Most Important HIV Research Reports from CROI 2015

From Jules Levin: perhaps the biggest stories out of CROI from my perspective are the development of 2 new HIV therapies – the new attachment inhibitor & the new maturation inhibitors, as well as the safety & efficacy of TAF, and an important message out of CROI is that TAF can also be used in HCV coinfected patients as a replacement for TDF in their ART regimen which will likely provide key safety improvements. Equally important are the HCV coinfection study results from Harvoni, daclatasvir+sofosbuvir, and Abbvie’s 3D Viekira Pak, and at CROI are a number of presentations on use of simeprevir+sofosbuvir as this therapy was the most potent HCV therapy available in 2014. Merck is in phase 3 with their 2 HCV drug regimen and developing a triple drug regimen with the study of the 2-drug regimen in combination with the nuke they acquired from Idenix. J&J is studying the nukes they acquired from Alios, they have GSK’s NS5A inhibitor, and they have a non-nuke polymerase in-house as well as simeprevir. Abbvie & Merck reported 2nd/3rd generation drugs at AASLD in pre & early clinical – protease, NS5A. Achillion reported high SVR rates in their early clinical studies with their potent nuke, potent NS5A & they have 2 protease inhibitors. Aging & comorbidities were a focus at CROI as well, particularly noteworthy is the research from the Mass General group reported again that subclinical heart disease is ever present in HIV+, that it can results in plaque buildup, particularly of note in HIV+ it results in non calcified plaque buildup which can rupture; they reported Atorvastatin reduced coronary artery noncalcified plaque and that plaque buildup is associated with a leaky gut, microbial translocation. Statins got quite a bit of attention with several reports including one from Grace McComsey that Rosuvaststin arrests progression of carotid intima media thickness in HIV+. Ken Lichtenstein reported the 4 heart disease algorithms underestimate risk for heart disease in HIV+ based on the SUN cohort. Bone disease is highlighted as well with Michael Yin reported modified FRAX underestimates risk for fractures among HIV+, and from HIV+ WIHS women experienced increased risk for fracture. Bigger font titles below indicate key reports, more NATAP reports coming including 9 specialized topical reports by expert researchers. Gilead has introduced a new HIV “cure” drug that appears to induce HIV reservoirs, TLR7, this immune based drug has been in ongoing research for several years at Gilead to treat HBV.

22nd Conference on Retroviruses and Opportunistic InfectionsSeattle WashingtonFeb 23 – 26, 2015

CROI Big Stories: new HIV ARTs attachment & maturation inhibitors; new HCV drugs study results in HIV/HCV coinfected – Harvoni, daclatasvir+sofosbuvir, Abbvie 3D – (Ombitasvir, Paritaprevir Co-dosed With Ritonavir, Dasabuvir, and Ribavirin ) – written by Mark Mascolini – (03/02/15) 

 Preventing one HIV infection in US saves $229,800 in modeling analysis – written by Mark Mascolini – (03/02/15) 

 Linkage to HIV care and viral suppression climb steadily in New York City – improvements to 76%, 73% – written by Mark Mascolini – (03/02/15) 

More time with high viral load, high VACS index, predicts MI in veterans HIV cohort, as well as time-updated viral load & CD4 – written by Mark Mascolini – (03/02/15)  

TAF noninferior to TDF through 48 weeks in elvitegravir combination – written by Mark Mascolini – (03/02/15) 

 Atorvastatin for 1 year trims coronary artery plaque volume and number in placebo trial – written by Mark Mascolini – (03/02/15) 

Varenicline (Chantix) helps French with HIV quit smoking in 48-week placebo trial – written by Mark Mascolini – (03/02/15) 

Modified FRAX tool underestimates fracture rates in older men with HIV – written by Mark Mascolini – (03/02/15) 

TAF easier on kidney and bone signals than TDF in 48-week trials – written by Mark Mascolini – (03/02/15) 

