The 2015 Conference on Retroviruses and Opportunistic Infections (CROI) took place in Seattle from February 23rd to the 26th. The major news that emerged from the meeting was the extremely high degree of protection from HIV infection obtained with pre-exposure prophylaxis in two studies, PROUD and IPERGAY. On the vaccine and cure fronts nothing was quite as headline grabbing, but there were a number of interesting presentations. Webcasts of all conference sessions are available on the CROI website along with the abstract book and, where available, PDFs of posters. Excellent coverage of CROI is available from several websites, including AIDSMap, i-Base and NATAP (whose reports often include slides from the talks).
TAG (along with AIDS Treatment Activists Coalition, AVAC and Project Inform) co-sponsored a pre-conference community workshop on cure research on February 22nd, covered by Gus Cairns for AIDSMap and Siegfried Schwarze for EATG; the EATG CROI 2015 Facebook page also has photos of some of the slide presentations.
Links to several CROI presentations and posters of possible interest are below.
Galit Alter, Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, United States
- A sprightly, enthusiastic and fairly optimistic review of the state of HIV vaccine science delivered by Galit Alter at the pre-conference workshop for young investigators.
James B. Whitney, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
- The most widely publicized of the cure-related presentations at CROI. A toll-like receptor 7 (TLR7) agonist being developed by Gilead induced SIV production from the latent reservoir in a small macaque study. A complementary poster presentation demonstrated activation of HIV production in latently infected cells isolated from individuals on ART. The compound in clinical development (GS-9620) has already been found safe in human trials for hepatitis B and C, and a small trial in HIV-positive individuals is underway and fully enrolled (although regrettably Gilead have not registered the trial in clinicaltrials.gov).
Dan H. Barouch, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
- This presentation includes a description of a small study of the broadly neutralizing antibody (bNAb) PGT121 combined with ART in macaques chronically infected with SHIV162P3. Overall the combination led to reductions in the viral reservoir compared to ART alone (although this was not seen in all recipients) and was associated with a delayed viral load rebound after ART interruption. As an aside, Barouch also mentions that the reductions in viral load being seen in phase I trials of bNAbs in HIV-positive individuals appear comparable to those reported in SIV-infected macaques. These studies presage larger planned trials that will evaluate the effect of ART plus bNAbs on the HIV reservoir.
Daniel Scott-Algara, Institut Pasteur, Paris, France
- Study results suggesting natural killer (NK) cell responses may be contributing to control of HIV viral load in the VISCONTI cohort participants. The analyses include a comparison of NK cell responses with an HIV-negative control group and it is worth noting that, so far, there has been no comparison between the VISCONTI cohort and HIV-negative controls when it comes to inflammatory and immune activation biomarkers. In the absence of this information, it is not yet clear if the long-term health of cohort members is likely to be comparable to uninfected individuals or if, like elite controllers, they have elevated inflammation levels that could lead to an increased risk of morbidity and mortality.
Jamal Tazi, University of Montpellier, Montpellier, France
- Report on ABX464, a novel antiretroviral targeting the activity of HIV’s Rev protein that caused a prolonged reduction in viral load after a course of treatment in humanized mice. A phase I safety study in humans has already been completed, and a phase II clinical trial is underway.
Aviremia 10-Year Post-ART Discontinuation Initiated at Seroconversion. Sabine Kinloch et al. Abstract Number: 377
- Case report of prolonged post-treatment control of HIV viral load after ART interruption. Reported in detail by Simon Collins on i-Base.
In vivo effects of Panobinostat and Romidepsin on HIV-1-specific CD8 T Cell Immunity. Rikke Olesen et al. Abstract Number: 369.
- An analysis of samples from two clinical trials indicating that HDAC inhibitors do not significantly suppress HIV-specific CD8 T cell responses in vivo, in contrast to the results of an in vitro study published last year.
Selectively Eliminating HIV Latently Infected Cells Without Viral Reactivation. Grant Campbell et al. Abstract Number: 387
- Laboratory study reporting latently infected cells may be distinguished from uninfected cells due to expression of X-linked inhibitor of apoptosis protein (XIAP), and that this may allow them to be selectively eliminated with an XIAP antagonist drug, GDC-0152. Sounds potentially exciting, but will need to be confirmed using primary latently infected CD4 T cells sampled from HIV-positive individuals on ART.
Targeting HIV-1 Latency With a Potent Tat Inhibitor. Guillaume Mousseau et al. Abstract Number: 413
- In the early 1990s clinical trials were conducted of a Tat inhibitor developed by Hoffman-LaRoche but it failed to show efficacy. This study describes a new candidate and suggests the idea should be revisited in the context of targeting HIV latency.
Immunogenicity of AGS-004 Dendritic Cell Therapy in Patients Treated during Acute HIV Infection. Cynthia L. Gay et al. Abstract Number: 344
- Small trial of a therapeutic HIV vaccine approach in acute HIV infection. Although HIV-specific immune responses were induced, this did not lead to sustained control of viral load after ART interruption in five out of the six participants, but one individual remains off ART after 268 days. The researchers plan to study AGS-004 in combination with a latency-reversing agent.
Measuring HIV Latency Over Time: Reservoir Stability and Assessing Interventions. Nancie M. Archin et al. Abstract Number: 406
- An assessment of the reproducibility of the quantitative viral outgrowth assay (QVOA) over time. Changes of >2.5 fold were fairly common, whereas changes >6 fold were rare, lead to the suggestion that the latter should be used as a threshold in evaluations of reservoir-depleting interventions.