HIV

Question 1

Incidence of HIV?

Answer 1

50% women
80% of reproductive-age

Question 2

Where is HIV most prevalent?

Answer 2

2/3rds live in sub-Saharan Africa

• more than 3/4 of all women infected live in sub-saharan Africa

Question 3

What are the rates of MTCT in the UK vs sub-saharan Africa?

Answer 3

<0.3% - UK
- 0.14% in those w/ suppressed
viral loads

45% - sub-saharan Africa

Question 4

What percentage of HIV is acquired thru heterosexual contact?

Answer 4

50%

Question 5

Prevalence of HIV in pregnancy in sub-saharan Africa?

Answer 5

5.3%

Question 6

Proportion of women on cART in pregnancy? (UK)

Answer 6

60%

Question 7

Clinical features of acute, primary HIV infection

Answer 7

• may be asymptomatic
• fever, fatigue, lymphadenopathy or
  rash
  
  • occurs 2 weeks - 3 months post
    exposure

Clinically latent phase
- lasts up to and beyond 10yrs (w/o
drug therapy)
- may cause (ALT):
1. Anaemia
2. Lymphopenia
3. Thrombocytopenia

Symptomatic disease includes:
- persistent generalized lymphadenopathy
- weight loss
- diarrhea
- neurological disease (encephalopathy and neuropathy)
- opportunistic infections: 4C, 2M, P
- candidiasis
- cerebral toxoplasmosis
- CMV retinitis
- cryptococcocus
- mycobacterium tuberculosis
- mycobacterium
avium-intracellulare
- pneumocystis pneumonia
- secondary cancers
- Non-Hodgkins lymphoma
- Kaposi’s sarcoma

Question 8

Clinical features of acute, primary HIV infection

Answer 8

• may be asymptomatic
• fever, fatigue, lymphadenopathy or
  rash
  
  • occurs 2 weeks - 3 months post
    exposure

Clinically latent phase
- lasts up to and beyond 10yrs (w/o
drug therapy)
- may cause:
1. thrombocytopenia

3. Anaemia
4. lymphopenia

Question 9

What are the principal routes of HIV transmission?

Answer 9

3 routes:
1. Sexual: unprotected anal/
vaginal intercourse
2. Parenteral/blood-borne:
-Sharing of needles
-blood transfusions
3. Perinatal/Vertical transmission:
-ante/intra/postpartum

Question 10

How can early HIV infection be identified?

Answer 10

High viral load

Question 11

What is HIV?

Answer 11

HIv is an RNA retrovirus that mainly targets the CD4+ T helper cells, gradually diminishing their population.
- Loss of these cells reduces cell-mediated immunity and humoral immunity, leading to the development of opportunistic infections and more rapid replication of HIV.

The hallmark of infection is progressive decline of CD4+ lymphocyte count - which falls by 60cells/mm3/year without treatment.

Question 12

What does CD4 count indicate?

Answer 12

Current degreee of immunosuppression

Question 13

What does viral load indicate?

Answer 13

It is the main predictor of the SPEED of disease progression

Question 14

How long does transplacentally transferred maternal antibodies persist in the fetal circulation post delivery? What is the significance of this?

Answer 14

Up to 18 months

Hence the true HIV status is difficult to determine without the use of PCR .

Question 15

When is screening for HIV offered?

Answer 15

At booking.

If mother refuses and is deemed high risk, offer again at 28 weeks.

Question 16

How are high risk for HIV infection?

Answer 16

1. Women from sub-saharan africa
2. Iv drug users
3. Sex workers
4. Partners of:
   
   • any of the above individuals OR
   • homo/bisexual males

Question 17

Advantages of HIV screening?

Answer 17

1. Early treatment of mothers to improve their long term outcome (e.g. prevention of development of AIDS and opportunistic infections)
2. Intervention to prevent MTCT
3. Knowledge of HIV status to protect sexual partners

Question 18

How does pregnancy affect HIV?

