|
TMC-114 in Expanded Access
The experimental HIV protease inhibitor drug TMC-114 went into expanded access in October, available for free to individuals who need it to form a treatment regimen and are not eligible for studies by the manufacturer, Tibotec. For information, healthcare providers and patients should call 1-866-889-2074 or visit www.Tibotec.com or www.clinicaltrials.gov. The drug is taken with a low dose of another HIV drug, Norvir (ritonavir).
Back to Top
Liver Toxicity in two CCR5 Studies
Disappointing news in October for a promising new class of HIV drugs: pharmaceutical GlaxoSmithKline put a stop to an advanced (Phase III) study of aplaviroc, a CCR5 inhibitor. This still-experimental type of drug stops HIV from entering the cell, and is part of the entry inhibitor class of drugs—they work in a variety of ways to stop HIV from infecting cells. One person in the study developed liver toxicity. The Phase III study began in July 2005, in people who’ve already taken HIV medications (“treatment experienced”).
A different aplaviroc study (in earlier Phase IIb development) was stopped in September 2005 after two participants had similar liver problems. That study, of people on HIV medication for the first time (“treatment naïve”), had 250 people with HIV. At that time, study in “healthy volunteers” (people without HIV, who are studied for safety data) was also stopped, as was enrollment of more people into the Phase III study while the other results were analyzed. The participants already enrolled in the Phase III study were given the option to continue, since these individuals had few treatment options and had not, at that time, shown signs of liver toxicity. There are no further studies planned with the drug.
In a report from the 10th European AIDS Conference (EACS), held in Dublin in November, Mark Mascolini wrote for NATAP (National Association for AIDS Treatment Advocacy, in New York City), “Why would a bare handful of liver problems—four, as it turned out—bring a megabucks clinical trial juggernaut to a clanging halt? Because, Glaxo’s [Helen] Steel explained, liver experts figure that the specific type of toxicity they saw will kill 10% to 50% of those who have it.” Mascolini also reported that the toxicities resolved after the individuals stopped taking aplaviroc.
In November, Pfizer reported a case of liver toxicity in its study of another CCR5 inhibitor, maraviroc. That individual, however, was on known liver toxic drugs at the time, isoniazid (INH) and cotrimoxazole (trimethoprim-sulfamethoxazole), and high doses of IV acetaminophen and was beginning to have liver function elevations before going on maraviroc. This person was also co-infected with hepatitis C. The individual had to stop taking maraviroc after five once-a-day doses, and had a liver transplant within two weeks. Pfizer also reported that approximately 1,300 patients with HIV had enrolled in this Phase 2b/3 study, with 75% of them receiving maraviroc.
Back to Top
False Positives with OraQuick
After experiencing a cluster of false HIV positive results with the OraQuick rapid HIV oral test, two centers in California discontinued using it. A cluster of false positive results was also reported in New York City.
The OraQuick oral test uses a swab inside the mouth and returns results in 20 minutes—a huge advancement in HIV testing, where more than half of people tested fail to return for results in the one to two weeks it takes with a blood test. (There is also an OraQuick rapid test with blood from a finger prick.) The U.S. Centers for Disease Control and Prevention (CDC) announced that guidelines for using the oral test remain the same while the situation is being assessed.
The San Francisco Chronicle reported in December that the city’s health department stopped using the OraQuick oral test at its largest HIV testing center, the City Clinic, but continued using it at other locations. The Los Angeles Gay and Lesbian Center announced that month that it had stopped using the OraQuick oral test after 13 false positive results occurred in November. The New York Times quoted a representative of the city’s health department as reporting finding 30 false positive results with the test in November, when normally the department sees five false positives out of the 3,600 to 3,700 HIV tests conducted each month.
No test is expected to be 100% accurate. The CDC reported that the test is within the limits required by the U.S. Food and Drug Administration (FDA), which oversees medical devices. Here at Test Positive Aware Network, no false positives have been seen with the QraQuick oral test. The Los Angeles Times quoted the county’s director of sexually transmitted disease program, Peter Kerndt, as saying the county has not found a high rate of false positives and that, “I think the wrong thing to do here is to stop using the test.”
All positive test results for HIV must be confirmed with a different test. The oral test does not look for HIV in saliva or mouth tissue, but only looks for antibodies to HIV, indicating the presence of the virus in the person’s body. Kissing is not considered to be risky behavior for transmission.
Back to Top
Generic Viramune
The FDA in December approved a generic version of the HIV drug Viramune. Meeting FDA standards means that the generic version of the drug can be bought by the President’s Emergency Plan for AIDS Relief (PEPFAR) for use in other countries. In the U.S., however, only Viramune can be bought, because of the drug patent held by Boehringer Ingelheim. The generic version is made by Aurobindo Pharma of India.
Back to Top
Declining Diagnosis
The CDC reported in November that new HIV diagnoses among African Americans have decreased by 5% a year since 2001, but they are still eight times more likely to be infected compared to Whites.
Also seeing a decline, of 9% per year, were injection drug users, and heterosexuals (4% a year). Infections among men who have sex with men (MSM), however, increased by 8% between 2004 and 2005, after being on a plateau from 2001 to 2003.
Back to Top
Fortovase Discontinued
As this issue of Positively Aware went to press, drug maker Roche announced the discontinuation of the U.S. sale and distribution of Fortovase, the soft-gel forumulation of the HIV protease inhibitor saquinavir, as of February 15, 2006. Roche stated it has taken the action because of the decreased demand for Fortovase, and also due to the fact that the updated HIV treatment guidelines issued by the U.S. Department of Health and Human Services (DHHS) no longer recommend Fortovase as a preferred or alternative first-line treatment.
The Invirase formulation of saquinavir will remain available and is associated with fewer stomach-related side effects and does not require refrigeration, and is available both as a 500 mg tablet and a 200 mg capsule. The dose of the 500 mg tablet formulation of Invirase is 2 tablets taken twice a day, and must be boosted with a small dose of Norvir.—Jeff Berry
Back to Top
|
