Symposium (SY04): ARVs for Prevention: Extrapolating from Data to Clinical Practice

The first presentation in the session by Marta Boffito highlighted the importance of both pharmacokinetic and pharmacodynamic studies in the evaluation of novel PrEP agents. She highlighted the important role of animal models, as well as Phase 1, 2 and 3 studies in providing data to guide dosing strategies but stressed the importance of understanding cellular pharmacology considerations for these drugs, which include drug penetration into relevant tissues and cell types, race/ethnicity/pharmacogenetics, gender and appropriate dosing strategies based on pharmacokinetic principles. Further, she highlighted, that while drug concentrations in animal models and in vivo human tissues may correlate well with efficacy (e.g. for TDF/FTC), some drugs do not always show optimal tissue exposure (e.g. Cabotegravir LA), thus understanding what and how new PrEP agents may be effective extends beyond just tissue concentrations.

Charles Dobard of the Centers for Disease Control and Prevention (CDC) discussed the use of animal models in preclinical studies of ARVs for PrEP. These models, particularly humanized mouse models and nonhuman primate models using macaques, allow for the assessment of biological efficacy of PrEP under highly controlled conditions, thus playing a key role in defining relationships between pharmacokinetics and pharmacodynamics of experimental agents. Dobard highlighted recent exciting advances including the elucidation of a Rhesus macaque model of penile SHIV transmission as well as animal model studies showing high efficacy against rectal, vaginal and penile SHIV using both Tenofovir Alafenamide (TAF) and long-acting cabotegravir regimens.

The second two presentations of the session focused on practical aspects of PrEP implementation. Irene Mukui, systematically described the impressive progress and lessons learned from the national roll-out of a PrEP program in Kenya. In May of 2017, 1425 Kenyans were currently on PrEP compared to 17,466 in August 2018. She described how this has been achieved through the coordinated effort of multiple national and international stakeholders, integration into existing systems (e.g. Existing ARV supply chains) as well as through community involvement and demand creation. Efficient, strategic information systems and epidemiologic mapping enabled focusing on specific geographic areas (high incidence clusters) and populations.

The last presentation from civil society activist Emily Bass reviewed the interplay between advocacy and implementation. She opted for a “power-point-less” presentation, but providing, nonetheless, a well-articulated, self-reflective examination of PrEP roll-out throughout most of SSA and the current and future role of advocates/activists in this. Bass and colleagues also described the importance of ensuring that demand creation for PrEP and other novel prevention methods was undertaken creatively, meaningfully and with intent.