Where are we now?

According to IAVI, as of July 2011, there were some 32 trials of HIV vaccine candidates taking place worldwide, not counting therapeutic vaccines (i.e. those which would help control infection, rather than prevent it).

Since the ending of RV144 there have been no Phase III efficacy trials.

There is one phase IIb trial in progress. This is HVTN 505, a prime-boost trial in 1350 US volunteers started in July 2009, consisting of an adenovirus vector and a DNA boost. In August 2011 the decision was taken to expand this trial to 2200 volunteers and to upgrade it to phase IIb. Phase IIb trials are ‘test of concept’ trials, which can begin to examine a candidate vaccine’s efficacy - its ability to protect people from HIV.

Only three other current trials include more than 100 volunteers  – the smallest number of subjects undertaking HIV vaccine studies since the early 1990s. This does not indicate discouragement; the field is in fact experiencing a resurgence in optimism, but this is accompanied by a realisation that before mounting large immunogenicity and efficacy trials, there needs to be a return to preclinical, animal and basic science research in order to develop candidates that are more likely to work.

But if therapeutic vaccines are included there are currently about 50 trials of 42 vaccine candidates occurring worldwide.¹ Twenty-two are using viral vectors (plus or minus other boost doses), ten are using artificially generated DNA, three are using HIV proteins, two are using replicating viral vectors such as CMV which spread the vaccine from cell to cell, and there are a handful of miscellaneous candidates. Twenty-eight are using a multiple-dose prime-boost design.

See the IAVI database of AIDS vaccines in human trials for a continuously updated list (www.iavireport.org/trials-db/Pages/default.aspx). A summary is also available form AVAC in pdf format at www.avac.org/ht/a/GetDocumentAction/i/3436.

The only trials classed as Phase II trials are being conducted by the HIV Vaccine Trials Network of NIAID. They are:

• HVTN 205: A similar trial using a poxvirus vector, enrolling 225 volunteers in the US and Peru.
• HVTN 204: A trial that has completed (it started in 2006) but whose results are being analysed. It recruited 488 volunteers in South Africa, USA, Haiti, Jamaica and Brazil. This trial used a DNA vaccine as a prime and an adenovirus vector as a boost.

The remaining studies are Phase I or Phase I/II trials of vaccine candidates that will test safety and then immunogenicity. If candidates are found to be immunogenic they will then be moved forward to larger Phase IIb proof-of-concept studies.

There is unlikely to be a ‘magic bullet’ HIV vaccine in the foreseeable future. In order to maximise the chances of finding one:

• Vaccine research must be multidisciplinary and integrated with other prevention research;
• Research may need to be conducted in novel ways that ensure a faster throughput of candidate vaccines and quicker identification of promising ones;
• Promising candidate vaccines need to be identified more quickly – four large efficacy trials in 15 years is not enough. The aim should be to more quickly identify candidates whose potential efficacy is promising enough for them to enter an efficacy trial and eliminate less promising ones;
• We urgently need to conduct research that establishes better correlates of immunity;
• We must find ways to test and later to deploy vaccines in ways that complement and reinforce other prevention methods, and vice versa.