HIV Health News

Maraviroc: First-in-Class CCR5 Antagonist

On August 6, the FDA granted accelerated approval of Pfizer's CCR5 antagonist maraviroc— marketed as Selzentry in the United States and Celsentri elsewhere— for treatment of adults with multidrug- resistant CCR5-tropic HIV. The new drug works by altering the shape of the CCR5 coreceptor on T cells so that HIV can no longer use it for cell entry.

Maraviroc out-performed comparator agents in Phase III clinical trials, but treatment advocates worry that the drug's $29- per-day price tag will limit its reach. Martin Delaney, member of the Fair Pricing Coalition and founding director of Project Inform, stated that "the company's pricing strategy is inappropriate and unwarranted. There was plenty of room for profit and additional funding for future research at a lower price point."

Vaccine Trial Halted

On September 21, the HIV Vaccine Trials Network and Merck announced a halt to vaccinations in the Phase II STEP study of the MRK-Ad5 vaccine candidate. A parallel trial in South Africa has also halted both enrollment and immunizations.

The adenovirus-based vaccine, which incorporated synthetic versions of HIV's own gag, nef, and pol genes, was designed to stimulate a T-cell response and guard against HIV infection or reduce viral load. An interim analysis determined that the product showed no efficacy in either protecting against infection or reducing viral load in participants who seroconverted during the three year study, which was scheduled to end in 2009.

Mitchell Warren, Executive Director of the AIDS Vaccine Advocacy Coalition, acknowledged the setback but emphasized that the MRK-Ad5 vaccine candidate is one of many in development: "Clinical testing of AIDS vaccines is a scientific process and, while this is a disappointment, it is in no way the end of the search for an AIDS vaccine."

Back to "Hit Early" Treatment Strategies?

Current NIH guidelines recommend initiating antiretroviral therapy when CD4 cell count falls to 200 cells/mm3. However, numerous sessions at the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, held July 22–25 in Sydney, explored the benefits—including lower risk for both AIDS-defining events and non-AIDS-related illnesses—seen by patients who start treatment with CD4 cell counts at or above 350 cells/mm3. The "Strategic Timing of Antiretroviral Therapy" (START) trial is the first randomized study designed to examine how timing of treatment initiation affects health outcomes; enrollment is expected to begin in early 2008.

Next Up: Raltegravir

Raltegravir, the lead agent in the new integrase inhibitor drug class, has demonstrated potent and durable anti-HIV activity in both treatmentnaive and treatment-experienced individuals in Phase II and III trials and also suppressed the virus more rapidly than did efavirenz (Sustiva). Like other candidates in this new class, raltegravir targets integrase, the enzyme responsible for integrating HIV's genetic material into the host cell's DNA—a key step in viral replication (see "Drug Watch" in the Summer 2006 issue of BETA for more information). An FDA panel reviewed Merck's application on September 5 and 6; the drug is expected to receive accelerated approval within the next few months.

SFAF's treatment journal, BETA, is available for free. To subscribe or find a pickup location, visit www.sfaf.org/beta or call 415-487-8060.