AIDS
Syndrome
Dr Arif Rahim Khan
MBBS, FCPS
Associate professor of Medicine
Nishtar Medical University Hospital
AIDS introduction
• AIDS is caused by Human Immunodeficiency Virus (HIV) which
progressively impairs cellular immunity and causes acquired
immunodeficiency.
• HIV is an enveloped RNA virus from Lentivirus Family
• HIV has 2 major subtypes HIV-1 and HIV-2
• HIV-1 is the cause of global pandemic
Epidemiology
• First case reported in 1959 in Congo
• 37 million people affected by 2015 worldwide
• Antiretroviral therapy ART has reduces the mortality and new
infection rates
Modes of transmission
1. Sexual contact
2. Exposure to blood or blood products (injection, unscreened blood,
healthcare workers exposure)
3. Infected mother to child (in utero, perinatal or breastfeeding)
• Risk of HIV infection after exposure depends on:
• Integrity of exposed site, type, volume of fluid and level of viremia in
infected person
Virology and immunology
• RNA enveloped virus
• A lipid membrane lined by matrix protein which has spikes gp-120 ans
gp41
• Inner cone shaped protein core p24 contains 2 copies of RNA and
enzymes
HIV genome
• Consist of 3 characteristic genes and 6 regulatory genes
• Gag: structural proteins
• Pol: for enzymes … reverse transcriptase, integrase and protease
• Env: for envelop proteins
Transmission
• HIV binds to CD4 cells through surface protein spikes gp-120
• Chemokine receptors CCR5 or CXCR4 is essential for binding
• Membrane fusion
• Penetration
• Uncoating
• Reverse transcriptase forms DNA from RNA
• Integrase fixes the viral DNA into host cell genome
Replication and viremia
• The infected cell produces new virions via transcription of viral
messenger RNA
• Mature virions infect other CD4 cells and cycle repeats
• CD4 cells are primarily destroyed by host immune response rather
than virus itself.
• Some CD4 t helper cells go into latent phase which is why ART is
unable to eradicate HIV infection.
Host immune response to HIV
• Host response is both humoral and cellular and defects at both levels
causes AIDS syndrome
1. Humoral response:
• Development of antibodies to a wide range of viral antigens
2. Cellular response
• CD8 cytotoxic cells kill activated CD4 cells
• CD8 lymphocytes do not kill latent CD4 HIV infected cells
• Decline of CD4:CD8 ratio
Host immune response to HIV
• After initial spike of infection the plateau phase comes when there is
gradual decline in T cells.
• T lymphocytes play a key role in cellular immunity and there attrition
makes patient susceptible to opportunistic infections
• B lymphocytes defect occurs in impaired antibody production to
continuously varying antigens
• Increase in gamma globulins
• Increased risk of encapsulated bacteria
Diagnosis and investigations
1. Screening tests
• Most commonly by detecting host antibodies to HIV either through
rapid kit of ELISA (enzyme linked immunosorbent assay)
• Screening can also be done with p24 antigen detection.
2. Confirmatory test
• Western blot assay. But it is expensive and not easily available.
• PCR of HIV RNA. This is used in infants of HIV positive mothers.
Infants carry antibodies of HIV from mother for 15 months.
Diagnosis
• A positive antibody test from two different immunoassays is
sufficient to confirm the infection (screening kit and ELISA)
• CD4 LYMPHOCYTES COUNT
• CD4 lymphocyte counts are detected through flow cytometry
• CD4 counts indicate the degree of immunosuppression
• CD4 counts and decline rate helps management and clinical staging
Diagnosis and investigations
• Normal CD4 lymphocytes count is 500 cells/mm2
• Repeated every 3-6 months
CD4 counts Manifestations
200-500 Oral thrush, tuberculosis, herpes zoster,
Kaposi sarcoma
100-200 Pneumocystis carinii pneumonia,
histoplasmosis, coccidiomycosis
<100 Toxoplasmosis, cryptococcosis,
cryptosporidiosis
<50 Cytomegalovirus, mycobacterium avium,
CNS lymphoma, progressive multifocal
leukoencephalopathy
Diagnosis and investigations
• Viral Load
• Measured by PCR to HIV RNA
• For monitoring the response to ART
• High viral lead (>100000/ml) leads rapid decline in CD4 counts
• Important note: patient can be asymptomatic with low CD4 counts
and a major manifestation of AIDS may present with high CD4
Other baseline investigations
• CD4 counts
• Viral load
• Hep B and C screening
• LFT
• RPM
• CBC
• CUE
• Tuberculin skin test
• Syphilis serology
• Cervical screening
Clinical manifestations of HIV
• Clinical staging is important for
• Prognostic information
• Initiating prophylaxis
• 4 stages
1. Primary HIV infection
2. Asymptomatic infection
3. minor HIV associated disorders
4. Acquired immunodeficiency syndrome
1. Primary HIV infection
• Asymptomatic in 50% of cases
• Incubation period is 2-4 weeks
• Initial symptoms mimic infectious mononucleosis
• Fever, maculopapular rash, pharyngitis, myalgia, lymphadenopathy,
diarrhea, oral and genital ulcers
• D.D of primary HIV infection is EBV, CMV infection, rubella, secondary
syphilis or primary toxoplasmosis.
