Accomplishments Year 1

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 (< marasmic line); 11 >3%; 1 only at 50% • Ht : 6; <3%; 8: >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, childrenand 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 andZDV 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 andZDV 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% < 25% or HIV RNA > 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% < 25% or HIV RNA > 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