Author Interviews, CDC, HIV, Sexual Health, Technology / 15.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25221" align="alignleft" width="172"]Dr. James M. Smith Ph.D Laboratory Branch, Division of HIV/AIDS Prevention Centers for Disease Control and Prevention Atlanta, Georgia Dr. James M. Smith[/caption] Dr. James M. Smith Ph.D Laboratory Branch, Division of HIV/AIDS Prevention Centers for Disease Control and Prevention Atlanta, Georgia MedicalResearch.com: What is the background for this study? Dr. Smith: Our laboratory has been developing a macaque model for testing drug release, safety and efficacy of intravaginal rings (IVR) for preexposure prophylaxis (PrEP) against HIV for several years. The initial studies involved both matrix rings, where the drug is dispersed in the silicone matrix of the device, and reservoir rings, which are essentially a polymer tube filled with drug. In collaboration with the Oak Crest Institute of Science and Auritec Pharmaceuticals, Inc., we began testing a new type of intravaginal ring, the pod-IVR. In this innovative design the ring itself is a scaffold that contains compressed polymer-coated drug tablets, or pods, within the ring. Each pod is separate, allowing for a customizable release rate for each drug by varying the number and diameter of the drug release ports for each individual pod. The macaque pod-IVR can accommodate up to six pods whereas the human pod-IVR can accommodate up to 10 pods. The IVR design was developed to allow the delivery of drug combinations and for simple, cost-effective manufacturing.
Author Interviews, Hematology, HIV, Stem Cells, Transplantation / 15.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25218" align="alignleft" width="120"]Joseph Alvarnas, MD Associate clinical professor Department of hematology and Director of value-based analytics City of Hope National Medical Center Duarte, CA Dr. Joseph Alvarnas[/caption] Joseph Alvarnas, MD Associate clinical professor Department of hematology and Director of value-based analytics City of Hope National Medical Center Duarte, CA MedicalResearch.com: What is the background for this study? Dr. Alvarnas: Patients with HIV infection have a significantly increased risk of non-Hodgkin lymphoma and Hodgkin lymphoma. Prior to the availability of effective anti-retroviral therapy, HIV-infected patients with lymphoma had very poor treatment outcomes. Following the availability of effective anti-HIV therapy, patient outcomes for HIV-infected patients now parallel those of non-infected patients. Historically, however, HIV infection has been used as a criterion for not offering patients autologous blood stem cell transplantation outside of centers with unique expertise. The purpose of this trial was to evaluate outcomes, complication rates, and immunological reconstitution of HIV-infected patients following autologous blood stem cell transplantation.
Abuse and Neglect, Author Interviews, Heart Disease, HIV, JAMA / 31.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24761" align="alignleft" width="120"]Steven Grinspoon, MD Professor of Medicine, Harvard Medical School MGH Endowed Chair in Neuroendocrinology and Metabolism Director, MGH Program in Nutritional Metabolism and Nutrition Obesity Research Center at Harvard MGH Boston, MA 02114 Dr. Steven Kyle Grinspoon[/caption] Steven Grinspoon, MD Professor of Medicine, Harvard Medical School MGH Endowed Chair in Neuroendocrinology and Metabolism Director, MGH Program in Nutritional Metabolism and Nutrition Obesity Research Center at Harvard MGH Boston, MA 02114 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Grinspoon: Numerous epidemiologic studies have shown that people living with HIV face a 1.5 to 2-fold increased risk of heart attack, or myocardial infarction, as compared to individuals without the virus. Mechanisms underlying the increased risk of myocardial infarction in HIV are incompletely understood. It is possible that among people living with HIV, increased systemic immune activation fuels arterial inflammation. Arterial inflammation may, in turn, promote the development of high-risk morphology coronary atherosclerotic plaque, which is liable to rupture and result in myocardial infarction. For people diagnosed with HIV, the overall health benefits of immediate antiretroviral therapy (ART) are clear. However, the effects of newly-initiated antiretroviral therapy on arterial inflammation have not previously been studied. In this study, we set out to assess among a cohort of treatment-naive HIV-infected subjects, the effects of newly-initiated ART with a contemporary regimen on both immune function and arterial inflammation. We found that among treatment-naive HIV-infected individuals without clinical cardiovascular disease, newly initiated combined antiretroviral therapy has discordant effects to restore immune function without reducing the degree of arterial inflammation.
