CFAR's Highlights from Virtual CROI - Monday 3/9

Courtesy of the CFAR leadership, we have decided to send you a short summary of notable abstracts from each day of the “Virtual CROI” conference. Please note that this summary is by no means meant to be a comprehensive overview of all the abstracts presented at CROI, but a highlight of the oral abstracts from each day with a focus on those presented from investigators from UCSF and our UCSF-Gladstone CFAR affiliates.

Treatment as Prevention

  • “Community Viral Load” is a major determinant of HIV incidence.
    • Our own Maya Peterson (UC Berkeley and 2010 CFAR Awardee) used data from the large Universal Test & Treat trials from sub-Saharan Africa (HPTN071 or PopART study; BCPP; ANRS 12449 or TasP; SEARCH trial), totaling over 250,000 participants, to establish that communities with higher proportions of PWH maintaining viral suppression experienced lower HIV incidence rates. This is compelling new observational evidence from the largest pooled study of its kind that greater population-level viral suppression decreases HIV incidence. https://www.croiconference.org/abstract/decreasing-community-viremia-is-...
    • Denton Callander (UNSW, Sydney) also showed compelling observational evidence in >12,000 PWH and 46,000 HIV-negative men at risk for HIV infection in Australia that greater community viral suppression rates among PWH were associated with decreased HIV incidence (correlations > 0.9). https://www.croiconference.org/abstract/decreasing-community-viremia-is-...

Models of HIV Care in Resource-Limited Settings

HIV Cure

  • TLR7 agonist given to ART-treated “viremic controllers” results in a modest delay of HIV rebound during acute treatment interruption (ATI) Former UCSF ID fellow and 2014 CFAR Awardee, Devi Sengupta (Gilead), in collaboration with Steve Deeks, presented a placebo-controlled trial of the TLR agonist Vesatolimod in treated “viremic controllers.” The TLR agonist appeared to delay viral rebound modestly, potentially through immunologic mechanisms (though these need further characterization). Viral setpoint after ATI also appeared lower than the pre-ART setpoint. Interestingly, it took several weeks before natural control of viral replication was re-established during rebound, which has implications for the duration of ATIs necessary to assess the efficacy of future cure strategies and therapeutic vaccine trials. https://www.croiconference.org/abstract/safety-and-analytic-treatment-in...
  • Progress on translating the “Miami Monkey” model of a Drug-Free HIV Remission: Joe Casazza from the Vaccine Research Center/NIH presented a late breaker talk (41LB) showing durable HIV-1 neutralizing antibody production in PWH after AAV8-mediated gene transfer. After a single IM injection, the bNAb VRC07 was detected in plasma at high levels for up to a year or more. Anti-drug (anti-VRC01) antibodies emerged in 2 of 7 participants within a few months, which presents a challenge that will need to be overcome with this approach. An ATI was not undertaken here to prove that the antibodies could maintain control, but this is the closest the field has come to a viable gene therapy approach to achieve a sustained HIV remission. One can also easily envision combination antibody approaches in the future. https://www.croiconference.org/abstract/durable-hiv-1-antibody-productio...

HIV Comorbidities:

  • Greater burden of cerebrovascular disease in PWH: UCSF’s own Felicia Chow (2013 CFAR Awardee) used novel MR angiography imaging approaches to demonstrate that PWH had an over 4-fold higher number of enhancing arterial segments in the brain compared to those without HIV. https://www.croiconference.org/abstract/greater-burden-of-intracranial-a...
  • People with HIV have worse clinical outcomes after an acute coronary syndrome than those without. UCSF’s own Monica Parks presented data from Symphony Health, a nationwide data warehouse, on clinical outcomes after acute coronary syndromes (ACS), among 1,125,126 patients, of whom 6612 (0.59%) had HIV. Following treatment for ACS, people living with HIV had worse outcomes in terms of adjusted 30-day all-cause readmissions, 1 year mortality and in taking guideline-recommended medical therapy.  https://www.croiconference.org/abstract/postdischarge-outcomes-following...
  • Exogenous testosterone use associated with progression of atherosclerosis. Sabina Haberlen (JHU) presented work from the MACS-CCS, demonstrating that men with HIV who continued or started exogenous testosterone therapy were twice as likely as non-users to have progression in coronary calcium scores over 4 years.  https://www.croiconference.org/abstract/testosterone-therapy-and-subclin...

Injectable Antiretroviral Therapy:

  • Durable VL suppression with long-acting injectable CAB+RPV, without further increases in drug resistance. Chloe Orkin (Queen Mary U, London) presented the 96 week results from the FLAIR trial of switching to long- acting cabotegravir + rilpivirine (administered IM monthly) vs. oral ABC/3TC/DTG (Abstract 482). Only 3% of participants in each arm had virologic failure (defined as viral loads >50 copies/mL) at week 96, and there were no new participants with confirmed virologic failure in the CAB-RPV arm at week 96 (1.4% at week 48, 3 of 4 participants with NNRTI and INSTI mutations). Those in the ABC/3TC/DTG arm had 4 confirmed virologic failures at week 96 as well, but none developed mutations. http://www.croiconference.org/sessions/long-acting-cabotegravir-rilpivirine-hiv-treatment-flair-week-96-results
  • Injectable CAB+RPV every 2 months is non-inferior to monthly injections. Turner Overton for ATLAS-2M team: The original ATLAS trial examined cabotegravir (CAB) + rilpivirine (RPV) injections given every 4 weeks after an oral lead-in phase of these two agents in participants on suppressive ART and found high and comparable rates of virologic suppression to those who remained on their oral ART. The ATLAS-2M study then recruited original ATLAS participants and others on suppressive ART and randomized them to injected CAB/RPV every 4 or 8 weeks. The virologic suppression rate at 48 weeks in the two arms (of every 4 or 8 weeks) was comparable with VL > 50 in 1.7% in those in the 8 week arm and 1% in the 4 week arm. There were 8 confirmed virologic failures in the 8 week arm compared to 2 in the 4-week arm. Of those 8 failure sin the 8 week arm, 6 had emergent RPV-associated resistance mutations and 5 had emergent INSTI mutations. Of the 2 people with failure in the 4 week arm, both had treatment emergent INSTI mutations and 1 had a RPV mutation. Indeed, cabotegravir does not have the same genetic barrier to resistance that we have seen with dolutegravir and bictegravir. https://www.croiconference.org/abstract/cabotegravir-rilpivirine-every-2...

PrEP:

  • Cost-effectiveness of TAF/FTC vs TDF/FTC for PrEP: Rochelle Walensky (MGH) presented a cost effectiveness analysis suggesting that TAF/FTC, while it would help prevent a modest number of fractures and ESRD events, would increase HIV infections if its higher pricing (compared to generic TDF/FTC) resulted in fewer at-risk individuals being able to access PrEP. The analysis suggested that TAF/FTC would have to be priced no greater than $750 over generic TDF/FTC to be cost effective and avoid causing harm. https://www.croiconference.org/?s=+TAF%2FFTC+vs+TDF%2FFTC+for+PrEP