JC102 (Medicine) - HIV infection Flashcards
HIV
Genus, Family
Subtypes
Genus: lentivirus
Family: retroviridiae
Two subtypes including HIV-1 and HIV2
• HIV-1 is more virulent which is causing the global HIV pandemics
HIV
Routes of transmission
Transmission:
- Sexual- semen, vaginal fluid, breast milk: Heterosexual or homosexual
- Blood: IV drug use, contaminated bloods transfusion, contaminated organs, needles
- Vertical: Mother to child
HIV
- Screening and confirmation tests
- Window period
HIV antibodies:
- Screening with ELISA to detect anti-HIV-1 ***
- Confirmation by Western blot *** of IFA or HIV RNA viral load (virological test) by RT=PCR
- Indeterminate Western blot = repeat blot in 1 month
Window period: between contracting HIV and positive HIV antibody test
- 3 months to 6 months
Outline the HIV reporting system in HK
- Major fields of information
- Sources of reports
Info:
- Gender, Age
- Ethnicity
- Source of reports
- Progression to AIDS
- Route of transmission
- Suspected place of infection
Reporting:
- Voluntary, anonymous reports from physicians and confirmatory laboratories
Population group with highest HIV incidence rate in HK
- gender, ethnicity, sexual orientation, age, source of infection, source of reporting
Male
Chinese
Homosexual > heterosexual
Age: 30-39 peak, followed by 20-29 and 40-49
Sexual contact (80%) - mostly male-to-male
Reporting: Most from public hospitals, clinic, labs
Reporting centers for HIV in HK
Public and private hospitals, clinic, laboratories
Drug rehab centers AIDS service organisations HK Red Cross Blood Transfusion Service AIDS unit in Department of Health Social hygiene clinics in Department of Health
AIDS-defining illnesses/ Definition of AIDS
Definition of AIDS
o CD4+ T-cell count < 200/μL (OR)
o Presence of any AIDS-defining conditions
AIDS-defining Illnesses:
- Pneumocystis pneumonia** and recurrent bacterial pneumonia
- Esophageal candidiasis
- HIV wasting syndrome
- Kaposi’s sarcoma
- Tuberculosis and Non-MTB infections
- CMV infections
- HIV encephalopathy and CNS Toxoplasmosis
Others: lymphomas, recurrent bacterial and fungal infections, paracytic infections…etc
Examples of HIV testing services by community organisations
Selected population group that requires regular HIV testing every 12 months
MSM - men who have sex with men
Transgender
Female sex workers and their male clients
IVDU
Spouse/regular partner with HIV infection
Name one other virus that infects MSM patients at risk of HIV
HAV
Risk factors of HIV infection
High HIV viral load
Lack of circumcision
Unprotected sex (0.08% per act for male to female; 0.04% per act for female to male)
Anal sex (1.7% risk per act)
Presence of ulcerative STD: genital herpes, syphilis (10x - 300x)
HIV superinfection or co-infection
All HIV infected pt will develop AIDS eventually
True or False?
- HIV + AIDS-defining conditions = AIDS
- Half of infected people without treatment will progress to AIDS in 10 years
- HIV treatment effectively prevents progression to AIDS
Factors influencing local HIV epidemiology
Individual behaviors
• Expanding local epidemic in MSM in HK
• IVDU in HK
Social environment
• International travelling/ sex networking increase risk to epidemic growth
• Fear of HIV-related stigma and discrimination reduces practice of preventive measures
Physical environment
• Availability of free condom
Health services
• Advances in antiretroviral therapy and HIV treatment services
Phases of HIV infection
Primary infection
Acute HIV syndrome - wide dissemination of virus, seeding into lymphoid organs
Long clinical latency phase: progressive depletion of CD4+ Th cells
AIDS-phase: Constitutional symptoms with AIDS-defining illnesses
Death
Mechanism of progressive immunodeficiency in HIV infection
Immunodeficiency resulting from progressive quantitative and qualitative deficiency of CD4+ helper T-cells in a setting of polyclonal immune activation
Mechanism of cellular depletion
• Direct infection and destruction of cells by HIV
• Immune clearance of infected cells
• Cell death associated with aberrant immune activation
• Immune exhaustion due to aberrant cellular activation
Pathogenesis of primary HIV infection
Primary infection and initial dissemination of virus
• Disruptions in mucosal barriers facilitate viral entry and efficiency of infection
• Virus infects resting and activated CD4+ T-cells and establish infection
• Replication in lymphoid tissue (NOT detectable in plasma)
Dissemination of virus to draining LNs and other lymphoid compartments with dense concentration of CD4+ T-cells
o Allow burst of high-level viremia
Pathogenesis of chronic HIV infection
Once infection is established, HIV is Never eliminated completely despite mounted cellular and humoral immune response
