N. Shema 1, L. Tsague 2, J.D.D. Bizimana 3, P. Mugwaneza 1, A. Lyambabaje 3, E. Munyana 2, J. Condo 3, J.C. Uwimbabazi 4, E. Rugigana 3, J. Muita 2 1- TRACPlus/Ministry of Health; Kigali, Rwanda; 2- UNICEF – Rwanda; 3- National University of Rwanda, School of Public Health; 4 - National Reference Laboratory ; Kigali, Rwanda ADD LOGO TRACPLUS and MOH REPUBLIC OF RWANDA MINISTRY OF HEALTH

Maternal and Child Heath Indicators, Rwanda, (DHS 2005, Mini DHS 2008) Fertility rate –6.1→ 5.5 children per woman At least 1 ANC visit uptake –94% → 96% Delivery assisted by trained health care worker –24% → 63% Immunization coverage in children –94.8% for DPT1 ( DHS 2008) 2

Rwandan National PMTCT program Millestones ( ) 3 3. Initial sites expansion (GF, MAP) 1. PMTCT pilot project (Kicukiro) 2. TRAC defines National PMTCT program based on Sd- NVP regimen 2. TRAC defines National PMTCT program based on Sd- NVP regimen 5 – Initial expansio of early infant HIV diagnostic (DBS- PCR) - Expansion of More Ef-ARV -PMTCT Acceptability study 5 – Initial expansio of early infant HIV diagnostic (DBS- PCR) - Expansion of More Ef-ARV -PMTCT Acceptability study – More Efficacious ARV regimens and early infant diagnostic using DBS-PCR introduced; - PMTCT and ART program Scale- up (GF, PEPFAR) 4. - More Efficacious ARV regimens and early infant diagnostic using DBS-PCR introduced; - PMTCT and ART program Scale- up (GF, PEPFAR) 2009– 6. – Transition to MER-ARV; - Impact study of national PMTCT program - Adaptation of 2009 WHO ARV recommendations for PMTCT 6. – Transition to MER-ARV; - Impact study of national PMTCT program - Adaptation of 2009 WHO ARV recommendations for PMTCT

4 Package of services for Mother-infant pair in the PMTCT program, Rwanda, 2009 HIV+ pregnant women Routine opt-out counseling and HIV testing (Promotion of couple counseling and testing) Laboratory investigation: FBC, CD4 count, routine pregnancy check-up, liver function Routine pregnancy medications: Malaria prevention ( Bed nets), anemia prevention (Iron/Folic acid), etc.. ARV prophylaxis  HAART for women eligible  Bi-prophylaxis (AZT+SdNVP; Tail AZT/3TC)  Sd-NVP ; Tail AZT/3TC (discordant couple, labor room CT) Safe practices delivery Infant feeding counseling and support Family planning services Psychosocial and adherence support HIV exposed infants Post-exposure ARV prophylaxis –Sd-NVP + AZT (4 weeks) Drug package (CTX prophylaxis) –CTX starts at 6 weeks Clinical monitoring –Growth monitoring –Symptoms of early HIV infection Early Infant diagnostic (DBS-PCR) –DNA-PCR PCR1: at 6 weeks PCR2: 6 weeks before end of BF Serology 9 months (1rst) 18 months (2 nd )

Study Objectives Evaluate the effectiveness of the national PMTCT program in Rwanda 8 years after its inception. –The outcome variables were:  Prevalence of HIV infection among 9-24 month old exposed children  Risk of dying by 9 months among HIV exposed children  HIV-free survival at 9 months

Methods (1) Design: Cross-sectional household survey between February - May 2009 Population: HIV+ and HIV- mothers who were expecting a child between March 2007 and June 2008 and have used antenatal services in Rwanda and their 9-24-month-old children. Sampling strategy: Two-stage cluster sampling (Health facilities; pregnant women in ANC) Ethical considerations: Study protocol was approved by the Rwanda National Ethics Committee and the National Institute of Statistics. Statistical analysis: Quantitative data was analyzed in Stata 10.1.

