Promise Pep Study

This study took place at Cecilia Makiwane Hospital in Mdantsane, East London between 2010 and 2013. The Promise Pep/ANRS 12174 study compared the efficacy and safety of prolonged infant peri-exposure prophylaxis (PreP) with:

Lopinavir/ritonavir (LPV/r) versus lamivudine. To prevent HIV-1 transmission through brestmilk in HIV exposed infants born to mothers not eligible for HAART during the full duration of breastfeeding (max 1 year).

Method: HIV-uninfected newborns were randomized at 7 days post-partum to receive either of the two drugs.

Infant HIV-infection status was assessed at day 7 and every 3 months using HIV-1 DNA PCR.

By end April 2012, the study completed enrolment in four African countries: Burkina Faso, Uganda, Zambia and South Africa.

Blinded interim analysis presented in 2012: transmission and mortality rates combining the two arms.

The final sample size was 1273.

The conclusion was the infant PreP strategy (the WHO option A) using LPV/r or lamivudine during the whole duration of breastfeeding can achieve a very low rate of postnatal transmission well within the target of elimination (<5%).

On 29 July, 2013 a Report Back Session and lunch was held at the Health Resource Centre in East London. It was attended by 47 people including Debra Jackson from UWC in Cape Town, Professor Cheryl Nicodem from the University of Fort Hare in Alice, ECRU staff, Frere Maternity staff, Cecilia Makiwane staff and Department of Health staff from Bisho, King Williams Town and East London.

In September 2014 a close-out visit to CMH, Eastern Cape was undertaken by Dr Isidore Traore from Centre Murz Bobo-Dioulasso, University of Ouagadougou in Burkina Faso.

 

ANRS/PROMISE-PEP STUDY CLOSING ACTIVITIES
Principal Investigators: Prof Justus Hofmeyr and Prof Debra Jackson
Study Coordinator: Dr Mandisa Singata
Project Description
Postnatal transmission of HIV-1 through breast milk remains an unsolved problem in many resource-poor settings. In Sub-Saharan Africa, especially in the rural areas, replacement feeding has proven a problematic alternative because of social, cultural, economic and hygienic constraints. Moreover, studies have shown that exclusively or predominantly breastfed infants have a substantially reduced risk of succumbing to common childhood infections such as diarrhoea and pneumonia; diseases that also inflict a substantial nutritional insult. Therefore, strategies to prevent MTCT of HIV-1 that allows for maintenance of BF for an optimal period of time are urgently needed. In observational studies, Exclusive breast feeding (EBF) was associated with a reduced risk of HIV-1 transmission as compared to mixed feeding (1-3).


The PROMISE PEP study is a randomised double-blind placebo-controlled multi-centre trial that will measure the efficacy of prolonged peri-exposure prophylaxis (PEP) with lamivudine (3TC) to prevent HIV-1-transmission through breast milk and death in children born to HIV-1-infected mothers not eligible for HAART and having benefited from WHO-recommended enhanced perinatal antiretroviral (ARV) regimens. The study will recruit 1900 mother-infant pairs in 4 African countries.


The ANRS/PROMISE-PEP Study, a collaboration between the School of Public Health at the University of the Western Cape, the University of Montpellier France, University of Bergen Norway, Centre Muraz Burkina Faso, University of Zambia and Makarere University Uganda, completed data collection in April 2013. Over the past few months the project has successfully completed several important study close-out activities.
Finalisation of the 6-Year PROMISE-PEP Study


In July 2013, we made a report back to local and Provincial stakeholders in East London, Eastern Cape. This event was attended by approximately 50 stakeholders. We presented preliminary study findings and discussed implications for the PMTCT and infant services in South Africa and beyond.
In September 2013, we held our final ANRS/PROMISE-PEP Steering Committee meeting in Montpellier France which was attended by all the principal investigators and study coordinators. We reviewed study findings and discussed sub-studies and publications.
Both events were very successful and the study is looking forward to presenting our final results at the CROI 2014 conference in Boston in March 2014, and publishing the results in high impact journal.


Preliminary results abstract presented at East London Report Back Meeting
Background
The WHO recommendations (2010) for the prevention of mother-to-child postnatal transmission of HIV-1 proposes the use of infant prophylaxis using nevirapine (option A) or maternal HAART prophylaxis (option B) for the entire period of breastfeeding. However, the efficacy of option A during 12 months has never been assessed.


Methods:
The PROMISE PEP/ANRS 12174 study (ClinicalTrials.gov Identifier: NCT00640263) is a randomised controlled trial comparing the efficacy and safety of prolonged infant peri-exposure prophylaxis (PreP) with lopinavir/ritonavir (LPV/r) versus lamivudine to prevent HIV-1 transmission through breast milk in children born to HIV-1-infected mothers not eligible for HAART (CD4 above 350 cells/μL) during the full duration of breastfeeding (1 year). HIV-uninfected newborns at 7 days post-partum were randomised for either drug with a 1:1 ratio. Infant HIV-infection status was assessed at day 7 and every 3 months using HIV-1 DNA PCR. The study has now completed enrolment (April 2012) in four African countries: Burkina Faso, Uganda, Zambia and South Africa. The April 2012 meeting of the Data monitoring Committee recommendation is to continue and complete the study as planned. Because the study was highly powered to provide tight estimations of the overall HIV transmission using the PreP approach (i.e in both arms), we report data from the first 763 children who completed follow-up without unblinding to inform policy makers.


Results:
Of the 1273 children enrolled in the trial and randomised, 763 of them had, or should had completed the 50 weeks follow-up by mid-July 2012, accumulating 669 child-years of follow-up. The mothers of these children were aged 27 years on average, and had a mean CD4 count of 527 cells/μL. Overall, 9 transmissions have been identified by HIV DNA PCR on dried blood spots, representing a transmission rate of 1.3 per 100 child-yrs (95%CI: 0.5-2.2). Interestingly, 5/9 transmissions occurred after 6 months of breastfeeding. Overall, 18 deaths were identified giving a mortality rate of 2.6/100child-yrs (95%CI: 1.4-3.8). The HIV-free survival at 28 and 50 weeks was 98.5% and 96.2%, respectively.


Conclusions:
The infant PreP strategy (the WHO option A) using LPV/r or lamivudine can achieve a very low rate of postnatal transmission in Africa, well within the target for mother to child transmission of HIV elimination.