1. Safer Conception Will Contribute to Elimination of Perinatal HIV Transmission
Lynne M. Mofenson, M.D.
Senior HIV Technical Advisor
Elizabeth Glaser Pediatric AIDS Foundation

2. Where are We in the Plan to Eliminate New Pediatric HIV Infection?
Major Progress in Preventing Perinatal Infection in Past Decade
But we have not yet reached the goal of global elimination
1.6 million pediatric
infections averted
~400 new pediatric
infections every day!
In 2015, still 150,000 new pediatric HIV infections
70% decrease in new pediatric infections since 2000

3. Prevention Gaps in Elimination of Perinatal Transmission
New infections in reproductive age women (especially young women) have not declined in past 5 years.
Continued high rates of incident infection in pregnant and breastfeeding women.
Widespread need for family planning exists in many countries, resulting in many unplanned pregnancies in women living with HIV.
HIV testing remains suboptimal so women with HIV don’t know their status and become pregnant; >300,000 women did not receive any ARV for prevention in 2015.
Late initiation of ART results in lower efficacy in prevention of perinatal transmission.

4. What Do We Know About These Gaps and Could Safer Conception Practices Help Overcome Them?

5. Barriers to Elimination of Perinatal HIV Transmission
Continued Acquisition of HIV Infections in Women, Especially Young Women & During Pregnancy/Breastfeeding

6. New Infections Among People Aged >15 Years, by Region, 2005-2015
Annual new infections in adults years in all regions has essentially remained flat, except Eastern Europe where it has ↑↑.

7. Adolescents and Young People Are Disproportionately Represented in New HIV Infections
Persons Living with HIV Globally 2015
New HIV Infections Globally, 2015
Adolescents yrs accounted for 3% and young people yrs 8% of 36.7 million people LWH.
However, of 2.1 M new HIV infections in 2015, 12% were in adolescents yr & 32% in young people yr.

8. New HIV Infections Among Young Women Aged 15-24 Years Global 2005-2015
OVER 1,000 NEW INFECTIONS EVERY DAY
Between 2010 and 2015, new infections in young women
aged years ↓ by only 6%, from 420,000 to 390,000.

9. High Rates of Incident HIV during Pregnancy/BF Drake AL et al
High Rates of Incident HIV during Pregnancy/BF Drake AL et al. PLosMed 2014;11:e
Meta-analysis of data from 19 studies (all Africa)
4.7 (3.3, 6.1)
2.9 (1.8, 4.0)
3.8 (2.0,4.6)
Pregnancy
Postpartum
Pregnancy and Postpartum
Overall
Significantly higher perinatal transmission with incident compared to chronic HIV infection:
2.3-fold ↑ risk with incident infection during pregnancy
2.9-fold ↑ risk with incident infection while breastfeeding

10. Desire to Conceive a Child May Be a Common Reason for Seroconversion in Discordant Couples
Tang PLosOne 2016;11:e :
53 seroconversions/4,481 sero-different couples in China.
Compared 40 seroconverting couples to 80 couples without seroconversion, matched for age, gender and region residence.
Multivariate analysis showed that the desire to conceive a child significantly increased the odds of HIV seroconversion (aOR 5.18, 95% CI ).

11. Desire to Conceive a Child May Be a Common Reason for Seroconversion in Discordant Couples
Brubaker SG et al. HIV Med 2011;12:316-21:
41 seroconversions/532 sero-different couples in Kenya.
20 seroconversions in 186 HIV-negative persons in sero-different couples where pregnancy occurred (10.8% acquiring HIV) .
21 seroconversions in 353 HIV-negative persons in sero-different couples where pregnancy did not occur (5.9% acquiring HIV).
1.8-fold increase in relative risk of HIV acquisition in sero-different couples when pregnancy occurred (95% CI , p<0.05).

12. How Can Safer Conception Overcome This Barrier?
Safer conception promotes knowledge of HIV status, enabling uninfected women to understand their risk and women living with HIV to access ART.
Safer conception can prevent new infections in uninfected women in sero-different couples through use of PrEP by the woman and ART by her partner living with HIV.
Preventing infection in women is the key to preventing infection in their children.

13. Barriers to Elimination of Perinatal HIV Transmission
Unplanned/Unintended Pregnancy

14. Sub-Saharan Africa need was 24%, double the world average in 2015.
% Women Years Married or in a Union with Unmet Need for Family Planning 2015
Globally in 2015, 12% women had unmet family planning need; % in the least developed countries.
Sub-Saharan Africa need was 24%, double the world average in 2015.

