1. Accomplishments Year 1 Encouraged HIV testing counseling with referrals to Phidisa 1 Education of Nursing Staff on Pediatric Wards Lectures to Medical Officers and Interns in Pediatric Unit Training in US US Collaborator: 2 week visit Treatment SOP for children (needs refinement)

2. Accomplishments: HIV testing of 27 children: 24 were positive 10 did not return for test results and were infected 9/14 qualified for treatment Age: 1-10 CD%: 0.76%-32.9% HIV RNA : imdetectable-1,382,000/copies/ML Weight: 3 severely malnourished ( 3%; 1 only at 50% Ht : 6; 3%: 10 yo at 25%

3. Accomplishments ARVs for 9 thus far: 2: d4T/3TC/Kaletra (1 severe encephalopathy: cannot walk) 7: d4T/3Tc Efavirenz Outcome 1 month: minimum weight gain 1 Kg

4. Goals Establish a Multidisciplinary Family Clinic: to provide primary and tertiary care: to start one day per week and then as needed ensure access to research and adherence with research and treatment protocol visits. Recruit and Train multidisciplinary team: Pediatrics, Ob/Gyn, Internal Medicine, Nutrition, Mental Health, Community Health ( Vaccinations), Occupational Health, Neurodevelopmental, Nursing and Social work Case Management to care for women and children affected by HIV.

5. Goals Assure that all staff are trained to discuss educate patients on benefits of research through Phidisa. Incorporate research in all aspects of care and integrate clinical and research staff so that all patients are offered access to research protocols

6. Goals Enroll into Phidisa-1: 500 HIV infected infants, children and their mothers and provide ARVs where eligible through PEPFAR. Routine Maternal prenatal visits q month then weekly as per standard OB protocol Pediatric routine clinical visits q 1-3 months. For infected neonates at 2 weeks, 4-6 weeks, 4, 6 month 9, months, 12, 15 months and then routinely Integrate maternal and infant/child visits with Phidisa 1 research visits at 6 month intervals as per Phidisa 1 protocol

7. Goals Reduce Perinatal Transmission to 0-2%: Establish 2-3 Perinatal Centers  starting with open sites-1 and 2 MH to include Ob, Pediatric and Internal Medicine providers to manage and deliver perinatal care to HIV+ pregnant women and their neonates.  Specialized Trained Staff in labor and delivery Rapid test available in the Delivery Room  Establish 24 hour call system for Ob/Peds  Collect Research data on pregnancy, co-infections ( TORCH, Grp B Strep) and labor and delivery complications, and infant outcomes (Apgars, wt/ht etc)

8. Goal: Reduce Perinatal Transmission to 0-2%: Provide Routine Prenatal Care to HIV+ pregnant women: Start with one half day a week clinic Utilize a standardized perinatal care and treatment protocol across sites  in terms of routine visits, and obstetrical practices in labor and delivery. ( ie no forceps,, what to do with PROM, high viral load, presentation without prenatal care etc.) at designated delivery sites  Coordinate care OB care with HIV care  Early involvement with Pediatrics to review care and discuss breastfeeding risks of transmission  Review risk/benefits of traditional healers

9. Goal: Reduce Perinatal Transmission to 0-2%: Enroll in Phidisa-1 HIV+ pregnant women and through PEPFAR provide treat/prophylaxis with HAART for maternal health and prevention of perinatal transmission for 800 HIV+ pregnant women and their neonates.  Treatment for naïve women: ZDV/3TC, ZDV/ddI + NVP (if CD4 count <250) ( to be discussed)  Treatment for when past ARV HX depending on viral load  Achieve RNA <50 copies  Monitor for viral rebound  Monitor closely for toxicity (especially liver enzymes): Final protocol to be determined  Alter regimen with no response or inadequate response within 2 weeks, and one month

10. Drug Regimen for Mother Treatment for naïve women: ZDV/3TC, d4T/3TC,ZDV/ddI + NVP (depending on CD4)//Nelfinavir/ Kaletra (poor PK?) during pregnancy/ IV ZDV at delivery or ? Oral ZDV/3TC (Pending final approval by OBs) Treatment with past ARV HX or Phidisa 2 pregnancy or high CD4 depending on viral load; d4t/3TC, AZT/ddI; EFV  Nelfinavir ( good data) ; Kaletra (Need better PK Data??) remains as is. Monitor RNA closely;  Achieve RNA <50 copies  Alter regimen with no response or inadequate response within 2 weeks, and one month If on Phidisa 11- Change Efavirenz to NVP if RNA < 50 copies/mL and CD4 < 250 Change Efavirenz to PI with detectable RNA