Author Interviews, HIV, University of Pennsylvania / 06.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24043" align="alignleft" width="200"]Robert Bonacci MPH, MD Candidate’16 University of Pennsylvania School of Medicine Robert Bonacci[/caption] Robert Bonacci MPH, MD Candidate’16  University of Pennsylvania School of Medicine MedicalResearch.com: What is the background for this study? Response: During the mid-2000’s, the HIV incidence rate stubbornly persisted around 50,000 infections per year. Responding to this trend, President Obama released the first comprehensive US National HIV/AIDS Strategy (NHAS) in 2010. The NHAS hoped to spur a more coordinated national response and set ambitious targets for reducing HIV incidence (25 percent) and the transmission rate (30 percent), among other goals, by 2015. To evaluate whether the U.S. achieved the NHAS goals by 2015, we used mathematical models drawing on data from the U.S. Centers for Disease Control and Prevention (CDC) on HIV prevalence and mortality for 2007 to 2012, and our own previously published incidence estimates from 2008-2012. Changes seen from 2010 through 2012 were extrapolated for the time period 2013 through 2015.
Author Interviews, Hepatitis - Liver Disease, HIV, JAMA, Vaccine Studies / 13.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23342" align="alignleft" width="160"]Odile Launay MD, PhD Paris Descartes University Assistance Publique Hôpitaux de Paris, Cochin Hospital Dr. Odile Launay[/caption] Odile Launay MD, PhD Paris Descartes University Assistance Publique Hôpitaux de Paris, Cochin Hospital  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Launay: In patients with HIV infection, responses to standard HBV vaccination regimens remain suboptimal compared with responses in HIV seonegative individuals. We previously reported that alternative regimens (a 4 injection IMdouble dose regimen and a 4 injection intradermal low dose regimen) improve antibody response compared with the standard HBV vaccination regimen (ANRS HB03 VIHVAC-B study). Further precision on the duration of response achieved with alternative HBV vaccination regimes was needed. We report in this paper the results from the follow-up of the study. The results of this study show that the 4 dose IM regimen induces higher seroconversion rate but also higher long term seroprotection in HIV infected patients
Author Interviews, Emory, HIV / 01.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22226" align="alignleft" width="202"]Dr. Igho Ofotokun MD MSc Division of Infectious Diseases, Department of Medicine Emory University School of Medicine, Atlanta, Georgia Grady Healthcare System, Atlanta, Georgia Dr. Igho Ofotukun[/caption] Dr. Igho Ofotokun MD MSc Division of Infectious Diseases, Department of Medicine Emory University School of Medicine, Atlanta, Georgia Grady Healthcare System, Atlanta, Georgia MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Ofotokun:  This work is focused on preventing further bone loss in HIV-infected patients and thus reducing the risk of future bone fractures. HIV infection is associated with a state of enhanced bone loss. HIV treatment with highly active antiretroviral therapy (HAART) further worsens rather than improve bone loss. Almost all HAART regimens that have been examined have been associated with bone loss. The consequence of this skeletal assualt is markedly elevated fracture prevalence among individuals living with HIV across a wide age range. It turns that the predominance of HAART associated bone loss occur within the first year of initiating therapy. In this study, we administered a single dose of 5 mg IV zoledronic acid, a long-acting bisphosphonate at the same time of HAART initiation to prevent HAART associated bone loss. At this dose, zoledronic acid prevented enhance bone resorption in all participants and completely blunted bone mineral density loss over the 48 weeks study follow up period.
Author Interviews, HIV / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22087" align="alignleft" width="200"]Wim Parys MD Global Head R&D Global Public Health Janssen Dr. Wim Parys[/caption] Wim Parys MD Global Head R&D Global Public Health Janssen  Medical Research: What is the background for this study? What are the main findings? Dr. Parys: In collaboration with ViiV Healthcare, we are working to develop the first long acting all-injectable combination regimen of Janssen’s rilpivirine and ViiV’s cabotegravir. Yesterday, we have announced promising Phase 2b data of this combination regimen which when given together every 4 or 8 weeks was able to maintain viral suppression with similar efficacy to a daily oral regimen of three HIV medicines. The results show that the combination met its primary endpoint at week 32. The study will now continue in its randomized controlled design for another 64 weeks enabling us to assess longer term outcomes. In parallel to this we will work to initiate the next stages of clinical development.
