October 1, 2007

New Hope for Viral Suppression in All HIV Patients

New agents for treatment-naïve individuals offer the promise of well-tolerated, convenient, and highly active therapy for all patients with HIV, according to Joseph Eron, Jr., MD, professor of medicine at the University of North Carolina. Speaking at the “State of the Art in HIV Care and Treatment” symposium at the 45th Annual Meeting of IDSA, in San Diego, he said for all patients, there should be “zero tolerance” for virologic failure. 

HIV virions 250Dr. Eron emphasized the importance of using at least two fully active agents. Clinicians should draw upon newly approved agents, including the integrase inhibitor raltegravir and the entry inhibitor maraviroc, as well as enfuvirtide (T-20) and medications in expanded access, with choices dependent on treatment history, resistance testing, and tolerability, he said.

New Agents, New Strategies

In another presentation, Joel Gallant, MD, MPH, of the Johns Hopkins School of Medicine, said maraviroc is highly effective in treatment-experienced patients with R5-tropic virus—virus that enters cells through the CCR5 receptor. However, approximately half of treatment-experienced patients are not candidates for maraviroc because of the presence of X4-tropic virus, which enters the cell using the CXCR4 coreceptor. The tropism assay (Trofile) required to identify whether the patient is infected with R5-, X4-, or dual/mixed (D/M)-tropic virus is expensive and can sometimes miss the presence of X4- or D/M-tropic virus present at low levels. 

Because of the dosing inconvenience of enfuvirtide, most patients with suppressed viral loads on this agent will want to substitute a new agent, Dr. Gallant said. Raltegravir is probably the best drug to replace enfuvirtide, although this strategy has not been formally studied.  Substitution with maraviroc is rarely possible, since tropism testing requires a viral load of at least 1000 copies/mL.  

Those with R5 virus and/or virus susceptible to darunavir, tipranavir, or etravirine may not need enfuvirtide. However, enfuvirtide will still be necessary in some highly treatment-experienced patients with cross-resistance to the second generation non-nucleoside reverse transcriptase inhibitors and protease inhibitors and with and D/M- or X4-tropic virus. 

When to Start?

There is growing evidence of benefit with earlier initiation of ART, according to Dr. Gallant. Although the magnitude of additional benefit achieved with earlier therapy is smaller than for later therapy, he said the risk-to-benefit ratio favors earlier initiation now that therapy is more convenient, better tolerated, and less toxic. 

Furthermore, he added, a modeling approach that compared starting ART with a CD4 count greater than 350 cells/mm3 versus 200 to 350 cells/mm3 found that starting earlier is a cost-effective strategy in the United States. Dr. Gallant’s opinion, which he emphasized is not necessarily consistent with evolving treatment guidelines, is to treat anyone with a CD4 count of less than 350 cells/mm3, anyone with hepatitis B virus (HBV)/HIV co-infection needing treatment for HBV, pregnant women, and patients with conditions that require ART, such as HIV-associated nephropathy or neurocognitive dysfunction. 

He said he would defer treatment for patients in the setting of some acute opportunistic infections (to avoid immune reconstitution inflammatory syndrome), long-term non-progressors (or those who might be), and patients who are not ready, motivated, or likely to be adherent.  Dr. Gallant said that therapy could be considered in motivated, adherent patients with clear evidence of immunologic progression regardless of CD4 count, or in patients at high risk of transmitting HIV infection. However, he pointed out that a thorough discussion of the pros and cons of early therapy is especially important in patients starting therapy earlier than is recommended by current treatment guidelines.  

Slides from this session and many others from IDSA 2007 are available online.

Audio files of individual sessions or a full-conference CD-ROM are available for purchase from Sound Images.

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