HIV sign and symptoms, medications and new clinical trends

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HUMAN IMMUNE VIRUS (ACQUIRED
IMMUNO DEFICIENCY SYNDROME)

4. H = Infects only Human beings
I = Immunodeficiency virus weakens the
immune system and increases the risk of
infection
V = Virus that attacks the body
HIV DEFINITION

5.  A unique type of virus (a retrovirus)
 Invades the helper T cells (CD4 cells) in
the body of the host (defense
mechanism of a person)
 Threatening a global epidemic.
 Preventable, manageable but not
curable.

6.  Icosahedral (20 sided), enveloped virus of the
lentivirus subfamily of retroviruses.
 Retroviruses transcribe RNA to DNA.
 Two viral strands of RNA found in core
surrounded by protein outer coat.
 Outer envelope contains a lipid matrix within which
specific viral glycoprotein's are imbedded.
 These knob-like structures responsible for binding to
target cell.
STRUCTURE OF HIV

8. The outer shell of the virus is
known as the Viral enevlope.
Embedded in the viral envelope is
a complex protein known as env
which consists of an outer
protruding cap glycoprotein (gp)
120, and a stem gp14. Within the
viral envelope is an HIV protein
called p17(matrix), and within this
is the viral core or capsid, which is
made of another viral protein
p24(core antigen).

9. (a) HIV (red) attaches to two cell-surface receptors (the CD4
antigen and a specific chemokine receptor).
(b) The virus and cell membrane fuse, and the virion core enters
the cell.
(c) The viral RNA and core proteins are released from the virion
core and are then actively transported to the nucleus.
(d) The viral RNA genome is converted into double-stranded DNA
through an enzyme unique to viruses, reverse transcriptase (red
dot).
(e) The double-stranded viral DNA moves into the cell nucleus.
(f) Using a unique viral enzyme called integrase, the viral DNA is
integrated into the cellular DNA.
(g) Viral RNA is synthesized by the cellular enzyme RNA
polymerase II using integrated viral DNA as a template. Two
types of RNA transcripts shorter spliced RNA (h) and full-length
genomic RNA (j) are produced.
(h) Shorter spliced RNAs are transported to the cytoplasm and
used for the production of several viral proteins that are then
modified in the Golgi apparatus of the cell (i).
(j) Full-length genomic RNAs are transported to the cytoplasm (k).
(l) New virion is assembled and then buds off.
(m) Mature virus is released.
Life cycle of HIV

11. MODES OF TRANSMISSION

12.  Two species of HIV infect humans:
1. HIV-1
 More virulent, relatively easy to transmit
 Majority of HIV infections globally
 3 types of HIV-1: (based on alterations in
env gene)
 Clades M, N, and O
2. HIV-2
 Less transmittable
 Largely confined to West Africa
TYPES OF HIV

13. Primary
Clinical latency
AIDS
STAGES OF HIV

14.  Symptoms are relatively nonspecific.
 HIV antibody test often negative but
becomes positive within 3 to 6 months, this
process is known as seroconversion.
 Large amount of HIV in the peripheral
blood.
 Primary HIV can be diagnosed using viral
load titer assay or other tests.
 Primary HIV syndrome resolves itself and
HIV infected person remains asymptomatic
for a prolonged period of time, often years.
PRIMARY

15.  HIV continues to reproduce, CD4 count
gradually declines from its normal value of 500-
1200.
 Once CD4 count drops below 500, HIV infected
person at risk for opportunistic infections.
 The following diseases are predictive of the
progression to AIDS:
 persistent herpes-zoster infection (shingles)
 oral candidiasis (thrush)
 oral hairy leukoplakia
 Kaposi’s sarcoma (KS)
CLINICAL LATENCY

16.  Opportunistic infections and malignancies that
rarely occur in the absence of severe
immunodeficiency (eg, Pneumocystis pneumonia,
central nervous system lymphoma).
 Persons with positive HIV serology who have ever
had a CD4 lymphocyte count below 200 cells/mcL or
a CD4 lymphocyte percentage below 14% are
considered to have AIDS.
AIDS

17.  CD4 count drops below 200 person is considered to have
advanced HIV disease
 If preventative medications not started the HIV infected
person is now at risk for:
 Pneumocystis carinii pneumonia (PCP)
 cryptococcal meningitis
 toxoplasmosis
 If CD4 count drops below 50:
 Mycobacterium avium
 Cytomegalovirus infections
 lymphoma
 dementia
 Most deaths occur with CD4 counts below 50.

