Recent Developments in AIDS Diagnosis & Treatment - PowerPoint Presentation

Slide1

Recent Developments in AIDS Diagnosis & Treatment

Presented by Joyce Lee, Kobika Thiyagasothy & Stephen YeeSlide2

Overview

Introduction to AIDSDiagnosis of HIV-AIDSTreatment of HIV-AIDS SummarySlide3

Introduction to AIDSSlide4

What Is HIV/AIDS?

Human Immunodeficiency Virus (HIV) causes Acquired Immune Deficiency Syndrome (AIDS)Origin of HIV HIV-2 from soty

mangabeys

HIV-1 from chimps Slide5

Viral Life Cycle

2 phases: Extracellular & Intracellular Virus targets CD4 Receptor and Co-Receptor on T-helper cellsReverse transcription of viral genome into a DNA copy followed by integration into host genomeNew virions

assembled and bud off from hostSlide6

How Does HIV Spread?

Transfer of bodily fluidsHetero and homosexual sexOral SexNeedle SharingTransfusion of contaminated blood products

Childbirth & BreastfeedingSlide7

HIV/AIDS Mechanism

Immune system battles with virusDepletion of helper T-cellsHost becomes vulnerable to secondary infectionsSlide8

HIV/AIDS Mechanism

3 Phases of InfectionAcute PhaseInitial spike in viral loadFollowed by host immune response

Chronic Phase

Immune system remains highly activated

Results in depletion of helper T-cells

AIDS PhaseSlide9

AIDS as a Public Health Issue

First case in 198113 400 newly infected with HIV every day8 500 die of AIDS everydaySlide10

Methods of DiagnosisSlide11

Symptom Diagnosis

Compromised immune systemHigh vulnerability to opportunistic infectionsSeverity of symptoms can encompass multiple organ systemsSlide12

Symptom Diagnosis

PulmonaryPneumoncytis Pneumonia (PCP)Tuberculosis (TB)Gastrointestinal

Esophagitis

Chronic Diarrhea

Salmonella,

Shigella

, Listeria, CampylobacterSlide13

Symptom Diagnosis

NeurologicalTaxoplasmosisProgressive Multifocal Leukoencephalopathy

(PML)

Tumors

Epstein-Barr Virus (EBV)

Kaposi’s Sarcoma-Associated

Herpesvirus

(KSHV)

Human Papillomavirus (HPV)Slide14

Symptom DiagnosisSlide15

Antibody Tests

Enzyme Linked Immunosorbent Assay (ELISA)High degree of sensitivity for screeningWestern Blot Test

Viral proteins are separated first

Rapid Antibody Test

Qualitative immunoassays

OraQuick

,

Orasure

&

UniGoldSlide16

Antibody Tests

Enzyme Immunoassays (EIA) 3rd GenerationWells contain recombinant proteins or synthetic peptidesAlso contains anti-HIV

IgG

and

IgM

antibodies

Change in colour indicates presence of anti-HIV

IgG

and

IgM

Faster detection of HIV infection than previous 2 generationsSlide17

Antigen Tests

P24 antigen test for HIV specificityA capsid protein of the virusVery short window of viabilitySlide18

Antibody TestsSlide19

Nucleic Acid-Based Tests

Has been used to detect diseases and genetic implicationsDetection of target HIV gene sequencesPCR is one method used to detect diagnostic DNA fragmentsSlide20

Nucleic Acid-Based Tests

Polymerase Chain Reaction (PCR) uses heat stable DNA polymerase and 2 primers to amplify a target sequenceReal-time PCR Assays: Quantitative Method to measure PCR product as it is producedAllows quantification of number of pathogens in a sampleSlide21

Nucleic Acid-Based Tests

Abbot RealTime HIV-1 AssayNested set of hybridization probes of various lengthsFluorescein (FAM) label at the 5’ endDabcyl

or BHQ 1–

dT

at the 3’ endSlide22

Nucleic Acid-Based Tests

In absence of target sequence, the quencher in close proximity of FAM absorbs the fluorescent signalIn presence of target sequence, the hybridization probe binds to target sequenceQuencher separates from FAM resulting in fluorescent emissionSlide23
Slide24

