PMTCT HIV AND SYPHILIS IMPLEMENTATION

Dr John Kinuthia, MBChB, MMED, MPHConsultant Obstetrician & Gynaecologist

Honorary Lecturer, Department of Obstetrics & Gynaecology, UoNHead, Research & Programs, Kenyatta National Hospital

20th International AIDS Conference , July 20th 2014, Melbourne, Australia.

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Background• ~1.6M Kenyans living with HIVo10% children <14 yearso 57% women

• 11000 new infections among children in 2012

• PMTCT program in Kenya implemented in 2000

• In 2012, >9,000 health facilities offering PMTCT services

*KAIS 2012

HIV prevalence among adults and adolescents aged 15–64 years by region*

Men = 4.4%Women = 6.9%Pregnant = 6.5%

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Trends in HIV screening during pregnancy in Kenya

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KDHS 2003; #KAIS 2008-9; *Kinuthia 2010; **Kiarie 2011;***KAIS 2012

• PMTCT programs focus on women with chronic HIV infection

• Women in window period & those infected after HIV after after HIV testing go unrecognizedo Increased HIV incidence during pregnancy reported**o Increased MTCT risk***

New HIV infections among children reducing

*UNAIDS, 2013;NASCOP, 2011;**Drake 2014; Kinuthia 2010;Gray 2005;*** Kourtis, 2010; Ioannidis, 1999; Pitt ,1997; Garcia,1999; Mofenson,1999

Estimated number of new infections in children aged (0-14): Global trends and projections 2001-20015

oIncreased HIV otesting*

oIncreased availability

o& use of ARVs*

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HIV-1 incidence during pregnancy and postpartum Kinuthia CROI 2014

• Prospective cohort

• Study populationo HIV-1 rapid antibody test negative

– Day of enrolment or within 3 monthso Resident until 9 months postpartum

• RPR as part of ANC

• HIV testingo Pooled nucleic acid amplification test

(NAAT)– 10 samples

Bondo Hospital HIV prevalence at ANC 26%

Ahero Hospital HIV prevalence at ANC 22%

Rapid test ≤3 months

NAAT testPooled Individual NAAT

-ve Serial NAAT

+ve

-ve

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Antenatal care services & enrolment

Laboratory

Study clinic• 1304 (56%) enrolled*• RPR 1020 (78.2%)

_

MCH Clinic

Laboratory

HTC • 38 (0.9%) Declined • 799 (18.8%) HIV-1+ve• 3408 (80.3%) HIV-1-ve

Clinical ANC • Palpation• Hematinic• IPT and ITN• TT injection• Infant feeding

coundeling• ARVs

Antenatal profile• Hemoglobin• RPR• Blood group• Urinalysis

Home

Registration• 4245 women• May 2011-June 2013

ReviewNurse/clinician

*2351 women met eligibility criteria

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Baseline characteristics (n=1304)Characteristic N n (%) or Median (IQR)Age 1304 22 (19 - 27)

Education level (years) 1304 8 (7 - 10)

Married 1304 1022 (78)

Marriage duration (years) 1019 4 (1 - 8)

Partner age difference* 1171 6 (4 - 10)

Gravida 1304 2 (1 - 4)

History of STI 87 (7)

Partner HIV statusPositiveNegativeUnknown

130418 (1)841 (64)445 (34)

* Years older

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HIV-1 incidencePre-enrollment Enrollment Follow up

24 New HIV infections2.34

(0.56 – 4.34)

5 Seroconversion detected at enrollment 1.11 (0.61 – 2.00)

-ve +ve5 Acute infection detected at enrollment 5.00

(0.62 – 19.38)

-ve +ve14 Acute infection detected during follow-up 3.11

(0.38 – 5.84)

-ve –ve

Incidence rate95% CI

+ ve repeat rapid antibody test

- ve repeat rapid antibody test

+ ve NAAT test

Rapid test ≤3 months

NAAT testpooled Individual NAAT

-ve Serial NAAT+ve

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Correlates of acute HIV-1 infectionOR (95% CI) p

Age (per year increase) 1.0 0.9 – 1.0 0.2

Married 0.7 0.3 – 1.7 0.4

Shorter marriage duration (yrs) 1.14 0.3 – 1.7 0.05

Partner age difference* 1.00 0.98 – 1.02 0.88

History of STI 3.8 1.4 – 10.6 0.01

CT 2.6 0.7 – 8.8 0.14

GC 1.8 0.2 – 14.1 0.58

TV 1.2 0.7 – 2.3 0.50

Syphilis 10.0 2.0 – 46.0 0.005

BV 2.6 1.2 – 5.8 0.019

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Baseline STIs/genital tract Infections

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Challenge of incident maternal HIV infections to eMTCT

• High HIV viral load*

• Mother not known to be HIV infected

• No HIV PMTCT interventionoNo maternal ARVoNo infant ARVoObstetrical interventionsoEnhanced counseling on

exclusive breastfeeding

• Infant infection due to• Maternal infection after• ANC testing o 26% (2008) to 34%

(2014) in South Africa**

o 43% of infant infections iBotswana in 2007***

*Kourtis 2010; Ioannidis 1999; Pitt 1997; Garcia1999; Mofenson 1999; **Johnson 2012; ***Lul CROI 2009

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J Acquir Immune Defic Syndr. 2012 ;59(4):417-25. The contribution of maternal HIV seroconversion

during late pregnancy and breastfeeding to mother-to-child transmission of HIV**

16th CROI 2009. Montreal. Abstract 91HIV Incidence in Pregnancy and the First Post-

partum Year and Implications for PMTCT Programs, Francistown, Botswana, 2008

“In this mature and successful PMTCT programme, new and undetected maternal infections may be causing nearly half of infant infections.” Lul et al