Answer 18

• pregnancy has no effect on progression of disease in asymptomatic women
• women with symptomatic disease are at higher risk of deterioration due to the disease status rather than the pregnancy.
• women may be less likely to present to investigate opportunistic infections due to concerns about the fetus. This leads to a worse prognosis for the mother.
• In women with an unknown status, symptoms made mimic normal symptoms in pregnancy (e.g.) breathlessness, resulting in a delay in diagnosis.
• Even though cd4 levels decreased in a normal pregnancy due to the depression of cell-mediated immunity
  
  • there is no evidence to suggest that pregnancy increases the risk of 1. progression to AIDS OR 2. a fall in CD4 to <200/mm3

Question 19

What is the effect of HIV on pregnancy?

Answer 19

HIV, esp advanced disease, is associated with:
1. Miscarriage
2. FGR/low birthweight
- related to the stage of maternal
disease; poor nutritional status
is associated with advanced
disease and recurrent infections
3. Preterm delivery
- associated increased prenatal
morbidity and mortality
3. MTCT/transmission of HIV from mother to child

Question 20

How does MTCT occur?

Answer 20

Via 3 routes:

1. In utero/transplacental
   
   • antepartum
2. During delivery
   
   • intrapartum from. Exposure to maternal bodily fluids.
3. Postpartum from breastfeeding

Question 21

What are the rates of MTCT WITHOUT prophylactic therapy in the UK sub-saharan Africa and the US?

Answer 21

Uk: 15- 25%
US: 15- 30%
Sub-saharan Africa:25-45%

Question 22

When is MTCT most likely to occur?

Answer 22

At delivery (2/3rds).

• breastfeeding postpartum can DOUBLE the transmission rate (15% to 30%), esp if mother acquired infection postnatally.

Question 23

What factors increase the risk of MTCT?

Answer 23

20 factors 🙃:
1. high maternal VL
2. seroconversion DURING
pregnancy
3. Vaginal delivery if VL detectable
4. Advanced maternal disease
5. Poor immunological status
- low CD4 count & low cd4:cd8
ratios
6. Prolonged ROM
- ROM >4hrs DOUBLES the risk of
transmission
7. Preterm Labour
8. Antepartum invasive procedures (choriocentedis, amniocentesis, fetal blood sampling)
9. Intrapartum invasive procedures ( fetal scalp electrodes, episiotomy, instrumental delivery)
10. Prematurity <35weeks
11. Low birth weight
12. Chorioamnionitis
- infection disrupts placental
barrier
13. Intercurrent STDs, esp w/ ulceration
14. Unprotected sex with multiple partners
15. Hep C co-infection
-increases vertical transmission
of both infections
16. Breastfeeding
17. Mixed breast and bottle feeding
18. Smoking
19. Illicit drug use, esp cocaine
20. Vitals A deficiency

Question 24

How is HIV in pregnancy managed?

