Photograph by Paul Kidd.

Medical conferences are often held in exotic locations. Choosing a host city with great scenery, warm weather or bargain-priced shopping tends to increase the chances of tempting busy doctors away from their lucrative practices, or so the story goes.

On the face of it, Rio de Janeiro, with its wide sandy beaches, year-round hot weather and spectacular mountain setting, seems to fit the bill perfectly. But there’s a more serious reason why the International AIDS Society (IAS) chose Rio as the host city for this year’s major AIDS conference. Brazil, after all, is one of the few countries in the developing world which seems to be meeting the challenges of the AIDS epidemic head-on.

In the early 1990s, following predictions that Brazil could have 1.2 million people living with HIV/AIDS by 2000, the Brazilian government instituted a widely-acclaimed program of aggressive HIV prevention and universal access to treatment. The country still has a large HIV-positive population – around 660,000 people according to the most recent figures in 2003 – but by cutting those early predictions in half, Brazil has shown what can be done if there is the political will and capacity to make a difference.

One thing that sets Brazil apart is its emphasis on treatment. The Brazilian government began its program of universal treatment access in 1996, and today around 160,000 Brazilians receive free antiretrovirals through the public health system. There are 17 drugs available – nine ‘brand name’ versions and eight locally-manufactured generics.

With its well-developed domestic pharmaceutical industry, Brazil is one of only a handful of developing countries able to manufacture generic antiretrovirals. Added to that, the Brazilian government has shown strong leadership in taking on ‘big pharma’, capitalising on international rules which permit it to override patent protections on HIV medicines where there is a pressing national health emergency.

As if on cue, just before the conference the Brazilian government issued a very public ultimatum to pharmaceutical giant Abbott Laboratories: lower the price of Kaletra or we’ll start making our own. Abbott was quick to come to the negotiating table, and in early July the company offered a deal which would save the Brazilian health budget a reported A$339 million over six years.

Brazil’s health minister is still negotiating a final deal with Abbott on the price of Kaletra, which currently accounts for about a third of the country’s total antiretroviral bill. But he is doing so in the knowledge that the country holds a trump card in that, if a deal can’t be struck to Brazil’s liking, he can walk away from the table and issue an order allowing local companies to make a generic version of Kaletra for people in Brazil.

The country is also reportedly in negotiations with other drug companies over the price of other drugs including efavirenz and tenofovir, and is wielding the same big stick: make your drugs affordable, the country is telling the pharmcos, or we will make your drugs ourselves.

Brazil’s negotiating strength is also having an effect in neighbouring countries. In August, a group of 11 Latin American countries reached an agreement with 26 drug manufacturers to secure price cuts of up to 66 percent across the region, and Brazil has recently announced an agreement to share pharmaceutical manufacturing knowledge with neighbouring Argentina.

With all these developments in the background, Brazil was a very appropriate host country for the 2005 IAS Conference. The fact that it also boasted beautiful scenery, warm weather and an exotic location was merely a bonus.

The conference took place over three days in a cavernous conference centre on the outskirts of the city. The hour-long early morning bus ride from the hotels of Copacabana and Ipanema past Rio’s slums and industrial areas to the down-at-heel conference centre was an annoyance that many conference-goers complained about, but the stark contrasts of the journey served as a reminder of the importance of the work that we were there to do.

Circumcision controversy

The big news of the conference – certainly the only thing that was widely reported in the mainstream media – was a study which found a stronger-than-expected protective effect for circumcision in preventing HIV transmission.

The French-sponsored trial, the first ever randomised control trial of male circumcision as a preventative measure, enrolled 3273 men aged 16-24 living near Orange Farm township in South Africa. The men were randomly assigned to two groups: participants in one group were circumcised at the start of the trial, while the other group was to be offered the procedure 21 months later.

The study was ended prematurely after it became clear that the rate of HIV transmission was much lower among the men who were circumcised at the outset. An analysis of the data concluded that the protective effect of circumcision in this trial was 75 percent – much higher than had been found in earlier studies.

It’s important to note that the effect that was observed was seen over a relatively short period of time (20 months) in a group of young, highly sexually active heterosexual men in an area with extremely high HIV prevalence (31.9 percent).

CCR5 excitement

The IAS Conference is a relatively new event, held every two years in the ‘off’ year from the International AIDS Conference, also run by the IAS. The idea behind this second, smaller, conference is to focus on the latest advances in HIV science and medicine, while the International AIDS Conference looks more broadly at medical science, social science, policy, community advocacy and government. Because of this, the IAS Conference attracts a more ‘hard core’ scientific crowd, and has a greater emphasis on cutting-edge ‘basic’ science.

