On World AIDS Day in 2009, the US DHHS released an updated version of the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, in a move that harkens back to the "Hit Hard, Hit Early" era. The two major updates include changes to when to start and what to use as first line therapy. These changes reflect the challenging discussions that have taken place over the past couple of years in reaction to newer data on when to start.
The previous edition of the Federal HIV Treatment Guidelines recommended as an "option" to start therapy between 350 and 500 CD4s. The current edition has changed and now recommends that everyone with CD4s below 500 be on therapy. Some Guidelines Panel members even recommend starting at CD4s above 500. While more convincing study data point to the benefits of starting before CD4s drop below 500, the data for starting above 500 CD4s are not as strong. Some experts on the Guidelines Panel disagree with this last point, however.
This edition marks a significant development in updating the Guidelines. With any recommended change, the Panel seeks agreement by at least 2/3 of its members. This did not happen this time around. Despite agreeing on starting between 350 and 500, the Panel was divided on the strength of the data that supports this change. For the first time, the Guidelines state that the "Panel was divided on the strength of this recommendation: 55% of Panel members for strong recommendation and 45% for moderate recommendation". Then, a second statement was made regarding starting therapy above 500 CD4s: half the Panel favored starting therapy while the other half viewed it as optional.
The benefit of starting therapy at higher CD4s comes from several retrospective studies (such as the large NA-ACCORD) that have generated useful information but are not the gold standard method used in randomized, prospective studies. A large international when-to-start study (START) is now underway, but its results may not be available until 2012 or later. Given the mix of data from these retrospective studies and the absence of data from randomized studies, the Panel members came to their new conclusions in the Guidelines.
The possible benefits of starting treatment earlier include lower rates of many non-AIDS conditions due to reducing inflammation and immune activation, better overall health, longer-term survival, use of current therapy that's more effective and easier to take and tolerate, and lower rates of passing HIV onto others. The possible risks of starting earlier include higher risk of short- or long-term drug complications, drug resistance, and running out of options earlier.
As with the previous edition, these Guidelines continue to recommend that anyone with an AIDS-defining condition or with CD4s below 350 should be on therapy, as should anyone who is pregnant, has HIV-related kidney disease or has hepatitis B where treatment is warranted, regardless of their CD4 count.
Two noteworthy changes took place in the section on what to start. The first added the new integrase inhibitor, Isentress (raltegravir), as a preferred drug. The second down-graded Kaletra (lopinavir/ritonavir) from preferred to an alternative option, except in pregnant women where it's still a preferred option.
The new list of preferred HIV drugs for first line therapy now includes Isentress, Prezista (darunavir) boosted with ritonavir, boosted Reyataz (atazanavir), and Sustiva (efavirenz). For a full potent regimen, each of these should be combined with Truvada (Emtriva + Viread). Atripla (Emtriva + Viread + Sustiva) is the only one-pill, once-a-day regimen out of the 4.
In addition to consulting these new Guidelines, Project Inform recommends that anyone who considers starting treatment weigh the potential benefits and risks of lifelong HIV therapy. Deciding to start therapy creates a significant change in a person's life and it should be individualized and based on up-to-date information. The decision should also take into account a person's ability to adhere to the regimen and other lifestyle factors that could impact therapy.
The resistance testing section was updated to reflect using genotypic tests as the preferred method to test for resistant HIV in recently diagnosed individuals (most effective at viral loads above 1,000) as well as for people on their first and second regimens. This is mostly due to a faster turnaround for results, lower cost and higher accuracy on detecting resistant virus. Phenotypic tests are recommended as an added method for cases where there's a known or suspected complex drug resistance mutation pattern, particularly to protease inhibitors.
Despite the Guidelines recommending an earlier start to HIV therapy, some individuals may choose not to start. However, many conditions point to more urgent situations where starting is more warranted. These include pregnancy, CD4s below 200, rapidly declining CD4s (>100 cells/year), an AIDS-defining condition, acute opportunistic infections, higher viral loads above 100,000, hepatitis B treatment, and HIV-related kidney disease.
This new section was added with respect to treating people with HIV-2. HIV-2 is mostly found in West Africa, so the testing and treatment of HIV-2 should be considered in people of West African origin and those who have had sexual contact or shared needles with persons of West African origin. HIV-2 disease progression is somewhat different from HIV-1 and co-infection with both viruses is possible, so additional considerations are necessary when treating HIV-2 disease.
A new large section on hepatitis C evaluation and treatment has been added. About 1 in 4 people with HIV also live with chronic hepatitis C, so additional guidance around evaluating liver health and the need for treatment has been included.
New side effects information based on the most recent published data in the newest approved agents is now included in the guidelines.
A new section on preventing secondary infection with HIV has been added. It covers the somewhat neglected opportunity of providing prevention messages during doctor visits; encouraging strategies to change risky behaviors such as safer needle use and safer sex; and the role of HIV therapy in preventing HIV transmission.