply (e.g., because of missing information on
CD4+ T lymphocyte test results), the stage is U (unknown).
EPIDEMIOLOGY
q HIV infection affects 33.3 million people worldwide, with 2.6 million new
cases annually.

q From 2001 to 2009, 33 countries have decreased HIV incidence by over

25%, while 23 others have stabilized their case numbers. The
Philippines is one of only seven countries, and the only one in
Southeast Asia, to have seen an increase of more than 25% HIV
prevalence in this time period (UNAIDS, 2011)
EPIDEMIOLOGY
q While doubling time for new cases in the Philippines took 10 years from 1996 to
2006, acceleration of the doubling time to just 2 years between 2007 and
2009, and to 1 year from 2009 to 2010 is alarming.

q New infections are currently being diagnosed at a rate of six new cases per
day (NEC, 2012)

q The DOH declared an HIV epidemic in July 2010, and case numbers continue
to increase
ETIOLOGIC AGENT
q HIV is the etiologic agent of AIDS.
q Family: human retroviruses (Retroviridae)
q Subfamily: lentiviruses

The most common cause of HIV disease

throughout the world is HIV-1, which comprises
several subtypes with different geographic
distributions.

The AIDS pandemic is primarily caused by the

HIV-1 M group viruses.
 TRANSMISSION
SEXUAL TRANSMISSION
INJECTION DRUG USE

TRANSFUSED BLOOD AND

BLOOD PRODUCTS
OCCUPATIONAL: HCWS,
LABORATORY WORKERS
MOTHER TO CHILD

HIV is transmitted primarily by sexual contact (both heterosexual and male to male); by blood
and blood products; and by infected mothers to infants intrapartum, perinatally, or via breast
milk. After four decades of experience and observations, there is no evidence that HIV is
transmitted by any other modality.
RISK OF HIV TRANSMISSION FOR VARIOUS TYPES OF EXPOSURES
 PATHOPHYSIOLOGY AND IMMUNOPATHOGENESIS
qThe hallmark of HIV disease: profound immunodeficiency resulting from a progressive
quantitative and qualitative deficiency of the subset of T lymphocytes referred to as
helper T cells that are defined phenotypically by the expression on the cell surface of the
CD4 molecule, which serves as the primary cellular receptor for HIV.

q A co-receptor must be present with CD4 for efficient entry of HIV-1 into target cells.

qThe two major co-receptors for HIV-1 are: the chemokine receptors CCR5 and CXCR4.

qThe CD4+ T lymphocyte and cells of monocyte lineage are the principal cellular targets of
HIV.

1. PRIMARY INFECTION
2. ESTABLISHMENT OF CHRONIC AND PERSISTENT
INFECTION
3. ADVANCED HIV DISEASE
 PATHOPHYSIOLOGY AND IMMUNOPATHOGENESIS
1. PRIMARY INFECTION
q Following initial transmission, the virus infects CD4+ cells, predominantly
T lymphocytes, monocytes, or bone marrow–derived dendritic cells.

q Both during this initial stage and later in infection, the lymphoid system is
a major site for the establishment and propagation of HIV infection.

q The gut-associated lymphoid tissue (GALT) plays a role in the

establishment of infection and in the early depletion of memory CD4+ T
cells.

Essentially all pts undergo a viremic stage during primary infection; in

some pts this is associated with the “acute retroviral syndrome,” a
mononucleosis-like illness . This phase is important in disseminating
virus to lymphoid and other organs throughout the body, and viral
replication is ultimately contained only partially by the development of
an HIV-specific immune response.
 PATHOPHYSIOLOGY AND IMMUNOPATHOGENESIS
2. ESTABLISHMENT OF CHRONIC AND PERSISTENT
INFECTION
q Despite the robust immune response that is mounted following primary infection, the virus is
not cleared from the body. Instead, a chronic infection develops that persists for a median
time of 10 years before the untreated pt becomes clinically ill.

q During this period of clinical latency, the number of CD4+ T cells gradually declines, and few if
any clinical signs and symptoms may be evident. However, active viral replication can almost
always be detected as plasma viremia and in lymphoid tissue.