One area of treatments research that received a lot of attention in Rio was the development of CCR5 inhibitors. Like T-20, CCR5 inhibitors could prevent HIV from entering and infecting healthy cells, although via a different mechanism to that used by T-20. As such, they could offer a substantial step forward in HIV treatment and so a number of the major companies are developing drugs in this class.

On the other hand, there’s a possibility that CCR5 inhibitors could also encourage HIV to switch to a potentially more virulent form, something which is a cause of concern to people with HIV but of considerable interest to scientists for whom such a development, unfortunate though it may be, could add to our understanding of the way HIV works and perhaps lead to better treatments in the future.

New data were presented in Rio for two experimental CCR5 inhibitors, Pfizer’s maraviroc and Schering-Plough’s vicraviroc, both of which are currently in phase 2/3 clinical trials, and for a ‘CCR5 monoclonal antibody’, Progenics’ PRO-140, which is still in preclinical development.

Both maraviroc and vicraviroc appear to have strong antiviral activity, with decreases in viral load of greater than 1.5 logs when given over short periods with no other HIV drugs. Test-tube data on PRO-140 shows that it is strongly synergistic with the CCR5 inhibitors, perhaps suggesting a possible future ‘CCR5 combination therapy’. Further trials are planned for all three.

❧ GlaxoSmithKline has halted work on its CCR5 inhibitor, aplaviroc – see Treatments Briefs on page 8.

Protease performers

Two new protease inhibitors – Boehringer Ingelheim’s tipranavir and Trimeris’s TMC-114 (to be marketed in Australia by Janssen-Cilag) – were the focus of a considerable amount of attention. Both of these are well-developed drugs, with tipranavir already licensed in the US and TMC-114 currently in phase 3 trials, in Australia and overseas.

Both offer the welcome advantage of being active against HIV which has become resistant to other protease inhibitors, and both are the subject of studies designed to demonstrate their effectiveness in people with protease-resistant virus.

In particular, TMC-114 generated a lot of interest with data presented from the POWER 1 study, a phase 2 trial involving 318 people who had previously taken treatments from all three major drug classes. Participants in this study were randomised to receive, in addition to an optimised background regimen, either a ‘control’ protease inhibitor or one of three doses of TMC-114, boosted with ritonavir.

After 24 weeks, the results in the TMC-114 arms were significantly better than those seen with other PIs – 77 percent of patients taking the strongest of the three TMC-114 doses had viral load decreases greater than 1 log, compared with 25 percent of the control group. Side effects were “mostly mild” and similar to those seen with other PIs. Further research is ongoing and more results are expected by the end of 2005.

The return of monotherapy?

A couple of interesting studies are looking at the use of protease inhibitors as monotherapy (taking just the PIs with no other drugs).

The OK (“Only Kaletra”) study, in particular, was interesting not just for the results but for the methodology used. This small study enrolled 42 people who had maintained undetectable viral load on triple-drug regimens for at least six months. Half the participants were switched to Kaletra monotherapy, the rest were kept on their existing treatments. The researchers then used a super-sensitive viral load test, capable of detecting viral loads as low as 3 copies/ml, to watch for the emergence of resistance. After 48 weeks, 17 of 21 patients switched to Kaletra were still undetectable. In the other four, switching back to triple-drug treatment quickly brought their HIV back under control.

A second study, ATARITMO, is looking at using atazanavir in a similar way. Interim results presented at Rio found that 22 of 24 patients switched to a simplified atazanavir/ritonavir regimen were still undetectable after 24 weeks.

Both these studies are interesting in themselves but also for the way they suggest that simpler, less toxic treatment regimens could be possible, at least among people who have responded well to triple-drug treatment and have avoided the development of resistance. Both studies are ongoing and, of course, further research will be needed before protease-only regimens are recommended in the real world.

But wait! There’s more

Attending these international HIV conferences is simultaneously exhilarating, inspiring, exhausting and overwhelming. There is much more to report than would fit on this page, but the take-home message seems to be optimistic: treatments are slowly improving, our understanding of HIV is expanding, and the political will to do what it takes to save people’s lives is increasingly there.

❧ The next IAS Conference on HIV Pathogenesis and Treatment will be held from 22-25 July 2007 in Sydney, Australia. Some additional reports from this conference are included in Treatments Briefs on page 8.