Brian Rice

Anthony Fauci (NIH, USA) explored two key paths toward durable remission: use of intermittent non-ART interventions, and the induction of durable immune-mediated virus control. As the recipient of the Jonathan Mann Human Rights Award, Ambassador Deborah Birx (PEPFAR, USA) then spoke to data for equity in the HIV/AIDS response.

Antiretroviral-drugs can drop viral-loads to sustained-suppression – Dr Fauci asked “why not do the same with antibodies?”. Therapeutic vaccination studies, and an open-label ATI study of vedolizumab, so far failed to durably control viral-rebound in the absence of ART. However, passive transfer of bNAbs in non-human primates has shown promising results. Dr Fauci concluded that durable ART-free control of viremia in the absence of eradication is “a feasible concept that deserves vigorous pursuit”. Ambassador Birx shared a 1992 quote from Jonathan Mann - “Information can help liberate us from this confusion and uncertainty.” This remains true. Presenting a plethora of data from across the globe, Ambassador Birx concluded “Progress is possible and has been demonstrated utilizing the best science and tools, triangulation of program data, qualitative data and community surveys has shown us our successes and failures and we must continuous address all aspects of our programming to improve impact.”.

In the Jonathan Mann lecture data were presented at the macro (national/global) and micro (clinic/sub-population) level. Presenting key metrics at the macro level is useful for understanding where we currently are, and for political / resource advocacy. The methods used to attain these data vary greatly across and within countries thereby resulting in data of varying quality – data-quality assessments informing data-improvement / standardization strategies would help facilitate accurate comparisons / interpretation. The power of routine data-use at the clinic level was highlighted – monitoring viral suppression performance across clinics helped target clinics for intervention to improve clinical-outcomes.

Julie Mitchell

In his talk, Dr. Fauci described the advancements and challenges of achieving sustained HIV remission through two means: intermittent non-ART interventions or durable immune-mediated control of the virus.

Intermittent interventions to achieve ART-free control of infection include therapeutic vaccination and passive transfer of broadly neutralizing antibodies (bNAbs). Unfortunately, durable control of viral rebound has not been seen in placebo-controlled efficacy trials of therapeutic vaccines. Clinical trials have shown that bNAb administration is capable of delaying viral rebound, but the length of the delay is still too short. To induce durable immune-mediated control, administration of antibodies to integrin α4β7, a gut homing receptor and marker of CD4 T cells highly susceptible to HIV infection, has been studied. While an initial study indicated that anti-α4β7 administration could induce virological control after treatment interruption in non-human primates, the same results were not seen when the study was repeated or in an open-label human trial of vedolizumab. Finally, it has been shown that infusion of bNAbs early during acute HIV infection can induce long-term control of HIV in an animal model.

In light of the data presented, further work is needed to increase the potency and half-life of bNAbs, and study their use in combination. Further, placebo controlled trials are needed to determine the effectiveness of vedolizumab and early administration of bNAbs to lead to viral control in humans. Dr. Fauci noted that the risk:benefit ratio of attempts at HIV eradication should be considered in light of the effective single-pill ART options available. For control without eradiction, he clearly stated that interventions should be “low risk to the patient, scalable, and potentially lead to induction of durable immune-mediated control of virus.”