Antibody Tests

Enzyme Immunoassays (EIA) 4th GenerationWell coated with HIV antigen and P24 antibodyColour change indicates anti-HIV antibody or P24 antigen

Detection of P24 allows for earlier diagnosis of HIV infectionSlide25

Algorithm Tests

Future AlgorithmsTesting algorithm proposed to use the most sensitive test possible with assays that differentiate HIV-1 from HIV-2 antibodiesIf reactive for Ag / Ab but negative for antibodies, then tested for HIV-1 RNA

RNA establishes diagnosis of AHI which alerts doctors for urgent careSlide26
Slide27

SIMBAS

Self-Powered Integrated Microfluidic Blood Analysis System (SIMBAS)Future cell powered chipWorks like pregnancy test but checks for HIV or TBChip separates plasma from blood cells and detects if Vitamin B7 or Biotin was presentDiagnosis in a matter of minutesSlide28

Methods of Treating HIV/AIDS PatientsSlide29

Treatment

Isolated to homosexuals, hemophiliacs and heroin usersNo actual curePrevention based treatmentSexual EducationDrug AwarenessSlide30

Treatment

AZTStructure similar to normal nucleotide ThymidineHas a –N3

group which interrupts DNA synthesis

Proved effective and halted loss of macrophages and T-cells

In 1989 patients stopped responding

Mutations were located in active sites of reverse transcriptaseSlide31

Antiretrovirals

Delay onset of infectionsLifetime commitment drug planDetermined necessity by CD4 testGoal is to keep HIV in the body at a low levelSlide32

Antiretrovirals

5 Major ClassesProtease InhibitorsFusion or Entry InhibitorsIntegrase

Inhibitors

Nucleoside/Nucleotide RT Inhibitors

Non-Nucleoside RT InhibitorsSlide33

Combination Therapy

AIDS is virus with high fidelity Capable of developing resistance quicklyCross ResistanceSalvage TreatmentSlide34

Side-Effects

Drug Specific Side-EffectsEfavirenz causes psychiatric symptomsProtease inhibitors raise cholesterol and triglyceride levelsHigh Blood Pressure

Susceptibility to Hepatitis infectionsSlide35

Side-Effects

Common antiretroviral symptomsDiarrheaNausea & VomitingRashes

Lipidystrophy

with Loss or Gain of Fat

Lipid AbnormalitiesSlide36

Maturation Inhibitors

Immature HIV particles composed of Gag precursor proteinsMature infectious particle contains dense nucleoprotein Nucleocapsid and RNABevirimat

delays or blocks mature infectious particles from formingSlide37

Maturation InhibitorsSlide38

Maturation InhibitorsSlide39

Integrase Inhibitors

RaltegravirDolutegravirSuccessful HIV replication requires 3 enzymes

Reverse Transcriptase,

Integrase

& Protease

Inhibiting

integrase

blocks integration of HIV-1 DNA to host genome

Prevents HIV replication and infection of new cellsSlide40

Treatments

CCR5 ∆32/ ∆32 Stem Cell TransplantationPatient remains without any sign of HIV infection after successful transplantationSize of viral reservoir was reduced over timeCells of persons homozygous for the CCR5 gene variant ∆32 are naturally resistant to R5 HIV strainSlide41

Treatments

ImmunotherapyHIV infection results in CD4+ T-cell deficiencyCorrelation between a low CD4

+

T cell count with higher morbidity

Helps maintain high level

of CD4

+

T-helper

cellsSlide42

Treatments

The Thai Trial$105 million, 6 year trial in ThailandExperimental Vaccine 31% effective in preventing HIV infectionRV144 a combination of ALVAC and AIDSVAXStudy group includes low-risk heterosexual adultsSlide43

Time to Go HomeSlide44

Conclusion

Permanent cure unlikely because of rapidly reproductive nature of HIVNew combinatorial drug therapies are on the horizonStill an importance on preventative measuresSlide45

References

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/

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, Teresa H., and Martin Markowitz. "HIV-1

Integrase

Inhibitors."

PRN Notebook

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Huang

,

Shihai

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Salituro

,

Ning

Tang,

Ka

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Luk

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Jr

Hackett, Priscilla Swanson, Gavin

Cloherty

,

Wai

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Mak

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Klara

Abravaya

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;.

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