Author Interviews, Global Health, HIV, NEJM, OBGYNE / 22.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21920" align="alignleft" width="200"]Jared Baeten, MD PhD Vice Chair, Department of Global Health Professor, Departments of Global Health, Medicine, and Epidemiology Co-Director, International Clinical Research Center University of Washington Dr. Jaret Baeten[/caption] Jared Baeten, MD PhD Vice Chair, Department of Global Health Professor, Departments of Global Health, Medicine, and Epidemiology Co-Director, International Clinical Research Center University of Washington MedicalResearch.com: What is the background for this studies? Dr. Baeten: Women account for nearly 60 percent of adults with HIV in sub-Saharan Africa, where unprotected heterosexual sex is the primary driver of the epidemic. While several studies have shown that antiretroviral medications (ARVs) are highly effective in preventing HIV, other studies – such as VOICE and FACTS 001 – suggest that for young, at-risk women in Africa, ARVs delivered as a vaginal gel or as a tablet may not be acceptable. Products must be used to be effective, and that was not the case for most of the participants in previous studies. Medical Research: What was the aim of ASPIRE and The Ring Study? Dr. Baeten: As Phase III clinical trials, ASPIRE and The Ring Study were designed to determine whether a vaginal ring containing an antiretroviral (ARV) drug called dapivirine is safe and effective in protecting women against HIV when used for a month at a time. These trials also sought to determine whether women find the vaginal ring practical and easy to use. As sister studies, ASPIRE and The Ring Study were designed as the centerpiece of a broader licensure program to provide the strength of evidence to support potential licensure of the dapivirine vaginal ring for preventing HIV in women. Because at least two Phase III efficacy trials are usually needed for a product to be considered for regulatory approval, ASPIRE and The Ring Study were conducted in parallel to accelerate the timeline to the ring’s potential approval.
Author Interviews, CDC, HIV / 21.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21878" align="alignleft" width="158"]Martin Hoenigl, MD Postdoctoral Fellow AntiViral Research Center, Department of Medicine University of California, San Diego Dr. Martin Hoenigl[/caption] Martin Hoenigl, MD Postdoctoral Fellow AntiViral Research Center, Department of Medicine University of California, San Diego Medical Research: What is the background for this study? Response: The detection of acute HIV infection (AHI) is critical to HIV prevention and treatment strategies. Many field-based testing programs rely on point-of-care HIV antibody testing, which will reliably identify persons with established infection, but fail to detect persons with AHI. In many of these programs additional tests for AHI are only performed / recommended in persons presenting with signs and symptoms consistent with an acute retroviral syndrome (ARS). These signs and symptoms are unspecific and include fatigue, headache, pharyngitis, skin rash, GI symptoms, night sweats and others. However, the proportion of persons with acute HIV infection presenting symptomatic for their diagnostic test remains unknown. The objective of our study was therefore to determine the proportion of persons with acute HIV infection presenting with signs and symptoms consistent with ARS for HIV screening. Medical Research: What are the main findings? Response: We analyzed signs and symptoms in 90 patients diagnosed with acute HIV infection in a community-based program in San Diego that offered universal HIV-1 nucleic acid amplification testing, independent of signs and symptoms. Forty-seven (52%) patients reported ongoing signs or symptoms consistent with ARS on the day of NAT screening. Another 25 (28%) reported signs or symptoms that had occurred during the 14 days before testing, but had resolved by the testing date. Another 12 (13%) reported signs and symptoms that started after the diagnostic test. Only 6/90 (7%) reported no signs and symptoms consistent with ARS. As a secondary finding, viral loads were significantly higher (p=0.001) in the 72 individuals reporting signs and symptoms consistent with ARS before or at the time of NAT screening compared to the 18 participants who did not report signs and symptoms at their diagnostic test. Most frequently reported ARS signs and symptoms included fever, myalgia, fatigue and headache.
