One person trying to bring greater global attention to the adherence issue is Margaret Chesney, professor of medicine at the University of California at San Francisco and co-director of the Center for AIDS Prevention Studies. "This problem needs to be put on the international agenda, side by side with actual drug development and distribution."

Two major factors need to be emphasised with medication adherence, says Chesney. "One is the welfare of the patient. Drugs can’t work if people don’t take them as prescribed. Second -- and this is often overlooked -- is the public health issue. Non-adherence can result in the emergence of drug-resistant strains. Once this happens, a person can transmit that version of the virus to an uninfected person."

Chesney was co-investigator on a recent study that reported a man had become infected with a strain of HIV resistant to six of the 11 approved antiretroviral drugs, including four protease inhibitors. "This study shows that we can do more harm than good if we don’t help patients take their medications correctly," says Chesney.

Julio S.G. Montaner, national co-director of the Canadian HIV Trials Network and professor of medicine at the University of British Columbia in Canada, has a similar message. Apart from the inherent ability of drug cocktails to raise CD4 counts and cut viral loads to below detectable levels, "the single most important determinant of the treatment’s success is the ability to take medications as prescribed -- not a small challenge. The main point is that the treatments are cumbersome and priority should be to simplify them."

He points to a recent national study in the US in which 43% of patients on anti-HIV regimens admitted that in the week before the survey they didn’t take their medications as prescribed. In another study of patients by Chesney and colleague Jeannette Ickovics for the AIDS Clinical Trials Group (ACTG), 18% of respondents reported missing at least one dose in the previous two days; 25% said they didn’t know there were special instructions for their medication, such as taking capsules on an empty stomach.

"We’re fortunate that emerging data suggests that similar degrees of effectiveness can be achieved when the total daily amount of certain protease inhibitors can be taken in two rather than three doses, 12 hours apart," says Montaner. "If preliminary data can be confirmed, this apparently small change may have important implications for adherence."

For both Montaner and Chesney, though, reducing the number of pills is only a start. "We shouldn’t think that if we cut the numbers of doses to twice a day or the number of pills from 30 to 15, that this problem of adherence will go away," says Chesney. "That will help, but patients indicate that there are other equally important factors such as confidentiality and fitting the medication into their lifestyles."

Kathy Graham is a pharmacist and university teacher who also provides adherence counselling at an HIV clinic in Florida. She recalls the case of a young man who was looking forward to attending a family reunion but didn’t want his family to know he was HIV-positive. He seriously considered stopping his medication regimen to avoid raising suspicions about his health. With the clinic’s advice, he eventually decided to stay on his medication and attend the reunion. Putting his pills in inconspicuous containers helped him safeguard his secret.

Graham also sees lack of privacy in pharmacies as a deterrent to adherence. A person waiting in line at a pharmacy counter, she says, isn’t likely to ask for clarification about taking anti-HIV tablets or capsules when other customers may overhear.

For Marc Vesin, head of the Haute-Savoie chapter of AIDES, an HIV/AIDS support and prevention NGO in France, the solution to adherence problems has to come mainly from those taking the medication, though they must always "have the right to say 'stop'." In addition, "less stressful and less strenuous combination therapies" are needed to boost adherence.

"The drug companies should try to go beyond generating cash and give a helping hand so that people can return to a more normal life and, in many cases, start working again," says Vesin. "We've been good guinea pigs for a long time, but we need continued help from governments and drug companies."

In a session held yesterday, the International AIDS Society –USA released their 1998 treatment guidelines which refer explicitly to this problem. They state that "therapy should not be initiated until treatment goals and need for close adherence to a regimen are understood and endorsed by the patient."

Involving the person taking the medication is key to Montaner and other practitioners. They've begun to use a "practice" method to help their patients decide whether to start therapy or wait. Montaner offers them the "jellybean test." "We'd rather know in advance if people will have difficulty with a particular regimen. If they experiment with the real drugs, resistance becomes an immediate issue." Instead, Montaner prescribes a similar course of jellybeans for a couple of weeks. This allows for "practice time" as well as a means for people to decide if they can cope with the regimen. "Someone may always miss a lunch-time dose if they're at the gym or a late- night dose if they go to bed early. That's important information that we can work with to arrive at a regimen they can live with."

Side effects cause other problems. Unfortunately, says Chesney, "physicians sometimes wait until people develop side effects before treating them. From our experience, if you know that a significant proportion of patients will have nausea and vomiting, then physicians should prescribe medication for that condition at the time they are given the antiretrovirals, with clear instructions on how to use them."

At her medication adherence clinic in Florida, "the number one intervention ended up being side effect management," says Graham. Diarrhoea, and gastrointestinal problems in general, are amongst the most common problems, especially with protease inhibitors. The clinic not only recommends medication, such as immodium, but also makes a point of reminding patients that side effects usually disappear within a month. With such encouragement, the clinic’s volunteers increase the chances that clients see the light at the end of the tunnel and adhere to the drug regimen.

Chesney, who has 22 years’ experience in the area of medication adherence, believes the best recipe for success in long-term HIV treatment is for adherence to be addressed before therapy begins. "Before a person walks out of the doctor’s office, he or she should have a clear picture of what the regimen is tomorrow. They can’t rely on what’s marked on the pill bottle or prescription pad. The complexity of these anti-HIV regimens is matched only by that of regimens followed by people who have had liver transplants. It’s naive to think that you can explain it to them in a minute or two and that they can then adhere to them."

Millions of PLWHAs around the world still have little or no access to antiretroviral therapy. Even drugs to treat opportunistic infections are scarce. If the global AIDS community succeeds in changing this situation, adherence to medication regimens will become a growing focus of attention for the South.

The high cost of drugs and unsteady supply are two major hurdles to adherence in Africa, says Godfrey Sikipa, a Nairobi-based regional director of the NGO, Family Health International. Since public health agencies in Africa rarely have a large stock of drugs, especially antiretrovirals, the small number of PLWHAs using them "are getting them through private importation." Often, friends or relatives ship drugs home from industrialised countries. But after a few months, the supply runs out and there may not be another follow-up shipment.

For PLWHAs buying antiretrovirals privately, "the majority can’t afford to take the prescribed regimen for any length of time, largely because of the cost," says Sikipa.

Tougher living conditions also makes adherence a bigger burden for PLWHAs in Africa than for those in the North. "It’s just the general atmosphere. People are struggling with the day-to-day necessities of life. They may find taking drugs a bit more difficult. There may not even be fresh water for them to take their pills, as when the water supply is turned off. Or, late at night you have to take a tablet but the lights have gone off." Lack of home refrigeration is also a key problem.

He adds that the strength of African extended families, and the support they provide, could make a difference.

Praphan Phanuphak, a Thai physician and director of the Thai Red Cross Research Centre, echoes Sikipa’s comments about the high cost of drugs and consistent supply. In Thailand, the majority of PLWHAs do not have access to antiretrovirals. Government employees are, in theory, eligible for treatment with AZT, ddI, and ddC. Yet, in practice, says Phanuphak, hospitals do not stock such drugs, mainly because of the high cost but also because they would end up having to refuse so many requests.