Antiretroviral therapy should be started by all HIV-positive people with CD4 counts below 350, according to revised HIV treatment guidelines released earlier this week by the United States Department of Health and Human Services (DHHS). The agency has also made some changes to its laboratory testing recommendations—viral load is no longer a factor in deciding when to start therapy, whereas new assays to prevent allergic reactions to abacavir (found in Ziagen, Epzicom and Trizivir) and poor responses to treatment with maraviroc (Selzentry) are now suggested.

DHHS recommendations regarding when to begin antiretroviral therapy have fluctuated over the years. Until recently, DHHS recommended treatment for all HIV-positive people with CD4 counts below 200, whereas antiretroviral therapy was only suggested for those with CD4s between 200 and 350.  A detailed look at the new recommendations regarding when to begin antiretroviral treatment, along with existing guidelines detailing which medications to use, can be found in the AIDSmeds.com lesson, “When Should I Start Treatment, and What Should I Take First?”

One reason why the when-to-start bar has been raised to 350 CD4s is the observation that HIV-positive people not on treatment, despite having relatively healthy immune systems, are at an increased risk for a number of non-AIDS-related complications. These include cardiovascular disease, liver-related problems, kidney damage, and a variety of cancers. While these health problems were initially thought to be long-term side effects of HIV treatment, research conducted over the past few years has concluded that such complications are more likely to be seen in patients not on treatment, compared with those with “maximally suppressed” viral loads while on antiretroviral therapy.

Based on these new data, DHHS now recommends antiretroviral therapy for all HIV-positive people with CD4 counts below 350. Whether starting HIV drug treatment even earlier—when the CD4 cell count falls below 500, for example—will further reduce the risk of both AIDS- and non-AIDS-related health problems has yet to be determined.

DHHS now recommends antiretroviral therapy for certain HIV-positive people, regardless of their CD4 cell count. These include HIV-positive women who become pregnant; individuals diagnosed with HIV-associated nephropathy, a form of kidney disease; and people infected with HIV who do not yet require antiretroviral therapy but do require treatment for chronic hepatitis B virus (HBV) infection, given that some of the most effective drugs used to manage HBV are also highly active against HIV.

There are some notable changes to laboratory testing guidelines as well.

Using viral load to determine when to begin treatment is no longer a DHHS recommendation. Past versions of the guidelines recommended HIV treatment for patients with health CD4 counts who also had high viral loads—above 100,000 copies, for example—based on the theory that they may experience a rapid decline in CD4s. Recent studies, however, suggest that there may not be a solid connection between patients’ viral loads and their rate of CD4 cell loss.

Viral load testing is still an essential component of HIV treatment, to ensure that antiretroviral therapy is working effectively once started.  As specified by the DHHS guidelines, and reviewed in "When Should I Change My Treatment, and Which Drugs Should I Switch To?", if a patient’s viral load becomes detectable or continues increasing while you’re on treatment, it may be necessary to modify or switch the durg regimen being used.

The guidelines now recommend genotypic testing, prior to beginning treatment, to find out if they may have been infected with a drug-resistant strain of HIV. For the most accurate results, the guidelines suggest, patients should be tested for HIV drug resistance soon after they are diagnosed as HIV positive, even if they won’t be starting treatment for several months or years.

Finally, the recommendations spell out the use of two new assays that can be used to determine if specific HIV medications should be used.

An inexpensive laboratory test is available to look for an inherited gene, called HLA-B*5701, that has been linked to a serious allergic (hypersensitivity) reaction in approximately 5 percent of HIV-positive people taking abacavir. While not all people with this gene experience an allergic reaction while taking abacavir, most do. To prevent this allergic reaction, the DHHS now recommends the use of this test before using either Ziagen, Epzicom or Trizivir.

For patients hoping to use Selzentry, Pfizer’s entry inhibitor, DHHS recommends the use of a tropism assay. Selzentry is only effective against HIV that uses, or targets, the CCR5 receptor on CD4 cells. It will not be effective against virus that uses another CD4 cell coreceptor, called CXCR4—and the drug will have a limited affect against HIV that uses both receptors. Because CXCR4-“tropic” and “dual-tropic” HIV is more common in people who have been infected with HIV for several years—the people who are most likely going to be using Selzentry—tropism testing, to determine which receptor a patient’s HIV is using, is necessary before the medication is prescribed.