1. PMTCT program in Arua Uganda Lessons learned after 5 years of experience Experts Roundtable 23-24 June 2008 Geneva

2. Arua PMTCT program (1) Started in January 2000 1 st ante-natal visit : HIV voluntary counselling & testing HIV+ enrolled in PMTCT program

3. Arua PMTCT program (2) National PMTCT protocol (2000 to 2005) – Mother : NVP at labour onset – Infant : AZT (1 wk) or NVP (<72 h) Follow-up – Cotri prophylaxis + feeding education – Infant formula (up to June 2004)

4. Arua PMTCT program (2) National PMTCT protocol (2000 to 2005) – Mother : AZT from 36 wk or NVP at labour onset or ART – Infant : AZT (1 wk) or NVP (<72 h) Follow-up – Cotri prophylaxis + feeding education – Infant formula (up to June 2004) Pregnant women in ANC n=30 536 Pre-test counseling n=22 105 (72%) HIV-test refused  Routine ANC n=3 088 (14%) HIV-tested n=19 017 (62%) HIV– n=17 980 (95%) HIV + n=1 037 (5%) PMTCT n=517 (49.8%) Routine ANC n=520 (50.2%)

5. Objectives Describing characteristics of mothers & infants Quantifying and describing reasons for loss to follow-up (LTFU) Estimating HIV transmission Evaluate the performance of the PMTCT program of Arua by:

6. Methods (1) Retrospective cohort analysis – Inclusion: Women enrolled in PMTCT between July 2000-July 2005 Description of infant outcomes Active tracing of LTFU Cross-sectional survey – Interview of caregivers (reasons for LFU) – Clinical examination and HIV testing for infants

7. Methods (2) Survival Analyses (Kaplan-Meier) HIV transmission – HIV testing for children alive – HIV-related deaths*: severe infection or persistent diarrhoea AND > 1 HIV-related symptom at last MCH visit Risk factors for HIV-transmission (multiple logistic regression) * Ghent Int. Working Group on MTCT of HIV

8. Results: PMTCT Program (July 2000 – July 2005) Enrolled: – Mothers (N=517) – Infants (N=567) Infant outcomes (n=567)

9. Results: PMTCT Program (July 2000 – July 2005) Enrolled: – Mothers (N=517) – Infants (N=567) Cross-sectional survey – Mothers (N= 327, 63%) – Infants (N= 368, 65%) Infant outcomes (n=567)

10. Maternal characteristics at PMTCT enrolment (N=327) 32 (10) On ART 368 [200 -535]Median CD4+ cells/ml; n=201 [IQR] 5 (2) 164 (50) 144 (44) 13 (4) WHO stage (%) Asymptomatic Stage I/II Stage III Stage IV 4 (1) 72 (22) 233 (71) 18 (6) Trimester of pregnancy (%) First Second Third At/after birth 28 [25-32]Median age (yr) [IQR]

11. Newborn characteristics (N=368) Place of delivery (%) Arua Regional Hospital Home/on the way Health centre/other hospital 280 (76) 70 (19) 17 (5) Female (%)182 (50) Median weight, kg [IQR] (n=334) 3 [2.7 - 3.4] Timing of ARV start for mother ART ≥ 3 months before birth ART < 3 months before birth NVP prophylaxis at birth AZT prophylaxis at birth None 44 (12) 21 (6) 253 (69) 19 (5) 24 (7) ARV post-partum prophylaxis (%) NVP single dose AZT one week None 288 (78) 12 (3) 65 (18)

12. Follow-up characteristics of infants (N=368) Median nb of post-natal consultation visits [IQR]4 [0 -9] Type of feeding received (%) Exclusive breastfeeding Exclusive infant milk formula Mixed feeding 103 (29) 96 (27) 154 (44) Median age at weaning start [IQR] (n=353)6 [4 - 6]

13. HIV transmission 8.3% (24 / 288) of children were HIV+ Overall transmission = 15.5% (57 / 367)

14. Risk factors for MTC HIV transmission * Characteristics HIV+ (%) Multivariate analysis OR (95% CI)p-value Age (yr) >=25 vs. <259 (9)0.4 (0.1- 1.2)0.09 WHO stage 3/4 vs 1/27 (9)0.7 (.22 - 1.9)0.45 CD4+ (cells/mm3) >=350 vs. < 350 11 (14)1.7 (0.5 - 5.2)0.38 Home delivery/on the way 7 (26) 3.7 (1.2 - 11.3)0.03 Females 4 (6)0.4 (0.1 - 1.4)0.15 ARV prophylaxis vs. none13 (10) 3.6 (0.6 - 23.1) 0.17 Type of feeding Infant formula vs. breast feeding Mixed feeding vs. breast feeding 2 (6) 10 (15) 1.14 (0.2 - 7.5) 2.6 (0.7 - 10.3) 0.30 Weaning at 6 months 7 (14) 1.5 (0.5 - 4.7) 0.46 *Among children tested for HIV (n=288) Mother Child

