HIV-infected adults should start antiretroviral therapy as soon as possible, regardless of CD4 count, according to a recommendation from the International Antiviral Society–USA presented at the AIDS 2012 meeting in Washington.
The recommendation represents a major change from the last set of guidelines, issued in 2010. Those earlier guidelines recommended starting antiretrovirals when CD4 counts fell beneath 500 cells/mL, and "considering" treatment in patients with higher counts.
In writing the new guidelines, which also appear in the July 25 issue of JAMA (2012;308:387-402), Dr. Melanie A. Thompson and a panel convened by the International Antiviral Society–USA (IAS-USA) conducted a literature review of all new published data and data presented at scientific conferences between July 2010 and May 2012.
All recommendations were applicable only to HIV-infected adults in resource-rich settings, and dealt with antiretroviral therapies that were either already approved or in late-stage development.
The field of HIV prophylaxis has also seen significant progress since the 2010 update, and the new guidelines reflect those advances.
"Recently, antiretroviral therapy used as oral pre-exposure prophylaxis (PrEP) has been shown to be effective in three large trials using daily tenofovir/emtricitabine or tenofovir in gay and bisexual men and transgender women (iPrEx), heterosexual HIV-serodiscordant couples (Partners PrEP), and heterosexual men and women (TDF2)," wrote Dr. Thompson of the AIDS Research Consortium of Atlanta.
Indeed, following the iPrEx results, the Centers for Disease Control and Prevention issued interim guidance (MMWR 2011;60:65-8) for HIV-negative homosexual men who elect to take tenofovir/emtricitabine for prophylaxis.
And July 16, the Food and Drug Administration approved the use of an oral once-daily combination antiviral medication, Truvada (tenofovir and emtricitabine), for prevention in uninfected people at high risk for acquiring HIV.
While efficacy in PrEP has been positively correlated with medication adherence (as measured by serum drug levels), "pharmacokinetic and pharmacodynamic variability and the presence of vaginal or rectal inflammation also may affect outcome."
As in the 2010 recommendations (JAMA 2010;304:321-33), the initial choice of prophylactic therapy "continues to be based on a combination of two nucleos(t)ide reverse transcriptase inhibitors and a potent third agent," the authors noted, with the once-daily fixed-dose combination of tenofovir plus emtricitabine remaining the first choice.
Although tenofovir is well tolerated, its use has been linked with kidney injury, "which appears to increase in incidence with long-term administration and concurrent [protease inhibitor, ritonavir-boosted] use," the authors cautioned.
Tenofovir is also associated with decreased bone mineral density of the spine and hip. Thus, given the increased risk of fragility fractures in postmenopausal women, ‘it may be prudent to consider avoiding tenofovir as part of initial therapy in this group," the authors wrote.
Another choice, the once-daily abacavir/lamivudine fixed-dose combination, is now a recommended initial therapy. In 2010, it was considered only a possible alternative.
"Screening for [the HLA-B*5701 gene] markedly reduces the risk of potentially life-threatening hypersensitivity reaction to abacavir," the guideline authors wrote.
In addition, some studies have found abacavir to be associated with a higher risk of acute myocardial infarction.
Dr. Thompson and her colleagues disclosed multiple financial and professional relationships with several pharmaceutical companies, including the makers of antiretroviral therapies. They stated that members of the panel who developed the recommendations did not participate in industry promotional activities such as speakers bureaus or lectures during their membership, and that members with previous conflicts recused themselves from evaluating evidence when a conflict was present.
The development of the recommendations was sponsored by the IAS-USA, according to the authors.