Impact of Specific Antiretroviral Drugs on Non-AIDS Mortality; the D:A:D Study – – written by Mark Mascolini – (03/02/15) 

Smoking and heavy drinking tied to atherosclerosis in MACS men with HIV – written by Mark Mascolini – (03/02/15) 

SVR12 in over 90% of HCV/HIV null responders stating daclatasvir/asunaprevir plus PR – written by Mark Mascolini – (03/02/15) 

Cardiovascular Disease Risk Prediction in the HIV Outpatient Study (HOPS)….. “Among participants with any length of follow-up, the four risk prediction equations underestimated the 10-year risk of CVD” – (03/02/15)

 High cancer risk among the HIV-infected elderly in the United States – (03/02/15) 

HIGH SVR REGARDLESS OF TIME TO SUPPRESSION WITH OMBITASVIR/PARITAPREVIR/R & DASABUVIR + RBV – (03/02/15) 

Fracture incidence is increased in aging HIV-infected women (WIHS) – (03/02/15) 

Cardiovascular Disease in HIV Patients: An Emerging Paradigm and Call to Action – (03/02/15) 

Statin Therapy Reduces Coronary Noncalcified Plaque Volume in HIV-infected Patients: a Randomized Controlled Trial – (03/02/15) 

Calcified Plaque Burden is Associated with Serum Gut Microbiota-Generated Trimethylamine in HIV – (03/02/15) 

Anal high-risk human papillomavirus (HPV) infection among HIV-infected MSM in the SUN Study, 2004-2011 – (03/02/15) 

Daclatasvir in Combination With Sofosbuvir for HIV/HCV Coinfection: ALLY-2 Study – (02/27/15) 

Exposure to antiretrovirals and development of chronic kidney disease – D:A:D Study Group – written by Mark Mascolini – (02/27/15) 

Fat and lean mass changes similar with raltegravir and PIs in ACTG analysis – written by Mark Mascolini – (02/27/15) 

Rosuvastatin halts carotid artery wall thickening in placebo-controlled trial – written by Mark Mascolini – (02/27/15) 

Do gut flora play key role in cardiovascular disease with HIV? – written by Mark Mascolini – (02/27/15) 

Lower CD4 count, higher viral load tied to primary MIs in NA-ACCORD – written by Mark Mascolini – (02/27/15) T

AF easier on kidney and bone signals than TDF in 48-week trials – written by Mark Mascolini – (02/27/15) 

Earlier ART in primary infection leads to bigger drop in cellular HIV DNA – written by Mark Mascolini – (02/27/15) 

Attachment Inhibitor Prodrug BMS-663068 in Antiretroviral-Experienced Subjects: Week 48 Analysis – (02/27/15) 

Treatment with a TLR7 Agonist Induces Transient Viremia in SIV-Infected ART-Suppressed Monkeys – (02/27/15) 

TLR7 Agonist GS-9620 Activates HIV-1 in PBMCs from HIV-Infected Patients on cART – (02/26/15) 

BMS-955176: Antiviral Activity and Safety of a Second-Generation HIV-1 Maturation Inhibitor – (02/27/15) Renal and Bone Safety of Tenofovir Alafenamide vs Tenofovir Disoproxil Fumarate – (02/27/15) 

Ledipasvir/sofosbuvir for 12 Weeks in Patients Coinfected With HCV and hiv-1: ION-4– (02/27/15)

 Renal and Bone Safety of Tenofovir Alafenamide vs Tenofovir Disoproxil Fumarate – (02/27/15) 

GILEAD ANNOUNCES SVR12 RATES FROM PHASE 3 STUDY EVALUATING HARVONI® FOR THE TREATMENT OF CHRONIC HEPATITIS C IN PATIENTS CO-INFECTED WITH HIV – (02/27/15) 

Study of Next-Generation Investigational HIV-1 Maturation Inhibitor Shows Positive Results in Preventing Viral Replication via Different Mechanism of Action Than Current Therapies – (02/27/15) 

