23 - HIV

Question 1

What is the pathogenesis of HIV?

Answer 1

HIV 1 (most common) and HIV2 (West Africa)

1. Fusion: using CD4 receptor and co-receptor CCR5
2. Reverse Transcriptase: make DNA from viral RNA
3. Integrase: viral DNA into host DNA
4. Protease: for protein processing
5. Budding and Maturation

Question 2

How is HIV transmitted?

Answer 2

• Unprotected oral, vaginal, anal sex
• Vertical Transmission during birth
• Blood in eye
• Contaminated needles
• Blood products that are infected

Question 3

What groups of people are at an increased risk of contracting HIV?

Answer 3

• Men who have sex with men (MSM)
• Female sexual contacts of MSM
• Trans women
• Black Africans
• Those from a country with high diagnosed seroprevalence
• Those with sexual contact with anyone from a country with high seroprevalence
• Those with a mother with HIV who have not themselves been tested
• Those who use injectable drugs
• Sex workers
• Prisoners

Question 4

What are the three stages of HIV if left untreated?

Answer 4

1. Acute seroconversion: Occurs 1-6 weeks after infection as antibodies being made. Can be flu-like/mono symptoms like muscle aches, fever, sore throat, mouth ulcers, diarrhoea. Can also be asymptomatic

2. Chronic Infection: After around 6 months, stable viral loud, CD4 count starts to drop. Lasts about 8-10 years

3. Late Stage/AIDS: CD4 below 200. Lots of opportunistic infections and malignancies. Average survival of 12-20 months

Question 5

What are some examples of AIDS defining illnesses?

Answer 5

Question 6

Who should be tested for HIV?

Answer 6

• MSM
• Pregnant
• TOP
• TB
• People living in areas of high prevalence of HIV
• AIDS defining illnesses

Question 7

How is HIV tested for and when?

Answer 7

Can take up to three months to develop antibodies so do one at 4 weeks and one at 3 months as 4 weeks might be false negative

• Point of Care Test/Self Sampling: Looks for antibody, can show 21-24 days after exposure. Rapid so good if pt doesn’t want to leave contact details, need to explain if positive will need serological confirmation. Also if negative but <3 months will need a repeat
• Serological blood test: PCR for HIV RNA, HIV p24 antigen and HIV antibody. Takes 45 days to show, earlier for antigen

Question 8

Once a patient has a HIV positive diagnosis, what other investigations need to be done?

Answer 8

• HIV-1/HIV-2 differentiation immunoassay
• Viral load
• CD4+ T cell count (above 500 is normal)
• Viral hepatitis serology
• Full STI screen (including syphilis serology)

Offer women cervical cytology yearly!

Question 9

What classifications of medicine are there in Highly Active Anti-Retrovirus Therapy Medication (HAART)?

Answer 9

• Protease Inhibitors
• Integrase Inhibitors
• Nucleoside Reverse Transcriptase Inhibitors
• Non Nucleoside Reverse Transcriptase Inhibitors
• Entry Inhibitors
• CCR5 Inhibitors e.g Maraviroc
• Fusion Inhibitors

Question 10

What is the typical HAART regime for HIV and when do you start patients on this?

Answer 10

Start them as soon as diagnosed regardless of viral load and CD4 count. Aim is to make viral load undetectable and keep CD4 high

• Two NRTIs (tenofovir and emtricitabine)

PLUS

• Third agent (PI, II, NNRTI)

Question 11

How is HIV monitored after starting HAART?

Answer 11

• Viral Load: repeat every 6-12 months after suppression achieved
• CD4 Count: If >350 twice in one year then routine monitoring not needed

Question 12

What is the prognosis with HIV?

Answer 12

If detected early, CD4>350 and viral load undetectable then can have normal life expectancy

If AIDS (CD4<200) then 12-20 months average

Question 13

Apart from HAART, what extra medications/regular investigations do HIV patients need?

NB CARD

Answer 13

• Statins: high risk of developing CVD so monitor lipids
• Yearly cervical smears: more risk of HPV
• Vaccinations: Flu, Pneumococcal, Hep A/B, Tetanus all need to be up to date but AVOID live vaccines
• CD4<200: Need prophylactic co-trimoxazole against PCP

Question 14

What advice should you give a HIV positive patient about conceiving?

Answer 14

• Advise condoms and dams even when both partners positive
• Regular HIV tests for partner
• Can have sperm washing and IVF
• If viral load undetectable can have unprotected sex at time of ovulation safely as unheard of if low viral load to pass on

Question 15

How can transmission of HIV be prevented during birth?

Answer 15

• Mode of delivery depends on viral load of mother
• Prophylaxis to Baby: If viral load <50 then Zidovudine for 4/52 to baby. If viral load >50 give Zidovudine, Lamivudine and Nevirapine for 4/52
• Avoid breastfeeding even if viral load undetectable

Question 16

What are some malignancies associated with HIV?

Answer 16

AIDS defining

• Kaposi Sarcoma
• High grade B-Cell Non-Hodgkins Lymphoma
• Invasive Cervical Cancer

Non-AIDS defining

• Burkett’s Lymphoma
• Anal cancer
• Non-Hodgkin’s Lymphoma

Question 17

What are some neurological differentials in HIV?

Answer 17

• Stroke
• Meningitis
• Toxoplasmosis
• Primary CNS lymphoma
• Progressive multifocal leucoencephalopathy
• CMV encephalitis
• HIV associated neurocognitive disorder

Question 18

What are some ophthalmological differentials in HIV?

Answer 18

• Retinitis
• Conjunctivitis
• Keratitis
• Episcleritis
• CMV retinitis
• Herpes Simplex ulcers
• TB
• Occular malignancies

Question 19

What are the most common symptoms of primary HIV infection?

