CFAR's AIDS 2020 Recap: July 9, 2020

Live program for Friday July 10 for the COVID-19 conference

How to access the conference: Go to https://covid19.aids2020.org/ and ensure you have registered (free to register)

PLENARIES

Dr. Deborah Birx, Global AIDS Ambassador and Head of PEPFAR, started out the morning plenary (called “Targets”) with a talk on HIV Targets and beyond: An assessment of progress towards global commitments. She reminded us that – despite COVID-19- PEPFAR has made significant strides and also helped build the infrastructure for SARS-CoV-2 testing being used today in the most recent pandemic. This was followed by a Q&A with Rosemary Mburu from WACI Health which was about how nothing can be achieved without community, especially women, in Sub-Saharan Africa.

Congresswoman Barbara Lee delivered the 2nd plenary on Representative, Responsive, Resilient: Women in Leadership in the HIV Response and it was great. She reminded us all on the disproportionate impact of HIV on African American women in the U.S. and of her role in helping to get AIDS 2020 to Oakland/ San Francisco!

ABSTRACTS

Track A

There were no Track A oral abstract sessions on Thursday July 9, but we wanted to highlight an outstanding symposium on HIV cure, Pushing the boundaries: New approaches to a cure, co-moderated by Tony Fauci and Sharon Lewin.

Novel B Cell Genetic engineering approach: James Voss (Scripps) presented an elegant series of studies in mice demonstrating that one can engineer B cells to express bNabs (in this case VRC01). This approach has the advantage of avoiding the anti-drug antibodies often seen in the transfecting of non-B cells with bNAb-expressing genes (i.e., the Miami monkey), allows the antibodies to continue to mature upon challenge by antigen, and also helps maintain peripheral tolerance, avoiding autoreactivity. This exciting approach may now be explored in rhesus/SHIV models.

Editing HIV out of infected cells. Joachim Hauber (Heinrich Pette Institute) presented an elegant approach to excising HIV from cells, which is currently being tested in PWH undergoing autologous stem cell translplant for lymphoma. The approach integrates Brec1 into cells under a Tat-responsive promoter. Brec1 then recognizes integrated HIV in host DNA and excises it. The nice thing about this approach is that it avoids off target effects by only turning on the gene editing in cells that are currently expressing HIV Tat. Brec1 has already been shown to effectively excise HIV from infected cells in humanized mice. The hope is that the HIV resistant cells will outcompete HIV-susceptible cells during a subsequent treatment interruption and eventually help control the infection. Whether this approach could ever be effective outside of the setting of ablative chemotherapy remains to be seen.

Modeling Immunotherapy for HIV cure. Miles Davenport (Kirby Institute) presented an interesting talk modeling how theoretical immune-based interventions would affect the likelihood and duration of an ART-free remission based on their potency, tolerability, and sustainability.

CCR5 Gene Editing. Paula Cannon (USC) presented an update on her approach to attempt to recapitulate the successes in the Berlin and London patients by editing out CCR5 from autologous hematopoietic stem cells. There are less toxic new conditioning regimens being explored as well as pairing CCR5 knock out with knock in of eCD4 Ig as an additional mechanism of protection.

Tracks B/C

PrEP

Donnell D et al. Incorporating PrEP into standard of prevention in a clinical trial is associated with reduced HIV incidence: Evidence from the ECHO Trial, Abstract OAC0105, 2020.

Dr. Deborah Donnell and colleagues presented an analysis on the impact of PrEP availability on HIV incidence within the ECHO trial. The ECHO trial (published in 2019) randomized over 7,800 HIV-uninfected women in several countries in sub-Saharan Africa to DMPA vs copper IUD vs levonogestrel implant. Overall HIV incidence in the trial was extremely high: 4.26/100 py (3.77-4.59) among women <25 years of age. At AIDS2020, Donnell and colleagues reported that PrEP was offered as part of the standard of prevention at South African study sites toward the end of the trial. Approximately 25% of eligible participants at these sites started PrEP (~2% of total follow-up in the study occurred after PrEP initiation). The investigators analyzed HIV incidence among all participants (not only PrEP initiators) and found ~50% lower HIV incidence after PrEP access (2%) compared to before (4.6%; aIRR 0.45; 95% CI 0.25-0.82). This complements the SEARCH PrEP data we discussed yesterday on the high efficacy of PrEP among women under conditions of PrEP access in Africa.

Krakower DS et al. Impact of COVID-19 on HIV preexposure prophylaxis care at a Boston community health center. Abstract OACLB0104.