18.  EARLY SYMPTOM:
Most don’t exhibit symptoms when first
infected
However, may have flu-like symptoms
(fever, headache, tired, enlarged lymph
nodes) 1-2 months after exposure
Very infectious during this period
SYMPTOMS

19.  Later Symptoms:
 More severe symptoms may not appear until after 10yrs, however this
varies with each individual
 Decline in number of CD4 + T cells
 The most advanced stage of AIDS is classified as having < 200 CD4+ T
cells/cubic millimeter of blood (in healthy adults CD4+ T-cell counts =
1,000+)
 Onset of AIDS is characterized by:
 weight loss,
 fatigue
 rashes/flaky skin,
 persistent yeast infections,
 Pelvic inflammatory disease in women will not respond to treatments,
 short-term memory loss,
 frequent and severe herpes infections,
 shingles
 coma
 deaths

20. ELISA
Agglutination tests
Dot-Blot Testing
Western blot
PCR
DIAGNOSTIC TESTS

21.  First serological test developed to detect HIV
infection.
 Easy to perform.
 Easily adapted to batch testing.
 Highly sensitive and specific.
 Antibodies detected in ELISA include those
directed against: p24, gp120, gp160 and gp41,
detected first in infection and appear in most
individuals
ELISA

22. Generation of ELISA Tests
First Second Third *Fourth
Uses crude viral
lysate
Detects IgM and IgG in
“Sandwich” EIA
Uses recombinant HIV
antigens or peptides
Detects HIV antibodies
and p24 antigen
*Not US FDA-approved as of
10/1/12

23. •Based on color
change/fluorescence
•Change compared with
standardized cut-off
•Result positive or negative
•No specific antibody reaction
information
•Multiple samples run with
traditional EIA
96-Well Microtiter Plate EIA Interpretation of ELISAs

24.  Most popular confirmatory test.
 Utilizes a lysate prepared from HIV virus.
 The lysate is electrophoresed to separate out the HIV proteins
(antigens).
 The paper is cut into strips and reacted with test sera.
 After incubation and washing anti-antibody tagged with
radioisotope or enzyme is added.
 Specific bands form where antibody has reacted with
different antigens.
 Most critical reagent of test is purest quality HIV antigen.
 The following antigens must be present: p17, p24, p31, gp41,
p51, p55, p66, gp120 and gp160.
WESTERN BLOT

25. Human HIV Antibodies
(from patient serum)
Y YY Y
HIV Western blot Strip
YY
HIV Antigens
(on Western blot)
YY Y
Antihuman IgG Antibodies
Enzyme Detector
Color Reagent

26. Sample HIV-1 Western Blot
YY
Y
YY
Y
Y
Y
YY
Y
Y
Antibodies to gp120
Anti-human IgG
Enzyme Detector
HIV gp120 antigen
Color Reagent
Antibodies to p24
Enzyme Detector
HIV p24 antigen
Color Reagent
Anti-human IgG
Test Completed gp120 & p24 bands
Visible

27. Agglutination tests using latex
particles, gelatin particles or
microbeads are coated with
HIV antigen and will
agglutinate in the presence of
antibody
AGGLUTINATION

29.  Dot-Blot Testing utilizes paper or
nitrocellulose impregnated with antigen,
patient serum is filtered through, and
anti-antibody is added with enzyme
label, color change is positive.
DOT BLOT TESTING

31.  Looks for HIV DNA in the WBCs of a person.
 PCR amplifies tiny quantities of the HIV DNA present, each
cycle of PCR results in doubling of the DNA sequences
present.
 The DNA is detected by using radioactive or biotinylated
probes.
 Once DNA is amplified it is placed on nitrocellulose paper
and allowed to react with a radiolabeled probe, a single
stranded DNA fragment unique to HIV, which will
hybridize with the patient’s HIV DNA if present.
 Radioactivity is determined.
PCR

32. Treatment with antiretroviral medicines,
against the retrovirus (HIV), which resides
and multiplies within the human body
HIV; etiological agent of AIDS
Hallmark of HIV; RNA virus that transcripts
DNA from RNA via the Reverse
Transcriptase enzyme
TREATMENT

