Paris conference ends with new promises to fight AIDS.
The major international AIDS conference for 2003 has ended with encouraging signs of growing international commitment to fight AIDS in the developing world, and with several promising medical developments.
Held in Paris to commemorate the 20th anniversary of the discovery of HIV by French researchers in 1983, the Second International AIDS Society (IAS) Conference on HIV Pathogenesis and Treatment brought together over 6000 researchers, clinicians and AIDS advocates from around the world.
The conference focused heavily on the continuing AIDS crisis in developing countries, and the need for the wealthy countries of the world to develop a coordinated plan and provide the massive funding needed to halt the epidemic.
With new projections warning of at least 70 million people dead from AIDS before the end of the decade, former South African president Nelson Mandela told the opening ceremony that the HIV pandemic was now “the greatest health crisis in human history.”
“The world must do more, much more, on every front in the fight against AIDS,” Mandela said. “There is no excuse for delay – if we discard the people who are dying from AIDS, then we can no longer call ourselves decent people.”
In response, European Commission president Romano Prodi made a “personal promise” that Europe would contribute US$1 billion (A$1.52bn) to the Global Fund to Fight AIDS, TB and Malaria in 2004.
“I am the guarantor for the one billion,” Prodi told the closing ceremony. But there’s a catch — the rest of the EU needs to agree before Prodi’s ‘personal’ promise can be delivered, “and we don’t always agree on everything,” he acknowledged.
“Sometimes we work a little like the turtle in the fable: we may sometimes work slowly, but we can be trusted to reach our goals in the long run.”
At least one EU leader, French president Jacques Chirac, is supporting Prodi’s offer. Describing the Global Fund as an “outstanding instrument,” Chirac called on the US to equal Europe’s commitment.
Protesters outside the ceremony remained unconvinced by the rhetoric inside.
“The wealthiest countries in the world are refusing the amounts of money needed in 2003 and 2004 to begin to save our lives,” Vuyiseka Dubula from South Africa’s Treatment Action Campaign told the media.
With 42 million people living with HIV, the Global Fund says it needs up to US$8 billion a year if it is to turn the tide of the epidemic. Since its inception in 2002, the Fund has received grants of just US$1.5bn.
Despite making a promise to spend US$10bn to fight AIDS over the next four years, the US government has promised the Global Fund just US$1bn, and so far has failed to deliver even that.
Australia is yet to make any commitment to support the Global Fund.
Drug resistance is common among newly-infected
A study by Dutch researchers has found that almost 10 percent of newly diagnosed people in Europe already have signs of resistance to antiretrovirals. The CATCH study examined blood samples from 1600 HIV-positive people who had never taken treatment. The participants came from 17 European countries (which did not include Britain and France).
Primary resistance to at least one drug was found in 9.6 percent of participants, with 1.7 percent resistant to two or more classes of drugs. Nucleoside analogue resistance was found in 6.9 percent, PI resistance in 2.2 percent and 1.7 percent of patients were resistant to non-nucleoside drugs.
Given the importance of an effective first combination in combating the virus, the study authors recommended that previously untreated patients undergo resistance testing before commencing treatment.
New drugs
Drug-drug interaction data was presented for two of the most heavily hyped new antiretrovirals, atazanavir (ATV, Reyataz) and tenofovir (TDF, Viread). Atazanavir levels are reduced by about 25 percent when combined with tenofovir. Kate Squires from the University of Southern California presented a paper suggesting that boosting atazanavir with ritonavir (300mg ATV + 100mg RTV once daily) is a way to avoid this problem.
Another new drug, tipranavir, is an experimental protease inhibitor that shows promise for treatment of people who have experienced treatment failure on other PIs due to its unique resistance profile. In very early results from a phase 2/3 trial of 216 heavily treatment-experienced patients, tipranavir appears to be fulfilling this promise, with 80 percent of patients having viral load reductions of at least 1 log after two weeks. The final results of this trial, which is planned to last for 32 weeks, will be eagerly awaited.
Treatment breaks
More discouraging news was presented about the potential for structured treatment interruptions. The STACCATO trial, a two-year study of 600 patients in Switzerland, Thailand and Australia, found that more than half the patients receiving a one-week-on/one-week-off antiretroviral regimen experienced treatment failure after eight weeks, leading to discontinuation of this arm of the study, which is looking at several different strategies for intermittent therapy.