15. Infant survival 33 / 72 deaths were HIV-related Most frequent causes of death –Acute or chronic diarrhoea (34.7%) –Respiratory tract infections (20.8%) 0.81 (95% 0.77 – 0.85)

16. Mother/baby pair LTFU Median time at LTFU was 1 month (IQR : 0 – 5) Reasons for LFU (n=197) – 30% mothers' ignorance of the importance of FU – 27 % infant death – 13 % discouraged by the partner – 12 % address change

17. Discussion (1) Mothers 40% women refused to be tested Among the HIV +, 50% refused to be enrolled in the PMTCT Among the enrolled women, 50% drop out First visit in third trimester of pregnancy 50% accessed ANC in earlier HIV disease 21% home delivery

18. Discussion (2) Infants 18% did not receive PMTCT prophylaxis HIV transmission rate reduced from 35% to 15.5% Mother/baby pairs LTFU 53% LTFU before tracing Main reasons for LTFU = mother’s ignorance of importance of FU & infant death BUT 30% of pairs untraced

19. Recommendations Improve the message delivered to mothers at enrolment Increase resources for PMTCT ( HR, logistics…) Reconsider Feeding strategy Early diagnosis and treatment for children

20. Acknowledgments Ugandan Ministry of Health in Arua and Kampala MSF team in Arua and Kampala Epicentre in Kampala and Paris CDC laboratory in Entebbe (Ugandan Virus Institute)

22. ARUA REFFERAL REGIONAL HOSPITAL PMTCT From May 2007 to end of February 2008

23. Organigram Flow of patient PMTCT AN +HIV f/up Mother and child f/up until 1 year ANC VCT HIV clinic Women became pregnant Maternity ward Labour suite Home delivery Mother 1year after delivery Child+ after 1 year

24. Treatment protocol Antepartum treatment Labour treatment Postpartum treatment Child treatment Pregnant women Cd4<350 HAART AZT 1ml bd 7 days ( *4 weeks if the mother begins treatment less than 1 month before delivery) Pregnant women Cd4>350 AZT 300mg bd >28 WA Sd NVP 200mg + (AZT-3TC) (600/300) stat Tail AZT-3TC (300/150) bd 7 days Sd NVP 0.6ml + AZT 1ml bd 7 days ( or *)

25. Data from ANC from May 2007 to end of February 2008 63% women accept to be tested 75% of mother tested HIV+ are enrolled in PMTCT HIV prevalence at ANC is 4 % during the period Total first ANC9923 Total pregnant women tested6252 Total tested HIV +256 Total enrolled in PMTCT191

26. Mothers enrolled in PMTCT May 2007 to End of February 2008 (1) Weeks in pregnancyTotal (%) < 28 weeks273 (54%) > 28 weeks and < 36 weeks83 (16%) > 36 weeks48 (9%) With baby99 (20%) Total503 (100%)

27. Mothers enrolled in PMTCT May 2007 to End of February 2008 (2) Median CD4 : 448 /mm 3 WHO staging (from ANC only ) Total (%) Stage 1125 (64%) Stage 238 (20%) Stage 319 (10%) Stage 49 (5%) Total191 (100%) 85%

28. Mothers enrolled in PMTCT May 2007 to End of February 2008 (3) 8% are lost to follow-up 40% are on ARVs (10% in 2000-2005) 62% of the mothers enrolled in PMTCT are coming from HIV clinic Total (%) Total enrolled503 (100%) death1 (0%) Lost of follow-up41 (8%) Transfered4 (1%) Followed with no ttt252 (50%) Followed on ARV203 (40%) Unspecified2 (0%)

29. Prophylaxis and treatment (1) Ante partum drugs% HAART40% AZT (> 28 weeks)33% None25% Unknown1.5% Intra partum drugs HAART40% NVP+ (AZT/3TC)13% AZT+NVP4% Stat NVP10% AZT13% None17% 73% 57%

30. Prophylaxis and treatment (2) Post partum prophylaxis HAART43% Tail AZT/3TC19% None20% Baby prophylaxis Stat NVP+ AZT37% Stat NVP17% None26%

31. Location of delivery May 2007 to End of February 2008

32. Feeding Option PMTCT May 2007 to End of February 2008

33. Outcome of children Will need to wait 2009 regional meeting…. Thanks

34. WHO stage & CD4 at PMTCT enrolment <350 CD4 cells/ml >=350 CD4 cells/ml No CD4Total Stage 1&237 (21.9) 61 (36.1) 71 (42.0) 169 Stage354 (37.5) 44 (30.5) 46 (32.0) 144 Stage4 2 (15.4) 3 (23.1) 8 (61.5) 13 No staging0 (0) 0 (0) 1 (100) 1 Total 93 (28.4) 108 (33.0) 126 (38.6) 327

35. Maternal characteristics at follow-up (N=327) Partner/family aware of HIV status : 297 (90.8%) Partner aware of PMTCT enrolment : 242 (74.0%) Participation in PMTCT  No problems : 279 (85.3%)  Separation/divorce : 22 (6.7%)  No male involvement/conflict : 15 (4.6%)  Family stigma/conflict : 9 (2.8%)  Other : 2 (0.6%)