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Professor of Medicine
Division of HIV, Infectious Diseases, and Global Medicine
University of California, San Francisco
Ward 86 HIV Clinic
San Francisco General Hospital
San Francisco, California
Monica Gandhi, MD, MPH, has no relevant conflicts of interest to report.
The 2020 Conference on Retroviruses and Opportunistic Infections (CROI) will feature more than 1000 abstracts sharing the latest data on preventing, managing, and potentially curing HIV infection. As a physician specializing in HIV management, here are some of the studies that I am most excited about.
Investigational Long-Acting Injectable ART
CROI 2020 will include eagerly awaited results from the phase III ATLAS-2M trial (abstract 34), which is assessing long-acting cabotegravir (CAB) plus rilpivirine (RPV) by intramuscular (IM) injection every 4 or 8 weeks in patients with virologic suppression on their current regimen (either standard-of-care ART or IM CAB plus RPV every 4 weeks or current ART for participants transitioning from the ATLAS trial). That 8-week injection interval is the key difference between ATLAS-2M and ATLAS, which demonstrated that switching to CAB plus RPV injected every 4 weeks maintained virologic suppression through Week 48. Although abstract content is currently embargoed, a press release in 2019 announced that CAB plus RPV every 8 weeks met the primary noninferior efficacy endpoint vs every 4 weeks. If the FDA approves this long-acting injectable regimen, I anticipate that this 8-week injection interval would be easier for patients and require less logistical support for clinics. Furthermore, an analysis of patient-reported outcomes indicates that our patients are ready for this option.
Additional data to be presented on injectable CAB plus RPV include 96-week results from the phase III FLAIR trial (abstract LB 482), which is comparing INSTI-based oral triple therapy induction followed by maintenance with injectable CAB plus RPV vs continuing oral INSTI-based ART. The investigators reported last year that the injectable dual therapy was noninferior through Week 48. We will also see data addressing the important clinical question about the pharmacokinetic “tail” of long-acting CAB plus RPV after discontinuation (abstract 466).
Regarding other intriguing long-acting ART strategies in the pipeline, I anticipate learning more about the dose-response relationship of the HIV-1 capsid inhibitor GS-6207, which is administered subcutaneously (abstract 469). Data from a first-in-human phase I study indicated that GS-6207 is well tolerated and could be dosed at a 12-week interval. We will also hear about metabolic outcomes associated with islatravir (formerly MK-8591) from the new class of nucleoside reverse transcriptase translocation inhibitors (abstract 686).
Current HIV Treatment Strategies
Weight Gain: Important clinical questions must be answered about recent data suggesting that patients gain more weight when receiving INSTIs or tenofovir alafenamide (TAF) vs other ARV agents. First, what is the mechanism behind this weight gain? Second, what are the clinical health implications? Several reports at CROI 2020 will hopefully provide some answers, including a presentation on the risks of metabolic syndrome, diabetes, and cardiovascular disease among participants in the phase III ADVANCE trial (abstract 81), a noninferiority study comparing dolutegravir (DTG) plus emtricitabine (FTC) with either TAF or tenofovir disoproxil fumarate (TDF) vs efavirenz (EFV)/FTC/TDF in previously untreated South African patients. The ADVANCE investigators reported in 2019 that there was significantly greater weight gain with DTG vs EFV and with TAF vs TDF (both P < .01). At the same session, we will hopefully gain mechanistic insights into the relationship between CYP2B6 genotype and differential weight gain with DTG and EFV (abstract 82).
Pregnancy: Findings from the Tsepamo study in 2018 and 2019 drew attention to the general lack of safety data on ARVs in pregnancy, particularly early pregnancy, and the pressing need for larger analyses to better characterize the risk of rare adverse outcomes such as neural tube defects. Multiple abstracts at CROI 2020 will address ARV safety during pregnancy, including safety and efficacy results from the phase III IMPAACT 2010 (VESTED) trial (abstract LB 130). This National Institute of Allergy and Infectious Diseases-sponsored trial is comparing DTG plus FTC/(TAF or TDF) vs EFV/FTC/TDF in pregnant women and examining safety outcomes in their infants.
Specific Populations: CROI 2020 features several studies on bictegravir (BIC)/FTC/TAF in key subpopulations. We will see data from a randomized switch trial to BIC/FTC/TAF in black patients (abstract 36) and 144-week outcomes with first-line BIC/FTC/TAF in adults aged 50 years or older (abstract 477).
Pre-Exposure Prophylaxis (PrEP): I look forward to seeing more analyses of the phase III DISCOVER trial, which demonstrated that daily PrEP with FTC/TAF is noninferior to FTC/TDF in cis-men who have sex with men and transgender women. We will see 96-week safety results (abstract 92) and 96-week outcomes in black and Hispanic/Latinx participants (abstract 990), along with information on HIV-1 drug resistance (abstract 1002), risk factors for low adherence (abstract 1028), and the interaction between hormones and PrEP in transgender women (abstract 1020).
Cure: Finally, I am curious about the safety and pharmacokinetic data of elipovimab (formerly GS-9722) in HIV-negative individuals and people living with HIV (abstract 39). Elipovimab is a novel, broadly neutralizing anti-HIV antibody that kills HIV-infected cells by engaging gp120/gp41 on infected T-cells and Fcγ receptors on innate immune effector cells.
As CROI 2020 unfolds, visit the CCO HIV Web site for downloadable slidesets and short video highlights summarizing the data from these and other studies. Please join our expert faculty for a series of live Webinars featuring their take on the clinical implications of these new data. After the meeting, look for more ClinicalThought commentaries from US and EU experts, along with a CME/CE-certified expert analysis module.