Gilead Sciences Inc. announced that the US Food and Drug Administration (FDA) has sent the company Complete Response Letters for its New Drug Applications (NDAs) for elvitegravir and cobicistat for use as part of HIV treatment regimens.

According to the company, in communications from the FDA, the agency states that it cannot approve Gilead’s applications in their current form, due to deficiencies in documentation and validation of certain quality testing procedures and methods. The agency said these deficiencies were observed during recent inspections by the agency.

Gilead said that it is working with the FDA to address the questions that were raised in the Complete Response Letters and move the applications forward.

Elvitegravir and cobicistat are components of Gilead’s HIV-1 regimen Stribild. Stribild is a once-daily single tablet comprised of elvitegravir 150 mg, cobicstat 150 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg. Stribild was approved by the FDA in August of 2012 for treatment-naïve adults with HIV. Stribild is not affected by this regulatory action.

Elitegravir is a member of the integrase inhibitor class of antiretroviral compounds, which blocks HIV’s ability to integrate into the genetic material of human cells.

Gilead’s cobicistat is the company’s proprietary potent mechanism-based inhibitor of cytochrome P450 3A (CYP3A). CYP3A is an enzyme that metabolizes drugs in the body. Cobicistat, unlike ritonavir, acts only as a pharmacoenhancing agent and has no antiviral activity.

The NDAs for elvitegravir and cobicistat were submitted by Gilead in June 2012. Additionally, marketing applications are pending in Europe.

Source: Gilead Sciences Inc.

Last Updated: 4/29/13; 11:25AM EST

The National Institute of Allergy and Infectious Disease (NIAID), part of the National Institutes of Health (NIH), announced that it will halt the trial of an investigational HIV vaccine regimen after a review showed that the vaccine did not prevent HIV infection, nor reduce viral load for those recipients who became infected with HIV.

The NIAID said it will no longer give the injection which involves a series of three immunizations over eight weeks including a combination of a DNA-based vaccine to prime the immune system and a booster shot with a weakened virus carrying genetic material that expressed HIV antigens.

The Phase IIb HVTN (HIV Vaccine Trials Network) 505 clinical trial began in 2009 to determine whether the vaccine regimen could prevent HIV infection and/or reduce the viral load in the blood of vaccine recipients who became infected with HIV. Earlier trials that tested the vaccine on fewer people suggested that the vaccine could produce an immune response to HIV, as well as has a good safety record; however the larger trial found a non-statistically significant increase in HIV acquisition for those in the vaccine group compared to those in the placebo group.

The study involved 2,504 volunteers consisting of men who had sex with men and transgendered people who have sex with men. There were 1,250 volunteers who received the vaccine and 1,244 who received the placebo. The first analysis evaluated participants who were diagnosed with HIV infection after having been in the study for at least 28 weeks and found that 27 HIV infections occurred in the vaccine group compared to 21 HIV infections among the placebo group. For those who became HIV-infected during the first 28 weeks, 14 cases of HIV occurred in those who received the vaccine and 9 occurred in those who received the placebo.

Overall, from enrollment day through the month 24 study visit, there were a total of 41 cases of HIV infection in those receiving the vaccine compared to 30 cases of HIV in those receiving the placebo. Additionally, after at least 28 weeks after entering the study, of those who acquired HIV and had been followed for at least 20 weeks after diagnosis, there were 30 participants with measurable viral load, 15 who received the vaccine and 15 who received the placebo.

Closer follow-up of participants beyond their month 24 study visit has been recommended. The NIAID and research team of the HVTN 505 study are working together to better understand why the vaccine did not work and to guide future vaccine development efforts.

Source: National Institute of Allergy and Infectious Diseases

Last Updated: 4/26/13; 12:10PM EST

MADISON, N.J. , March 27, 2013 /PRNewswire/ -- A new test based on gene sequencing may be used to assess a patient's suitability for treatment with CCR5 antagonists, a class of HIV antiretroviral therapies, under new medical guidelines issued by the U.S. Department of Health and Human Services (DHHS).

The new genotypic test performs comparably to the standard culture-based phenotypic tropism technique for predicting response to CCR5 antagonists, but at about half the cost and with faster results, according to Quest Diagnostics (NYSE: DGX), the leading provider of diagnostic information services. Quest Diagnostics is believed to offer the only genotypic HIV tropism test service in the United States to demonstrate comparable performance to the standard phenotypic method, previously the only method available nationally to help physicians predict response to CCR5 antagonists.

