New US treatment guidelines favour the initiation of HIV treatment by patients with a CD4 cell count between 350 and 500 cells/mm3, earlier than current European and British recommendations.
The guidelines panel was evenly split on whether to start HIV treatment when a patient’s CD4 cell count is above 500 cells/mm3.
Issued on World AIDS Day, December 1st, the US Department of Health and Human Services guidelines for the use of antiretroviral drugs include a number of important revisions, most notably about when HIV treatment should be started.
Earlier treatment favoured
Retained in the guidelines is a recommendation that HIV treatment should be started by all patients with an AIDS-defining illness, or a CD4 cell count below 350 cells/mm3.
Starting treatment at a CD4 cell count of this level has been shown to reduce the risk of HIV-related illnesses and some other serious diseases such as those of the heart, kidney and liver, as well as some cancers.
There has been debate about the value of starting treatment at higher CD4 cell counts. Some research has shown that this can have benefits, but not all studies have confirmed that there is an additional benefit to starting treatment at a CD4 count above 500.
The guidelines panel was persuaded that therapy should be recommended for patients with a CD4 cell count between 350 and 500 cells/mm3 but disagreed on the strength of the recommendation. 55% of the panel said this should be a strong recommendation, while the remaining 45% supported a `moderate` recommendation for treatment in this CD4 range.
It's the first time that the US guidelines panel has issued a split recommendation of this sort, and the split verdict indicates the divergent views about the strength of the evidence for earlier treatment.
The panel was evenly split on whether treatment should be started by individuals with a CD4 cell count above 500 cells/mm3 or whether it should be considered optional.
However, certain groups of patients are recommended to start antiretroviral therapy regardless of their CD4 cell count. These include pregnant women, those with HIV-associated nephropathy (kidney disease), and patients co-infected with hepatitis B virus when therapy for hepatitis B is necessary.
Also included in the guidelines are recommendations for first-line antiretroviral therapy.
Raltegravir “preferred” for first-line therapy, but Kaletra dropped
A combination of raltegravir (Isentress) plus Truvada (FTC and tenofovir) joins Atripla (efavirenz, FTC and tenofovir), ritonavir-boosted atazanavir (Reyataz) with Truvada, and ritonavir-boosted darunavir (Prezista) plus Truvada as preferred first-line regimens.
Notably, Kaletra (lopinavir/ritonavir) is no longer “preferred” for first-line therapy and is only listed as an “alternative” drug. Some study results have shown an independent association between treatment with Kaletra and an increased risk of heart attack.
However, Kaletra has been shown to effectively prevent mother-to-child transmission of HIV and it remains a preferred option for use during pregnancy when it should be used with Combivir (3TC and AZT).
Best use of resistance tests
More specific recommendations about the use of genotypic and phenotypic resistance testing are also provided.
Genotypic testing is recommended as the preferred test for patients with a suboptimal response to their first or second antiretroviral combination.
Additional phenotypic testing is supported for patients with known or suspected complex resistance patterns, especially to protease inhibitors.