hiv Flashcards
There are two types of HIV:
I. HIV-1
▪ Which is found worldwide and is responsible for the worldwide
pandemic.
▪ HIV-1 has many subtypes, often varying in transmissibility and virulence, as
well as other characteristics.
II. HIV-2
▪ Which is found mainly in West Africa, Mozambique and Angola
▪ HIV-2 is less pathogenic and makes little or no contribution to pediatric AIDS.
The HIV life cycle in the host cell can be divided into several steps;
- Binding; HIV binds to cells via interaction between the HIV envelope
glycoprotein (gp120) and the host cell receptors(CD4molecule) and co-receptors. - Fusion; binding results in the insertion of the trans-membrane glycoprotein
(gp41) into the cell membrane of the host cell, with fusion of the two
membranes. - Entry; The virus particle leaves its membrane behind(uncoating)and the core of
the virus is released into the cytoplasm of the host cell. - Reverse transcription; For the virus to multiply, the viral (single strand) RNA
must first be converted into (double-strand)DNA by reverse transcriptase. - Integration and replication; the viral DNA is then able to enter
the host nucleus and the viral enzyme integrase is used to insert
the viral DNA into the host cell’s DNA. - Budding; newly formed immature viral particles gather at the
membrane of the CD4 cells and push through the cell membrane
by budding. - Maturation; The gp160, embedded in the cell membrane, is
cleaved by the enzyme protease to produce functional
gp41andgp120 to form a mature virus, which is then ready to
infect a new cell.
Transmission
✓ Mother to child (MTCT)
✓ Sexual abuse
✓ Blood products or transplant
✓ Unsterile injections, Unsterile surgeries
✓ scarification e.g. tattoo
Risk factor for vertical transmission
Maternal factors
✓ High viral load
✓ Low CD4 count
✓ Micronutrient deficiency (e.g. vit A)
✓ Artificial rapture of membrane(
Amniotomy),or rapture of membrane >4hr
✓ Chorioamnionitis, STIs, APH(antepartum
hemorrhage)
✓ Cracked nipples, breast abscess
✓ Vaginal; instrumental delivery
* Infant factors
✓Prematurity (<34 wks.)
✓Breast-feeding
✓Oral lesion (thrush, ulcer)
✓Fetal scalp monitoring
✓Instrumental deliveries
✓First twin (3 folds)
✓Resuscitation
✓Congenital defects
Mechanism of depletion of CD4 in adults and children
✓HIV meditated single cell killing
✓Formation of multinucleated giant cells of infected and uninfected CD4
cells
✓Virus specific immune responses
✓Super antigen mediated activation of T cells
✓Autoimmunity
✓Programmed cell death
Children prenatally infected with HIV fit into one of 3 categories:
Category 1 (25–30%): Rapid progressors, who die by the age of one and
who are thought to have acquired the infection in utero or during the
early perinatal period.
Category 2 (50–60%): slow progressors Children who develop
symptoms early in life, followed by a downhill course and death by the
age of three to five.
✓Category 3 (5–25%): Long-term survivors, who live beyond the age of
eight
diagnosis by
antibody testing
dna pcr
virologic testing
Antibody testing
who
when
how many tests
who arent breast feeding
but EFF after 18 months
EBF after 24 months
wait 3 months after breast feeding cesation
✓2 positive different rapid tests confirm diagnosis.
✓Or 1 positive rapid test confirmed by a PCR (viral load)
Virologic tests
✓ Specialized virologic tests are used:
✓ HIV DNA /PCR
✓ HIV RNA/ PCR
✓ p24 Antigen
✓ Viral Culture
* Two positive virology tests = HIV infection
* One positive virology test = Presumed HIV infection
HIV DNA PCR
ideal time why
when to repeat
✓At 6 weeks of life or
✓At first visit (if >6 weeks of age)
✓6 weeks is ideal time as most infants have their first visit for
immunizations and growth monitoring
f antibody is negative and infant is still breastfeeding, repeat rapid
antibody 6-12 weeks after cessation of breast feeding.
