Twenty-five years ago virtually nobody had heard of AIDS. Two decades ago most people thought that tuberculosis was a disease of the past, defeated by vaccines and antibiotics. However, in a strange twist of history the two diseases have dovetailed together to form a devastating health problem, with an estimated 12 million co-infected with both diseases of the 40 million living with HIV. And far from being a disease of the 19th century, TB is the biggest cause of death in people with HIV, particularly in developing countries.
An estimated 21 per cent of all the world's cases of TB are in the African countries most affected by HIV, with the disease spreading rapidly in other areas where HIV is widespread, most notably Eastern Europe and South East Asia. Although only two per cent of cases of TB are in industrialised countries like the UK, there have been recent outbreaks of multi-drug resistant TB amongst HIV patients in London.
Therefore the Global Alliance for TB Drug Development is calling for a concerted public - private effort not only to provide antiretroviral drugs to combat HIV, but to develop and give wider access to improved anti-TB drugs. Effective TB treatment would, they argue, extend the quality and length of life for people co-infected with both diseases and help slow the spread of both the TB and HIV epidemics.
As the international lobbying organisation points out, no new drugs to fight TB have been developed in the past 30 years, partly because the disease was considered long beaten.
This has particularly worrying implications for people with HIV, who are far more likely to develop active (symptom causing) TB than healthy individuals. In addition, latent (non-active) TB is much more likely to become active in people co-infected with HIV. Active TB may also accelerate the progression of HIV disease and in sub-Saharan Africa one in three Aids deaths is caused by TB.
Even more worryingly, TB is fast becoming resistant to the arsenal of existing drugs developed in the 1950s to 1970s, partly because TB therapy has to be taken for a period of months for a cure to be achieved. At the moment it is necessary to take at least two drugs for a minimum of six to nine months for active TB to be effectively treated and three months of therapy is needed to control latent TB infection. The countries hit hardest by HIV also have the worst TB problems and lack the health care resources to provide effective TB treatment programmes, just as HIV antiretrovirals are beyond their reach.
The inability to adhere to six month TB treatment programmes means that multi-drug resistant TB can develop, which requires treatment with up to five drugs for 18 months to two years. Reducing the length of time that TB treatment needs to be taken is a major research and development objective, but agents which are active against multi-drug resistant strains of TB are also urgently needed. Second-line treatments that can be used against strains with reduced suscpetibility to first line treatments are more toxic and less effective.
Improving the treatment of latent TB, by reducing the 3 month treatment period to just one month of treatment, and by using a more effective drug, could have a substantial impact on cases of TB in HIV-positive individuals, according to the Global Alliance
The Global Alliance for TB Drug Development is therefore calling on governments and pharmaceutical companies to work together to develop faster acting and easier to take TB medicine.
Dr Giorgio Roscigno of the Global Alliance said: "The urgency for comprehensive treatment for both TB and HIV cannot be overstated...the development of faster acting drugs against all forms of TB will radically change the way we fight both diseases." He added: "A new TB drug would accelerate our ability to reach and treat Aids patients with active TB and allow us to treat more of those with to treat more of those co-infected with latent TB, thereby lowering Aids mortality levels."
The Global Alliance for TB Drug Development is advocating public-private partnership to develop new drugs, by providing financial support for research into new agents, by developing networks to carry out international studies, and by building interest in the pharmaceutical industry in the market for new agents.
The projected market for anti-TB drugs in 2010 is also highlighted, with a conservative estimate of the size of the market for supply of the public sector and international tenders ($190 million maximum). The projected market for a new TB drug, if an effective agent can be brought to market within eight years, is at least $300 million, according to the lobbying group, and with differential pricing that allows a higher profit in the developed world, the market increases to around $400 million.
The Global Alliance highlights several classes of drugs that deserve further investigation for TB control:
- Long acting rifamycins (eg rifapentine, rifabutin, rifalazil)
- Fluoroquinolone compounds (eg levofloxacin, moxifloxacin, gatifloxacin)
- Oxazolidinone compunds
- Nitroimidazopyrans