Interim data from two studies of a dapivirine vaginal ring-DREAM and HOPE-lend further credence to the potential benefits of using the device for HIV prevention. Plus: FDA authorizes direct-to-consumer BRCA1/BRCA2 test. Also: A new Zika virus test extends window for accurate diagnosis.
Interim data from two studies of a dapivirine vaginal ring-DREAM and HOPE-lend further credence to the potential benefits of using the device for HIV prevention. Presented at the Conference on Retroviruses and Opportunistic Infections (CROI), the results build on data presented at CROI 2016, which showed that the ring was well tolerated and reduced HIV risk by about 30% overall in two large Phase III clinical trials in Africa-The Ring Study and ASPIRE.
Interim analyses of DREAM, a Phase IIIb study, showed an increase in ring use over its parent Phase III study, up from 83% in the Ring Study to 96% in DREAM, with use varying from intermittent to consistent. The interim analyses also suggest that the overall HIV incidence rate among women in the DREAM study is 54% lower than would be expected without its use, based on statistical modeling. That finding is limited in that DREAM is an open-label study with no placebo group.
DREAM is being conducted by the International Partnership for Microbicides (IPM) at six former Ring Study sites in South Africa and Uganda and enrolled 940 women aged 20 to 50. The interim analysis was conducted on 900 women enrolled in the study as of September 2017. The risk reduction data were calculated using a bootstrap sample. That is, the observed HIV-1 incidence rate of 1.8% in the participants was compared to an incidence rate of 3.9% in a simulated placebo group with similar characteristics.
Results nearly identical to those from DREAM were reported at CROI for the HOPE trial, a parallel open-label Phase IIIb study being led by the US National Institutes of Health-funded Microbicide Trials Network (MTN). Dream is scheduled for completion in December and HOPE in October, with final results in 2019.
The dapivirine ring is flexible silicone and provides sustained release of the antiretroviral (ARV) drug locally to the site of potential infection during vaginal sex with minimal systemic absorption. Women insert the product themselves and replace it every month. IPM is also developing a version of the dapivirine-only ring that would be changed only once every 3 months and would offer increased convenience and lower annual costs, and a ring that combines the ARV drug with a contraceptive.
IPM is seeking a positive opinion about the dapivirine ring’s device’s safety, efficacy, and quality from the European Medicines Agency and the World Health Organization. Once that is received, the organization will submit applications for approval of the product to the South African Health Products Regularity Authority and the US Food and Drug Administration.
FDA authorizes direct-to-consumer BRCA1/BRCA2 test
The US Food and Drug Administration has approved a direct-to-consumer test of three specific BRCA1/BRCA2 gene variants. These specific variants are the most common in individuals of Ashkenazi (Eastern European) Jewish descent and no prescription is required to request testing.
The Personal Genome Service Genetic Health Risk (GHR) Report for BRCA1/BRCA2 (Selected Variants) will be marketed by 23andMe.
The test results are based on analysis of DNA acquired from a self-collected saliva sample. Reports for women reflect risk of developing breast or ovarian cancer. Reports for men reflect risk of breast cancer or prostate cancer. Because the test detects only three BRCA mutations and there are more than 1000 known BRCA mutations, FDA advises that consumers and health care professionals not use the results to determine a treatment plan. The three tested mutations are present in about 2% of Ashkenazi Jewish women, but rarely appear (0%-0.1%) in other ethnic populations.
FDA’s approval came after review of data through the agency’s de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device. The agency is establishing special controls that set forth FDA’s expectations in assuring the 23andMe test’s accuracy, reproducibility, clinical performance, and labeling.
Study: New Zika virus test extends window for accurate diagnosis
A diagnostic blood test for Zika virus (ZIKV) in development can extend the window of accurate detection to months after the onset of infection, according to a study published in mBio. The ZIKV-NS2B-concat ELISA is also is less expensive than currently available ELISA tests.
Diagnosing ZIKV can be difficult since current molecular tests for exposure are only reliable in the first 2 to 3 weeks after infection while the virus is still circulating in the bloodstream and infected patients do not exhibit obvious symptoms during the acute phase of infection. Another issue with previous ZIKV diagnostic tests is serological confounding by cross-reactivity with other flaviviruses endemic in the areas where ZIKV is prevalent.
Led by researchers from Columbia University, the authors developed the ZIKV-NS2B-concat ELISA by collecting blood samples from children in the Nicaraguan Pediatric Dengue Cohort study, all of whom had previously tested positive for ZIKV. A microarray was used to identify a unique peptide sequence that binds with antibodies to ZIKV but not with antibodies to similar viruses like dengue, yellow fever, and Japanese encephalitis. The researchers then customized an ELISA to work with the peptide sequence. This customization improves on current versions of the ELISA test which use larger sections of the proteins that bind to the virus.
The ZIKV-NS2B-concat ELISA can detect up to 200 samples in 4 hours and the research group anticipates the cost to be similar to other ELISA tests used in clinical settings. It also has a much lower rate of false positives and false negatives than current blood diagnostics: It identified 96% of ZIKV sera positive in the peptide array with 94% specificity. In the researchers’ protocol using a threshold of an 0.90 optical density, the ELISA detected immunoglobulin G antibodies in 47% of sera from subjects with acute disease (1 to 6 days after onset), more than 95% of sera from subjects in early convalescence (2 to 3 weeks after onset), and 55% of sera from subjects in late convalescence (more than 6 months after onset).
Noting the profound impact ZKV has had on global health, the researchers stressed the importance of accurate diagnoses and hope this test will help healthcare professionals diagnose infected patients more quickly and accurately throughout disease progression.