Opportunistic Infections

Monday, March 14, 2005

Cotrimoxazole prophylaxis in Asia: What are we waiting for?

Remember the days before antiretrovirals were available? The days before AZT? Just ten years ago there wasn’t much that could be done when someone developed AIDS. Some of us well remember the powerlessness and pain.

One thing we could do at the time was to give cotrimoxazole – an antibacterial agent that helps prevent and treat Pneumocystis carinii pneumonia. The two common brands, Septra or Bactrim, were cheap, widely available, and easy to administer. For years, cotrimoxazole was almost the only thing we knew that could help save lives.

In the clinical world the gold standard for determining whether a treatment is effective is a successful “Cochrane review”. The process is named after Archie Cochrane, who was one of the first to popularise reviews of scientific evidence. One of these reviews has recently been performed to examine evidence for the effectiveness of cotrimoxazole prophylaxis.

The results are very positive. Three African trials have shown a significant beneficial effect from cotrimoxazole, which prevents people from dying with a low incidence of side effects. The impacts of the drug are similar in people with both HIV and AIDS.

The results are not yet 100% conclusive: the Cochrane review found little information about cotrimoxazole’s effectiveness in areas with bacterial resistance to it, and not enough information about the effectiveness of cotrimoxazole prophylaxis in people taking antiretroviral therapy.

Cotrimoxazole not only prevents Pneumocystis carinii pneumonia, but is also effective against toxoplasma, which can cause encephalitis. It may also help fight deadly falciparum malaria – the most severe form of the disease, caused by Plasmodium falciparum. In Africa, cotrimoxazole has also been found to reduce other infections.

Side effects appear limited. A few people with AIDS who take cotrimoxazole develop a rash. But if they begin taking it three times a week, then increase to once a day after the first month, they probably reduce the chance of developing it.

Cotrimoxazole is commonly given to pregnant HIV-positive women. Also, trials in Africa have shown that people with TB who receive cotrimoxazole live longer than those who don’t receive the drug.

Some public health physicians in Africa are concerned that the widespread use of cotrimoxazole may accelerate drug resistance to sulfadoxine-pyrimethamine treatment, a combination therapy increasingly used for the treatment of acute, uncomplicated malaria.

Some are also concerned that the germ that causes simple, pneumococcal pneumonia will also become resistant to the drug. That may mean that Africa needs to adopt the use of Asia’s “superdrug” artemisinin.

For many, though, these theoretical possibilities are not so important when people are dying.

In March 2000, UNAIDS and the WHO jointly recommended that cotrimoxazole prophylaxis be used for people living with HIV/AIDS in Africa, to be administered as part of a package of care. The advice applies to all adults who have developed any opportunistic infection.

Four years have passed since then; why is cotrimoxazole prophylaxis not used more in Asia?

Official treatment guidelines are one place to start. Thailand and Cambodia both include cotrimoxazole prophylaxis in their official national treatment guidelines. Thai guidelines have included cotrimoxazole prophylaxis for at least ten years.

The only other Asian country with a generalised epidemic is Myanmar. Official national guidelines have yet to be released there. China, Malaysia and the Philippines have already included it in their guidelines. India will probably include it in its guidelines soon. It is thought that Vietnam, Indonesia and Sri Lanka will include the drug in their own guidelines in the near future.

But official guidelines are merely pieces of paper unless the recommendations are implemented. What is common practice?

Application varies widely from country to country. In Cambodia, cotrimoxazole has been promoted by non-governmental organisations for several years, and many people living with HIV are now taking it. In Myanmar, cotrimoxazole prophylaxis is almost unknown.

In Vietnam, despite intensive advocacy by international health organisations, and being recommended by the WHO for the last six years, national guidelines still do not include the drug. The germs are not resistant in Vietnam – it is the doctors who sit on the guidelines development committee who show resistance. Once again it is people living with HIV who are leading the way; word is out, and the medication is being taken. Health insurance is nonexistent, but fortunately, locally produced cotrimoxazole costs less than fifteen dollars a year.

In terms of effectiveness, Thailand is most instructive. Many people living with HIV began to take cotrimoxazole in 2001, when the health minister announced that drugs for prevention and treatment of opportunistic infection would be covered by health insurance. Non-governmental organisations then conducted an intensive patient education programme to promote widespread uptake of the medicine.

The WHO has two Asian regional offices, but neither has released any new regional treatment guidelines in the wake of the “3 by 5” initiative, launched in December 2003. The WHO already recommends cotrimoxazole in Southeast Asia, and these recommendations are being revised to include a wider range of people living with HIV/AIDS. There are, however, apparently no plans for the same revisions in western Pacific guidelines.

In any case, guidelines need to be backed with promotion. We already know that cotrimoxazole can save lives in Asia. What are we waiting for?

HDN Key Correspondent
Email: correspondents@hdnet.org

(July 2004)