Earlier the HPTN084 study team at BAYLOR COLLEGE OF MEDICINE CHILDREN’S FOUNDATION UGANDA and the #crs leadership at Baylor hosted the HPTN084 protocol team.
The team led by Prof. Sinead Delany-Moretlwe ( the protocol chair for the HPTN084 study) included Ms. Estelle Estelle Piwowar-Manning (HPTN Lab Center Deputy Director, and Ms.Lebah Lugalia( HPTN Quality Assurance specialist).
The Baylor Uganda site has moved from the blinded phase of the HPTN084 study ( a practice where study participants are prevented from knowing certain information that may somehow influence them—thereby tainting the results.) to the open label extension.
The study already demonstrated that the long acting cabotegravir injection (CAB LA shots) prevents HIV in adults and adolescents (youths) weighing at least 35 kilograms (77 pounds) hence can be used for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV. This product has been approved by FDA for this purpose and currently approval is being sought by FDA from the local regulatory authorities.
The purpose of the HPTN084 Open label extension ( OLE) study is to allow participants who were initially randomized to TDF/FTC to switch to CAB LA (All participants may choose between either open-label CAB LA or open-label TDF/FTC for 48 weeks). Transitioning into this phase has taken/ is taking place at all the 20 sites in SubSaharan Africa that carried out the initial phase of the study.
The aim of the visit was to use this opportunity to meet the team implementing this OLE phase of the study to listen to and share experiences of best practices from Baylor and other sites .Current CRS activities were shared by Dr Addy R Kekitiinwa( CRS leader) and Dr Patricia Nahirya Ntege( HPTN084 study PI) shared updates of the HPTN084 study under the open label extension phase. Prof. Sinead Delany-Moretlwe mainly shared issues around the pregnancy and infant sub study of the HPTN084 OLE, the first of its kind in the world on follow up of babies born to mothers who have been on the long acting molecules such as – CABOTEGRAVIR, managing HIV seroconversion and an update the upcoming OLE 2 phase that should start next year. This was a great cross -learning session on issues identified so far and how they are being resolved. These will be shared with a wider team to support protocol revisions that will improve implementation of the study. The Baylor team was actively engaged in the QA sessions. Prof. Sinead noted that BU had the unique advantage of handling the KPs. As such they can greatly contribute to the pending question on how this population will best handle this CAB LA.
Objectives of open label extension.
- To estimate the incidence of HIV among participants who use CAB LA, combining blinded, unblinded and OL periods
- To evaluate the safety of open-label CAB LA with and without an oral leading over 48 weeks
- To evaluate the acceptability (uptake, continuation, discontinuation) of OL CAB LA over 48 weeks
- To describe the diagnostic test profile, PK, HIV drug resistance, and response to antiretroviral treatment in those who become infected after CAB LA exposure, combining blinded, unblinded and OL periods
- To characterize pharmacokinetics and duration of detectable drug among those who discontinue CAB LA injections, combining blinded, unblinded and OL periods.
- To estimate the incidence of pregnancy among participants during the OL period
- To evaluate safety and infant outcomes among pregnant participants
- To evaluate the PK of CAB LA among pregnant participants, combining blinded, unblinded and OL periods
- To evaluate CAB concentration in breastmilk and infants among women who receive CAB LA injections during pregnancy and/or the early post-partum period