15. Women Living with HIV Have High Rates of Unintended Pregnancy in the Option B+ Era
South Africa (Sheree R et al. PLosOne 2012;7:e36039): 850 non-pregnant women with HIV in 4 public ART clinics Johannesburg ; by 2 yrs post-ART, 25% >1 pregnancy, 35% by 3 yrs post- ART. 62% unplanned.
Malawi (O’Shea MS et al. AIDS Care 2016;28: ): 220 women living with HIV on ART >6 mos before pregnancy. 75% reported current pregnancy unintended (21% mis-timed, 79% unwanted).
Botswana (Mayondi GK et al. BMC Public Health 2016;16:44): 941 pregnant women with and without HIV; 44% reported unintended pregnancy; HIV status not associated (adjusted analysis). But 61% women reported not wanting more children after this pregnancy, 3.9-fold (95% CI ) higher in women living with HIV than uninfected women.

16. How Can Safer Conception Overcome This Barrier?
Safer conception includes provision of modern contraception to allow women and couples to plan for pregnancy, thus reducing unwanted and unplanned pregnancies.
By allowing women and couples to choose when they become pregnant, they can optimize their ability to prevent perinatal transmission (e.g., ensuring women living with HIV are on ART and suppressed prior to pregnancy).

17. Barriers to Elimination of Perinatal HIV Transmission
HIV Testing
Remains Inadequate
and
ART is Being Initiated Too Late

18. HIV Testing Remains Inadequate, Including in Pregnancy
Globally, in 2015 only an estimated 61% of pregnant women received an HIV test.
61%
Data from annual UNAIDS/WHO reports

19. ARV Duration in Pregnancy and Perinatal Transmission
For Maximal Efficacy, Early ART Initiation Needed
Tariq S et al. JAIDS 2011;57:326-33
7,573 women receiving ART Europe delivering
Duration of ART (start)
% Transmission

20. Delivery RNA and Transmission According to Time ART Initiation
Pre-conception ART Has Greatest Efficacy in PMTCT Madelbrot L et al. CID 2015;61:
French Perinatal Cohort (no BF): Overall transmission 0.7%
*threshold if assay LLD >50 c/mL
Delivery RNA and Transmission According to Time ART Initiation
Started before conception Started 1st trimester Started 2nd trimester Started 3rd trimester
0.2% % % %
Transmission:
No infections in women on ART pre-conception & RNA <50 c/mL

21. How Can Safer Conception Overcome This Barrier?
Women living with HIV need to know their HIV status prior to pregnancy and plan their pregnancy to maximize prevention for themselves and their infants.
By knowing their status, women living with HIV can ensure they start ART and have viral suppression prior to becoming pregnant to optimize prevention of transmission to infant and partner – and protect maternal health.

22. Safer Conception is an Integral Part of Elimination of Perinatal Transmission
Through promoting HIV testing, it will reduce sexual HIV transmission to uninfected women in sero-different couples who want to have children by ensuring PrEP provision for the uninfected partner and ART for the partner living with HIV.
Data to date suggest use of TDF PrEP is safe in pregnancy and breastfeeding, with very low to no TDF present in breast milk (Mofenson et al. AIDS ;31:213-32; Mugwanya KK et al. PLosMed 2016;13:e ). Although continued surveillance is warranted, as noted by WHO, pregnancy and breastfeeding should not be contraindications to use PrEP.

23. Safer Conception is an Integral Part of Elimination of Perinatal Transmission
Through helping women and couples plan for pregnancy, it will reduce unplanned pregnancies.
How to optimize integration of family planning into HIV care and HIV care into family planning remains an important operational research issue.
Acknowledging fertility desires of couples and counseling sero-different couples regarding safer conception strategies is critical to reduce sexual HIV transmission risk (and perinatal transmission) during condomless sex intended for conception.

24. Safer Conception is an Integral Part of Elimination of Perinatal Transmission
Through ensuring women test and know their HIV status, women living with HIV can initiate ART prior to conception and ensure viral suppression before pregnancy and prevent transmission.
Perinatal transmission risk can be basically eliminated in women living with HIV on ART prior to conception with maintained viral suppression.
While data to date are reassuring regarding safety (Chagomerana MB. JAIDS 2017;74:367-74, Uthman OA. Lancet HIV ;4:e21-30), surveillance of fetal safety will be important as new ARV drugs are introduced.

25. Thank you for your attention!