HIV retesting in pregnancy• High acceptability*

• Cost effective **

• Limitationo Increased workloado Overstretched workforce o Late initiation of ANCo Miss infection during window

period

• Role of more sensitive assays****Willams 2013; Kinuthia2010; **Soorapanth 2006;Sansom 2003; ***Busch1997;Morandi 1998;Quinn 2000; Hecht 2002

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Obstet Gynecol. 2003 Oct;102(4):782-90.Human immunodeficiency virus retesting during pregnancy: costs and effectiveness in preventing

perinatal transmission**

• 6.2 per 1000 person-years HIV incidence• 192 infections in women detected • 37 infant infections prevented• 655 infant life-years saved per 100,000

women tested• 5.2 million US$ net saving

“Second test would result in net savings in populations with HIV incidence of 1.2 per 1000 person-years or higher” Sansom

• HAART for HIV infected pregnant and breast feeding women irrespective of CD4 count, WHO stage

• Option A and B is being phased out

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Syphilis in pregnancyPLoS Med. 2013;10(2)

Global estimates of syphilis in pregnancy and associated adverse outcomes: analysis of multinational antenatal surveillance data

Bull World Health Organ. 2013 Mar 1;91(3):217-26

Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review

and meta-analysis

Prematurity or low birth weight; 6%

Neonatal death; 9%

Congenital syphilis; 15%

Fetal loss or stillbirth,; 21%

Not affected; 49%

Chart Title

Premature or low birth weight infants; 65000

Neonatal deaths; 90000

Congenital syphilis; 150000

Still births or early neonatal

deaths; 215000

Chart Title

. *Newman;**Gomez

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Syphilis increase risk of HIVAIDS. 2006 Sep 11;20(14):1869-77.

Maternal syphilis infection is associated with increased risk of mother-to-child transmission of HIV

in Malawi

• Maternal syphilis associated with Intrauterine HIV MTCT, after adjusting for maternal log10 HIV-1 viral load and low birth weight

ARR, 2.77; 95% CI, 1.40–5.46]

• Maternal syphilis associated with Intrapartum/postpartun MTCT after adjusting for recent fever, breast infection, LBW and maternal log10 HIV-1 viral load

ARR, 2.74; 95% CI, 1.58–4.74)

• Concurrent maternal syphilis infection associated vertical HIV transmission compared with only history of treated syphilis 100% vs. 21%, P = 0.01 or

100% vs. 14% ,p = 0.0015 for women with no history of syphilis

• Non-Zidovudine exposed women with concurrent syphilis transmitted HIV to their infants compared to those with only a history of syphilis

100% vs. 0% (P = 0.006)

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Mwapasa 2006

Int J Gynaecol Obstet. 1998 Dec;63(3):247-52.Maternal syphilis and vertical perinatal transmission of human immunodeficiency virus type-1 infection

Lee 1998

Prevalence of syphilis and HIV among pregnant women - Kenya

KAIS 2007 KAIS 2012

HIV positive; 8.9%

HIV & VDRL nega-tive; 89.5%

VDRL Positive; 1.6%

HIV positive; 6.5%

HIV negative; 93.5%

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Screening for syphilis during pregnancy

• Routine test in antenatal care

• 1st ANC visit o CDC recommends repeat in 3rd trimester*

• Non-treponomal tests o RPR/RPR

*CDC 2002;** KAIS 2012

Counselled on MTCT Counselled on HIV testing Counselled on syphilis screening

0%10%20%30%40%50%60%70%80%90%

100%

76.6%90.1%

47.2%

Counselling experience among women aged 15 -54 years attending ANC**

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• Barriers to screeningo Costo ANC non-attendanceo Stock out of test kitso Wait time for results

Correlates of Syphilis infection (n=1020)OR (95% CI) p

Age (years) 1.05 (0.97-1.16) 0.2

Education (years) 0.82 (0.64-1.05) 0.11

Married 3.12 (0.40-24.3) 0.3

Ever trade sex 1.22 (0.54-2.73) 0.63

History of STI 10.36 (3.20-33.55) <0.001

Partnership duration (yrs) 1.09 (1.00-1.19) 0.055

Unknown partner HIV status 1.71 (0.53-5.42) 0.37

Multiple sex partners 11.36 (1.30-98.7) 0.03

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*yrs=years

X

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Dual eliminations strategies supports attainment of MDGs • Prevent Congenital syphilis

• Fewer spontaneous abortions•

• Fewer still births

• Reduced risk of HIV acquisition

• Reduced HIV shedding

• Reduce risk of MTCT of HIV

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Why combine efforts towards elimination of MTCT of HIV and syphilis

• Sexually transmitted infections that can affect foetus/infant

• ANC entry point for care

• Point of care testing possible

• Effective interventions availableo Syphilis treatableo PMTCT of HIV reduce risk to <2%

• Combined services more efficient

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Acknowledgements• Mama Salama Study participants

• Ahero and Bondo study staff

• Research team

• KNH/UoN• John Kinuthia• Daniel Matemo• James Kiarie

• UW• Grace John-Stewart• Alison Drake• Katherine Odem-Davis• Barbara Lohman Payne• Barbra Richardson• Jennifer Slyker• Jennifer Unger• Julie Overbaugh• Scott McClelland • Carey Farquhar • Anjuli Wagner • Gwen Ambler

• CDC/KEMRI• Clement Zeh• Lisa Mills

• Funding• NIH (P01 HSD 064915)• CFAR (P30 AI27757)

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