Development of chronicity with persistent viral replication
o Establishment of a sustained level of replication»_space;> generation of viral diversity via mutation and recombination against antibodies
o Clinical transition from acute primary infection to clinical latency
Clinical presentation of Acute HIV infection
General symptoms (non-specific, think general viral infection) • Fever • Pharyngitis • Lymphadenopathy • Headache/ Retro-orbital pain • Arthralgia/ Myalgia • Lethargy/ Malaise • Anorexia/ Weight loss • Nausea/ Vomiting/ Diarrhea
Neurological symptoms ***
• Meningitis/ Encephalitis
• Peripheral neuropathy
• Myelopathy
Dermatological symptoms *** (higher yield)
• Erythematous maculopapular rash
• Mucocutaneous ulceration
Clinical presentation of HIV infection without AIDS
Asymptomatic infection
Persistent generalized lymphadenopathy (PGL)
Symptomatic infection: Non-AIDS-defining conditions
e.g. Vaginal candidiasis, Oral hairy leukoplakia, Peripheral neuropathy, Cervical dysplasia, Idiopathic thrombocytopenic purpura
Outline history taking questions for HIV infection
History taking (5Ps) - Partners: number of partners in the last 12 months, sex of partners
- Prevention of pregnancy: contraceptive methods
- Past history of STDs, partner STDs
- Protection from STDs: Contraceptive methods, condom use, correct condom use
- Practice: Vaginal, anal, oral sex
Risks:
- IVDU
- Paid sex/ prostitution
Monitoring methods for HIV infection
Monitor plasma HIV RNA viral load every 4 weeks after initiation of therapy
CD4+ T-cell count:
- CD4+ T-cell count < 200/μL = Primary prophylaxis for P. jiroveci is indicated
- CD4+ T-cell count < 50/μL = Primary prophylaxis for CMV, M. avium complex (MAC) and T. gondii is indicated
Medical treatment options for HIV
- Standard regimen, types of drugs
2 NRTI (backbone) + 1 NNRTI/ boosted PI / Integrase inhibitor/ CCR5-antagonist
NRTI: Nucleotide/ nucleoside reverse transcriptase inhibitors - Nucleoside analog Abacavir Zidovudine Lamivudine - Nucleotide analog Tenofovir
NNRTI: Non- nucleoside reverse transcriptase inhibitors
Efavirenz
Nevirapine
Integrase inhibitor: Raltegravir
Protease inhibitor:
Indinavir
Ritonavir
Lopinavir
CCR5/ Entry or fusion inhibitors
Maraviroc
Enfuvirtide
Primary prevention against HIV in HIV negative patients
Avoid high-risk sexual behaviors
Avoid risk behavior by needle sharing
Voluntary male circumcision
Antiretroviral-based pre-exposure prophylaxis:
Tenofovir disoproxil fumarate-emtricitabine (TDF-FTC)
o TDF and FTC: 2 NRTIs
o Reduce risk of HIV transmission > 90%
Secondary prevention in HIV +ve patients
Partner counselling and referral (PCRS)
- Marital partner or regular sex partner: regular screening
- Non-commercial or non-regular sex partner: regular screening
- Regular or non-regular needle-sharing partner: stop IVDU, refer to rehab, methadone program
- Offspring with HIV+ve mother
Prevention of sexual transmission: Intensive behavioral counselling, Referral to supportive services
Prevention of transmission through needle sharing
Routine Screening of STIs
Prevention of vertical transmission of HIV
Antepartum + Intrapartum + Post-partum + Infant prophylaxis
combination ART:
Intrapartum = Zidovudine + Lamivudine + Nevirapine
Postpartum = Zidovudine + Lamivudine
Antiretroviral treatment for newborn prescribed by paediatrician
NRTI
MoA
Examples
Inhibit DNA synthesis
Structurally similar to nucleosides/ nucleotides
Competitive inhibitors of reverse transcriptase
Blocks the attachment of next nucleotide to the growing DNA chain
Terminate DNA chain
Nucleoside analog
Abacavir
Zidovudine
Lamivudine
Nucleotide analog
Tenofovir
NNRTI
MoA
Examples
Inhibit DNA synthesis
Non-competitive inhibitors of reverse transcriptase
Direct binds to reverse transcriptase and changes its structure
Active site of enzyme is disrupted
Unable to convert viral RNA to viral DNA
Efavirenz
Nevirapine
Integrase inhibitor
MoA
Examples
Inhibit integration of viral genome
Inhibit HIV enzyme called integrase
Integrase facilitates the incorporation of HIV genome into host cell genome
Raltegravir
Protease inhibitor
MoA
Example
Inhibit the activation of proteins
Block active site on HIV proteases
Inhibit HIV proteases from cleaving proteins such as reverse transcriptase and integrase
Prevent release of individual core proteins
Viral particles cannot be matured
Indinavir
Ritonavir
Lopinavir
Entry/fusion inhibitors:
MoA
Examples
Reduces viral attachment to plasma membrane
Maraviroc:
Block transmembrane chemokine receptor CCR5
Decreases viral attachment
Enfuvirtide:
Binds to glycoprotein 41 (gp41) subunit of the viral envelop
Prevent conformational changes needed for the fusion of membranes
Decreases viral attachment