q The level of steady-state viremia (referred to as the viral set point) at ∼6 months to 1
year post-infection has important prognostic implications for the progression of HIV
disease: individuals with a low viral set point at 6 months to 1 year after infection progress to
AIDS more slowly than do those whose set point is very high at this time.
PATHOPHYSIOLOGY AND IMMUNOPATHOGENESIS
3. ADVANCED HIV DISEASE

q In untreated pts or in pts in whom therapy has not controlled viral

replication, after some period of time (often years), CD4+ T cell counts will
fall below a critical level (∼200/µL) and pts become highly susceptible to
opportunistic diseases.

q The presence of a CD4+ T cell count <200/µL or an AIDS-de6ining

opportunistic disease establishes a diagnosis of AIDS.

Control of plasma viremia by effective antiretroviral therapy, particularly

maintaining the plasma viral load consistently at <50 copies of RNA per mL,
even in individuals with low CD4+ T cell counts, has dramatically increased
survival in these pts, including those whose CD4+ T cell counts may not increase
significantly as a result of therapy.
DIAGNOSIS
OF HIV
DIAGNOSIS: ELISA
q A common laboratory-based platform is the ELISA, also referred to as an enzyme
immunoassay (EIA).
q This solid-phase assay is an extremely good screening test with a sensitivity of >99.5%
q Most commercial EIA kits are able to detect antibodies to both HIV-1 and 2 and many also
detect the HIV core antigen p24.

q EIA tests are generally scored as:

ü Positive (highly reactive)
ü Negative (nonreactive)
ü Indeterminate (partially reactive).

While the EIA is an extremely sensitive test, it is not optimal with

regard to specificity. This is particularly true in studies of low-risk
individuals, such as volunteer blood donors.
 DIAGNOSIS: ELISA
FACTORS ASSOCIATED WITH FALSE-POSITIVE EIA TESTS
q Antibodies to class II antigens (such as may be seen following pregnancy, blood
transfusion, or transplantation),
q Autoantibodies
q Hepatic disease
q Recent inCluenza vaccination
q Acute viral infections
q Administration of an HIV vaccine
For these reasons, anyone suspected of having HIV infection based on
a positive or inconclusive fourth-generation EIA result should have the
result confirmed with a more specific assay such as an HIV-1– or HIV-2–
specific antibody immunoassay, a Western blot, or a plasma HIV RNA
level.
 DIAGNOSIS
CDC RECOMMENDATION
CDC recommendations indicate that a positive fourth-
generation assay confirmed by a second HIV-1– or
HIV-2–specific immunoassay or a plasma HIV RNA
level is adequate for diagnosis. The Western blot,
which had previously been used for a confirmatory test,
is no longer used for this purpose.
DIAGNOSIS: WESTERN BLOT
q The Western blot detects antibodies to HIV antigens of specific molecular
weights. Antibodies to HIV begin to appear within 2 weeks of infection,
and the period of time between initial infection and the development of
detectable antibodies is rarely >3 months.

q Plasma p24 antigen levels rise during the first few weeks following
infection, prior to the appearance of anti-HIV antibodies.
MONITORING OF PATIENTS
WITH HIV INFECTION
CD4+ T-CELL COUNTS

HIV RNA DETERMINATION

 CD4+ T-CELL COUNTS
q The best indicator of the immediate state of immunologic competence in
patients with HIV infection.

q Correlates very well with the level of immunologic competence.

Place patient on Primary prophylaxis

<200/uL regiment for PCP
Prophylaxis
<50/uL for MAC unless the
patient is immediately
started on ART
P. JIROVECII CMV
MAC
T. GONDII
 CD4+ T-CELL COUNTS
q Patients with HIV infection should have CD4+ T-cell measurements
performed at the time of diagnosis and every 3–6 months thereafter.

q More frequent measurements should be made if a declining trend is

noted.

q For patients who have been on ART for at least 2 years with HIV RNA
levels persistently <50 copies/ mL and CD4 counts 300-500/μL,
monitoring may be decreased to every year.