HIGH SVR REGARDLESS OF TIME TO SUPPRESSION WITH OMBITASVIR/PARITAPREVIR/R & DASABUVIR + RBV – (02/27/15) 

Gilead Announces Phase 3 Results for Investigational Once-Daily Single Tablet HIV Regimen Containing Tenofovir Alafenamide (TAF) – (02/27/15) S

afety of Tenofovir Alafenamide in Renal Impairment – (02/27/15)

 Tenofovir Alafenamide (TAF) in a Single-Tablet Regimen in Initial HIV-1 Therapy – (02/26/15) 

HIV-1 Attachment Inhibitor Prodrug BMS-663068: Pharmacokinetics, Pharmacodynamics and Model-Based Dose Selection – (02/26/15) 

HIV-1 Attachment Inhibitor Prodrug BMS-663068: Interactions with DRV/r and/or ETR – (02/26/15) 

Little or no DNA reservoir draining with chemo plus autologous stem-cell transplant – written by Mark Mascolini – (02/26/15) 

Size of active HIV reservoir predicts rebound when antiretroviral therapy stops – written by Mark Mascolini – (02/26/15) 

Viral load above 1500 copies 23% of time in CDC study of 6 clinics – written by Mark Mascolini – (02/26/15) 

Levonorgestrel contraception fails in 15% of women taking efavirenz – written by Mark Mascolini – (02/26/15) 

NCI sees “sizeable absolute risk” of cancer in elderly with HIV – written by Mark Mascolini – (02/26/15) 

Lower CD4 count, higher viral load tied to primary MIs in NA-ACCORD – written by Mark Mascolini – (02/26/15) 

Almost half of US women with HIV not in regular care in CDC analysis – written by Mark Mascolini – (02/26/15) 

Little or no DNA reservoir draining with chemo plus autologous stem-cell transplant – written by Mark Mascolini – (02/26/15) 

Drug Interactions Between the anti-HCV Regimen Ledipasvir/Sofosbuvir and Ritonavir Boosted Protease Inhibitors plus Emtricitabine/Tenofovir DF– (02/23/15) 

HCV recurrence after SVR 20 times more frequent with HIV/HCV than HCV alone – written by Mark Mascolini – (02/23/15) 

As-Needed PrEP Cuts HIV Rate 86% in French-Canadian Ipergay Trial – written by Mark Mascolini – (02/23/15) 

Pre-Exposure Prophylaxis for HIV Prevention: What we know and What we still need to know for implementation – (02/23/15) 

Daily TDF/FTC PrEP Provides 86% Protection From HIV in Gay British Men – written by Mark Mascolini – (02/23/15) 

PrEP plus ART yields “near elimination” of HIV in Partners cohort – written by Mark Mascolini – (02/23/15) 

Wider PrEP Use in San Francisco Could Cut New HIV Rate by 70% – written by Mark Mascolini – (02/23/15) 

As-Needed PrEP Cuts HIV Rate 86% in French-Canadian Ipergay Trial – full slide presentation below – written by Mark Mascolini – (02/23/15) 

Early ART, continuous suppression, tied to lower HIV DNA in CHER trial children – written by Mark Mascolini – (02/23/15) 

Poor kidney function predicts neurocognitive decline with undetectable viral load – written by Mark Mascolini – (02/23/15) 

Doubled risk of virologic failure with 3TC vs FTC in Dutch cohort analysis – written by Mark Mascolini – (02/23/15)

 Anal cancer diagnosed earlier in HIV+ men, but cancer-specific survival similar to HIV- men – written by Mark Mascolini – (02/23/15) 

Poor balance confidence–not physical function–predicts falls in older men with HIV – written by Mark Mascolini – (02/23/15) 

Extensive cervical lesions common in HIV-positive women screened for ACTG trial – written by Mark Mascolini – (02/23/15)