COVID-19 has impeded healthcare in the US since March 2020 so these authors looked at the impact of COVID-10 on PrEP at the Fenway, a Boston community health center specializing in sexual healthcare. Of 3520 PrEP patients, the mean (SD) age was 36.9 (11.2), 72.7% were white, 13.6% Latinx, 92.1% cisgender men and 12.9% publically insured. From January to April, PrEP initiations decreased by 72.1% (122/month to 34/month), refill lapses increased by 278% (140/month to 407/month), and the number of PrEP patients decreased by 17.9%. The total number of people with an active PrEP prescription dipped by 18.3%, from 3197 on January 20 to 2984 on April 20. The number of in-person patient visits collapsed from January to April, but tele-health filled the gap. Gap outcomes were worse among younger and Latino individuals. They could not ascertain if sexual behavior went down, but in a 394-person nationwide US study also reported at AIDS 2020, 90% of PrEP users reported no sex or less sex during the COVID-19 epidemic, and one third stopped PrEP (Brawley et al. AIDS 2020. Abstract OADLB0101).

HIV and COVID-19

So far, the data from case series in New York City, Spain and Italy has shown us to date that people living with HIV may be a bit more susceptible to COVID-19 but that severe outcomes are not increased. However, there are three late-breaker abstracts at this meeting that looks at the data. Two were presented in the Track B Late Breakers session today and one was presented yesterday in the Co-Chairs Session.

Patel VV. Clinical Outcomes by HIV Serostatus, CD4 count and viral suppression among people hospitalized with COVID-19 in the Bronx, NY. Abstract OABLB0102 (Track B late breaker session today)

This retrospective cohort study examined SARS-CoV-2 PCR-positive patients admitted to a large tertiary academic health system in the Bronx, New York between March 10 and May 11, 2020 (N=4662), of whom 77 (1.7%) had HIV. HIV status was not significantly associated with mortality, intubation, length of stay or acute renal insufficiency. In exploratory analyses among PLWH with CD4 count available (N=73), higher CD4 count was associated with intubation (adjusted odds ratio 1.36 per 100 cells/uL, 95% CI 1.02-1.82). None of the 10 viremic PLWH were intubated, versus 10/57 (18%) among suppressed PLWH. The authors thus concluded that, hospitalized patients with COVID-19, there were no significant differences in mortality between PLWH and without HIV and that the preliminary findings regarding intubation among PLWH warrant further examination

Ho H, Peluso M (co-first authors). Immunologic characteristics of acute COVID-19 in people with HIV. Oral abstract OABLB0104.

Dr. Michael Peluso from UCSF was the co-first author on this abstract (and JID paper) and it was presented by Dr. Ho from Mt. Sinai. Authors conducted a retrospective study of clinical and immunologic outcomes of COVID-19 in 93 PLWH presenting to 5 New York City emergency departments who tested positive for SARS-CoV-2. They found that - of 72 PLWH hospitalized with COVID-19, 16 (22.2%) died, 48 (66.7%) recovered, and 8 (11.1%) remained hospitalized at the time of analysis. Those who died had significantly lower nadir absolute lymphocyte counts during COVID-19 compared with those who recovered (see slide above). Peak inflammatory markers including CRP, fibrinogen, and IL-6 were significantly higher in those who died. The conclusion was that PLWH who died of COVID-19 had significantly higher levels of soluble markers of immune activation and inflammation and more severe lymphopenia than those who survived. There was no comparison group of patients without HIV but this certainly suggests that PWH are not “protected” from severe disease.

Davies M. Western Cape: COVID-19 and HIV / Tuberculosis. Abstract OAXLB0106



This study looked at 12,987 patients COVID-19 in Western Cape Town, South Africa. After adjusting for other risk factors, HIV increased mortality with COVID-19 by factor of 2.75, and active TB by factor of 2.58. However, these were far eclipsed by other traditional risk factors that increase the risk of death from SARS-CoV-2 which were older age, comorbidities (hypertension and diabetes). Therefore, there was a modest effect from HIV on COVID-19 related mortality (<10% of COVID-19 deaths in setting of this generalized HIV epidemic due to HIV).

Other Track B Late Breaker Abstracts (both relevant to pregnancy and ART)

Asif et al. The predicted risk of adverse pregnancy outcomes from treatment-induced obesity in the ADVANCE trial. OABLB0103.



This study showed that horrible increase in weight gain with DTG/TAF that the ADVANCE study showed us yesterday and then went on to predict the bad outcomes that could result from maternal obesity during pregnancy from DTG/TAF or DTG/TDF compared to EFV/TDF like preterm delivery, gestational diabetes, gestational hypertension, pre-eclampsia, and postpartum hemorrhage. They predicted 53 excess adverse outcomes per 1000 pregnancies with DTG/TAF/XTC versus 28 excess adverse outcomes with DTG/TDF/XTC versus 4 with EFV/TDF/FTC. To be fair, this was predicted from what we know about maternal obesity and bad outcomes (and certainly wasn’t seen in the ADVANCE trial- they didn’t have 1000 pregnancies).