q For those with CD4 counts >500/μL, the monitoring of the CD4 count is
felt by many to be optional.
 HIV RNA DETERMINATION
q While the CD4+ T cell count provides information on
the current immunologic status, the HIV RNA level
predicts what will happen to the CD4+ T cell count In most instances of effec-ve
in the near future. an#retroviral therapy, the
plasma level of HIV RNA will
q Measurements of plasma HIV RNA levels should be drop to <50 copies/mL
within 6 months of the
made at the time of HIV diagnosis and every 3–6 ini#a#on of treatment.
months thereafter in the untreated patient. During therapy, levels of HIV
RNA should be monitored
every 3–6 months to
q Following the initiation of therapy or any change in evaluate the con-nuing
therapy, plasma HIV RNA levels should be monitored effec-veness of therapy.
approximately every 4 weeks until the effectiveness of
the therapeutic regimen is determined by the
development of a new steady-state level of HIV RNA.
 CLINICAL
MANIFESTATION
ACUTE HIV (RETROVIRAL) SYNDROME

ASYMPTOMATIC INFECTION

Gratitude Hope
SYMPTOMATICthe DISEASE
Venus has a beautiful name and is
Mercury is the closest planet to the
second planet from the Sun. It’s
Sun and the smallest one in the Solar
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 ACUTE HIV (RETROVIRAL) SYNDROME
q Approximately 50–70% of infected
individuals experience an acute
syndrome following primary
infection. The acute syndrome
follows infection by 3– 6 weeks.

q It can haveGra<tude multiple clinical Hope

features , lasts
Mercury weeks,
1–2 planet
is the closest to the and Venus has a beautiful name and is
the second planet from the Sun. It’s
resolves spontaneously
Sun and as an
the smallest one in the Solar
hot and has a poisonous atmosphere
System—it’s only a bit larger than
immune response to HIV develops
the Moon
and the viral load diminishes from
its peak levels.
 ASYMPTOMATIC INFECTION
q The length of time between HIV infection and development of disease in
untreated individuals varies greatly.

q The median is estimated to be 10 years.

q HIV disease with active viral replication usually progresses during this
Gratitude Hope
asymptomatic period, and, in the absence of combination antiretroviral
Mercury is the closest Venus has a beau-ful name and is
therapy (cART) CD4+planet to the counts invariably
T cell fall.from
the second planet The rate
the Sun. It’s of disease
Sun and the smallest one in the Solar
progression
System—it’sisonly
directly correlated
a bit larger than the with hot
plasma
and hasHIV RNAatmosphere
a poisonous levels.
Moon
Pts with high levels of HIV RNA progress to
symptomatic disease faster than do those with low
levels of HIV RNA.
 SYMPTOMATIC DISEASE
q Symptoms of HIV disease can develop at any time during the course of HIV
infection. I

q In general, the spectrum of illness changes as the CD4+ T cell count declines. The
more severe and life-threatening complications of HIV infection occur in pts with
CD4+ T cell counts <200/µL
Gratitude Hope
Venus has a beau-ful name and is
the second planet from the Sun. It’s
hot and has a poisonous atmosphere
 PERSISTENT
GENERALIZED
LYMPHADENOPATHY
qPalpable adenopathy at two or
more extrainguinal sites that
persists for >3 months without
explanation other than HIV
infection.

qMany pts will go on to disease

progression.
 CONSTITUTIONAL
SYMPTOMS

qFever persisting for >1 month,

involuntary weight loss of >10%
of baseline, diarrhea for >1
month in absence of
explainable cause.
 NEUROLOGIC DISEASE

q Most common is HIV-associated

neurocognitive disease (HAND);

q Other neurologic complications include

opportunistic infections such as
toxoplasmosis and cryptococcal menigitis,
primary CNS lymphoma, CNS Kaposi’s
sarcoma, aseptic meningitis, myelopathy,
peripheral neuropathy and myopathy.
 SECONDARY INFECTIOUS
DISEASES

q Common secondary infectious agents include P. jiroveci

(pneumonia), CMV (chorioretinitis, colitis, pneumonitis,
adrenal-tis), Candida albicans (oral thrush, esophagitis), M.
avium intracellulare (localized or disseminated infection),
M. tuberculosis (pulmonary or disseminated)

q Cryptococcus neoformans (meningitis, disseminated

disease), Toxoplasma gondii (encephalitis, intracerebral
mass lesion), herpes simplex virus (severe mucocutaneous
lesions, esophagitis), Cryptosporidium spp. or Isospora belli
(diarrhea), JC virus (progressive multifocal
leukoencephalopathy), bacterial pathogens (pneumonia,
sinusitis, skin).
SECONDARY NEOPLASMS

