Diagnosis Issues in PMTCT: Experience in Cambodia. Eric Nerrienet Institut Pasteur du Cambodge Les Pensières 16-17/09/2010

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1 Diagnosis Issues in PMTCT: Experience in Cambodia Eric Nerrienet Institut Pasteur du Cambodge Les Pensières 6-7/09/00

2 Background Thailand Cambodia: 4,364 million inhabitants HIV prevalence (5-45): 0.7% (end 09) PLWHA: 67,00 PP 37,000 on HAART (end 09) including,300 on nd line regimen Gulf of Thailand Viet Nam Annual report 009, NCHADS 7/09/00

3 Background Thailand Crude Birth Rate: 8.5 : 40,000 pregnancies/year HIV prevalence among ANC attendees:.% 4,500 HIV-exposed newborn per year Gulf of Thailand PP Viet Nam PMTCT national policy: 000 At the end of 007: HIV testing and counseling in /956 ANC clinics ( %) National Strategic Plan for PMTCT % MTCT under prophylaxis 35% MTCT without prophylaxis 450 babies infected per year,600 7/09/00 3

4 Early Infant Diagnosis in Cambodia central laboratories in Cambodia National Institute Public Health Pasteur Institute HIV RNA VL EDTA blood, Biocentric (005:8$) HIV DNA VL DBS, Roche (008: FOC) DBS, Biocentric (006: 8$) HIV Drug Res ANRS (005: 50-70$) 4

5 Maternities/Hospitals referring DBS to IPC Kantha Bopha Maternity ward Calmette Hosp Mat. Ward Magna Children at Risk NMCHC AKS Hopsital Pochentong HC Toul Kork HC Daun Penh HC Kompong praing HC Kantha Bopha Peadiatric Hosp,, 3 & 4 since jul 0 Siem Reap Phnom Penh Chey Chumnas Hosp Takmao ELIMINARY 5

6 VEID, EID and PMTCT Experience of IPC, Cambodia 4,000 deliveries/year Associated maternities Collaborative work Magna Children at Risk Takmao Hospital 33,000 deliveries/year 363 exposed children/year 5,000 deliveries/year Calmette Hospital Maternity Ward VEID VEID IPC EID VEID 4,000 deliveries/year Kantha Bopha Siem Reap National Pediatric Hosp Phnom Penh EID EID Angkor Hosp for Children, Siem Reap Maternity wards Pediatric services 6

7 If HIV DNA Pos Blood EDTA tube HIV RNA confirmation CD4 count DO-D3 Data released within week If HIV DNA Neg (V)EID Algorithm If HIV DNA Pos W6 If HIV DNA Neg Blood EDTA tube HIV RNA confirmation CD4 count Breastfeeding Formula M after If HIV DNA Pos Blood EDTA tube HIV RNA confirmation CD4 count HIV Neg 7

8 Since 006, 94 exposed infants less than 8 months have been diagnosed for HIV infection on DBS PMTCT Mothers Not documented 4.% No prophylaxis 6,9% sdnvp 9,9% AZT/sdNVP 3,9% 55,% Haart PMTCT newborn No prophylaxis 3,7% sdnvp AZT 4 weeks 6,%,9% Not documented sdnvp 9,3% 68,% sdnvp AZT week 8

9 94 EID (D0-M8): 900 HIV Negative, 4 HIV Positive (4.5%) 76/94 screened early after birth 8/76 HIV positive (.4%) 5 (0.6%) in utero 3 (.7%) in peripartum 8/94 screened in pediatric services 4/8 HIV positive (3.3%) D0-D3 D4 D7 D8 D3 W W3 W4 W5 W6 M M3 M4 M5 M6 M7 M8 M9 M0 M M M3 M4 M5 M6 Age at time of first diagnosis 9

10 Mother and Child Prophylaxis Regimen 4 HIV-infected infants 4/4 PMTCT mother PMTCT child 3 none none 4 none sd NVP/AZT 4 weeks 7 Not documented Not documented 3/4 sd NVP only sd NVP only sd NVP only sd NVP/AZT 4 weeks AZT sd NVP sd NVP/AZT 4 weeks 8/4 AZT sd NVP sdnvp 6 AZT sd NVP sd NVP/AZT week HAART nothing 7/4 4 HAART sd NVP only HAART sd NVP/AZT week 0

