Main article: Revised WHO Treatment Guidelines - deadline for comments 14 November

Revised WHO guidelines on antiretroviral treatment in resource-limited settings now available for comment - deadline for comments Nov 14th.

The World Health Organisation has published new draft treatment guidelines for use in resource-limited settings, with an emphasis on the use of fixed dose drug combinations wherever possible. The guidelines are designed to encourage the scale-up of antiretroviral therapy in the absence of comprehensive laboratory monitoring. WHO is inviting comments from interested parties to be submitted by November 14.

The guidelines recommend that drug combinations should use either efavirenz or nevirapine as cornerstones, with either AZT/3TC or d4T/3TC as the nucleoside analogue backbone. The guidelines are intended to help countries choose which drugs to use as the lead regimen in national programmes, but in practical terms it is likely that countries will need to maintain a formulary of the five drugs in order to allow switching between nevirapine and efavirenz, and between AZT and d4T, and to accommodate patients with tuberculosis and pregnant women.

In practical terms, it is likely that the WHO guidelines will encourage very wide use of generic antiretrovirals manufactured in India and South Africa. Two weeks ago the Clinton Foundation announced that it had reached agreement with Indian and South African manufacturers to sell a fixed dose combination of d4T, 3TC and nevirapine for $132 a year to Mozambique, Tanzania, Rwanda and South Africa and nine Caribbean states.

WHO also recommends a three tier approach to monitoring. At community heath centre level, rapid HIV antibody testing, haemoglobin testing and pregnancy testing are the only tests recommended. Haemoglobin testing is only necessary if AZT is included in the regimen, and it can be done using a haemoglobin colour scale published by WHO. Haemoglobin testing for anaemia is necessary because the condition can worsen when AZT treatment begins. Pregnancy testing is only needed if efavirenz is included in the regimen.

At district hospital level, rapid HIV antibody testing and confirmatory testing using a second method are recommended, together with CD4 counting. WHO says it is committed to working with member states to make CD4 counting as widely available as possible. Full blood counts and liver enzyme measurements are also encouraged, as is sputum smear testing for tuberculosis. A full blood count and differentials is preferred to haemoglobin in this setting for measuring anaemia and neutropenia, and for calculating total lymphocyte counts where CD4 cell counting is not possible. Total lymphocyte count is judged to be a useful measure of immune system damage in symptomatic patients, but cannot be used for monitoring responses to treatment.

Treatment failure can be judged by the appearance of new symptoms (not to be confused with immune reconstitution syndrome), or the recurrence of a previous opportunistic infection. If CD4 counting is available, the guidelines recommend that treatment should be switched if the CD4 cell count falls below the pre-treatment baseline, or falls at least 50% below its peak level. In either case, clinicians should rule out the effects of tuberculosis. Reinfection with TB could occur without treatment failure.

Second line treatment should be based on ddI plus tenofovir or abacavir and either lopinavir/saquinavir or saquinavir/ritonavir. However, both require a secure cold chain for storage of the ritonavir element. Atazanavir, a new protease inhibitor which can be taken once daily and which does not require cold storage, is judged to be too new for use in resource-limited settings.

To download the draft guidelines, click on the link below:

WHO Draft guidelines for a public health approach to scaling up antiretroviral therapy in resource limited settings

News headlines

A selection of news stories which have appeared since October 23 2003.

Low viral load rebound does not affect medium term outcome says French

study

A low rebound in viral load in patients taking a protease inhibitor does

not have significant clinical or immunological consequences in the

mid-term at least, according to a French study published in the December

1st edition of the Clinical Infectious Diseases, which is available now

online.

New CD4 counting method may lead to cheaper tests in developing world

**A simple enzyme-based method that uses dried blood spots could

significantly reduce the cost of CD4 cell counting for developing

countries now implementing antiretroviral treatment programmes,

according to findings published today in The Lancet.

Scaling up treatments and monitoring in Asia

**Access to HIV treatments and diagnostics is improving in some parts of Asia, the Annual Conference of the Australasian Society for HIV Medicine heard last week in Cairns.

Triglycerides can normalise after switch from d4T to tenofovir

**Triglyceride levels returned to normal levels in one third of patients

with elevated triglyceride levels within 12 weeks of switching from d4T to tenofovir, according to findings from the Recover study, a large

Spanish trial following adverse events among patients receiving

nucleoside analogue treatment.

http://www.aidsmap.com/news/newsdisplay2.asp?newsId=2383

**Response to the new protease inhibitor atazanavir is blunted in

individuals with four or more protease inhibitor-associated resistance

mutations, even when drug levels are boosted with ritonavir, according to an analysis of the 045 study presented yesterday at the Ninth European AIDS Conference in Warsaw. However, lopinavir-treated patients in the same study showed a similar fall off in response, suggesting that most of the current crop of protease inhibitors begin to lose their clout in roughly the same territory.

Combination of indinavir/AZT/3TC still effective for majority of

patients at 6 years, says US study

**A HAART regimen comprising indinavir, 3TC and AZT is still being taken by a majority of patients enrolled in a study into the combination`s safety and efficacy six years later, according to US research published in the November 7th edition of AIDS. Investigators also established that the combination was continuing to suppress HIV viral load to below 500 copies/mL in a clear majority of patients, and to below 50 copies/mL in a little under 50% of individuals.

Herpes and genital warts most common symptoms of immune reconstitution inflammatory syndrome (IRIS)

Immune reconstitution inflammatory syndrome (IRIS) is the name given to a diverse group of syptoms that can occur soon after the initiation of HAART. This can include the first appearance or the recurrence of previously-treated opportunistic infections, like TB, CMV, PCP or MAI, or the flare-up of viral infections that include hepatitis and herpes.

Induction/maintenance approach revived but will patients stick with it?

In the early years of the protease inhibitor era, there was much

interest in an approach called induction/maintenance starting with

three or four drugs and stepping down to one or two after viral load had been controlled. Results were disappointing and the approach fell into disuse. At this weeks Ninth European AIDS Conference, results of a trial called TIME showed that drug companies at least have not given up on the idea of induction/maintenance. Whether it will suit patients is another question.

Clinton Foundation secures triple HIV therapy for $132 a year

A new benchmark promising further downward pressure on drug prices emerged yesterday with the announcement that the Clinton Foundation has secured an agreement from Indian and South African drug manufacturers to supply a triple combination of AZT/3TC and nevirapine for $132 a year.

Don't assume African patients in UK are treatment-naive, report UK

docs

**Physicians in the UK who prescribe HAART to Africans should not assume that their patients are naïve to antiretrovirals, caution doctors from Portsmouth writing in the November 7th edition of AIDS (now available online).