The Observatory

Oct. 22, 2015

Infectious Disease

CDC supports new WHO early release HIV treatment and PrEP guidelines. The CDC has endorsed the recent announcement by the World Health Organization (WHO) of new Early Release HIV Treatment and Pre-Exposure Prophylaxis (PrEP) guidelines that will significantly increase the number of people eligible for life-saving anti-retroviral treatment (ART) and expand access to a powerful tool for preventing HIV among those at greatest risk.

The new guidelines call for treatment for all individuals living with HIV, regardless of CD4 count. This is a shift from existing WHO guidelines that recommend ART for those with compromised immune systems (CD4 counts less than 500) and other vulnerable populations such as children, pregnant women, and people with TB. The new guidelines also recommend daily oral PrEP as an additional prevention choice for those at substantial risk for contracting HIV as part of a combination prevention approach.

Recent scientific breakthroughs show that early and effective treatment not only reduces HIV transmission but also significantly improves health outcomes for those living with HIV. PrEP has been shown in many studies and “real world” situations to reduce the risk of HIV infection by more than 90 percent among those who regularly take their meds.

The WHO announcement aligns with two key U.S. recommendations. In 2012, the U.S. Department of Health and Human Services (HHS) issued treatment guidelines recommending ART for all patients diagnosed with HIV infection. In 2014, CDC issued clinical guidance recommending physicians consider advising the use of PrEP for gay and bisexual men, heterosexuals, and injection drug users at substantial risk for HIV infection.

Cancer

Researchers report genetic clue to breast cancer relapses. British scientists have discovered a genetic clue to why some breast cancers relapse, which could lead to better treatment. A research team from Wellcome Trust Sanger Institute in Cambridge found that cancers that return were more likely to contain certain genes or combinations of genes. Targeting these genes with early treatments could be key. The study was presented at the recent European Cancer Congress in Vienna.

In approximately one in five people with breast cancer, the disease will return—either to the same place as the original tumor or another part of the body. Lucy Yates, MD, and her colleagues analyzed data from the tumors of 1,000 breast cancer patients, including 161 people whose cancer had recurred or spread. Comparing primary and secondary tumors, they found noticeable genetic differences, and several of the mutations that were present in the secondary cancers were relatively uncommon in cancers diagnosed for the first time.

Yates said the patterns they found suggested that the complement of cancer genes in some primary cancers may make them more likely to relapse in the future, while additional cancer genes acquired after diagnosis may drive the cancer relapse. She said doctors might be able to use this knowledge to identify patients at high risk of their cancer returning and pick the best treatment for targeting particular genetic mutations. This would mean taking regular samples of cancer tissue to track how the disease is progressing and changing.

Study shows K17 protein promotes cancer. Keratin 17 (K17), a protein previously believed to provide only mechanical support for cancer cells, appears to play a crucial role in degrading a key tumor suppressor protein in cancer cells called p27. This finding, published in Cancer Research, is based on the work of researchers in the Department of Pathology at Stony Brook University School of Medicine. They found K17 has the ability to enter the nucleus of cancer cells, leading to the degradation of p27. The work illustrates that a keratin can function to promote the development of cancer. Furthermore, the research details that tumors with high levels of K17 are biologically more aggressive and have a worse prognosis than low K17 tumors.

The protein p27 is a master regulator of organized cell division and growth found in the nucleus of cells, and it is commonly inactivated in cancer cells. In the paper, “Keratin-17 Promotes p27K1P1 Nuclear Export and Degradation and Offers Potential Prognostic Utility,” lead author Luisa Escobar-Hoyos, a Molecular Pharmacology graduate student working on her PhD thesis project under the direction of Kenneth Shroyer, MD, PhD, Professor and Chair of the Department of Pathology, and colleagues, investigated if K17 interferes with p27 processes. Their findings validate previous observations from the Shroyer lab that reveal high K17 cervical cancer patients have a decreased chance of long-term survival when compared to patients who express little to no K17 in tumor tissue. In addition, it was discovered that K17 increases chemotherapy resistance in cancer cells.

This research suggests that K17 testing could provide valuable information that may be used to distinguish between “clinically identical” cancer patients, identifying cases with more aggressive tumors at the time of diagnosis, and potentially guiding personalized treatment based on individual K17 status.

Ebola

Portable, rapid DNA test can detect Ebola and other pathogens. Using technical advances not yet developed when the 2014 Ebola outbreak began, University of California San Francisco-led scientists completed a proof-of-principle study on a real-time blood test based on DNA sequencing that can be used to rapidly diagnose Ebola and other acute infections. The researchers say that the test can be used even where lab space and medical infrastructure are scarce.

Charles Chiu, MD, PhD, led a team that detected the genetic fingerprints of Ebola in stored blood samples from two African patients who had acute hemorrhagic fever, completing the diagnosis within five hours of opening the samples. The DNA sequencing took just 10 minutes.

Most commercially available or research-based genetic diagnostic tests target specific pathogens. But Chiu and colleagues have pioneered techniques that do not require suspected pathogens to be identified beforehand in order to detect their unique genetic fingerprints. This unbiased approach of analyzing all DNA in a clinical sample without knowing which species are present, which was used in the Ebola detection, is called “metagenomic” analysis.

To obtain such quick results, the researchers developed new analysis and visualization software and used it on a laptop computer to leverage an emerging DNA-sequencing technology called nanopore sequencing

In the same set of experiments, the researchers were able to detect the Chikungunya virus just as quickly from a blood sample. In another example, detection of hepatitis C virus in blood from an infected patient, present at a much lower concentration than the other viruses, took just 40 minutes from the start of sequencing.