Mashi Study Dr T Gaolathe Botswana Harvard School of Public Health AIDS Initiative Partnership

Botswana National Program for PMTCT (Launched June 1999; country-wide Nov 2001)

The Mashi Study: QUESTION #1 Formula Feed …OR… Breast Feed mo AZT 6 mos AZT 1 mo AZT 6 mos AZT

The Mashi Study: QUESTION #2 (MOTHER) (MOTHER) 1 Medication …OR… 2 Medications 1 Medication …OR… 2 Medications (AZT) (AZT + NVP) (AZT) (AZT + NVP)

Mashi: Study Design  Randomized partially blinded placebo controlled clinical trial with a 2 x 2 factorial design  1200 HIV-1 infected pregnant women enrolled at 34 weeks gestation  Mothers and infants are followed until 2 years after delivery  1 urban and 3 rural locations in Botswana Gaborone, Molepolole, Mochudi, and Lobatse Gaborone, Molepolole, Mochudi, and Lobatse

MOTHER AZT SD NVPSD NVP Placebo Formula Feeding + 1 mo infant AZT Breast Feeding + 6 mos infant AZT Breast Feeding + 6 mos infant AZT Formula Feeding + 1 mo infant AZT BABY SD NVP Placebo The Mashi Study: Original Design MOTHER

AZT SD NVPSD NVP Placebo Formula Feeding + 1 mo infant AZT Breast Feeding + 6 mos infant AZT Breast Feeding + 6 mos infant AZT Formula Feeding + 1 mo infant AZT BABY SD NVP The Mashi Study: Amended Design MOTHER

Botswana National Program for PMTCT (amended) Additional Provisions for: Mother NVP:Single-dose (200mg) at onset of labour upon admission to L&D Infant NVP:Single-dose (3mg / kg) stat after delivery

The Mashi Study: QUESTION #1 Formula Feed …OR… Breast Feed mo AZT 6 mos AZT 1 mo AZT 6 mos AZT

Mashi Study Results: Question #1 (Infant HIV Positivity) VisitFF n = 591 BF+ ZDV n = 588 n = 588 p value* Month 1 5.0%4.6%0.76 Month 4 5.2%7.9%0.11 Month 7 5.6%9.1%0.04 *Z-test based on difference in Kaplan Meier estimates with stratification by the 4 arms

Mashi Study Results: Question #1 (Infant Mortality) FF n = 591 BF+ ZDV n = 588 p value Month 1 4.3% 1.5 % p = Month % 4.9 % p = Month % 9.5 % p = 0.46 Predominant causes of infant death: diarrheal disease and pneumonia

Mashi: Feeding Strategy Results OutcomeFF BF + AZT Statistical Significance 7 month HIV positivity 5.6%9.1% Significant difference P= month Infant Mortality 8.4%4.4% Significant difference P= mo mortality or HIV positivity 14.2%15.6% No significant difference p=0.45

Mashi Study Results: Question #1 (Infant HIV Infection or Death) FF n = 591 BF+ ZDV n = 588 p value Month % 6.1 % 0.07 Month % 12.9 % 0.87 Month % 15.6 % 0.41 By 18 months:  HIV-free survival 85.8% in FF and 84.4% in BF+ZDV arms  79 endpoints in FF (33 HIV positive,46 deaths)  88 endpoints in BF (54 HIV positive, 34 deaths)

Conclusion: Mashi Question #1 (Thior et al, JAMA 2006)  Formula feeding was associated with lower 7-month HIV transmission rates but higher mortality rates than [breastfeeding + ZDV] for 6 months  18-month HIV-free survival rates were comparable and high in the FF and BF+ZDV arms (85.8% and 84.4%, respectively)  Both FF and BF+extended ZDV are reasonable strategies for PMTCT Choice of strategy should depend upon local circumstances Choice of strategy should depend upon local circumstances

The Mashi Study: QUESTION #2 (MOTHER) (MOTHER) 1 Medication …OR… 2 Medications 1 Medication …OR… 2 Medications (AZT) (AZT + NVP) (AZT) (AZT + NVP)

Conclusion: Mashi Question #2 (Shapiro et al, AIDS 2006)  No advantage to maternal SD NVP when: Pregnant woman receives > 4 weeks of AZT received antenatally, and Pregnant woman receives > 4 weeks of AZT received antenatally, and Infant receives sd-NPV immediately after birth plus 4 weeks of AZT Infant receives sd-NPV immediately after birth plus 4 weeks of AZT  An effective short-course PMTCT strategy that spares maternal NVP exposure is possible for regions where prophylactic maternal and infant ZDV can be used.

Aknowledgement:  BHP Study Team  Carolyn Wester