11 HIV-infected infants virological follow-up 4/4 HAART pending Age in months Code Birth w6 w U0706 U04703 U0709 C0003 4/4: on HAART. HIV RNA VL after HAART pending Code B w6 w ,8 5,9 6 TT A , 6,7 TT E0397 6, TT E040 6, TT DBS - DBS + Dectectable HIV RNA VL TT HAART Initation

12 HIV-infected infants virological follow-up 9/4 die after diagnosis Code D0-D3 w6 w S.K/Cal E06 * E00 E098 E035 7,5 E TT E00 * TT E046 5,8 U /4 lost of follow up after diagnosis E037 * LFU E007 LFU E088 LFU DBS - DBS + Detectable HIV RNA VL TT HAART Initiation

13 HIV-infected infants virological follow-up /4 with undetectable VL after HAART initiation Code B w6 w ART D 6,4 ART ,9 E004 E05 D* E05 D* E09 6, E05 6,9 T ,3 E07 E085 * E0303 6,5 DBS - DBS + VL>.4 TT HAART initiation VL<.4 3

14 HIV-infected infants virological follow-up /4: VL still detectable after HAART initiation Code B w6 w E038 5,5 E097 D D 5,8 E07 D D 6, E E05 D D 6, E040 7,3 E054 E095 D D 5,8 E0380 E0366 7,3 E033 6,6 DBS - DBS + VL>.4 TT HAART initiation VL<.4 VL>.4 After HAART Initiation 4

15 Resistance profile before E033 E0380 E095 /4: VL still detectable after HAART initiation HAART After VL Log NVP ng/ml < 50 Y8C M84V E0366 3TC/FTC, NVP/EFV 7.3 Y8C M84V E097 3TC/FTC, NVP/EFV Y8C 5.4 E07 NVP/EFV 3. Y8YC M84V E099 3TC/FTC, NVP/EFV Y8C M84MI 6. E040 3TC/FTC, NVP/EFV 7.3 L74LV Y8YC V75M K03N Y8C M84V E038 DDI, NVP/EFV D4T, 3TC/FTC, NVP/EFV 5. Y8YC K03NS Y8C M84V G90AG E054 NVP/EFV 3TC/FTC, NVP/EFV 4.9 Y8YC Y8C M84V E05 NVP/EFV 3TC/FTC, NVP/EFV 3. 5

16 (V)EID, HAART and virological follow up 4 HIV+ 9 3 LFU 6 on HAART 4 not yet treated /4 (8.6%) VL<.4Log / (50%) VL >.4Log 4 VL pending 3 ARV sensitive 8 ARV resistant with low VL after control did not take drugs 3* Before HAART 4* After HAART 6

17 Conclusions EID on DBS now available in central labs in Cambodia IPC+ NIPH,000 EID/year: not enough compared to 4,500 HIV-exposed newborn/y in Cambodia HIV prevalence is higher among kids attending pediatric services (3.3% versus.4%) PMTCT is efficacy: low rate of in utero and per partum transmission In Utero transmission < Per partum transmission (p not significant) The risk of death and Lost of Follow Up after (V)EID and HAART initiation remains very high (/4 30%) 4/ 64% ARV sensitive 8/ resistant to ARV including: - 3 before HAART - 4 after HAART: Adherence? Suboptimal ARV dosage? Other? 7/09/00 7

18 Perspective Shorten the period between diagnosis and treatment Strengthen and improve counseling on Adherence (compliance / adherence) before and during treatment Strengthen the virological monitoring in ARV-treated infants Adapt the ARV-treatment in infants exposed to maternal RTIs WHO:. For infants exposed to maternal or infant NVP or other NNRTIs used for maternal treatment or PMTCT, start ART with lopinavir/ritonavir (LPV/r) + NRTIs. (Strong recommendation, moderate quality of evidence) Question: what is the situation at the national level? National evaluation? 7/09/00 8

19 Acknowledgment Calmette Maternity Ward: Chhim Khereana / Meng Ly Ek /Im Sthehikar/ Sim Kruy Leang Magna Children at Risk: Denisa Augustinova / Romain Santon / Lakheana Say / Kong Chhunly/ Martin Bandzak Kantha Bopha Hospital Siem Reap: Denis Laurent/Beat Richner Angkor Hosp. For Children: Soeurn Seithaboth NPH Phnom Penh: Sam Sophann / Ung Vibol IPC: Sopheak Ngin /Chea Kim Lai / Kun Kunthea / Phon Kerya / Sreymom Ken / Janin Nouhin / Eric Nerrienet 7/09/00 9