Addiction, Author Interviews, HIV / 16.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21665" align="alignleft" width="200"]Pedro Mateu-Gelabert, Ph. D. Principal Investigator National Development Research Institutes, Inc. New York, NY 10010 Dr. Pedro Mateu-Gelabert[/caption] Pedro Mateu-Gelabert, Ph. D. Principal Investigator National Development Research Institutes, Inc. New York, NY 10010  Medical Research: What is the background for this study? What are the main findings? Dr. Mateu-Gelabert: Heroin production in Colombia increased dramatically in recent decades, and some studies point to an increase in local heroin consumption since the mid-1990s. Despite this rapid increase, little is known about the effects of these activities on heroin injection within Colombia. One of the biggest concerns surrounding heroin injection is the potential spread of HIV through drug user networks. Medical Research: What should clinicians and patients take away from your report? Dr. Mateu-Gelabert: The key take home message in the paper is that a widespread early implementation of harm reduction services (e.g. opioid substitution therapy, HIV testing, syringe exchange programs)  can prevent HIV among young PWID (People Who Inject Drugs) before it rapidly spreads within drug injection networks. Reducing HIV among young drug injectors could prevent the spread of HIV from PWID to the general population.
Author Interviews, CDC, HIV, Sexual Health / 12.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21546" align="alignleft" width="141"]Laura Kann, PhD Chief of the School-Based Surveillance Branch (SBSB) Division of Adolescent and School Health (DASH). CDC Dr. Laura Kann[/caption] Laura Kann, PhD Chief of the School-Based Surveillance Branch (SBSB) Division of Adolescent and School Health (DASH). CDC  Medical Research: What is the background for this study? Dr. Kann:  Young persons aged 13–24 years accounted for an estimated 22% of all new diagnoses of human immunodeficiency virus (HIV) infection in the United States in 2014. Most new HIV diagnoses among youths occur among males who have sex with males (MSM). Among all MSM, young black MSM accounted for the largest number of new HIV diagnoses in 2014 (4,398 among blacks, 1,834 among Hispanics, and 1,366 among whites).  Although other studies have examined HIV-related risk behaviors among MSM, less is known about MSM aged <18 years. Medical Research: What are the main findings? Dr. Kann:  Among male students who had sexual contact with males, black students had a significantly lower prevalence than white students of drinking five or more drinks of alcohol in a row; ever using inhalants, heroin, ecstasy, or prescription drugs without a doctor’s prescription; and drinking alcohol or using drugs before last sexual intercourse. Black students also had a significantly lower prevalence than Hispanic students of drinking five or more drinks of alcohol in a row and ever using cocaine, inhalants, methamphetamines, ecstasy, or steroids without a doctor’s prescription.  However, among male students who had sexual contact with males, black students had a significantly higher prevalence than white students of ever having had sexual intercourse and using a condom during last sexual intercourse; black students also had a higher prevalence than Hispanic students of ever having sexual intercourse.
Author Interviews, HIV, Social Issues, Yale / 10.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21438" align="alignleft" width="191"]Kristina Marie Talbert-Slagle, PhD Lecturer in Epidemiology (Microbial Diseases) and in Public Health (Health Policy); Senior Scientific Officer, Yale Global Health Leadership Institute Yale School of Public Health Dr. Talbert-Slagle[/caption] Kristina Marie Talbert-Slagle, PhD Lecturer in Epidemiology (Microbial Diseases) and in Public Health (Health Policy); Senior Scientific Officer, Yale Global Health Leadership Institute Yale School of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Talbert-Slagle: The interest for this study originally came as a result of work done by Elizabeth Bradley, PhD, co-author of The American Health Care Paradox.  In the book, Dr. Bradley compared spending rates of social services to health care services between the U.S. and other countries and found that while the U.S. invested more money in health care services than any other country we had worse health outcomes.  By contrast, countries that spent more on social services per dollar spent on health care had better outcomes. We applied that same idea to AIDS.  There are still more than 50,000 cases of HIV/AIDS diagnosed in the U.S. each year.  Although many medical advances have been made in treatment and prevention of this infection, we were curious as to why rates of HIV/AIDS have remained stagnate.  We wanted to explore how spending relates to differences in case rates among the states and found a significant difference among states regarding social service and public health spending related to HIV/AIDS.  We looked at all 50 states’ spending habits over the past 10 years and discovered that states that invested more money in social services such as education, housing, and nutrition per person in poverty had significantly lower rates of HIV/AIDS deaths.
