IMPAACT 2010 Pharmacy, Study Drug, and Concomitant Medication Considerations at Entry

Protocol References Section Title 6.2 Entry Visit 5.1 Study Drug Regimens 5.2 Study Drug Administration 5.7 Study Drug Adherence Assessment and Counseling 5.8.1 Maternal Concomitant Medications

Process Flow SES generates SIDs for mother and infant, START Informed Consent Obtained ? Initiate study drug and follow per SoE Assign PIDs Obtain screening number from SES yes yes Enrolled in SES ? yes Eligible? no STOP SES generates SIDs for mother and infant, and generates prescribing information for the maternal study drug regimen that corresponds to the random assignment

Process Flow at Each Site Who determines/confirms eligibility? Who completes enrollment in SES? How is SID and random assignment communicated to: Prescribing clinician? Pharmacist? Who prepares study drug for the mother? How much? Who dispenses study drug to the mother? Who provides study drug use and adherence information and counseling to the mother? How is the first dose handled?

We understand that enrolled mothers should be provided with sufficient study drug at each visit to last through the next visit, taking the target date and allowable windows into account. Is there a recommended quantity of study drug to be provided at the study Entry Visit? All sites must establish SOPs for prescribing and dispensing ARVs in this study. Clinic and pharmacy staff should work together on these SOPs to specify the most appropriate site-specific procedures to be followed.

We understand that enrolled mothers should be provided with sufficient study drug at each visit to last through the next visit, taking the target date and allowable windows into account. Is there a recommended quantity of study drug to be provided at the study Entry Visit? For the study Entry Visit, site SOPs may specify dispensing of either a 30-day supply or a 60-day supply of study drug, taking into consideration that the first maternal follow-up visit, which is the Antepartum Week 4 Visit, is scheduled four weeks (28 days) after the Entry Visit, ± 2 weeks.

We understand that enrolled mothers should be provided with sufficient study drug at each visit to last through the next visit, taking the target date and allowable windows into account. Is there a recommended quantity of study drug to be provided at the study Entry Visit? For sites that dispense a 30-day supply, special attention will be needed to ensure that mothers return for their Antepartum Week 4 Visits before running out of study drug. For sites that dispense a 60-day supply, mothers are expected to have at least a two-week supply remaining at their Antepartum Week 4 Visits, which can be returned to the mothers (if in good condition) and “topped up” at the visit. Please refer to the study-specific MOP for further consensus guidance on dispensing study drug at the Entry Visit as well as at antepartum and postpartum follow-up visits.

We expect that some but not all mothers will take their first dose at the study clinic on the day of enrollment. For mothers who do not take their first dose of study drug at the clinic, are we required to document the date and time of first dose? If so, when should this be done? Enrolled mothers are generally expected to take their first dose of study drug on the day of enrollment. If for some reason this is not possible, the first dose should be taken on the day after enrollment. The actual date of the first dose should be recorded; it is not necessary to record the time of the first dose.

We expect that some but not all mothers will take their first dose at the study clinic on the day of enrollment. For mothers who do not take their first dose of study drug at the clinic, are we required to document the date and time of first dose? If so, when should this be done? The protocol team strongly recommends that study staff proactively contact mothers who do not take their first dose at the clinic to confirm that the first dose was taken (e.g., by telephone or home visit), ideally on the day after enrollment. In addition to confirming the date of first dose, per protocol Section 6.3, “Between scheduled visits, particularly in the first month of study participation, study site staff are encouraged to contact mothers to address any issues or questions about their study participation, clarify instructions for use of study drugs, and/or provide adherence counseling as needed.” All study sites should establish SOPs describing how they will do this.

We expect that some but not all mothers will take their first dose at the study clinic on the day of enrollment. For mothers who do not take their first dose of study drug at the clinic, are we required to document the date and time of first dose? If so, when should this be done? The date of first dose of study drug will be entered into the Study Treatment Initiation eCRF (ADM10009) which is first required at the Entry Visit. If the first dose of study drug does not occur at the Entry Visit, this will need to be indicated on the ADM10009 entered for the Entry Visit, with the expectation that another copy of the ADM10009 will be entered at the Antepartum Week 4 Visit, to record the first dose. In this scenario, site staff must contact the Protocol Data Managers to request that a copy of the ADM10009 be added the Antepartum Week 4 Visit folder in Rave.

Adherence Counseling Study staff will provide adherence counseling to enrolled mothers throughout the period of study participation. Counseling may be provided by clinic and/or pharmacy staff consistent with local standards of care and site SOPs; site SOPs must also meet for minimum requirements specified in the study-specific MOP with respect to initial and ongoing counseling and support. Counseling should be provided in a client-centered manner, tailored as needed to the information, skills building, and support needs of each mother. Information on correct use of study drugs will be provided, particularly at the time of enrollment and in the early stages of follow-up, as well as at the time of any regimens changes. Counseling will also address challenges to consistent use of study drug over time, with the aim of supporting mothers in identifying strategies to address any such challenges. Reminder that many/most enrolled women will be newly diagnosed with HIV infection.

What are the key messages?

What are the key messages? ARVs ? How do ARVs work? What are the benefits of taking ARVs? What side effects to expect or look out for What to take When to take it How to take it How to remember to take it What to do if limited access to food or clean water What to do if forget instructions What to do if have trouble taking What to do if feel sick

Important Interactions with Commonly Used Concomitant Medications

Important Interactions with Commonly Used Concomitant Medications Mothers who have not initiated cotrimoxazole or isoniazid prophylaxis prior to study entry should preferably defer initiation of these medications until at least two weeks after initiation of their study drug regimen, if eligible to initiate such prophylaxis per local standards of care. Mothers in Arms 1 and 2 (i.e., the DTG-containing arms) who require cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications will be counseled to take these medications at least six hours before or at least two hours after taking DTG. Alternatively, DTG and supplements containing calcium or iron can be taken together with food.

DTG and Cation-Containing Concomitant Medications Package insert for DTG “Administer DTG 2 hours before or 6 hours after taking medications containing polyvalent cations.” Take DTG  wait 2 hours  Take medications containing polyvalent cations OR Take medications containing polyvalent cations  wait 6 hours  Take DTG

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