Presumptive diagnosis of HIV disease
In an HIV sero-positive infant less than18 months symptomatic with 2
or more of following:
✓ oral thrush,
✓ +/- severe pneumonia,
✓ +/- severe wasting/malnutrition,
✓ +/- severe sepsis or
✓ Any stage 4 Condition or AIDS defining condition
WHO pediatric clinical staging of infants and children with
established HIV infection
4 STAGES
stage 1
- Asymptomatic
- Persistent generalized lymphadenopathy (PGL)
stage 2
- Unexplained persistent hepatosplenomegaly
- Fungal nail infection
- Herpes zoster
- Recurrent oral ulceration (>2 episodes/ 6 months)
- Lineal gingival ulceration
- Papular pruritic eruptions
- Extensive wart virus infection
- Extensive HPV or mollosucm contagious contagiosum
- Unexplained persistent parotid enlargement
- Recurrent or chronic upper respiratory tract infection (URTI), otitis media, otorrhea,
sinusitis, tonsillitis (with at least 1 episode in the last 6 months)
URTI
SKIN LESION MC GINGIVA ULCERATION
PAROTID ENLARGEMENT
HEPATOSLEENOMEGALY
stage 3
- Unexplained moderate malnutrition (-2 SD or Z score) not adequately responding to standard
therapy - Unexplained persistent diarrhea (≥14 days)
- Unexplained persistent fever above 37.5 °C (intermittent or constant) for longer than 1
month - Persistent oral candidiasis (after first 6 weeks of life)
- Oral hairy leukoplakia
- Lymph node TB
- Pulmonary tuberculosis
- Severe recurrent bacterial pneumonia (current episode plus 1 or more episodes in previous
6 months) - Acute necrotizing ulcerative gingivitis/periodontitis
- Symptomatic lymphoid interstitial pneumonitis (LIP)
- Chronic HIV-associated lung disease including bronchiectasis
- Unexplained anemia
malnutrtion
diarhea
fever
oral candida
oral leukohairyplakia
LIP
anemia
Stage 4
- Kaposi’s sarcoma
- Esophageal candidiasis (or candida of trachea,
bronchi or lungs) - CNS toxoplasmosis (after the neonatal period)
- HIV encephalopathy
- CMV) infection; retinitis or CMV affecting another
organ with onset at age over 1 month - Extrapulmonary cryptococcosis, including
meningitis - Any disseminated endemic mycosis
(extrapulmonary histoplasmosis, coccidiomycosis) - Chronic cryptosporidiosis with diarrhea
- Chronic isosporiasis
- Disseminated non-tuberculous
mycobacterial infection - Acquired HIV-associated rectal fistula
- Cerebral or B cell non-Hodgkin’s
lymphoma - Progressive multifocal
leukoencephalopathy (PML) - HIV-related cardiomyopathy or
nephropathy
Opportunistic infections
microorganisms which are not harmful to our body
when our cell mediated- immunity is intact.
* Generally seen in children with severe depression of the CD4 count.
* In children with severe immunodeficiency clinical manifestations may
vary.
* Younger children have primary infection rather than reactivation.
Pneumocystis Pneumonia
triad
diagnosis plus gold standard
treatment
triad
tachypnea dyspnea fever
cxr interstitial infiltrates
bronchoalveolar lavage GS
treatment
cotrimoxazole
steroids
➢ Fungal infections
oral and esophagial candidiasis
clinical manifestation
Anorexia, dysphagia, vomiting, and fever
Parasitic infections
✓ intestinal cryptosporidiosis and microsporidiosis and rarely isosporiasis or giardiasis cause
significant morbidity.
✓ they cause severe chronic diarrhea in HIV-infected children with low CD4 counts, often
leading to malnutrition
Viral Infections
HSV
varicella zoster
cmv
measeles
mollouscum contagiosum
cmv manifestations
✓Occurs when there is severe CD4 depletion (<50 CD4 cells/µL for >6 yr.)