Author Interviews, CDC, HIV, Race/Ethnic Diversity / 10.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21447" align="alignleft" width="133"]Sharoda Dasgupta, PhD, MPH  US Public Health Service and Epidemic Intelligence Service Officer CDC Dr. Sharoda Dasgupta[/caption] Sharoda Dasgupta, PhD, MPH  US Public Health Service and Epidemic Intelligence Service Officer CDC Medical Research: What is the background for this study? Dr. Dasgupta: Roughly 1.2 million people in the United States are living with HIV, and about 40,000 diagnoses occur each year, according to the most recent CDC data. According to national estimates published by CDC, African Americans remain disproportionately affected by the virus. African Americans represent 12 percent of the U.S. population but accounted for almost 50 percent of HIV diagnoses in 2014. Some signs have emerged that HIV is loosening its grip on the African American community, but persistent disparities are prolonging HIV transmission. Antiretroviral therapy (ART) improves clinical outcomes for people living with HIV and reduces their risk of transmitting the virus to others. Racial and ethnic disparities in HIV care, however, limit access to ART, which perpetuates disparities in survival and HIV transmission. Although previous studies have mostly analyzed HIV care by race and ethnicity during a single year, the purpose of this study was to better understand how people living with HIV remain in care over a longer period in time – and whether their retention in care differed by race and ethnicity.  Medical Research: What are the main findings? Dr. Dasgupta: This analysis focused on 12 U.S. jurisdictions that reported comprehensive HIV lab results to CDC from January 2010 – December 2013. They represent approximately 25 percent of HIV diagnoses in 2010. The findings demonstrate yet another persistent disparity that prolongs the epidemic among African Americans. Only 38 percent of African Americans received consistent HIV care from 2011 – 2013, compared with 49% of whites and 50% of Latinos. Additionally, African American males were less likely to receive consistent medical care than African American females (35 percent and 44 percent, respectively). Among African Americans, receiving consistent HIV care was highest among those whose HIV infections were attributable to heterosexual contact. Those who received consistent HIV medical care for three years were considered consistently retained in care.
Author Interviews, Compliance, HIV, Lancet / 03.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21259" align="alignleft" width="134"]Dr Marcel Yotebieng, PhD Department of Epidemiology Ohio State University, 304 Cunz Hall Columbus, OH Dr. Marcel Yotenbieng[/caption] Dr Marcel Yotebieng, PhD Department of Epidemiology Ohio State University, 304 Cunz Hall Columbus, OH Medical Research: What is the background for this study? What are the main findings? Response: With the current World Health Organization recommended treatment for the prevention of mother-to-child HIV transmission (PMTCT), the risk of transmission of HIV from an infected mother to her baby can be cut from 35-45% to less than 5% in breastfeeding population and <1% in non-breastfeeding population. But in sub-Saharan Africa where over 90% of HIV-infected pregnant women worldwide live, transportation costs and opportunity costs to attend regular clinic visits (to collect drugs) have been identified as important barriers to PMTCT. The provision of economic incentives has the potential to help women overcome these economic barriers. In addition, by creating immediate rewards that “nudge” individuals towards positive health behaviors, financial incentives can also address psychological barriers to health-seeking behavior of HIV-infected pregnant and breastfeeding women. This is the first study to use small cash incentives to encourage women to attend clinic visit and received available PMTCT care. We found that, among newly diagnosed HIV-infected women, small, incremental cash incentives resulted in increased retention along the  prevention of mother-to-child HIV transmission cascade and uptake of available services.