Results

HIV + mothers HIV – mothers P-value Age, %, y (n=2969) Mean age, y Marital status, % (n=2963) Single/never married Lives with a partner Separated/divorced/widowed Religion, % (n=2970) No religion Adventist Catholic Protestant Muslim Others Socio-demographic characteristics of the respondents by HIV status

HIV + mothers HIV – mothers P-value Educational attainment, % (n=2965) Never attended school Primary school Vocational/technical Secondary school University Literacy, % (n=2969) can't or have difficult reading and/or writing can read but can't or have difficult writing can read and write easily Socio-demographic characteristics of the respondents by HIV status

Among HIV+ mothers, having completed at least four ANC visit is associated with delivering at the health centers HIV + Mothers Total (n=1434) All Less than 4 ANC visits4 or more ANC visitsP-value Child given ARV at birth, (n=1394) None NVP Dual therapy Don’t know Mother delivered at health center, (n=1445) Yes No Feeding options at birth, (n=1352) EBF BF and early cessation Formula Animal modified milk

24 months Child survival by maternal HIV status, Rwanda National PMTCT program, 2009 Kaplan-Meier survival analysis shows that children whose mothers are HIV negative are more likely to survive longer than children born to HIV+ mothers (p<0.001). Between 0-6 months, child survival is comparable. Note that survival deteriorates between 6-18 months among children born to HIV positive mothers.

24 months Child survival by maternal ANC visits, Rwanda National PMTCT program, 2009 Kaplan-Meier survival analysis shows that children whose mothers attended less than 4 ANC visits had poorer survival than children whose mothers attended more ANC visits (p=0.02). This factor seems to be associated to early child mortality (0-6 months). Survival deteriorates further between 6-18 months among children born to HIV positive mothers.

9-24 month HIV-free survival in National PMTCT program, Rwanda, 2009 Unweighted Total No %(95%CI) Yes %(95%CI) Death ( )2.75( ) HIV infection ( )3.96( ) HIV infection and death among exposed children ( )6.74( ) 2.75% exposed children died by the age of 9 months 3.96% among the 1340 exposed children alive were HIV infected. HIV-free survival was estimated at %( 95%CI: 92.05%-94.47%) at 9-24 months The risk of death in children born to HIV+ mothers is 3.5 times higher as compared to children born to HIV- mothers (aHR: 3.51, 95% CI: ) independently of child HIV status.

Multivariate analysis of determinants of HIV infection or death among HIV exposed children, National PMTCT program, Rwanda, 2009 Child HIV infection or death Adjusted OR95% CI ARV taken by the mother, (reference: none) NVP alone Dual therapy Triple therapy – – – 0.86 Location, (reference: rural) Urban – 1.25 Membership to a PLWH association, (reference: no) Yes – 0.94 Children whose mothers received highly active antiretroviral therapy (HAART) were 50% less likely to be infected by HIV and/or died compared to children whose mothers did not receive any ARV during pregnancy (adjusted Odd Ratio (aOR): 0.49, 95%CI: ). Being a member of an association of people living with HIV (PLWH) (aOR=0.61, 95%CI: ) was also associated with a 39% reduced likelihood of HIV infection or death in children.

Conclusions HIV free-survival among HIV exposed children is high (93.3%) by 9-24 months in Rwanda, However, survival among children born to HIV infected mothers decreases overtime as compared to the one of children born to HIV- mothers. Survival deteriorates further after 6 months of age among HIV exposed infants. The risk of death in children born to HIV+ mothers is 3.5 times as higher as in children born to HIV- mothers (aHR: 3.51, 95% CI: ) independently of child HIV status. The key determinants of HIV free-survival in the national PMTCT program include maternal initiation of highly active antiretroviral therapy (HAART) during pregnancy (adjusted Odd Ratio (aOR): 0.49, 95%CI: ) and being a member of an association of people living with HIV (PLWH) (aOR=0.61, 95%CI: ).

Acknowledgments All mothers and family who participated in the study All staff from the selected sites Staff at the National Reference Laboratory All HIV&AIDS implementing partners National University of Rwanda School of Public Health UNICEF for technical and financial support School of Public Health