guidelines for management of HIV discordant couple

1. ART IN HIV DISCORDANT
COUPLES
Dr Antima Rathore
Fellow (Reproductive Medicine)
Institute Of Human Reproduction
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2. Human Immunodeficiency Virus (HIV)
2

3. Modes Of Transmission
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4. 4

5. UNAIDS Gap Report 2016
India has the third largest HIV epidemic in
the world
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6. UNAIDS Gap Report 2016
• 2.1 MILLION PEOPLE
• 0.3% Adult HIV prevalence
• 86,000 new HIV infections
• 68,000 AIDS-related deaths
• 43% adults on antiretroviral treatment
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7. NACO 2015
• National adult (15–49 years) HIV prevalence
0.26% (0.22%–0.32%)
• Males - 0.30%
• Females - 0.22%
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8. 8

9. 1990
CDC
“recommended against reproductive
assistance to HIV serodiscordant
couples”
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10. • 1990-2002: European physicians > 3000 inseminations with no
seroconversion
• 2002 ASRM revised guidelines: HIV serodiscordant couples may
seek Rx
• 2004 ESHRE ethics task force: → ethically acceptable offer sperm
washing & assisted reproduction HIV serodiscordant couples →
adequate precautions
• 2010 ASRM Ethics Committee guidelines: fertility clinics offer
services HIV couples willing use risk - reduction therapies
• 2013 ASRM: guidelines reduce risk viral transmission
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11. Dr Augusto Enrico Semprini
11

12. 2003
HAART
(Highly active Antiretroviral therapy)
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13. WHO (2009)
“ All couples and individuals have the right to
decide freely & responsibly the number &
spacing of their children & to have access to
the information, education & means to do so ”
(including HIV infected couples)
13

14. 2010
Ethics Committee of the American Society for
Reproductive Medicine
“Human immunodeficiency virus (HIV) is a
serious but manageable chronic disease that
affects persons of reproductive age, many of
whom express a desire for biologic
parenthood”
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15. ETHICAL
ISSUES
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16. Against
• Potential transmission of the virus to an uninfected partner
or to the couple's offspring
• Problems for the child related to the shortened life span of
one or both infected parents
• False-negative result of the test that was used to detect any
residual HIV in processed semen before insemination
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17. For
• Inborn spontaneous desire to produce a child as it happens in
uninfected couples
• Better quality of life and increasing life expectancy though
HAART
• Vertical transmission rate down to < 2%
• Lack of apparent transmission of HIV to partner or child with
sperm washing and intrauterine insemination (IUI), or with IVF
with ICSI, therefore, ‘Harm Minimisation’
• Not different from those with chronic diseases or carriers of
autosomal recessive genes.
17

18. HIV – Risk of Transmission
• Transmission risk per contact - 1/1000
• High – ulceration, genital infection, viral load > 10,000
copies/ml
• Male to female - 0.3% per contact
• Female to male - <0.3% per contact
• Anonymous contact - 3.1% - 8.2%
• Male to female transmission is more efficient than female to
male
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19. HIV – Risk of Transmission
Risk reduction
• HAART = CONDOM
• HAART + No breast feeding
< 2%
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20. HIV And Sperm
• No receptors on sperm surface
• Attaches avidly to sperm via sperm surface mannose or
heparin sulfate receptors
• May infect morphologically abnormal sperm in semen
• Virions present freely in semen and Leukocytes in semen are
main mode of HIV infection
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21. HIV and the Oocyte
• Virus may be in follicular fluid & may attach to
granulosa cells
• Oocyte is protected by zona pellucida
• Wash oocyte thoroughly in sterile media to dilute
viral titer
• Presence of viral RNA does not connote infectivity
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22. • Weather the effect on gametes is because of
HIV virus or the HAART per se – not known
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23. Goals Of Reproductive Care
• Reduce the risk of infection for the
uninfected partner and the child
• Overcome an infertility problem
23

24. • Informed consent mandatory
• Testing for the presence of the virus be offered
to all couples requesting reproductive
assistance
• HIV screening test + confirmation assay
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25. Infertility
HIV positive and HIV negative workup
NO DIFFERENCE
ROUTINE FERTILITY ASSESSMENT
Semen Analysis
Assess Ovulatory Function & Ovarian Reserve
Assess Tubal Patency (HSG Or Laparoscopy)
Assess Uterine Cavity (Hysteroscopy)
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26. Important
• CD4 Count
• Blood plasma Viral load (HIV‐1, HIV‐2, HIV
variant)
HIV screening test of unaffected partner
before and after each ART attempt and
during pregnancy (ESHRE)
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27. HIV AND INFERTILITY
HIV + WOMAN
• Menstrual irregularities
(anovulation)
• Prolonged amenorrhoea
• STI’s & PID’s - tubal factor infertility
• ↓ Pregnancy rate (low CD4 count, HAART)
• ↓ Ovarian reserve (↓ AMH & ↓ Antral Follicle)
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28. HIV AND INFERTILITY
HIV + MAN
Sperm Parameters
• Low sperm volume
• Low sperm count
• Low sperm motility
• Abnormal sperm morphology
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29. CRITERIA GUIDE SELECTING HIV PTS
• High motivation childbearing
• Well-controlled HIV + stable CD4 count
>350 cells/µml
• Undetectable viral load (serum and semen)
Serum < 50 copies/ml
• 90 % ARV medication adherence
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30. Different Clinical Scenarios
• Only the Woman is HIV Positive
• Only the Man is HIV Positive
• Both partners are HIV Positive
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31. FEMALE + MALE –
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32. Goals
• Prevent transmission to male partner & fetus
• Female partner ARV therapy
• Male partner PrEP option
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33. No subfertility
Timed Unprotected Intercourse
CD4 count > 350/µl
Viral load in infected partner < 10,000 copies/ml
Propose LH-test (urine stick) and counsel correct timing of sex
Pre-exposure prophylaxis - TENOFOVIR - 2 Doses (36/12 h prior to
intercourse)
Vaginal estrogen gel (ASRM)
Unprotected Intercourse - Not allowed under CDC
regulations & not recommended by the ASRM
Self Insemination
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34. • Moderate male factor, unexplained infertility,
anovulation - IUI
• Severe male factor, tubal factor, failed IUI - IVF/
ICSI
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35. • Reducing the rate of vertical transmission is
the main concern in such couples
• HAART plus Avoiding Breastfeeding
< 2%
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36. MALE + FEMALE –
36

