Kivexa downgraded to alternative status in revised US HIV treatment guidelines

Kivexa (3TC and abacavir) has been downgraded from a “preferred” to an “alternative” NRTI backbone in updated US HIV treatment guidelines. The move is because of concerns that treatment with abacavir may increase the risk of heart attack, and because of evidence showing poorer virological outcomes in patients with a high viral load.

Also included in the new US guidelines is a recommendation that darunavir (Prezista) should be a “preferred” protease inhibitor for patients starting HIV treatment and that once-daily dosing of Kaletra (lopinavir/ritonavir) should be the preferred schedule for all patients except those with resistance to protease inhibitors and pregnant women.

There are few other substantial changes to the guidelines which still include the recommendation that HIV treatment should be started when a patient’s CD4 cell count is in the region of 350 cells/mm³. Some studies have recently suggested that initiating antiretroviral therapy at a CD4 cell count of 500 cells/mm³ is associated with better outcomes. The guidelines include a discussion of the pros and cons of treatment at CD4 cell counts above 350 cells/mm³, with the pros including a decreased risk of some serious HIV- and non-HIV-related illnesses and a “decreased risk of HIV transmission to others, which may have positive public health implications.”

Regarding the choice of initial antiretroviral regime, the guidelines state that it should include two nucleoside reverse transcriptase inhibitors (NRTIs) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor. Efavirenz (Sustiva, or Stocrin in some European countries, Australia, Latin America, South Africa, Brazil and some other regions), is the preferred NNRTI.

The recommended boosted protease inhibitors are atazanavir (Reyataz), darunavir (Prezista) fosamprenavir (Lexiva) in the US, Telzir in the UK and Europe) and the co-formulated Kaletra (lopinavir/ritonavir).

Darunavir is a new addition to this list, and the guidelines include the recommendation that it should be taken once daily at a dose of 800mg with 100mg of ritonavir. Once-daily dosing of Kaletra is also recommended, except for two groups of patients: those with resistance to protease inhibitors, and pregnant women.

Regarding the choice of NRTIs, Truvada (FTC and tenofovir) is preferred to Kivexa (3TC and abacavir). The downgrading of Kivexa follows the results of two studies (D:A:D and SMART) suggesting that abacavir may increase the risk of heart attack (although the manufacturer’s own study failed to find such a link), with another study showing that patients who start treatment with a viral load above 100,000 copies/ml are less likely to achieve and maintain an undetectable viral load if they take abacavir compared to tenofovir.

UK guidelines issued earlier this year have Truvada and Kivexa as equal options, noting that the use of Kivexa should be avoided by patients with a risk of heart disease and those with a high viral load. In earlier drafts of the guidelines, however, Kivexa was downgraded to alternative status because of these concerns.

The revised US guidelines also include a recommendation that resistance tests should be considered for patients experiencing virological failure whose viral is between 500 and 1000 copies/ml, although they note that the resistance testing at this level is not always reliable.