Answer 24

1. MDT
   
   • high risk obstetric clinic, HiV specialist, neonatologists, paediatrician, midwife experienced in managing these pregnancies, GP
2. STI screen for other concurrent infection (hep c increases risk of vertical transmission both infections; treat other infection to decrease vertical transmission & complications).
3. CD4 and VL - to classify disease & determine management
   - CD4 <200/mm3 = AIDS + prev ep of pneumocystis pneumonia = Co-trimoxazole/SEPTRIN prophylaxis + Folate 5mg OR nebulized pentamidine
   - CD4 >350 cells/microL and VL <50 w/o TX = ELITE controller
4. Commence/continue cART
   - all women should have started cART by 24 weeks gestation.
   - Dose adjustment of ARTs in pregnancy not required (except for raltegravir which becomes a bd dosing)
5. Haematological assesssments:
   - VL each trimester and at 36 weeks - CD4 count
   - LFTs - should be done prior to commencing ARTs as liver function can be affected
   - Lactate
   - OGTT to screen for GDM- protease inhibitors may increase the risk of GDM
6. Screen for aneuplodies (trisomy 13,18 and 21) using the combined test at 11+0 to 13+6 or biochemical tests at 15+0 to 20+0. This reduces the need for invasive testing.
7. Avoid invasive procedures (chorionic villus sampling/amniocentesis) until the VL is suppressed.
8. Intrapartum: MODE of delivery dependent on VL at 36 weeks:
   - <50 copies/mL: planned vaginal & VBAC
   - 50- 399 RNA copies/mL: elective LSCS
   - >400 RNA copies/mL: elective LSCS at 38-39 wks
9. Prophylaxis for MTCT (intrapartum):
   - continue cART in labour
   - untreated in labour? Oral + IV
   * nevirapine 200mg stat +
   * zidovudine 300mg + lamivudine
   150 mg po bd +
   * raltegravir 400mg po bd +
   * IV zidovudine for the duration of labour
10. Place of delivery must be in an institution with direct access to paediatric care/neonatal unit
11. Postnatal
    -Infant post-exposure prophylaxis:
    start BEFORE 4hrs to 4 weeks
    i)<50 copies/mL: Zidovudine monotherapy
    ii)50 or more RNA copies/mL: 3 drug therapy

• Neonate/infant HIV PCR testing at
  i. 48hrs
  ii. prior to discharge
  iii. 2 weeks (if high risk)
  iv. 6 weeks (2wks after end of prophylaxis)

Question 25

What treatment should be given to women with AIDS and a h/o pneumocystis pneumonia?

Answer 25

Prophylaxis with Co-trimoxazole/Septrin + Folate5mg Or nebulized Pentamidine To: 1. risk of recurrence of P. pneumonia and 2. Protect against toxoplasmosis reactivation *Folate 5mg to protects against effect of folic acid antagonism*

Question 26

Which agents does BHIVA (British HIV Association) recommend to start cART therapy?

Answer 26

1st agent: Tenofovir DF (disproxil fumarate) OR Abacavir + 2nd agent: Emtricitabine OR Lamivudine + 3rd agent: efavirenz OR atazanavir

Question 27

Which antiretroviral is associated either neural tube defects?

Answer 27

Dolutegravir 0.2% risk of neural tube defect if she conceives on dolutegravir. If this is the best ART for the woman and she wishes to remain on it prior to conception, also give 5mg folic acid. Can be considered AFTER 6 weeks Cranial neuropore closes on day 26. Caudal neuropore closes on the 4 th week

Question 28

What cART regimenis recommended if HIV is diagnosed after 28weeks?

Answer 28

A 3 or 4 dose regime containing Raltegravir.

Question 29

What is the aim of cART therapy in pregnancy?

Answer 29

To reduce the VL to less the current sensitive detection level of 50copies/mL by the time of delivery. This allows the mother the option of vaginal delivery as the risk of perinatal transmission is extremely low <1%.

Question 30

T/F. All women should have started cART by 26 weeks gestation?

Answer 30

FALSE - by 24 weeks gestation.

Question 31

When should cART be started?

Answer 31

T1 if CD4 <200 and VL >100,000 At the START of T2 if VL is 30,000 - 100,000. In T2 if VL 30,000 or less

Question 32

What is the drug regimen for a pt with HIV in labour, who is not maintained on cART?

Answer 32

Oral and IV meds: 200mg nevirapine po stat + 300mg zidovudine & 150mg lamivudine bd + 400mg Raltegravir bd + IV zidovudine for rest of labour

Question 33

What are the risks associated with cART?

Answer 33

1. GDM may be precipitated by protease inhibitors 2. Immune reconstitution syndrome (Which leads to:~) 3. Increased risk of preterm delivery 4. Increased risk of preeclampsia

Question 34

What is immune reconstitution syndrome? What are the characteristics?

