Virus 1 (RNA): HIV/AIDS

Question 1

How do you define viruses, bacteria, protozoa and parasites?

Answer 1

• Virus:
  
  • an infective agent that typically consists of a nucleic acid molecule in a protein coat, is too small to be seen by light microscopy, and is able to multiply only within the living cells of a host.
• Bacteria:
  
  • unicellular microorganisms which have cell walls but lack organelles and an organized nucleus
• Protozoa:
  
  • single-celled eukaryotes, either free-living or parasitic, which feed on organic matter such as other microorganisms or organic tissues and debris
• Parasites:
  
  • organism that lives in or on an organism of another species (its host) and benefits by deriving nutrients at the other’s expense

Question 2

Which viruses cause HIV and where are they found?

Answer 2

HIV-1: universally distributed

HIV-2: less common, West Africa

• Where both exist, HIV-1 is rapidly overtaking HIV-2 in prevalence
• Dual infection can occur and one does ot protect against the other
• Same immune defects with a similar disease
• HIV-2 does not usually cause Kaposi sarcoma or similar
• HIV-2 is less aggressive but it is also less amenable to many of the drugs that target HIV-1
• Where both a prevalent, make sure that testing is able to identify both diseases

Question 3

Who should we test routinely and what test do we use for patients with potential HIV?

Answer 3

• Risk populations: MSM, transgender, IVDU, sex workers, sero-negative partners in sero-discordant ocuples
• Opt-out testing to pregnant woman, inpatients, patients with TB or STIs -> provider initated testin and counselling
• Clinet-inititated voluntary counselling and testing
• Tests used:
  
  • Lab-based antibody Elisa - large numbers of samples
  • Rapid antibody ELISA - easy to use and store
  • Fourth generation assays: detect HIV antibody + HIV antigen p24 (therefore can be used in window period of acute HIV infection before antibody appears)
  • PCR for HIV RNA - used in infants exposed to HIV as mothers anitbodies to HIV stay up to 18months
• Postitive screens should be followed up with one alternative test
• If +ve screen for other blood borne viruses (HBV, HCV, syphilis, STI) and TB

Question 4

What is the global prevalence of HIV and how is it transmitted?

Answer 4

• 10% of world’s population
• HIV prevalence >20% in: Lesotho, Swaziland and Botswana
• Monitoring, especially of high risk groups and geographic regions important
• Sub-Saharan Africa majority of all new infections and AIDS cases
• Transmission:
  
  • Sexual transmission most significant
    
    • Highest risk: anal and MSM. Traumatic sex, such as in rape, has higher transmission rate. Underlying STIs increase risk of transmission. Uncircumcised men also more likely (circumcision reduces risk of transmission by 60%)
    • Highest risk for sexual transmission occurs during HIV seroconversion
  • Vertical transmission
    
    • 10% transplacentally, %% during delivery, 10% as a result of breastfeeding
    • Maternal viral laod most important factor
    • In resource poor setting: benefits of breast milk in reducing infant mortality outweighs risk of transmission
    • ART can hugely prevent this
  • Blood
    
    • Blood transfusion -> donors now screened
    • Needle sharing
    • Needle stick: 0.3%, less if PEP
      
      • Hep B 3%
      • Hep C 30%

Question 5

What is the pathogenesis of HIV?

Answer 5

• HIV infect CD4 T cells
• Progressive loss and depletion of CD4 cells
• Loss of CD4 cells leads to disruption of cell-mediated and humoral immune response
• Active replication of HIV in lymph nodes at all stages
• Initially, flu-like illness -> window period
• Early stages: good response to therapy, preserved immune system, high frequency of infection
• Later stages: Diminished response to therapy, atypical infections
• Pathogens at any stage: MTB, Strep pneumo, non-typhoidal salmonella
• Advanced infections: Cryptococcus, PCP, toxoplasma, HHV8, CMV, VZV
• Higher incidence of cancers: NHL, CNC lymphoma and Kaposi’s

Question 6

What are the different stages of HIV infection?