2. Asymptomatic infection
• After primary infection a prolonged period of latency
• Only persistent generalized lymphadenopathy <2cm in size
• Viral load declines and reaches a plateau for several years
• CD4 counts gradually decline over years
• Median time to develop AIDS is 9 years
3. Minor HIV associated
disorders
• As a result of impaired cellular immunity
• Category B of CDC classification
• Presents with wide variety of disorders including oral candidiasis, oral
hairy leukoplakia, bacterial meningitis, CMV infection, EBV, varicella,
herpes.
4. Acquired immunodeficiency
syndrome
• AIDS is defined as HIV infection with CD4 counts <200 and specific
opportunistic infections, cancers or defining conditions.
• Specific conditions and presenting problems of HIV Infections are
described below
Opportunistic infections in AIDS
• Pneumocystis jiroveci
• Symptoms and signs
• Pneumonia, dyspnea on exertion, dry cough, fever, chest pain
• Diagnostic test
• Bronchoscopy with bronchoalveolar lavage
• CXR reveals bilateral interstitial infiltrates and
• pneumothorax
• Treatment: TMP-SMZ, dapsone, atovaquine
Opportunistic infections in AIDS
• Cytomegalovirus
• Sign and symptoms
• Retinitis, esophagitis and colitis, diarrhea, fever, retrosternal chest
pain, encephalitis
• Diagnosis:
• Fundoscopy for retinitis,
• Colonoscopy and biopsy
• Treatment: ganciclovir, cidofovir
Opportunistic infections in AIDS
• Mycobacterium avium complex
• Sign and symptoms
• Fever, night sweats, anemia, diarrhea, wasting
• Diagnosis
• Blood culture
• Bone marrow culture
• Treatment
• Clarithromycin, ethambutol and rifabutin
Opportunistic infections in AIDS
• Toxoplasmosis
• Sign and symptoms
• Brain mass lesions, headache, confusion, seizures, focal neurological
deficit
• Diagnosis
• CT scan or MRI
• Ring enhancing lesion with edema and mass effect
• Treatment : pyrimethamine, sulfadiazine
Opportunistic infections in AIDS
• Cryptococcosis
• Sign and symptoms
• Meningitis, fever, headache and malaise
• Diagnosis
• Lumbar puncture CSF and staining with India ink
• Serum cryptococcal antigen test
• Treatment
• Amphotericin
Monitoring the immune system
• CD4 count is the most accurate method for determining what
infections and other diseases the patient is at risk for.
• CD4 count is the strongest predictor of disease progression and
survival
• Antiretroviral started at counts of less than 500
Viral load monitoring
• Monitoring viral load is the best method to check adequate response
to therapy
• A high viral load generally indicates that the level of CD4 cells is going
to drop more rapidly
• It also helps to decide when to initiate antiretroviral treatment
Chemoprophylaxis
• Primary prophylaxis is used to prevent the disease that have not
occurred yet
• Secondary prophylaxis is used to prevent recurrence of opportunistic
infections
• Co-trimoxazole is used in CD4 counts less than 200
• It is well-tolerated and prevent from : pneumocystis, cerebral
toxoplasmosis, bacterial pneumonia, bacteremia, malaria,
cyctoisosporiasis
• Chemoprophylaxis for TB is considered if Mantoux test is +.
Antiretroviral therapy
1. Nucleoside reverse transcriptase inhibitors
2. Protease inhibitors
3. Non-nucleoside reverse transcriptase inhibitors
Antiretroviral therapy
Group Drug name Major side effect
name
NRTI zidovudine Leukopenia, anemia, GI symptoms
Didanosine Pancreatitis, peripheral neuropathy
Lamivudine
Tenofovir
Abacavir Hypersensitivity, fever, rash
PI Indinavir Nephrolithiasis, hyperbilirubinemia
Ritonavir GI disturbance
Saquinavir GI disturbance
NNRTI efavirenz Neurological, confusion
Nevirapine Rash, hepatotoxicity
Delavirdine Rash
Guideline for starting therapy
• Start therapy when HIV is diagnose
• HAART THERAPY
• Highly active antiretroviral therapy is a combination therapy with
synergistic effects by acting different sites of viral replicative process
• 2 NRTI (zidovudine/lamivudine, tenofovir/emtricitabine) combined
with either 1 NNRTI (Efavirenz) or 1 PI atazanavir/ ritonavir.
Pregnant patients
• Infants carry antibodies to HIV for several months and will show HIV
positive on ELISA during that period
• 25-30% of children born to HIV positive mothers will be truly HIV
positive
• Pregnant women should be treated fully for HIV just like any other
• C-section only indicated when CD4 count and viral load are not
controlled by medications
• The only Contraindicated drug = efavirenz
Breastfeeding
• HIV is transmitted by breastfeeding
• Formula milk is preferred
• Resource poor settings may allow breastfeeding only in cases when
viral load is suppressed and CD4 counts are good
• In addition infant is also started antiretrovirals
Post-exposure prophylaxis
• 3 drug combination for 4 weeks
• zidovudine+ lamivudine+ nelfinavir
• After needle stick injury or exposure to contaminated blood this
therapy for 4 weeks will reduce the risk of transmission by 80%