Author Interviews, HIV, PLoS / 26.01.2016

[caption id="attachment_21005" align="alignleft" width="200"]Julian Falutz, MD Director, HIV Metabolic Clinic MUHC,  Coordinator of Chronic Viral Illness Service, HIV and Aging Clinic McGill University Health Center Dr. Julian Falutz[/caption] MedicalResearch.com Interview with: Julian Falutz, MD Director, HIV Metabolic Clinic MUHC, Coordinator of Chronic Viral Illness Service, HIV and Aging Clinic McGill University Health Center Medical Research: What is the background for this study? What are the main findings? Dr. Falutz: The long-term use of antiretroviral therapy (ART) in HIV-infected patients is associated with body composition changes, including visceral adipose tissue (VAT) accumulation. HIV-infected patients with excess VAT may be at increased risk of type 2 diabetes, cardiovascular diseases, and mortality. Tesamorelin is a synthetic analog of human growth hormone-releasing factor, also known as growth hormone-releasing hormone (GHRH), which is indicated for the treatment of excess abdominal fat in HIV-infected patients with lipodystrophy. The objectives of our paper were to 1) evaluate the utility of patient characteristics and validated disease-risk scores, including indicator variables for the metabolic syndrome and the Framingham Risk Score (FRS), as predictors of  visceral adipose tissue reduction during tesamorelin therapy, and 2) to explore the characteristics of patients who reached a threshold of VAT <140 cm2, a level associated with lower risk of adverse health outcomes, after 6 months of treatment with tesamorelin. The basis of the report was a pooled analysis of the two pivotal, randomized Phase 3 trials of tesamorelin in 806 HIV-infected patients with excess abdominal fat. Our results indicate that presence of metabolic syndrome, high triglycerides, and white race are associated with a greater likelihood of responding to 6 months of tesamorelin treatment. The most robust response appears to be in subjects with VAT above 140 cm2, as well as those in the overweight range for body mass index (BMI) measures.
Author Interviews, HIV / 05.01.2016

  [caption id="attachment_20435" align="alignleft" width="150"]Dr. Christina Polyak MD MPH Acting Instructor with the University of Washington Clinical research physician at the U.S. Military HIV Research Program Walter Reed Army Institute of Research at WRAIR Bethesda, MD 20817 Medical Research: What is the background for this study? What are the main findings? Dr. Polyak: Today, 35 million people are infected with HIV, the virus that causes AIDS. Cotrimoxazole (CTX) is low-cost and widely utilized broad spectrum antibiotic used to prevent opportunistic infections in patients with HIV. CTX prophylaxis is recommended by the World Health Organization (WHO) for HIV infected adults in settings with high infectious disease prevalence. In these settings, the threshold for CTX discontinuation is undefined. We designed a study to determine whether CTX discontinuation was non-inferior to continued CTX-prophylaxis in decreasing morbidity in adults with evidence of immune reconstitution (CD4 >350 and 18 months on ART). Our findings show that combined morbidity/mortality was significantly higher in the CTX discontinuation arm (RR=2.27, 95% CI 1.52-3.38;p<0.001), driven by malaria morbidity. This suggests that CTX discontinuation among ART-treated, immune-reconstituted adults in malaria-endemic regions resulted in increased incidence of malaria but not pneumonia or diarrhea. These data helped inform and support the 2014 WHO CTX guidelines. Medical Research: What should clinicians and patients take away from your report? Dr. Polyak: CTX discontinuation among ART-treated adults in a region with endemic malaria resulted in increased incidence of clinical malaria but not pneumonia or diarrhea. The implications are broad and our results suggest that CTX prophylaxis should continue in regions with endemic malaria. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Polyak: Understanding the burden of malaria, pneumonia and diarrhea in the HIV-uninfected community would be prudent to compare background rates of disease. Citation: Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial Christina S. Polyak ,Krista Yuhas, Benson Singa, Monica Khaemba, Judd Walson, Barbra A. Richardson,Grace John-Stewart Published: January 5, 2016 DOI: 10.1371/journal.pmed.1001934 Dr. Christina Polyak[/caption] MedicalResearch.com Interview with: Dr. Christina Polyak MD MPH Acting Instructor with the University of Washington Clinical research physician at the U.S. Military HIV Research Program Walter Reed Army Institute of Research at WRAIR Bethesda, MD  20817 Medical Research: What is the background for this study? What are the main findings? Dr. Polyak:    Today, 35 million people are infected with HIV, the virus that causes AIDS.   (CTX)  is low-cost and widely utilized broad spectrum antibiotic used to prevent opportunistic infections in patients with HIV.  CTX prophylaxis is recommended by the World Health Organization (WHO) for HIV infected adults in settings with high infectious disease prevalence.   In these settings, the threshold for CTX discontinuation is undefined.  We designed a study to determine whether CTX discontinuation was non-inferior to continued CTX-prophylaxis in decreasing morbidity in adults with evidence of immune reconstitution (CD4 >350 and 18 months on ART).  Our findings show that combined morbidity/mortality was significantly higher in the CTX discontinuation arm (RR=2.27, 95% CI 1.52-3.38;p<0.001), driven by malaria morbidity.   This suggests that CTX discontinuation among ART-treated, immune-reconstituted adults in malaria-endemic regions resulted in increased incidence of malaria but not pneumonia or diarrhea.  These data helped inform and support the 2014 WHO CTX guidelines.
