On Monday 22 April, the World Health Organization (WHO) issued new guidelines which call unequivocally for combination antiretroviral (ARV) treatment for all adults and children living with AIDS. This call is supported by the inclusion of twelve ARVs in the twelfth revision of WHO's model Essential Medicines List, for use in combinations of three or four drugs. The previous edition, issued in 2000, listed ARVs only to prevent mother-to-child transmission.
"The new treatment guidelines and the designation of ARVs as essential are vital steps in the battle against the AIDS pandemic. They should encourage both industrialized and developing country governments to make HIV treatment more widely available," says Gro Harlem Brundtland, Director-General of WHO.
WHO now recommends:
- combination ARVs for all adults and adolescents diagnosed with AIDS (WHO stage IV of HIV disease) OR with HIV and a CD4 count of 200 or less OR, where CD4 counts are unavailable, with symptomatic HIV disease (WHO stages II or III) and a total lymphocyte count below 1200/mm3;
- combination ARVs for HIV-infected infants under 18 months with clinical AIDS OR a CD4 cell percentage below 20% (also: infants diagnosed with AIDS AND a CD4 percentage below 20%, born to an HIV-positive mother, even in the absence of definitive virological tests);
- combination ARVs for antibody positive infants over 18 months with clinical AIDS OR a CD4 cell percentage below 15%;
- selection of a limited number of three- and four-drug combinations, preferably as fixed-dose multi-drug formulations, for first and second-line treatment;
- a strategic approach to clinical monitoring for toxicity and response, recognising that viral load tests are currently unaffordable in most countries and therefore defining them as "optional";
- avoidance of two-drug antiretroviral combinations - reflecting a wider commitment to respect scientific evidence and avoid substandard treatment;
- setting up surveillance programmes at a population level to check on levels of resistance to ARVs, to guide the choice of first-line treatments.
The guidelines advocate that countries select first and second line combinations based on two nucleoside analogues with the addition of either nevirapine, efavirenz, abacavir, nelfinavir or a ritonavir-boosted protease inhibitor (saquinavir, indinavir or lopinavir).
Considerations to guide choice include: risks of liver damage (favouring efavirenz or abacavir) including liver damage risk from rifampicin for TB (favouring efavirenz at an increased dose of 800mg per day or abacavir); HIV-2 or HIV-1 type O virus (favouring protease inhibitors or abacavir); likelihood of pregnancy (to be avoided when taking efavirenz).
The availability of AZT/3TC (zidovudine/lamivudine) as a combined tablet is mentioned in favour of that combination as a nucleoside analogue backbone, as well as extensive clinical experience with it. The guidelines appear to have been written before the Thai Government Pharmaceutical Organisation launched its low-cost three-in-one formulation of nevirapine, d4T (stavudine) and 3TC (see earlier news story).
WHO estimates conservatively that 6 million people with HIV in "developing countries" should currently be receiving treatment, out of 36 million living with the virus. At present, only 230,000 have access - and half of those are in one country, Brazil. WHO "believes that at least three million people needing care should be able to get medicines by 2005" but acknowledges that a wider range of actions will be needed, if this is to be achieved.
It is stressed that ARVs are not a cure for AIDS and do not reduce the need for other measures to limit HIV transmission.
The report challenges WHO itself to keep the guidelines up to date and, among other things, to evaluate new fixed-dose combinations of drugs as a matter of priority. It calls for further action on drug prices, notably for abacavir. It observes that if ritonavir-boosted protease inhibitors are to be used, the drug must be shipped and stored under refrigeration at all times. This requires efficient "cold chain" distribution systems, which can be hard to set up and maintain, but are equally necessary for vaccines and other medicines.
These moves by WHO are timely, since the Global Fund to fight AIDS, TB and Malaria is meeting this week in New York to decide on its first allocations of funding for national programmes.
Scaling up antiretroviral therapy in resource-limited settings: Guidelines for a public health approach is available here in PDF format as a 26-page "Executive Summary".
WHO's press-release can be read here and the twelfth model Essential Medicines List is available here.