q Kaposi’s sarcoma (cutaneous and visceral,

more fulminant course than in non-HIV-
infected pts)
q Lymphoma (primarily B cell, may be CNS or
systemic).
PNEUMOCYSTIS JIROVECII
q Pneumocystis pneumonia (PCP) is caused by the
fungus Pneumocystis jirovecii. Historically, the
etiologic agent was referred to as Pneumocystis
carinii, but the species jirovecii was used to
distinguish the causative agent of human PCP
from PCP in mice (Stringer et al., 2002).

q An ubiquitous environmental organism with

detectable antibodies in two- thirds of children
by the age of four.
PNEUMOCYSTIS JIROVECII
q PCP is one of the most frequent presenting OIs in
HIV patients prior to the routine use of anti-
retroviral therapy. It typically occurs at CD4
counts below 200 cells/μL (Phair et al., 1990)

q In the Philippines, PCP is the second most

common AIDS-deHining illness at presentation,
next only to TB (Salvañ a et al., 2012). PCP in HIV is
associated with a mortality rate of 10%-20% and
substantially increases if mechanical ventilation is
needed, even with appropriate treatment
 PNEUMOCYSTIS JIROVECII
CLINICAL MANIFESTATIONS
qGenerally present with fever and a cough that is
usually nonproductive or productive of only
scant amounts of white sputum.

qThey may complain of a characteristic retrosternal

chest pain that is worse on inspiration and is
described as sharp or burning.
 PNEUMOCYSTIS JIROVECII
CLINICAL MANIFESTATIONS
q HIV-associated PCP may have an indolent course
characterized by weeks of vague symptoms and should be
included in the differential diagnosis of fever, pulmonary
complaints, or unexplained weight loss in any patient with
HIV infection and <200 CD4+ T cells/μL.
PNEUMOCYSTIS JIROVECII
CXR-PA
q The most common Ninding on chest x-ray is
either a normal Hilm, if the disease is
suspected early, or a faint bilateral
interstitial inHiltrate. The classic 8inding of
a dense perihilar in8iltrate is unusual in
patients with AIDS.

q In patients with PCP who have been

receiving aerosolized pentamidine for
prophylaxis, one may see an x-ray picture of
upper lobe cavitary disease, reminiscent of
TB
PNEUMOCYSTIS JIROVECII
CT
q patchy ground-glass
appearance
 PNEUMOCYSTIS JIROVECII
LABORATORY FINDINGS
q A mild leukocytosis is common, although this may not be
obvious in patients with prior neutropenia.
q Elevation of lactate dehydrogenase is common.
q Arterial blood-gases may indicate hypoxemia with a decline in
Pao2 and an increase in the arterial-alveolar (a–a) gradient
 PNEUMOCYSTIS JIROVECII
DEFINITIVE DIAGNOSIS
q A deIinitive diagnosis of PCP requires demonstration of
the organism in samples obtained from induced
sputum, bronchoalveolar lavage, transbronchial
biopsy, or open-lung biopsy
 SUMMARY OF RECOMMENDATIONS

1. HIV-infected patients presenting with 5. Gram stain and culture of sputum is

exertional dyspnea, cough and fever should be useful for diagnosing concurrent bacterial
suspected to have PCP and worked up pneumonia but cannot be used to rule out
accordingly. PCP.

2.All patients with suspected PCP should be 7. Gram stain and culture of sputum is
evaluated with a chest x-ray (CXR), which can be useful for diagnosing concurrent bacterial
normal early in the course but typically shows pneumonia but cannot be used to rule out
bilateral, fluffy infiltrates. PCP.

3. Pleural effusions are rare in PCP, and

alternative or additional etiologies should be
sought.

