New Guidelines Recommend Early Suppression of HIV to Stave Off Progression

From Medscape Medical News
New Guidelines Recommend Early Suppression of HIV to Stave Off Progression

Daniel M. Keller, PhD

July 19, 2010 (Vienna, Austria) — New treatment guidelines for adults with HIV infection, presented here at AIDS 2010: XVIII International AIDS Conference, emphasize the importance of starting antiretroviral therapy (ART) early and continuing treatment without interruption, except in the setting of a clinical trial.
Dr. Melanie Thompson

At a news conference highlighting the July 21 issue of JAMA, a theme issue on HIV/AIDS, Melanie Thompson, MD, from the AIDS Research Consortium of Atlanta, Georgia, and chair of the International AIDS Society–USA Antiretroviral Therapy Guidelines Panel, outlined the new guidelines, updated from 2008.

The availability of the drugs and laboratory tools recommended mean that the guidelines apply to the international, developed-world setting. Currently, there are 23 antiretroviral drugs and 6 fixed-dose combinations commonly used in the United States, Dr. Thompson said.

"Increasing evidence that insidious damage occurs during 'asymptomatic' HIV infection underscores the potential benefit of ART, even when the risk of traditional AIDS-defining diseases is relatively low," the guidelines authors note.

On the basis of our understanding of the progressive destruction of the immune system by HIV infection and the finding that immune compromise can be prevented with newer drugs that suppress viral replication, the guidelines panel formulated broader recommendations than in the past for the initiation of treatment. They considered information that was presented or published between August 2008 and May 2010, including that on the timing of therapy, choice of regimens, monitoring of therapy, and the efficacy and safety of newer drugs.

Initiate ART as Early as Possible

ART can be started at any CD4+ cell count. It is recommended for asymptomatic individuals with counts at 500 cells/μL or below, and should be considered for asymptomatic individuals with counts above 500 cells/μL. The 2008 guidelines recommended a threshold CD4+ count of 350 cells/μL.

The new guidelines also recommends initiation of ART for patients with symptomatic disease regardless of the CD4+ cell count. Clinicians should confirm patient readiness for treatment before initiating ART.

Non-AIDS events can be a major contributor to morbidity and mortality in the presence of ongoing viral replication, suggesting that viral suppression with ART might improve the length and quality of patients' lives.

"Uncontrolled HIV replication is associated with immune activation and inflammation, which now we know is also associated with non-AIDS illnesses. These illnesses include cardiovascular disease, hepatic disease, renal disease, and certain kinds of malignancies," Dr. Thompson said.

Therefore, the guidelines recommend treatment for pregnant patients, patients older than 60 years, those infected with hepatitis B or C or with HIV-associated kidney disease, those with active cardiovascular disease or at high risk for it, and those with opportunistic diseases or symptomatic primary HIV infection. In addition, ART should be initiated when there is a high risk for HIV transmission, such as between serodiscordant sex partners.

The guideline authors note that many HIV-infected patients first present with advanced disease, and they recommend universal HIV testing and early provision of treatment to take best advantage of advances in ART, along with efforts at prevention. "Antiretroviral therapy and high CD4 counts are associated with decreased disease," Dr. Thompson said.

Treatment Should Be Individualized

Individual patient conditions should determine therapeutic choices. But in general, the guidelines suggest fixed-dose drug combinations for convenience. The initial recommended nucleoside or nucleotide-analogue reverse-transcriptase inhibitor combination consists of tenofovir and emtricitabine. A third component should be the nonnucleoside reverse-transcriptase inhibitor efavirenz, a ritonavir-boosted protease inhibitor, or the integrase inhibitor raltegravir.

The goal of therapy in both treatment-naive and treatment-experienced patients should be viral RNA suppression below detectable limits using commercially available tests. Frequent monitoring of plasma HIV-1 RNA levels is indicated when therapy begins or is changed because of virologic failure, and should continue until the viral load becomes undetectable and for some time thereafter. Monitoring can be done at 6-month intervals once the viral load is suppressed for a year and the CD4+ cell counts stabilize at 350 cells/μL or above in treatment-compliant patients.

When to Change Therapy and to What

If virologic failure occurs, it should be detected and treated as soon as possible with at least 2, and ideally 3, active drugs to head off the accumulation of resistance mutations. Switching to agents in new classes of drugs should be considered, keeping in mind previous and new HIV resistance profiles, previous drug exposure, drug interactions, and patient drug tolerance. If feasible, a regimen with the fewest drugs and lowest pill burden is desirable.

Conference moderator Catherine DeAngelis, MD, MPH, editor-in-chief of JAMA in Chicago, Illinois, told Medscape Medical News that the guidelines are a model for current best treatment practices in HIV. Dr. DeAngelis was not involved in the development of the guidelines.

"These guidelines are meant for resource-rich areas, not for the resource poor," she said. "Will it be an issue [to follow them] for a clinician functioning in a resource-rich environment? Probably not. Will it be a problem anywhere else? Probably yes, in fact, definitely yes."

This work was funded by the InternationalAIDS Society–USA. Panel members serve in volunteer capacities (i.e., are not compensated). No private sector or government funding was used to support the effort.

JAMA. 2010;304:321-333.

AIDS 2010: XVIII International AIDS Conference. Presented July 19, 2010.