37. Goals
• Prevent transmission to female partner & fetus
• Male partner ARV therapy
• Female partner PrEP option
• Sperm Washing - reduce risk transmission
• High CD4 count
• Low peripheral viral load
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38. • Normal tubes , normal semen analysis
Sperm washing, IUI
• Tubal occlusion, severe male factor
Sperm washing, IVF/ICSI
Donor sperm
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39. • Sperm isolated by Sequential Density Gradient &
Swim-up Techniques
• Sperm tested by PCR assays presence (HIV RNA
Method) 99.9% HIV sperm removal
• Sperm washing prior to IUI eliminates round cells,
seminal plasma & majority immotile sperm
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41. 41

42. Alternatives to swim‐up
• Double tube method to recover more sperm with
less contamination by leukocytes
• Modified double tube with tube insert will not yet
commercially available
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43. ESHRE
SPONTANEOUS OVULATION plus IUI
• Absence of infertility factors
• Woman with < 35 yr
• Normal hormonal profile
• >1 million spermatozoa after washing
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44. ESHRE
OVULATION INDUCTION plus IUI
• Clinical indication for the use of fertility drugs
• Woman with > 35 yr
• Failure to conceive after 3 timed IUI attempts
• >1 million spermatozoa after washing
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45. ESHRE
IVF-ET
• Severe pelvic infertility factor
• < 1 million spermatozoa after washing
• No pregnancy after repeated IUI attempts
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46. ICSI
• < 0.5 million spermatozoa after washing
• Severe asthenospermia or necrospermia
(incompatible with washing processing)
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47. ALTERNATIVE
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48. Donor insemination
Adoption
Pros
No risk of infection
Pros
No risk of infection
Cons
No genetic child
Psychological aspect
Cons
No genetic child
Long and difficult process
Possible discrimination
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49. Concerns
• Protection of staff
• Protection of other patient’s gametes
• Protection of patient’s own gametes
• Main risk to staff is through needle stick
& splash injuries
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50. Guidelines for Handling Infectious
Patients in the IVF Lab
Risk of infection of exposed employee is
approximately 0.3%
• Treat every body fluid as if it is contaminated
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51. Universal Precautions
• Scrubs, hat, shoe covers
• Gloves
• Mask
• Faceshield or goggles
• Avoid sharps
• Extra decontamination
• Extra hand washing
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52. • Proper disposal of biomedical waste
• No mouth pipetting
• Cover tubes - so no aerosol-borne viruses escape
• Use closed centrifuge
• Do not store food & beverages in refrigerators
designated for storage of clinical specimen &
laboratory material
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53. Semen analysis and processing
• If semen analysis is performed at a clinic, it should
also be available for known HIV-positive patients
• No special expertise or equipment is required other
than that used under Universal Precautions
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54. HIV and IVF
Separation in Space
• To reduce risk of cross-contamination
• Disposable contact materials
• Separate instruments/equipment
• A physically separate area
Alternatively
Separation in Time
Scheduling HIV-positive patients at a different time
• Undivided attention of personnel
• Time to sanitize completely before handling specimens from
other patients
• Process samples within a biosafety cabinet
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55. HIV and ICSI
• Possibility of introduction of HIV virus into the oocyte
• No evidence that ICSI is safer than IUI
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56. Semen Cryopreservation
& Storage
• Separation in time or space
• Separate frozen storage
• Special sperm washing ± viral check prior to
freezing
ASRM Practice Committee, Fertil Sterility 2012
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57. • Use specimen containers guaranted by the
manufacturer to withstand freezing temperature
& thawing cycles
• Double bagging – prevent direct contact of
cryocontainers with liquid nitrogen
• Store samples in Liquid Nitrogen Vapours instead
of liquid nitrogen itself
• Sperm Washing
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58. PRE-CONCEPTUAL COUNSELLING
Discuss
• Reproductive options available & treatment failure
• Effect of HAART on reproductive function
• Risk of vertical as well as horizontal transmission
• Factors affecting HIV transmission
• Long term health outcome & support networks
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59. • Emphasize no Rx option 100% risk free
• Risk of cancelled cycle if PCR is used & HIV is
detected in inseminate (3-8%)
Alternate options
• HIV + man: adoption or use donor sperm
• HIV + woman: surrogacy
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