New drugs, vaccines, gels and foams are on the way

More than 50 drugs, as well as vaccines and protective gels and creams, are in development as researchers search for new ways to tackle HIV, writes Roger Dobson

Millions of pounds a year are now spent on HIV research and development. Around 50 to 60 drugs are in development, and some are already in clinical trials. In addition, a number of vaccines and protective gels are being tested.

Although more than 20 antiretroviral drugs are being used against HIV, there is demand, not just for new types of medication, but for variations on existing drugs because of drug resistance or side effects. “The past three decades have seen extraordinary advances in HIV treatment and there has been some significant progress on the challenging path to developing new tools to prevent HIV,” says Deborah Jack, chief executive of NAT (National Aids Trust).

“HIV awareness and education will always be essential to HIV-prevention efforts, but no other health intervention is more cost effective or has a greater impact on public health than vaccination.

“An effective HIV vaccine could have the potential to eradicate the spread of the virus, but HIV has unfortunately proved to be a huge challenge to vaccinologists as it is a constantly changing virus with many sub-types. Developing a single vaccine which works on all strains of HIV will be a momentous task, but we have made some promising strides in this area.

“There have also been advances made in the area of microbicides. There is still a long way to go before the concept of an HIV vaccine or microbicide is fully realised, but we are optimistic that, with continued and increased investment, one day it will happen.”

An effective HIV vaccine could have the potential to eradicate the spread of the virus

There are two main types of vaccine: preventive, designed to protect HIV-negative people from becoming infected; and therapeutic, aimed at boosting the immune system in those already infected. Progress is being made and results from a study of the RV 144 HIV vaccine are the first to show evidence of efficacy.

“While there is still work to be done to improve on the levels of efficacy of any vaccine candidate, the results from this trial provide hope that we will one day have an effective and safe vaccine that can help put an end to the epidemic and save millions of lives around the world,’’ says Dr Kevin Fenton, director of the US National Center for HIV/Aids.

Most of the drugs in development fall into four main antiretroviral drug classes: fusion or entry inhibitors; integrase inhibitors; NRTIs (nucleoside analog reverse-transcriptase inhibitors); and NNRTIs (non-nucleoside reverse-transcriptase inhibitors). Fusion or entry inhibitors are designed to stop the virus from gaining entry to a cell; integrase inhibitors block the action of an enzyme produced by HIV which has a key role in an early stage of HIV replication inside human cells; NRTIs are designed to stop HIV replication; and NNRTIs stop HIV replicating by interfering with a protein.

Maturation inhibitors are a new class of drug designed to stop the virus becoming infectious by interfering with its transition from immature, non-infectious virus particles, to mature and infectious virions or virus particles.

The UK is a leading centre for HIV research and a number of pioneering studies are underway. A drug developed from genetically modified tobacco plants, for example, which could prevent HIV infection, is being tested at the University of Surrey.

Scientists have been given the goahead to test the safety of a monoclonal antibody and there are hopes that it will be used in a rub-on protective gel-like product for women. “The approval to proceed with human trials is acknowledgement that monoclonal antibodies can be made in plants to the same quality as those made using xisting conventional production systems. That is something many people did not believe could be achieved,” says Professor Julian Ma, joint co-ordinator of the project.

A number of rub-on gels, creams and foams, designed to be applied in the vagina or rectum before or after sex to prevent infection, are in development. These work in a number of different ways, including strengthening the body’s normal defences and halting the spread of the virus.

Results from one study in South Africa, show that women who used an experimental microbicide before and after sex were almost 40 per cent less likely to get HIV.

In the United States, a new laboratory trial at the University of California has shown that a gel containing a potent anti-HIV drug significantly reduced infection when applied to rectal tissue exposed to HIV.

As well as therapies that target the virus itself, there are a number of treatments in development aimed at some of the complications sometimes associated with the infection. Researchers at Northwestern University, in the US, are testing a drug that could protect patients from dramatic and acute bone damage associated with HIV drugs.

Another drug has shown potent anti-viral activity and also a potential anti-inflammatory benefit. This is important because HIV can increase the risk of heart disease, dementia and other age-related problems. And a Japanese trial is looking at the use of stem-cell transplantation as a way of restoring liver functioning in HIV-infected patients who have de-compensated liver cirrhosis.

DRUGS ON TRIAL

PRO 140 contains genetically engineered antibodies to fight infections. In one study, all patients showed at least a ten-fold decrease in HIV.

TNX-355 or ibalizumab blocks HIV from entering cells by binding to a protein on the cell surface.

Dolutegravir is being investigated as an option for patients who are resistant to other integrase inhibitors.

Elvitegravir is being studied as part of a quad-therapy which would combine four drugs into a single pill.

KP-1461 is an NRTI (nucleoside analog reverse-transcriptase inhibitors) that takes a unique approach to fighting HIV, called viral decay acceleration. The idea is to increase the rate at which HIV mutates when it replicates so that the virus soon becomes too deformed to survive.