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HAART highly effective, but better therapies still needed
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Within the past 15 years, there have been many improvements to highly active antiretroviral therapy, and more improvements and developments are expected in the future, according to a presentation at the 18th Conference on Retroviruses and Opportunistic Infections in Boston.
“HAART in 2011 is certainly better tolerated when compared with 1996,” said Patrick Yeni, MD, of the Hospital Bichat-Claude Bernard, University Paris. “However, it remains associated with significant toxicity and, therefore, underlies the fact that there is still a need for better new drugs.”
It is estimated that 50,000 of 150,000 patients with HIV are not aware of their HIV status. Although HAART is recommended early in the course of HIV infection, this recommendation does not reach most patients in need, Yeni said. According to the meeting session moderator Roy Gulick, MD, of the Weill Cornell Medical College in New York, AIDS was the No. 1 killer of young adult men and women in this country in 1995.
“In 1996, we turned a corner in the HIV/AIDS epidemic,” Gulick said. “This was the year that the first studies were presented showing that triple combination therapy can suppress viral load levels profoundly. This is also the year these results were translated into significant mortality benefits from using HAART. We can all recognize that this was not only a milestone for our field, but a milestone for all of medicine.”
For patients who are asymptomatic but have a CD4 cell count of 500/mcL or less, HAART is recommended. For asymptomatic patients with a CD4 count of more than 500/mcL, HAART should be considered, unless the patient is an elite controller or has a stable CD4 cell count and low-level viremia in the absence of HAART.
“HAART in 2011 is highly efficient,” Yeni said. “However, in patients with plasma HIV-RNA levels of less than 50 copies/mL, HIV infection is not cured. Low level viremia persists in 80% of patients, and chronic T-cell activation and inflammation persist.”
Currently, there are three new antiretroviral agents in phase 3 development: Rilpivirine (Tibotec Pharmaceuticals) is a non-nucleoside reverse transcriptase inhibitor, and Elvitegravir (Gilead Sciences) and dolutegravir (GlaxoSmithKline) are integrase inhibitors. Many other agents, including NNRTIs, nucleoside reverse transcriptase inhibitors and protease inhibitors, are also in phase 1 and phase 2 development.
According to Yeni, recommendations about when to start ART in patients with HIV are changing. There are studies under way to evaluate whether the “test-and-treat” approach is feasible.
“In the future, the question about initiation of antiretroviral therapy could possibly be the identification of patients who should not receive therapy, based on assessment of immunological, virological and, possibly, genetic and biochemical markers,” he said.
Yeni also discussed complementary non-ART for the treatment of immune dysfunction and chronic inflammation. These conditions are not fully reversed by HAART and are implicated as causally related to the premature onset of cardiovascular disease, cancer and osteoporosis. Examples of strategies to minimize immune dysfunction or chronic inflammation in patients with controlled HIV replication include recombinant human interleukin-7, drugs with anti-inflammatory activity and inhibition of the tryptophan oxidation pathway, among others. - by Emily Shafer
For more information:
- Yeni P. Paper #70. Presented at: The 18th Conference on Retroviruses and Opportunistic Infections; Feb. 27-March 2, 2011; Boston.
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