Tenofovir trial failure baffles researchers
The promise of once-daily antiretroviral dosing is fast becoming a key target of research. Hoping to find such a combination, a small American study looked at the combination of tenofovir, 3TC and abacavir dosed once daily. If effective, the combination would not only have been convenient for patients, but held out the promise of reduced long-term toxicities as well.
Unfortunately, this was not to be, with 11 of the 19 people enrolled in the trial experiencing treatment failure after eight weeks. With a further three participants withdrawing for other reasons, the trial was discontinued. The researchers are unsure quite what went wrong, but noted that a higher-than-usual number of participants had very high viral at the start of the trial.
Protease inhibitors and heart disease
A large cohort study which examined the medical records of nearly everyone who started HIV treatment in the province of British Columbia, Canada between 1996 and 2001 has found that people taking protease inhibitors are about three times more likely to develop cardiovascular disease compared with people on non-PI drug combinations.
The study conclusions, drawn from blood test results, prescription data, hospital admissions and death certificates from almost 3000 people with HIV/AIDS, appear to support earlier findings from small studies, although the study did not look at other heart disease risk factors. “The signals we are seeing about cardiovascular risk say that we cannot ignore it any longer,” study author Julio Montaner told the conference.
Lipodystrophy
Researchers from the FRAM study, a large American cohort study which is looking at body fat changes in HIV-positive people, looked into the differences between men and women in experiencing lipodystrophy. Previous reports from this study have found that lipoatrophy (fat loss) is much more common than previously thought and, controversially, that fat accumulation may not be related to lipodystrophy at all.
The researchers found that fat loss was much more common in women than previously reported, with 28.3 percent of HIV-positive women having some degree of fat loss, compared with 4.2 percent of their HIV-negative counterparts. Despite this, most HIV-positive women did not feel they had lost any body fat.
Disturbingly, HIV-positive women had much higher levels of insulin than HIV- women, suggesting widespread insulin resistance (which may lead to diabetes) among positive women.
Nuke-sparing regimen
Developing antiretroviral treatment regimens which “spare” one of the three main classes of drugs is a key part of HAART. Most class-sparing regimens focus on sparing either the protease inhibitor or non-nucleoside class, but the emerging long-term toxicities of nucleoside (NRTI) drugs suggest that regimens sparing this class could also be useful. Preliminary results from a small pilot study of a nucleoside-sparing regimen (Kaletra plus efavirenz) presented in Paris found that this approach has similar levels of efficacy to NRTI-containing regimens.
In the 86 patients on this open-label trial, 78 percent had undetectable viral load after 24 weeks, and the average increase in CD4 count was 116 cells. Side effects were problematic, however, with 40 percent of participants experiencing at least one grade 3 or 4 adverse event, and 14 patients withdrawing from the trial.
Hepatitis C coinfection
Researchers in British Columbia, Canada, suggest that HIV-positive people coinfected with the hepatitis C virus (HCV) tend to have less pronounced CD4 cell increases as a result of taking HAART, suggesting that HCV may weaken the immune system’s ability to rebuild itself after HIV replication is suppressed.
Reviewing the medical records of 552 HIV patients of whom 235 (42.5 percent) were coinfected with HCV, the researchers found that the group with HIV alone had an average CD4 increase of 230 after 1.5 years on treatment. Among the coinfected group, the increase was much smaller: an average of 120 cells.
Although it isn’t clear why the patients with HCV coinfection had less response, the study authors suggest that coinfected people may need to commence treatment earlier than people with HIV alone. Further research will be needed to ascertain whether this is so.
Calcium for nelfinavir-related diarrhoea
A Canadian study looked at the use of calcium supplements to help deal with diarrhoea associated with the protease inhibitor nelfinavir (Viracept). People taking nelfinavir have previously been advised to take moderate doses of calcium — usually 500mg per day — to help relieve this problem but it is not always successful; the Canadian study looked at whether increased doses of calcium, together with dietary intervention, might help.
The study recruited 18 people who had been taking nelfinavir for an average of 2.7 years and who had chronic problems with diarrhoea. Over a nine-week period, participants were given dietician advice to help avoid foods that might exacerbate the problem, took lactase and soluble fibre supplements and were given increasing doses of calcium carbonate — up to 2,500mg daily, or five times the currently recommended dose.
At the end of the study, all of the patients had significant relief of the problem and reported increased levels of quality of life as a result.