Asif et al. Faster virological suppression with dolutegravir versus efavirenz in pregnancy does not lower the risk of HIV mother-to-child-transmission: A meta-analysis of 5 clinical trials in 1074 pregnant women. OABLB0105



This meta-analysis looked at the five major RCTs that compared DTG to EFV, specifically DOLPHIN-1, DOLPHIN-2, IMPAACT 2010, ADVANCE and NAMSAL (n=1074). The primary endpoints included viral suppression, the number of stillbirths, neonatal deaths and mother-to-child-transmissions (MTCT).



Secondary endpoints included the number of infants experiencing preterm births. Preterm births and viral suppression rates were the only endpoints with a significant difference between treatments. The odds of viral suppression were almost 3 times higher in women using DTG (OR: 2.90, 95% CI:1.54, 5.46). The risk of preterm births was 4% higher in women using EFV (RD: -0.04, 95% CI:-0.07, -0.00). Interestingly, no significant difference was found between the treatments regarding the number of MTCTs. Two cases were reported in IMPAACT 2010 and three cases in DOLPHIN-2, all occurring among women on DTG (?). There was no explanation for this.

Other symposia and bridging sessions highlighting UCSF-Gladstone CFAR investigators

UCSF-Gladstone CFAR investigators were well-represented across a range of Thursday’s symposia and bridging sessions. TAPS fellow Dr. Glenda Baguso provided a rich overview of the state of PrEP utilization disparities affecting transgender women. The talk emphasized public policies that stand in the way of optimal use of PrEP by this key population. Of note is that Dr. Baguso used her conflict of interests slide (she had none) to make a powerful and timely reminder to us all: “I use this slide to remind myself to own my own privilege.” In another symposium, SFDPH’s Al Liu offered seven practical recommendations framed in a patient-centered care model for making it easy for people to start and stay on PrEP. These included offering PrEP to all who desire it, providing same day start of PrEP, and the importance of providing ongoing support and check-ins with persons taking PrEP. Dr. Dominika Seidman from the UCSF Dept of Obstetrics, Gynecology, and Reproductive Sciences gave an informative review of decades of successes and missteps in the implementation of long-acting injectable contraception in order to inform the roll-out and equitable implementation of injectable PrEP and ART. Learning from the past in terms of barriers related to access and side effects was one of the many valuable take-home messages from this rich presentation.

UCSF’s Dr. Diane Havlir presented the history of San Francisco’s successful approach to addressing the HIV epidemic, spanning innovative and proactive initiatives related to HIV prevention, testing, and treatment. This talk acknowledged the effects of the COVID-19 pandemic and how some of our gains are sure to be set back by this new pandemic. Dr. Eric Goosby gave a talk in the Health Equity Series called The Great Magnifier: COVID-19, HIV, and Disparities, which gave us a poignant look on how infectious diseases pandemics have always highlighted the fault lines and disparities in our society. The disproportionate impact COVID-19 is having on Black and LatinX populations in the U.S. is a powerful reminder that we are nowhere near to addressing these health disparities. And finally, Dr. Elise Riley organized and moderated a session on HIV, COVID-19 and Housing Instability in High-Income Cities moderated with presentations from Drs. Elizabeth Imbert and Matt Hickey on the POP-UP program at Ward 86. Liz described the POP-UP program and its “high intensity, low barrier” model of care that has already led to exciting increases in virologic suppression rates among a marginally housed population of people living with HIV without virologic suppression. Matt then took us into the world of how POP-UP outcomes was being influenced by COVID-19 and found that, in this highly specialized program where we focus on continuity of care and in-person care with the same group of providers, virologic suppression rates are not dropping (in comparison with the rest of the clinic). Dr. Marguerita Lightfoot gave an important talk in The whole person: Addressing all aspects of health of people living with HIV where she summarized an RCT in Zimbabwe where an intervention designed by her and her team increased parental disclosure of HIV and improved parent, child, and family outcomes. And in a special bridging session called Hands Across the Bay: Collaborations in HIV Science (cochaired by Dr. Marguerita Lightfoot), Drs. Paul Volberding and Hyman Scott spoke about Coalitions at the Heart of Effective Epidemic Response.



Important work by UCSF-Gladstone CFAR investigators all around!



And a special congratulations to Dr. Givano, colleague of Dr. Ted Ruel, for this award.