CROI 2016 – first reports: PrEP, new HIV drugs, cure and access

19 February 2016. Related: News.

Simon Collins, HIV i-Base 

Early reports from CROI

• Introduction
• Dual long-acting injections of cabotegravir plus rilpivirine: 32-week results from LATTE-2 study
  First data showing injectable ART could be a realistic option.
• New NRTI MK-8591 (EFdA): weekly oral dosing and once-yearly slow-release dosing has potential for HIV treatment and PrEP
  Exciting early reasult for an ARV that might only need annual dosing.
• Similar viral load reductions at week 4 when dolutegravir is used with 2- or 3-drug initial ART
  Less at CROI 2016 than expected but this small poster finds no difference in early viral load reducations.
• 48-week results for NNRTI doravirine compared to efavirenz
• Dramatic increase in use of oral TDF/FTC for PrEP in the US – plus a few cautions
  Overview of PrEP studies at CROI 2016 using oral TDF/FTC.
  
• First data on TAF as PrEP to prevent HIV infection
  Very effective in animal studies but unanswered questions about drug levels in humans.
  
• Long-acting cabotegravir as PrEP protects macaques against IV exposure but will need two-monthly injections
  Exciting animal data showing protection againgst very high risk exposure plus human studies showing that injection will need to be ecvery two rather than three months.
  
• Role for maraviroc as HIV PrEP likely to need dual combinations
  Several studies looking at whether maraviroc has a role as PrEP seem to support use in combinations.
  
• Future oral and long-acting formulations for PrEP: pills, films, gels, injections and depots
  Future PrEP might include slow release removable depots and once-a-year dosing – and the challenge for how to quickly, safely and ethically study new PrEP drugs…
• Dapivirine PrEP vaginal ring shows only limited PrEP protection against HIV in African women
  Results from this long awaited research into an antiretroviral slow release vaginal ring.
  
• Early data from dolutegravir use during pregnancy
• Dolutegravir: 48 week results in children age 6 to 12 years old
• New antiretrovirals could mean savings up to US $3 billion by 2025
  Predicted impact from access to better and less expensive ART in low- and middle-income countries.
  
• Countries with lower HIV prevalence have lower ART coverage
• Nigerian herbal medicines widely used by HIV positive people can contain antiretrovirals
• Cure research news from CROI 2016
  Impressive round-up of cure-related research.

Introduction

Every few years, the annual Conference on Retroviruses and Opportunistic Infections (CROI) returns to Boston for one of the most important scientific HIV meetings.

With over 1000 studies presented, there is far more to report than the key studies that make headline news.

A few selections below are likely to highlights to expect in 2016.

The programme is already posted to the conference website.
http://www.croiconference.org/electronic-materials

Although the programme is now online, abstracts are not publically available until after the conference ends. Webcasts are made available on the day after oral presentations and PDF files for posters are available after the meeting.
http://www.croiconference.org

This year, major studies will present research on basic and clinical science relating to prevention, treatment and access.

Overview of CROI 2016

PrEP: tenofovir/FTC

Dozens of studies will report on current oral PrEP: access programmes, monitoring, additional safety data and a few studies with cautions (mainly STIs and side effects but also the risk of infection with drug resistant HIV).

The big picture however, will be the success of this new intervention that is steadily transforming life for at least 40,000 people currently using PrEP in the US and increasing numbers globally.

PrEP: new drugs and formulations

Just as PrEP is gaining wider recognition as a word for the pill that prevents HIV transmission, CROI 2016 will complicate this with a range of other drugs, compounds and formulations that might become future PrEP.

• Other oral drugs that might be used for PrEP (TAF, maraviroc and MK-8591).
• Long-acting injections (cabotegravir LA plus rilpivirine LA).
• Rectal and vaginal gels (tenofovir, PC-1005 and MK-8591).
• A vaginal ring (daprivirine) with efficacy results from phase 3 studies.

New antiretroviral treatment

Even with current treatment that is highly effective and generally well tolerated, there is still a pipeline of new drugs.

CROI 2016 will include new clinical results on many new drugs.

• Dolutegravir results during pregnancy and in younger children (aged 6 to 12 years) – essential for global recommendations.
• Long-acting injections of cabotegravir plus rilpivirine, including tolerability of these injections – results from LATTE-2 study.
• Tenofovir alafenamide (TAF) – the new version of tenofovir: switching studies, longer term renal and bone safety and drug resistance.
• BMS compounds (now transferred to ViiV) that include a maturation inhibitor (BMS-955176), an attachment inhibitor (BMS-663068) and first data on a new compound with multiple sites of action (BMS-986197).
• Doravirine (an NNRTI) and MK-8591 (an NRTI), both from Merck.
• Frist clinical data on ABX464 – a new compound that might allow less than daily dosing.

ART strategies

• Plenty of studies about earlier treatment in various settings, including six studies from the START study and results from the POPART study.
• Immune responses in early infection and the CD4:CD8 ratio.
• Other approaches to treatment – including the monoclonal antibody VRC01, anti-PD-1, genetic therapy and stem cell research – all over-lapping with strategies to cure HIV.

HIV complications

Numerous studies and session with cover complications of HIV and/or ART.

• HIV and the brain – including neuroimaging.
• Bone health and treatment: overviews and links to specific drugs.
• Liver health, with and without hepatitis.
• Hepatitis C will have dozens of studies, including a late-breaker using only six weeks of treatment with new oral drugs for HIV positive people – likely to be gay men – whose HCV is treated in acute infection.
• HIV and the gut – and role of microbia.
• HIV and the heart – including lipodystropy and other side effects.

Cure research

• Measuring and activating viral reservoirs – a key step in current approaches to cure research. Incudes vacc-4x/Gm-CSF and romidepsin.
• Studies using the monoclonal antibody VRC01.
• Updates on gen therapy with SB-728.
• Intriguing results of animal studies using TLR-7.

Global access

Global access now features strongly every year including plenary and other oral presentations that will be webcast.

Updates on practical issues related to achieving 90:90:90 goals in different settings. This the UNAIDS target for getting 90% of people diagnosed, 90% of those on ART, and 90% of those with undetectable viral load.

Each stage is easier or more difficult in each setting. Even if this target is reached, only 72% of HIV positive people will have an undetectable viral load overall – showing the importance of aiming for higher.