Answer 34

An inflammatory syndrome that occurs AFTER ART is started. Is due to restored immunity to specific infectious or noninfectious antigens. Potential causes/mechanisms include i)partial recovery of the immune system and OR an exaggerated immunological response to to antigenic stimuli. Characterised by -Paradoxical worsening of a known condition OR - appearance of a NEW condition AFTER starting ART. - the infectious agents are usu Mycobacteria, Varicella zoster, herpes virus and CMV.

Question 35

Should HIV positive patients be allowed to breastfeed?

Answer 35

Ideally NO, as breastfeeding carries a 50-60% risk of transmission. However in developing countries, the benefits of giving the breastmilk may outweigh the risks of not giving it (e.g. starvation)

Question 36

Outline the screening for aneuploidies in an HIV positive woman.

Answer 36

Using non-invasive testing is important to minimize invasive testing, which increases the risk of virus transmission to the foetus. Combined screening: Maternal age + bhcg + PAPP-A + nuchal translucency at 11-13+6 wks - Detection rate of 92.6% and false positive rate of 5.2% Quadruple screen Bhcg + alpha fetoprotein + inhibin A and ue3/unconjugated estriol at 15-20 wks - use if pt presents too late for combined - most clinically effective and cost-effective screening test (triple can be used also, less sensitive). *HIV is associated with increased bhcg and afp and decreased oestriol, therefore there is an increased risk of FALSE POSITIVEs for aneuploidy/downs syndrome in these patients. - this may increase the number of invasive tests offered compared to the general population.

Question 37

What is the vertical transmission rate with VL <50 copies/mL?

Answer 37

<0.5% regardless of mode of deliver

Question 38

SROM at term with viral load >400. Next step?

Answer 38

Urgent/cat 2 csection Iv zidovudine from within 4 hours of rupture up to clamping of the umbilical cord

Question 39

SROM at or after 34 weeks. Next step?

Answer 39

- Group B strep prophylaxis in accordance with NICE guidelines - VL and duration of rupture dictate delivery ---- if <50 vaginal, above csection ---- immediate induction. If <50 copies ideally want to deliver by 4hrs post rupture but studies have shown no sig difference in risk of vertical transmission up to 24 hrs post rupture of this subset of patients. ---VL >50 immediate lscs ---if VL>50, then iv zidovudine from being 4hrs post ROM until clamping of umbilical cord.

Question 40

SROM @ < 34 weeks. Next step?

Answer 40

Management will take into account: 1.gestational age 2.Maternal VL 3.Coexisting comorbidities e.g. infection, preeclampsia 4.facilities available - Timing of delivery requires a discussion with the MDT and neonatal unit. A very preterm baby may not tolerate oral therapy, therefore loading the fetus via the transplacental route is recommended ---if VL>50, then iv zidovudine from being 4hrs post ROM until clamping of umbilical cord.

Question 41

Describe the neonatal ART regimes?

Answer 41

Zidovudine monotherapy if VL<50 Very low risk neonate - 2 weeks (VL<50 at 36 wks, VL<50 on 2 occassions during pregnancy at least 4 wks apart, mother on cART for >10wks) Low risk - 4 weeks (Not all of above criteria met but VL <50 at 36 wks; preterm delivery at <34wks but VL was <50) High risk = VL>50 - 4 weeks combination post-esposure prophylaxis/PEP (includes iv zidovudine, lamivudine and nevirapine) - start neonatal PEP asap/ within 4hrs of birth

Question 42

T/F. Non-breastfed babies should have a bath immediately post delivery and have a viral culture and PCR taken to determine HIV infection.

Answer 42

True

Question 43

Risk of MTCT w/o cART vs w/ cART?

Answer 43

25% vs <1%

Question 44

Advice for delivery of a pt with viral load <50 copies/mL at 36 wks?

Answer 44

Allow spontaneous vaginal delivery if no obstetric contraindications. - obstetric management follows the same guidelines for the unaffected population.