✓Retinitis, pneumonitis, esophagitis, gastritis with pyloric obstruction,
hepatitis, colitis, and encephalitis have been reported, but these
complications are rarely seen if cART is given
IRIS
Immune reconstitution inflammatory syndrome is characterized by an increased
inflammatory response from the recovered immune system to subclinical
opportunistic infections.
Patients with IRIS develop fever and worsening of the clinical features of the
opportunistic infection or new manifestations within the 1st few weeks after
treatment
cns infections
hiv encephalitis
cns lymphoma
cns toxo
HIV encephalopathy manifestations
▪ With progression marked apathy, spasticity, hyper reflexia, and gait
disturbance may occur, as well as loss of language and oral, fine, and/or
gross motor skills
▪ Imaging: cerebral atrophy, increased ventricular size, basal ganglia
calcifications and, less frequently, leukomalacia.
CNS lymphoma
✓C/f
New-onset focal neurologic finding, headaches, seizures and mental status
changes
✓Imaging:
✓include a hyperdense or isodense mass with variable contrast enhancement or a
diffusely or,
✓an infiltrating contrast-enhancing mass
CNS toxoplasma
associated with serum anti toxoplasma IgG as a marker of infection
respiratory system infections
Recurrent Upper Respiratory Tract Infections
Lymphocytic intestinal pneumonia
pneumonia
TB
Lymphocytic intestinal pneumonia
✓ most common chronic lower respiratory tract abnormality reported foR HIV children (25%).
✓ it is a chronic process with nodular lymphoid hyperplasia in the bronchial and bronchiolar epithelium, often leading to progressive alveolar capillary block over months to years.
✓ C/f: insidious onset of tachypnea, cough, and mild to moderate hypoxemia with normal auscultatory findings or minimal rales
renal disease nephropathy
Nephrotic Syndrome , is the most common manifestation of
pediatric renal disease characterized by edema,
hypoalbuminemia, proteinuria, and azotemia with normal
blood pressure
Skin manifestation
▪ Seborrheic dermatitis or eczema that is severe and unresponsive to treatment
may be an early nonspecific sign of HIV infection.
▪ Recurrent or chronic episodes of HSV, herpes zoster, molluscum contagiosum, flat warts, anogenital warts, and candida infections are common and may be difficult to control
Hematologic and Malignant diseases
anemia
leukopenia
thombocytopenia
malignancy
prevention
prong
Classes of Antiretroviral drugs
- Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs): Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Tenofovir, Zidovudine
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Efavirenz, Nevirapine, Rilpivirine
- Protease inhibitors Indinavir, Lopinavir/ritonavir Kaletra, Nefinavir, Ritonavir
- Fusion inhibitors (Enfuvirtide)
- Integrase inhibitors (Elvitegravir and Raltegravir)
- CCR5 Antagonist- (Maraviroc)
side effect of abacavir ziduvodin emitricabin nevirapin
lopinavir
abacavir hypersensitovity
zidovudin anemia neutopenia lactic acidosis
emitricabin pancreatitis
nevirapin hepatotoxity , SJS
lopinavir diarhhea nausea
failure
clinical
immunologic
virologic
clinical failure
✓ WHO clinical stage 3 and 4 clinical condition with exception of TB after 6 month of effective
treatment.
✓ Loss of neuro dev’tal milestones, or dev’t of HIV encephalopathy
✓ New or recurrent clinical event such as oral candidiasis unresponsive to treatment
Immunologic failure
✓Younger than 5 yrs.—-Persistent CD4 count < 200 cells/mm3 or <10%
✓Older than 5 years—–Persistent CD4 levels <100 cells/mm3
virologic failure
✓Persistent viral load >1000 RNA copies/ml after at least 24 weeks
on ART, and based on two consecutive measurements within 3
months, with adherence to treatment.
