As developing countries scale up their antiretroviral (ARV) treatment programmes, more and more people living with HIV are expected to develop resistance to their drug regimens and will need second-line medicines.
Many second-line drugs are either unavailable or prohibitively expensive in developing countries, and doctors often lack experience or knowledge of what combination of second-line ARVs to prescribe.
In a move aimed at helping governments formulate second-line treatment regimens, fast-track drug approvals and drive down prices, the World Health Organisation (WHO) has narrowed down the number of second-line ARVs it recommends.
The new guidelines, drawn from an expert meeting held in May 2007, have been released partly in response to requests from countries for more guidance on which second-line ARVs to include in their national treatment programmes.
"These new guidelines are good news," said Dr Tido von Schoen-Anderer, director of Campaign for Access to Essential Medicines run by Medecins Sans Frontiers. "Before there were so many different drug options and now there is much clearer guidance, and that has major advantages at the programme level and also the choice of drugs means it's going to be cheaper."
Of the two million HIV-positive people in low- and middle-income countries receiving treatment by December 2006, the WHO estimates that only about two percent were on second-line ARVs, but that number is rising because about three percent of ARV patients switch from first- to second-line treatment every year.
Second-line drugs can cost between two and nine times as much as fist-line drugs and few generic versions are available. The WHO has estimated that without price reductions, by 2012 as much as 90 percent of the funds for providing ARV treatment will be spent on second-line drugs.
According to the Clinton Foundation HIV/AIDS Initiative (CHAI), the prices of a number of generic second-line drugs in the pipeline or awaiting regulatory approval will depend on limiting the number of different drugs used for second-line treatment.
"Second-line access is still a challenge," said Andy Gray a consultant pharmacist for the Centre for the AIDS Programme of Research in South Africa (CAPRISA). He pointed out that South Africa, a middle-income country with much greater regulatory capacity than other countries in the region, still lacked a generic version of a second-line protease inhibitor, a class of ARV drugs that is a component of most adult regimens.
Gray welcomed the WHO's additional guidelines on second-line treatment, but worried that the choices might be too restrictive. "Limiting the number of second-line options may look attractive to a country programme, but in a middle-income country such as South Africa there's going to be a lot of pressure from clinicians that they need more options," he told IRIN/PlusNews.
"If countries like South Africa have enough well-trained clinicians, then of course they can offer more options," Von Schoen-Anderer responded, "but in terms of making second-line treatment more available, the only way forward was to make it simpler and easier to implement."
Second-line ARVs still too expensive
Gray and Von Schoen-Anderer agreed that many obstacles remained to making second-line drugs more cheaply available. "I don't think governments are doing enough to prepare for the numbers of people who are going to need second-line treatment," Gray said.
Few governments, for example, have so far taken advantage of safeguards provided in the World Trade Organisation's Trade Related Aspects of Intellectual Property Rights (TRIPS), which allow intellectual property rights to be balanced against public health priorities.
Under TRIPS, countries can override drug patents during a public health emergency by issuing a 'compulsory license' to manufacture or import cheaper generic versions, a move Von Schoen-Anderer predicted might be necessary, especially if pharmaceutical companies were successful in challenging an Indian law that allows the country to block patents for medicines that are modified versions of existing drugs.
"There's enormous dependence on generics from India so we look with a lot of concern now to what is going to happen there with the patents," said Von Schoen-Anderer.
The new WHO guidelines draw attention to an additional barrier to effective second-line treatment: the lack of capacity in many developing countries to carry out tests that diagnose first-line ARV treatment failure.
"In order to maximise the efficacy and durability of first- and second-line antiretroviral regimens," read the guidelines, "WHO continues to support the universal availability and use of appropriate and affordable CD4 [an indication of immune strength] and HIV viral-load testing."
In the absence of equipment to measure viral load [the amount of HI virus in the system], health workers have to rely on physical signs that the disease is progressing in spite of treatment. As a result, drug resistance is often quite advanced before its detected.