Answer 6

• Normal CD4 count 800 - 1500
• Important 2016: ART should be initiated in all persons living with HIV regardless of clinical stage or CD4 count
• Important 2018: Dolutegravir should be preferred first line treatment

Clinical stage 1:

• Primary HIV infection: Asymptomatic or seroconversion in a small minority
• At this stage CD4 count falls but then rises again at the end as individuals feel normal again
• Only p24 antigen tests will be positive

syndrome

• Asymptomatic or persistent generalized lymphadenopathy

(PGL)

Clinical stage 2:

• Weight loss <10% of presumed body weight
• Recurrent respiratory tract infections (including sinusitis and ear infections)
• Herpes zoster
• Oral ulcers
• Seborrhoeic dermatitis
• Fungal nail infections
• Angular chelitis

• Clinical stage 3:

• Weight loss of >10% presumed body weight
• Unexplained diarrhoea for >1 month
• Unexplained fever for >1 month
• Oral candida
• Oral hairy leukoplakia
• Pulmonary tuberculosis
• Severe bacterial infections (including meningitis,
• empyema, pneumonia, bone and joint sepsis)
• Vulvo-vaginal candidiasis for >1 month

• Clinical stage 4:

• HIV wasting syndrome
• Pneumocystis pneumonia
• Cryptosporidiosis or cystoisosporiaisis and diarrhoea for >1 month
• Chronic herpes simplex infection for > 1 month
• Oesophageal candidiasis
• Extrapulmonary tuberculosis
• Kaposi’s sarcoma
• Cerebral toxoplasmosis
• HIV encephalopathy
• CMV infection
• Cryptococcal infection
• Atypical mycobacterial infection
• Lymphoma

Question 7

What are the AIDS defining clinical criteria?

Answer 7

Question 8

What are the current guidelines for the treatment of HIV?

Answer 8

Enhanced prophylaxis not part of guidelines yet but show promising results (REALITY trial):

• Standard prophylaxis: co-trimoxazole
• Enhanced prophylaxis:

Co-trimox + 12 weeks isoniazid, pyridoxine, fluconazole + 5 days azithromycin + single dose albendazole

Question 9

What are the mechanisms of action of the different HIV drugs?

Answer 9

Question 10

What is immune reconstitution syndrome and how does it cause issues?

Answer 10

• High mortality in first 12 months of starting ART]
  
  • 8 - 26% in SSA die within 12 months of starting ART
  • Risk factors:
    
    • Los baseline CD4
    • WHO stage 4 disease
    • Low BMI
    • Anaemia

Question 11

Which conditions present contra-indication to starting ART?

Answer 11

Question 12

What happens after a patient is diagnosed with HIV?

Answer 12

Perform blood test for other conditions

Question 13

What is the UNAIDS 90-90-90 target, what are the 5 pillars of HIV prevention and where do current issues lie?

Answer 13

The five HIV prevention pillars:

• Programmes for young women and their partners in high prevalence areas
• Key population services in all countries
• Strengthened national condom programmes
• Voluntary medical male circumcision
• PrEP for high risk population

Issues:

• Many people never tested
• High mortality between testing and ARV initiation
• Very high mortality within first two months of ARV initiation
• Long term adherence, resistance, toxicity and NCD risks

Question 14

Characteristics, diagnosis and management of opportunistic infections: CMV

Answer 14

Characteristics:

• Herpesvirus that persists.
• Primary infection asx; reactivation in immunosuppressed
• End-organ damage when CD4<40
• Retinitis (75%) > Colon (ulceration, owl’s eye inclusion bodies)/Biliary > Lung (pneumonitis) > CNS

Question 15

Characteristics, diagnosis and management of opportunistic infections: Cryptococcus

Answer 15

Characteristics:

• Two species of yeast: Crytococcus neformans var neoformans // var gattii
• 80% in advanced HIV
• Often meningitis, raised ICP, encephalitis

Diagnosis:

• Crytococcal antigen
• India ink stain of CSF
• Culture
• CXR

Question 16

Characteristics, diagnosis and management of opportunistic infections: Toxoplasmosis

Answer 16

Characteristics:

• Immunocompetent host: 80 - 90% asymptomatic, if symptoms, extremely varied: generalised lymphadenopathy
• 11% of 6 - 49yo in US seropositive
• Cerebral toxoplasmosis

Question 17

Characteristics, diagnosis and management of opportunistic infections: Kaposi’s sarcoma

Answer 17

Characteristics:

• HHV8 infection
• 4 types:
  
  • Classic: indolent, med/ssa, LLs, cutaneous, >60yrs
  • Endemic (african): children + adults
  • Iatrogenic: exogenous immunosuppression, frequently visceral
  • AIDS-assoc: disseminated at low CD4

Question 18

Characteristics, diagnosis and management of opportunistic infections: PCP

Answer 18

Question 19

List of Non-AIDS defining illnesses

Answer 19

• Oral candidiasis
  
  • CD4 <100
  • Treat with fluconazole 7 - 14 days
• Oral ulcers
  
  • HSV, CMV, aphthous, HPV
  • Treat accordingly
  • HSV -> aciclovir
  • CMV -> Ganciclovir
  • HPV -> cauterisation
  • Apthous ulcers -> steroids
• Oral hairy leukoplakia
  
  • EBV
  • Do not scrape, responds to HAART
• Respiratory infections
  
  • Treat as for non-HIV
  • With HIV patients use co-amoxiclax + doxy rather than clari because clari can interact with ritonavir
• Chronic viral hepatitis
  
  • 350 million HBV and 170 million HCV
  • Similar transmission routes to HIV
  • Accelerates liver disease progression
  • Vaccinate, avoid alcohol
• Hep B
  
  • fatigue, myalgia, raised ALT
  • Treat with interferon/tenofovir/entecavir -> tenofovir is part of HIV regimen anyway
• Hep C
  
  • Use new treatment
• C. diff
  
  • treat with vanc
• Cryptosporidiosis
  
  • protozoan parasite
  • 10 - 20% of HIV/AIDS with diarrhoea
  • Restore immunity, treat with paromomycin

Question 20

What methods of contraception in HIV +ve women are best?

Answer 20

Copper IUD is always the best method - regular contraception and emergency

Condoms will prevent from STIs

If on a PI or older NNRTI:

• Mirena Coil, IUCD or depot provera

Newer integrase inhibitors and newer NNRTI’s should be ablo to accommodate for contraception

Emergency contraception:

• Copper
• If on PI -> double the dose of levonelle to 3mg

Question 21

What do you recommend to HIV+ve women who to get pregnant?

Answer 21

• Depends on whether one or both in the couple are positive
• Safe:
  
  • Adoption
  • Artificial insemination by donor
• Risk reduction
  
  • Sperm washing
• Undetectable HIV viral load -> uninfectious to sexual partner
• PrEP - tenofovir/emtricitabine 1 tab daily
• Generally good health, good CD4 count, check fertility (semen analysis)
• Weight
• Folic acid
• Stop smoking

Question 22

What measures are taken when a woman is diagnosed with HIV in pregnancy?

Answer 22

• Three sources of risk and methods of prevention:
  
  • In utero transmission
    
    • Use triple ART -> risk 1% if VL <50 then 0.5%
  • During delivery
    
    • Better to use CS
    • but normal delivery possible if VL <50
  • Post-partum
    
    • PrEP for baby
      
      • If VL <50 -> AZT syrup as PEP
      • Otherwise 4 weeks triple ART and septrin until status known
    • Formula feeding
• Overall risk without tx 18.5%
• Remember folic acid, especially if on septrin PCP prophylaxis

Question 23

What are the guidelines on breastfeeding in the UK?

Answer 23

Question 24

What does PEP and PrEP consist of?

Answer 24

PEP must be started within 72 hours after a recent possible exposure to HIV, but the sooner you start PEP, the better. Every hour counts. If you’re prescribed PEP, you’ll need to take it once or twice daily for 28 days.

Truvada and raltegravir. Dolutegravir is a suitable alternative to raltegravir.

Question 25

What are some general principles in prevention of an