4. A high-resolution CT scan of the chest can

demonstrate typical ground glass opacities, and
a normal finding is sufficient for ruling out
disease.
 PNEUMOCYSTIS JIROVECII
TREATMENT
q The standard treatment for PCP or disseminated pneumocystosis is
trimethoprim-sulfamethoxazole (TMP-SMX).
A high (20–85%) incidence of side effects, particularly skin rash
and bone marrow suppression, is seen with TMP-SMX in
patients with HIV infection.

q Alternative treatments for mild to moderate PCP include

dapsone/trimethoprim, clindamycin/primaquine, and atovaquone.

q IV pentamidine is the treatment of choice for severe disease in the patient

unable to tolerate TMP-SMX.

q DURATION: 21 days, followed by secondary prophylaxis

 SUMMARY OF RECOMMENDATIONS
The drug of choice for the treatment of severe PCP
is TMP-SMX.

The typical oral adult dose for the treatment of PCP

is two double strength tablets (800/160 mg per
tablet) three times a day for 21 days. If the IV
formulation is available, dosing is 5 mg/kg IV q8 of
the trimethoprim component for severe disease.

Clindamycin 300-450 mg PO/IV q6 to q8 plus

primaquine 30 mg daily is the typical alternative
regimen, to be given for 21 days.

In patients being treated with the alternative

regimen, G6PD testing (if available) should be done
prior to initiation of primaquine (30 mg a day), but a
lower dose of primaquine (15 mg a day) can be
started in patients with severe disease with close
monitoring for hemolysis while awaiting G6PD
results.
 PNEUMOCYSTIS JIROVECII
ADJUNCTIVE TREATMENT
q For patients with a Pao2 <70 mmHg or with an a–a gradient >35 mmHg,
adjunct glucocorticoid therapy should be used in addition to speciNic
antimicrobials.
 SUMMARY OF RECOMMENDATIONS

Adjunctive steroids for severe PCP pneumonia In patients presenting with severe PCP
should be started if the patient has a PaO2 of less pneumonia, and concurrent bacterial
than 70 mm Hg on arterial blood gas at room air or etiology cannot be ruled out, broad-
if the alveolar-arterial oxygen gradient is more than spectrum antibiotics with coverage for
35 mm Hg. Pseudomonas should be started
empirically.
The preferred steroid regimen is prednisone 40 mg
PO BID x 5 days, then 20 mg PO BID x 5 days, then
20 mg PO daily x 11 days. If the patient cannot take
oral medication, IV methylprednisolone at 75% of
the prednisone dose can substituted.

If methylprednisolone is not available, an equivalent

dose of IV hydrocortisone q8 can be used.

If concurrent TB is suspected and steroids need to

be started, send specimens for TB work-up and the
start empiric anti-TB treatment.
 PNEUMOCYSTIS JIROVECII
PROPHYLAXIS
q Prophylaxis for PCP is indicated for any HIV-infected individual:
ü who has experienced a prior bout of PCP
ü any patient with a CD4+ T-cell count of <200/μL or a CD4 percentage <15
ü any patient with unexplained fever for >2 weeks
ü any patient with a recent history of oropharyngeal candidiasis.
 PNEUMOCYSTIS JIROVECII
PROPHYLAXIS
q The preferred regimen for prophylaxis is TMP-SMX, one double-strength
tablet daily.

q For patients who cannot tolerate TMP-SMX, alternatives for prophylaxis

include dapsone plus pyrimethamine plus leucovorin, aerosolized pentamidine
administered by the Respirgard II nebulizer, and atovaquone.

q Primary or secondary prophylaxis for PCP can be discontinued in those

patients treated with ART who maintain good suppression of HIV (<50
copies/mL) and CD4+ T-cell counts >200/μL for at least 3 months.
 SUMMARY OF RECOMMENDATIONS

The preferred alternative regimen for
patients who develop allergy to TMP-SMX
is dapsone 100 mg PO daily, but should
not be used if the allergy to TMP-SMX is
severe, due to possible cross-reactivity.
The only other locally available regimen for
prophylaxis, clindamycin plus primaquine, has
limited effectiveness for prophylaxis and should not
be used routinely.
TRIAD OF HEPATITIS B AND C
q Diseases of the hepatobiliary system are a major
problem in patients with HIV infection.

q Approximately 15% of the deaths of patients with

HIV infection are related to liver disease.