11. Drug Regimen for Neonate If Mom has RNA <1,000 treat with oral ZDV for 6 weeks If maternal viral load > 1,000 add 3TC If no maternal ARVs no prenatal care: use triple therapy (Final in depth protocol for review) Early diagnosis with DNA PCR (birth, 2 weeks, 4-6 weeks, 4 months) with early treatment In utero DNA PCR+ infants begin treatment ASAP: HAART (zdv/ ddI or 3TC/NVP final regimen pending) Primary care coordinated with HIV care: growth and development/nutrition; vaccines (including varicella); drug toxicity monitoring. PCP prophylaxis for HIV unknown status and HIV+ neonates

12. Treatment Group 1: Infants < 6weeks of age – HIV exposed infection status not yet known Term Infants should receive NVP 6 mg (~2mg/kg) once (assuming that mother also received a dose) and ZDV 4mg/kg q 12hr + 3TC 2mg/kg q 12hr for 6 weeks. (Alternative to 3TC is DDI) For cases of no maternal treatment and/or high viral load consider continuing NVP for 6 weeks (check on dosing of NVP in neonatal period). Maternal Prenatal Care > 2 weeks formula fed (and HIV RNA < 1000) Term Infant should receive ZDV 4mg/kg q 12hr for 6 weeks

13. Treatment Group 2: Infants > 6weeks of age – HIV exposed infection status negative or unknown and breast feeding A.3TC 2mg/kg q 12 hr for 4 weeks then 4mg/kg q12 and ZDV 4mg/kg q 12hr for 4 weeks beyond termination of breast feeding. (Alternative to 3TC is DDI) B.NVP 2mg/kg qd x 14 days then 2mg/kg q 12hr and ZDV 4mg/kg q 12hr for 4 weeks beyond termination of breast feeding *Emphasize importance of stopping breastfeeding, if possible

14. Treatment Group 3: HIV infected infants < 12 months of age – Treatment indicated in all infected infants in first year of life without regard to CD4 count. Suggested Treatment Regimens 1 PI + 2 NRTIs or 1 NNRTI + 2 NRTIs First Line PI – Kaletra (LPV/rtv) – greater than 6 months. If unable to tolerate Kaletra then Nelfinavir or NNRTI are options First Line NNRTI – Nevirapine (NVP) First Line NRTI backbone: AZT + DDI if refrigeration is available. If not then d4T + 3TC Note that AZT and D4T are antagonistic when given together so this combination should never be used Group 4. HIV infected infants > 12 months of age and unable to take solid oral dosage medications Treatment indicated if AIDS (Clinical Category C) or CD4% 100,000 copies /mL. May be indicated in other patients if HIV is markedly symptomatic Suggested Treatment Regimens 1 PI + 2 NRTIs or 1 NNRTI + 2 NRTIs First Line PI – Kaletra (LPV/rtv) First Line NNRTI – Nevirapine (NVP) First Line NRTI backbone AZT + DDI (if refrigeration available) Group 5. HIV infected infants > 12 months of age and able to take solid oral dosage medications Treatment indicated if AIDS (Clinical Category C) or CD4% 100,000 copies /mL. Suggested Treatment Regimens 1 PI + 2 NRTIs or 1 NNRTI + 2 NRTIs First Line PI – Kaletra (LPV/rtv) First Line NNRTI – Efavirenz (EFV)

15. Resources Funds for HAART for 500 HIV+ infants and children (as per SOP) through PEPFAR Funds for HAART for 800 HIV+ pregnant women and ARVs for 800 newborns based on maternal history and maternal viral load ( as per SOP and Management Plans in progress) Training of program staff Funds for Laboratory testing (including DNA PCR) through PEPFAR for 500 HIV+ infected babies, 1300 HIV+ pregnant women and their neonates to include, HIV monitoring and resistance testing as needed.

16. Training needs Recruit and Train 2 pediatricians and 1 Ob/Gyn physicians as needed at each site. Training for clinic, delivery room and neonatal nursing staff. Train community social/outreach worker Through SANDF staffing for MDs, paraprofessionals and nursing and social work case management, ancillary support services etc.

17. Future Need statistics: Average number of children/Phidisa parents enrolled % tested and HIV+ Number of Pregnancies and deliveries per site Data collection system to monitor toxicities in pregnant women and newborns exposed to HAART