"CCR5 antagonists can be an important component of an effective and well-tolerated drug combination in some HIV-infected patients. Tropism testing is a requirement for using this drug class, and fast test results facilitate timely treatment decisions," said Jonathan M. Schapiro , MD, director of HIV/AIDS at the National Hemophilia Center, Tel Hashomer, Israel. "The inclusion of genotypic tropism testing by the DHHS HIV Guidelines is a very welcome development. Faster, cost-effective diagnostics are greatly needed to improve HIV management."

Testing for HIV tropism is necessary to predict response to CCR5 antagonist therapy. This therapy can help slow HIV disease progression in patients with a certain type of tropism, but offer no known clinical benefit in patients with other forms of tropism. Tropism refers to a type of cellular mechanism by which the HIV virus infects human cells.

The revised DHHS guidelines, titled Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, recommend "that a genotypic tropism assay be used as an alternative to a phenotypic tropism assay before initiation of a CCR5 antagonist-containing regimen." While prior HHS guidelines only recommended phenotypic assays, medical guidelines in Europe have supported genotypic HIV tropism tests since 2011.

The DHHS guidelines are available at: http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0/

"Genotyping is an example of how diagnostic innovation can expand clinical options for physicians while driving down costs for payers and patients," said Rick L. Pesano , M.D., Ph.D., medical director, infectious diseases, Quest Diagnostics. "We expect this method will provide the basis for developing additional diagnostic innovations that are clinically valuable and more cost effective than traditional techniques."

Quest Diagnostics has offered its clinical genotypic tropism test as a laboratory-developed test, named the Quest Diagnostics HIV-1 Tropism with Reflex to Ultra deep sequencing (UDS), since the spring of 2012. The company's advanced genetics laboratory in San Juan Capistrano, California, developed, validated and performs the test for clinicians in the United States. Quest Diagnostics can provide test results in as few as 10 business days, compared to average turnaround times of two to three weeks for phenotypic tests, and at roughly half the list price for the standard phenotypic test.

In late 2012, the peer-reviewed, open-access journal PLOS ONE published a study that found the Quest Diagnostics deep-sequencing genotypic method predicted response to HIV antiretroviral therapy as well as the industry's standard phenotypic test.

Quest Diagnostics has one of the most comprehensive HIV testing services menu in the diagnostic industry, with services that range from HIV screening, viral load, therapeutic monitoring, co-infection and resistance testing. In late 2012, the company launched the HIV proviral DNA tropism lab-developed test, which uses DNA extraction and sequencing followed by bioinformatic analysis to help enable genotypic tropism testing for patients with low or undetectable HIV-1 viral RNA (<1000 copies/mL).

About Quest Diagnostics
Quest Diagnostics is the world's leading provider of diagnostic information services that patients and doctors need to make better healthcare decisions. The company offers the broadest access to diagnostic information services through its network of laboratories and patient service centers, and provides interpretive consultation through its extensive medical and scientific staff. Quest Diagnostics is a pioneer in developing innovative diagnostic tests and advanced healthcare information technology solutions that help improve patient care. Additional company information is available at QuestDiagnostics.com. Follow us atFacebook.com/QuestDiagnostics and Twitter.com/QuestDX. Additional information for healthcare professionals, including access to ASCLS P.A.C.E.-certified webinars, is available at QuestDiagnostics.com/Education.

Quest, Quest Diagnostics, any associated logos, and all associated Quest Diagnostics registered or unregistered trademarks are the property of Quest Diagnostics. All third-party marks are the property of their respective owners.

SOURCE Quest Diagnostics

According to recent reports, a baby that was born with the AIDS virus two years ago in Mississippi has been cured of the infection.

The baby was put on antiretroviral therapy within hours of birth. Typically, infants are not started on drugs until at least six weeks after birth when infection is certain. Researchers are not sure if the cure is complete and permanent, or partial and long-lasting; however this provides hope for the 300,000 babies who are born with the infection each year worldwide. The baby was treated within thirty hours of birth before tests even confirmed that the infant was infected.

The baby has been off medication for about a year with no signs of infection. Scientists announced that this offers clues for efforts in eliminating the virus in children, especially those in plagued African countries. The announcement was made at a major AIDS meeting in Atlanta.

There are hopes that this can help prevent babies from being born with HIV.

There has only been one other person cured from the AIDS virus in 2007. This individual underwent a bone marrow transplant from a donor who is naturally resistant to HIV. This is a very rare and special case. Since the transplant that took place five years ago, Timothy Ray Brown has not needed HIV medications.

The researchers hid any personal details about the case. The infant’s sex was even concealed. Mother to child transmission is extremely rare in the United States, accounting for only 200 cases per year, but in this case the mother did not know she was HIV positive until a time that was too close to delivery. After repeatedly being considered HIV positive, 29 days after birth the baby had no detectable virus, which is the goal of treatment.

Last Updated: 3/4/13; 3:30PM EST