Closing in on answers to TB and hepatitis C

New drugs offer hope we can beat HIV's deadly companions. Elizabeth Finkel reports.

Sharon Lewin at AIDS 2014 in Melbourne. She says we need to build partnerships to bring the cost of treatments down. – International AIDS Society/ James Braund

HIV is deadly but the virus itself doesn’t kill people. It’s other microbes that come in for the kill once HIV has destroyed the defensive immune system. Chief amongst these are the tuberculosis bacterium and the hepatitis C virus (HCV).

TB is the major killer, accounting for a quarter of all AIDS-related deaths. But the hep C virus can also be deadly, particularly as HIV patients can carry it for years without realising. In the US an estimated 25% of HIV carriers are HCV-positive. The hepatitis virus attacks the liver and can cause severe cirrhosis within 10 years. Without HIV treatment it can progress even faster. “It’s crucial to cure people, both to stop liver disease and to stop the spread of the virus,” says Jean-Michel Molina from the University of Paris Diderot.

While hopes of an HIV cure have dimmed, some of the good news delivered at the AIDS 2014 conference was that researchers are closing in on cures for TB and hep C infections in people who are also HIV positive.

The new TB treatment comes from not-for-profit research organisation, the TB Alliance. It is testing a new cocktail of three drugs that seems to be effective against many types of TB – including some of the increasing number of strains resistant to standard antibiotics, so-called multi-drug resistant (MDR) TB. According to the WHO, MDR TB now represents 4% of all new TB cases and 20% of previously treated patients.

At present, patients with MDR TB require a long, extremely expensive treatment – 14,000 pills taken over 18-24 months as well as daily injections for six months. But the treatment can cause severe side-effects. That and the expensive lengthy treatment means many people stop taking their drugs, putting themselves at risk of picking up extreme drug-resistant (XDR) TB – strains that often fail to respond to all antibiotics. “New treatments are badly needed”, says Mel Spigelman, the president and CEO of the TB Alliance. Because TB is a disease of the poor there is little incentive for pharmaceutical companies to develop new drugs.

The newly tested drug mix, known as PaMZ, requires just 360 pills taken over four to six months. It is 10% of the cost of some current MDR TB treatments and does not interfere with HIV drugs. It uses a triple combination of two existing drugs, moxyfloxacin and pyrazinamide, and a new drug called PA-824 developed by the TB Alliance. The treatment recently completed a trial on 200 patients across South Africa and Tanzania – 20% of whom were co-infected with HIV. Compared to standard therapy for drug-sensitive TB it was faster and more potent.

The TB Alliance is now looking for funding to start a final trial of 1,500 patients in 10 countries. “This will be a game changer,” says Spigelman.

What’s still needed is a rapid test of a patient’s TB strain to determine which of the older drugs it can resist. Testing is crucial to prevent the development of resistance to the precious new drug PA-824. If a patient’s TB strain is resistant to both of the older drugs in the PaMZ mix, that would effectively mean that PA-824 is fighting solo, which makes it all too easy for the bacterium to evolve resistance. The TB Alliance is pushing for the development of a DNA-based test that could identify drug resistance within hours, rather than the three weeks it currently takes.

Spigelman estimates that a third of MDR TB cases can be treated with the new drug mix. For those who can’t be treated with PaMZ, as well as for XDR TB, the TB Alliance has two more new drug combinations in development that are planned to begin trials at the end of the year. “It’s really a welcome advance,” says Sharon Lewin, director of the Infectious Disease Unit at the Alfred Hospital and co-chair of the conference.

When it comes to the other killer, hepatitis C, treatments have appeared in the last couple of years, but because they interfered with HIV drugs they were unsuitable for people who were infected with both viruses. Furthermore there are at least four genetically different types of hep C virus, and many of the new drugs were active against only one.

Molina presented the findings of a trial that combined two drugs – an old one called ribavirin and a new one, sofosbuvir – manufactured by Gilead Sciences. In the trial 274 people who were infected with both HIV and the hep C virus in Europe and Australia were treated for 12 weeks. There was a dramatic reduction of hep C viral levels in more than 80% of cases, regardless of which genotype they were infected with, although the treatment was less effective in people with cirrhosis. “It’s amazing to us to see these two drugs alone suppressing all the HCV genotypes,” says Molina. And he points out this could spare the cost of having to pre-test patients for the type of virus they carry.

Lewin agrees “sofosbuvir is a wonder drug”. But with its hefty price tag – $94,500 for a 12-week course – she says it is currently inaccessible for patients in poor countries. Indeed at the conference protesters demonstrated against Gilead, bearing posters proclaiming amongst other things, “Gilead Kills”.

“We need to use the same advocacy and partnerships that we did for HIV drugs to ensure drug pricing comes down,” says Lewin.

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