Start HIV treatment when CD4 cell count is 350, say leading HIV doctors in BMJ

HIV treatment guidelines should be revised to recommend the initiation of antiretroviral therapy when an individual’s CD4 cell count falls to 350 cells/mm³, according to leading HIV physicians writing in the January 13^th edition of the British Medical Journal.

There is an increasing trend for doctors to consider the earlier initiation of HIV therapy. A study from United States reported recently on aidsmap found that patients who started HIV therapy with a CD4 cell count above 350 cells/mm³ were significantly more likely than those who delayed until their CD4 cell count was in the currently recommended 250 – 200 cells/mm³ range to experience an increase in their CD4 cell count to normal levels after long-term antiretroviral therapy.

Furthermore, the US government is backing a large international trial to investigate the benefits of commencing HIV therapy at higher CD4 cell counts.

Why the current guidelines and why are they being questioned?

Side-effects, questions about the viability of long-term adherence, and fears about the exhaustion of HIV treatment options led to the development of treatment guidelines that favoured the postponement of HIV therapy.

Current UK HIV treatment guidelines state that, although HIV therapy should be considered when an patient’s CD4 cell count has fallen to 350 cells/mm³, it should only be strongly recommended to individuals whose CD4 cell count has fallen to between 250 – 200 cells/mm³, or who are ill because of HIV.

However, an increasing body of recent research is favouring the earlier initiation of HIV treatment. The SMART treatment interruption study found, for example, that patients with CD4 cell counts between 200 – 250 cells/mm³ had a significantly greater risk of experiencing HIV disease progression. Furthermore, the DAD study of HIV treatment side-effects found that individuals with CD4 cell counts in the region of 200 – 250 cells/mm³ had an increased risk of death from certain non-AIDS-defining illness, such as heart disease, liver disease and some non-HIV-related cancers.

An improved understanding of side-effects also supports the earlier initiation of treatment, say the authors. The disfiguring body fat changes associated with early potent anti-HIV regimens have been found to be, primarily, caused by thymidine analogues (d4T, and to a lesser extent, AZT), the use of which is now avoided where-ever possible. It is also increasingly being understood how to avoid the cardiovascular complications that antiretroviral treatment can cause.

HIV therapy, the authors further argue, now has sufficient potency and convenience, to support its earlier initiation.

“We therefore suggest that guidelines should now recommend starting treatment at around 350 cells/mm³, so long as the patient is ready”, write the authors.

For patients with higher CD4 cell counts the authors say there is “need for an international randomised trial in patients with a CD4 count above 500 cells/mm³ comparing immediate treatment with deferral of treatment until CD4 cell count reaches 350 cells/mm³.” Such a study is being planned by the National Institutes of Health in the US, and aims to enroll 9,000 HIV-positive adults and children in both resource-rich and resource-poor countries around the world.

HIV therapy is now sufficiently potent, durable, convenient and tolerable to make such a study possible, the authors believe.

However, in resource limited settings the authors write, “the priority for initiation should continue to be those with the greatest level of immunodeficiency, where the clinical benefits are greatest.”