33.  NRTI (Nucleoside Reverse Transcriptase
Inhibitors)
 NtRTI (Nucleotide Reverse Transcriptase
Inhibitors)
 NNRTI ( Non-Nucleoside Reverse
Transcriptase Inhibitors)
 PI (Protease Inhibitors)
 Entry Inhibitors
 Integrase Inhibitors
CLASSIFICATION

34. Abacavir (ABC)
Didanosine (DDI)
Emtricitabine (FTC)
Lamivudine (3TC)
Stavudine (D4T)
Zidovudine (AZT)
Tenofovir (TDF) - NtRTI
NRTIs

35. Efavirenz (EFV)
Nevirapine (NVP)
Etravirine
Rilpivirine
NNRTIs

36.  Atazanavir (ATV)
 Durunavir (DRV)
 Fosamprenavir (f-APV)
 Indinavir (IDV)
 Lopinavir (LPV)
 Nelfinavir (NFV)
 Ritonavir (RTV)
 Saquinavir (SQV)
 Tripranvir (TPV)
PIs

37. Entry inhibitors: Enfuvirtide, Maraviroc
Integrase inhibitors: Raltegravir,
Elvitegravir
Maturation inhibitors: Beviramat

38. ART (Antiretroviral Therapy)
PMTCT (Prevention of Mother To Child
Transmission)
PEP (Post Exposure Prophylaxis)
PrEP (Pre Exposure Prophylaxis)
USES OF ART

39. Combines at least 3 ARVs from at least 2
different classes.
Why combination?
 Synergism
 Reduced toxicity
 Prevent resistance

40. 2 NRTI + 1 NNRTI
1 NRTI + 1 NtRTI + 1 NNRTI
2NRTI + boosted PI
1 NRTI + 1 NtRTI + boosted PI
3 NRTI (One must be Abacavir)
COMBINATIONS

41.  Maximal and durable suppression of viral replication
to prevent development of HIV, drug resistance and
treatment failure
 Restoration/ preservation of immunologic function
 Reduction of HIV-related morbidity and mortality
 Improvement of the patient’s quality of life
 Prevention of onward transmission of HIV infection
GOALS OF ART

42. Recommended first-line antiretroviral
regimens in treatment of naive adults and
adolescents are:
TDF + 3TC + EFV or NVP or
AZT + 3TC + NVP or EFV

43. Recommended second-line for patients
failing first line therapy

44. First-line
TDF + 3TC + EFV or NVP
AZT + 3TC + EFV or NVP
d4T + 3TC + EFV or NVP
Second-line
AZT + 3TC + LPV/r or ATV/r
TDF + 3TC + LPV/r or ATV/r
TDF + 3TC + LPV/r or ATV/r

45. NEW CLINICAL TRENDS

46.  Abstinence :
 It is the practice of restraining oneself from indulging in something, typically
alcohol or sex.
 Behavioral changes:
 Behavior change can refer to any transformation or modification of
human behavior.
 Condom usage:
 Use condom
 Male circumcision is the surgical removal of the foreskin (prepuce) from the
human penis. In a typical procedure, the foreskin is opened and then
separated from the glans after inspection
 Usage of antiretroviral to decrease the HIV.
Trends in prevention

47.  Usage of fourth generation ELISA. (ELISA is a popular format of "wet-lab"
type analytic biochemistry assay that uses a solid-
phase enzyme immunoassay (EIA) to detect the presence of a substance,
usually an antigen, in a liquid sample or wet sample)
 Home based HIV testing and counseling (HBHTC)
 CD4 count test is used to estimate the loads of viral. (CD4 is a glycoprotein
found on the surface of immune cells such as T helper cells, monocytes,
macrophages, and dendritic cells.)
 [Serostatus. The state of either having or not having detectable antibodies
against a specific antigen, as measured by a blood test (serologic test). For
example, HIV seropositive means that a person has detectable antibodies to
HIV; seronegative means that a person does not have detectable HIV
antibodies.]
Trends in diagnosis and monitoring

48. tenofovir and emtricitabine (new formulations )
Fixed dose combinations.
ART
Synthetic peptides and Env mimic peptide
drugs
HIV entry inhibitors
Trends in HIV management

49. ART
Gene therapy (gene editing through
CCR5)
Vaccination
Trends in cure

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