q While this is predominantly a reNlection of the

problems encountered in the setting of co-infection
with hepatitis B or C, it is also a re8lection of the hepatic
injury, ranging from hepatic steatosis to hypersensitivity
reactions to immune reconstitution, that can be seen in
the context of ART.
TRIAD OF HEPATITIS B AND C
q Among IV drug users with HIV infection, rates of
HCV infection range from 70 to 95% .
q It is associated with approximately a threefold increase
in the development of persistent hepatitis B surface
antigenemia.
q In studies of the 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.
q Lamivudine, emtricitabine,
adefovir/tenofovir/entecavir, and telbivudine alone
or in combination are useful.
TRIAD OF HEPATITIS B AND C
q HCV infection is more severe in the patient with HIV
infection

q In the setting of 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 chronically infected with both HCV and HIV.

q Use of directly acting agents for the treatment of

HCV leads to cure rates approaching 100%, even in
patients with HIV co-infection.
MYCOBACTERIUM AVIUM COMPLEX (MAC)
q The most common atypical mycobacterial infection is
with M. avium or M. intracellulare species— the
Mycobacterium avium complex (MAC).

q MAC infection is a late complication of HIV infection,

occurring predominantly in patients with CD4+ T-cell
counts of <50/μL with average CD4 + T-cell count of
10/uL at the time of diagnosis.
MYCOBACTERIUM AVIUM COMPLEX (MAC)
CLINICAL MANIFESTATIONS
q The most common presentation is disseminated disease with fever, weight loss
and night sweats.

q At least 85% of patients with MAC infection are mycobacteremic and large
numbers of organisms can often be demonstrated on bone marrow biopsy.
MYCOBACTERIUM AVIUM COMPLEX (MAC)
CHEST X-RAY
q The chest x-ray is abnormal in ~25% of
patients, with the most common pattern
being that of a bilateral, lower-lobe
infiltrate suggestive of miliary spread.

q Alveolar or nodular infiltrates and hilar

and/or mediastinal adenopathy also can
occur.
MYCOBACTERIUM AVIUM COMPLEX (MAC)
DIAGNOSIS

q The diagnosis is made by the culture of blood or involved

tissue.

q The Ninding of two consecutive sputum samples positive for

MAC is highly suggestive of pulmonary infection.

q Cultures may take 2 weeks to turn positive

MYCOBACTERIUM AVIUM COMPLEX (MAC)
MANAGEMENT

q Therapy consists of a macrolide, usually clarithromycin,

with ethambutol.

q May add third drug from among rifabutin, ciprofloxacin,

or amikacin in patients with extensive disease.

q 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.
MYCOBACTERIUM AVIUM COMPLEX (MAC)
PRIMARY PROPHYLAXIS

q Primary prophylaxis for MAC is indicated in patients

with HIV infection and CD4+ T-cell counts <50/μL not
immediately starting ART.

q This may be discontinued in patients in whom ART

induces a sustained suppression of viral replication
regardless of the change in CD4+ T-cell count.
 SUMMARY OF RECOMMENDATIONS
Treatment of MAC should include two or
more active drugs to prevent the
development of resistance. Clarithromycin
500 mg twice a day plus ethambutol 15
mg/kg/day is the recommended regimen for
disseminated MAC. A minimum of 1 year of
treatment is recommended.
Azithromycin 250 mg once a day can be
substituted for clarithromycin and is more
convenient to take and is associated with
less drug interactions.
For primary prophylaxis, HIV-infected patients with
CD4 count of <50cells/μL should receive either
clarithromycin 500 mg once a day or azithromycin
1000 mg once a week. Azithromycin prophylaxis
should be continued until CD4 count is >100 cells/
μl in response to ARV treatment.
For secondary prophylaxis, adult and adolescent
patients with a diagnosis of disseminated MAC
disease should be maintained on antimycobacterial
treatment unless CD4 count recovers to >100
cells/μL in response to ARV.
SYPHILIS
q Infections with T. pallidum, the etiologic agent of
syphilis, play an important role in the HIV
epidemic.

q In HIV-negative individuals, genital syphilitic

ulcers as well as the ulcers of chancroid are
major predisposing factors for heterosexual
transmission of HIV infection.
SYPHILIS
LUES MALIGNA

q an ulcerating lesion of the skin due to a

necrotizing vasculitis
SYPHILIS
CONDYLOMA LATA

The most common presentation of

syphilis in the HIV-infected patient is
that of condylomata lata, a form of
secondary syphilis.
SYPHILIS
NEUROSYPHILIS

q Neurosyphilis may be asymptomatic or

may present as acute meningitis,
neuroretinitis, deafness, or stroke.