Answer 19

1. Fever and Lymphadenopathy
2. Maculopapular rash on upper chest
3. Mouth ulcers

Question 20

What are the side effects of these classifications of HAART?

• NRTIs

Answer 20

• Tenovir: Renal Failure and Osteoporosis
• Lamivudine: Pancreatitis
• Abacavir: Avoid in CVD
• Emtricitabine: Hyperpigmention of palms and soles

Question 21

What are the side effects of these classifications of HAART?

NNRTIs

Answer 21

• Resistance
• CNS disturbance
• QT prolongation
• Drug induced hepatitis

Question 22

What are the side effects of these classifications of HAART?

Integrase

Answer 22

• Insomnia
• Weight gain
• Psychiatric issues

Question 23

What are the side effects of these classifications of HAART?

Protease inhibitors

Answer 23

Good for resistant strains

• Lipodystrophy
• Hyperlipidaemia
• Insulin resistance
• Hepatotoxicity

Question 24

How does Pneummocystitis pneumonia usually present?

Answer 24

• Fever
• Non productive cough (however can have superimposed bacterial infection)
• Exertional breathlessness (this stratifies severity)

Question 25

What investigations should you do if you suspect PCP in a HIV patient and what will these investigations show?

Answer 25

* **CXR:** bilateral bihilar interstitial infiltrates * **High resolution CT**: If above nil then do these for cysts and nodules * **Bronchoscopy associated with bronchoalveolar lavage:** Use Grocott's stain and will show ‘mexican hat’ appearance. DIAGNOSTIC

Question 26

How is PCP managed?

Answer 26

**Co-trimoxazole -** regardless of severity

Question 27

What is PEP and what is the regime with this?

Answer 27

Post Exposure Prophylaxis when risk of HIV exposure, **must be given within 72 hours** of exposure **Raltegravir** (Tenofovir) and **Truvada** (Emtricitabine) Given for **28 days** **Test for HIV immediately and then in 3 months,** abstaining from unprotected sex until they know they are negative

Question 28

What drugs are included in PrEP and when is it taken? pre exposure prophylaxis

Answer 28

**Tenofovir Disoproxil / Emtricitabine (TD-FTC)** Can either take **daily** tablet or **on demand**

Question 29

pre exposure prophylaxis

Answer 29

A preventive method for people who are HIV-negative but at high risk of contracting HIV (e.g., through sex or injection drug use) Daily oral pill (most common). 99% effective in preventing HIV via sexual contact when taken consistently. ~74% effective for people who inject drugs. Monitoring: Baseline HIV test (must be negative). Renal function tests. Regular follow-up every 3 months (HIV/STI screening, adherence review, renal monitoring)

Question 30

Who should be offered PrEP and what regime should they use?

Answer 30

**_MSM (either regime)_** * *HIV-negative MSM had condomless anal sex in the previous 6 months and ongoing condomless anal sex* * *HIV-negative MSM having condomless anal sex with partners who are HIV positive, unless partner has been on ART for at least 6 months and their plasma viral load is \<200 copies/mL* **_Heterosexual (daily)_** * *HIV-negative heterosexual men and women having condomless sex with partners who are HIV positive, unless the partner has been on ART for at least 6 months and their plasma viral load is \<200 copies/mL* **_Trans (daily)_** * Same as above, if condomless anal or HIV positive partner who has been on ART \<6 months **_IVDU_** * Needle exchange programmes only

Question 31

Before being started on PrEP, what steps need to be taken?

Answer 31

* **Initial HIV test** * **Counselling** on ongoing risk and side effects of medication. Explain risk of other STIs and how only works if adhere to regime * **Explain symptoms of seroconversion** and to present if have these * **Check U+Es and urinalysis** as CI if renal impairment * **STI and Hepatitis screen**

Question 32

When patients are on PrEP, what follow up and monitoring do they need?

Answer 32

* **HIV test** (3 monthly) * **STI screening** (3 monthly chlamydia, gonorrhoea and syphilis +/- hepatitis C) * **Renal function** (based on age and current eGFR) If woman consider pregnancy test and checking BMD at regular intervals

Question 33

what is the form of sex that increases spread of HIV

Answer 33

unprotected anal sex - which is why MSM is more high risk, but if a woman and a man are having unprotected anal sex then this is also a high risk factor

Question 34

What is the screening for HIV

Answer 34

nitial diagnostic test: 4th generation HIV test (combined HIV-1/2 antibody and p24 antigen test) If positive: Confirmatory HIV-1/2 differentiation immunoassay HIV viral load CD4 count Baseline/related investigations: Full STI screen (NAAT for chlamydia/gonorrhoea, syphilis serology) Hepatitis B and C serology Full blood count (FBC), U&Es, LFTs (for ART baseline) TB screening if risk factors present Urinalysis (if symptomatic) Pregnancy test in females of reproductive age

Question 35

how would you counsel someone before taking the HIV test

Answer 35

explain: - 4th generation test looks for antibodies and p24 antigens - the test may not be very accurate as it might only show up 4 weeks post exposure - if positive -> next steps - IT IS MANAGEABLE AND NON CURATIVE - RESULT IS CONFIDENTIAL -contact trace - support servixes

Question 36

4th generation test

Answer 36

If the last potential exposure was >6 weeks ago: No further testing is required. 4th generation tests detect both p24 antigen and antibodies and are considered highly accurate from 6 weeks post-exposure. 2. If exposure was <6 weeks ago: A repeat test is needed at 6 weeks post-exposure (some guidelines suggest at 4 and 12 weeks to cover window periods more conservatively, especially in very high-risk exposures). 3. If the exposure was within the last 72 hours: Discuss post-exposure prophylaxis (PEP) urgently. Start PEP as soon as possible — ideally within 24 hours, and certainly before 72 hours.