q The rate of neurosyphilis may be as high

as 1% in patients with HIV infection, and
one should consider a lumbar
puncture to look for neurosyphilis in
all patients with HIV infection and
secondary syphilis.
 SYPHILIS
NEUROSYPHILIS
q Dark-Mield examination of appropriate specimens
should be performed in any patient in whom syphilis
is suspected, even if the patient has a negative VDRL.

q ANY patient with a positive serum VDRL test,

neurologic Nindings, and an abnormal spinal Nluid
examination should be considered to have
neurosyphilis and treated accordingly, regardless of
the CSF VDRL result.

Approximately one-third of patients with HIV infection will experience

a Jarisch-Herxheimer reaction upon initiation of therapy for syphilis.
 IRIS
IMMUNE RECONSTITUTION
INFLAMMATORY SYNDROME
q Following the initiation of effective ART, a paradoxical
worsening of preexisting, untreated or partially treated
opportunistic infections may be noted.

q IRIS related to a known pre-existing infection or neoplasm is

referred to as paradoxical IRIS

q IRIS associated with a previously undiagnosed condition is

referred to as unmasking IRIS.

q The term immune reconstitution disease (IRD) is sometimes

used to distinguish IRIS manifestations related to opportunistic
diseases from IRIS manifestations related to autoimmune
diseases.
 IRIS
IMMUNE RECONSTITUTION
INFLAMMATORY SYNDROME
q The most common in patients starting therapy with
CD4+ T-cell counts <50 cells/μL who have a pre-
cipitous drop in HIV RNA levels following the
initiation of ART.

q Occurs 2 weeks to 2 years after the initiation of ART

and can include localized lymphadenitis, prolonged
fever, pulmonary inNiltrates, hepatitis, increased
intracranial pressure, uveitis, sarcoidosis, and
Graves’ disease.
 TB-IRIS
TB-ASSOCIATED IMMUNE RECONSTITUTION
INFLAMMATORY SYNDROME
q complication of TB-HIV coinfection in the post-ART era
q characterized by severe inflammatory features of TB
occurring after rapid reconstitution of the immune
system once ART has been initiated.
MANAGEMENT
ANTIRETROVIRALS

MAYOR HILARION A. RAMIRO SR. MEDICAL CENTER

DEPARTMENT OF INTERNAL MEDICIN
 Nucleoside/Nucleotide
Analogues

These agents act by causing

premature DNA-chain termination
during the reverse transcription of
viral RNA to proviral DNA and
should be used in combination
with other antiretroviral agents. Hope
Venus has a beautiful name and is
the second planet from the Sun. It’s
hot and has a poisonous atmosphere
 Nonnucleoside Reverse
Transcriptase Inhibitors

These agents interfere with the

function of HIV-1 reverse
transcriptase by binding to regions
outside the active site and causing
conformational changes in the
enzyme that render it inactive. Hope
Venus has a beau-ful name and is
Five members of this class, the second planet from the Sun. It’s
nevirapine, delavirdine, efavirenz, hot and has a poisonous atmosphere
etravirine, and rilpivirine are
currently available for clinical use
 Protease Inhibitors

These drugs are potent and

selective inhibitors of the HIV-1
protease enzyme and are active
in the nanomolar range. As with
other classes of antiretroviral
drugs, the protease inhibitors Hope
should be used only in Venus has a beautiful name and is
combination with other the second planet from the Sun. It’s
antiretroviral drugs. hot and has a poisonous atmosphere
 HIV Entry Inhibitors

These agents act by interfering

with the binding of HIV to its
receptor or co- receptor or by
interfering with the process of
fusion.
Hope
Venus has a beau-ful name and is
the second planet from the Sun. It’s
hot and has a poisonous atmosphere
HIV Integrase Inhibitors

These drugs interfere with

the integration of proviral
DNA into the host cell
genome.
Hope
Venus has a beautiful name and is
the second planet from the Sun. It’s
hot and has a poisonous atmosphere
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