Author Interviews, HIV, Immunotherapy, PLoS / 04.12.2015

[caption id="attachment_19703" align="alignleft" width="169"]Andreas Meyerhans, PhD ICREA Research Professor at the University Pompeu Fabra Infection Biology Group Department of Experimental and Health Sciences Universitat Pompeu Fabra Barcelona Spain Dr. Meyerhans[/caption] MedicalResearch.com Interview with: Andreas Meyerhans, PhD ICREA Research Professor at the University Pompeu Fabra Infection Biology Group Department of Experimental and Health Sciences Universitat Pompeu Fabra Barcelona Spain Medical Research: What is the background for this study? What are the main findings? Dr. Meyerhans: In brief, chronic HIV infections lead to a dampening of HIV-specific killer cells. This phenomenon is named exhaustion and is mediated by inhibitory proteins, such as PD-1, on the cell surface. A consequence of exhaustion is a reduction of the immune control over virus expansion. We have studied the effect of blocking the negative signaling from the inhibitory proteins by means of PD-1/PD-L1 pathway inhibition on effector and regulatory T cells (Treg). We found that one can augment antiviral immune control only when the virus load was well controlled in the HIV-infected individuals i.e. by antiviral drugs. In that case, PD-1/PD-L1 pathway blockage led to an expansion of anti-HIV killer cells over Treg cells. This latter are suppressive white blood cells also subject to the same inhibitory pathway regulation. In contrast, when blood cells from viremic HIV-infected individuals were analyzed, Treg cells expanded efficiently and thus reduced the effector to regulatory T cell ratio that controls HIV. Taken together, our data point to Treg cells as an important component in the outcome of PD-1/PD-L1 pathway inhibitor therapies and suggest a net gain in anti-HIV immune responses only when the HIV loads are well controlled during the administration of these novel compounds.
Author Interviews, CDC, Gender Differences, HIV / 03.12.2015

[caption id="attachment_19775" align="alignleft" width="200"]Dr. Andrew Auld MD, MSc Medical Epidemiologis Division of Global HIV & TB CDC Dr. Andrew Auld[/caption] MedicalResearch.com Interview with: Dr. Andrew Auld MD, MSc Medical Epidemiologist Division of Global HIV & TB CDC MedicalResearch: What is the background for this study? Dr. Auld: Equitable access to antiretroviral therapy for men and women living with HIV is a principle endorsed by most countries and funding bodies, including the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR). This analysis, including more than 765,000 adult patients starting antiretroviral therapy in 12 countries (10 African countries, Haiti, and Vietnam), is the most up-to-date and comprehensive assessment of differences in HIV treatment access among men and women with HIV in developing countries. MedicalResearch: What are the main findings? Dr. Auld: Investigators showed that in all 10 African countries and Haiti, women with HIV were far more likely to be on treatment than men. In these 11 countries, women were 23%–83% more likely to access antiretroviral therapy than men with HIV. In addition, in six African countries and Haiti, gender imbalance in HIV treatment access appears to be getting worse over time.
Author Interviews, HIV, NEJM, Sexual Health / 02.12.2015

[caption id="attachment_11351" align="alignleft" width="129"]MedicalResearch.com Interview with: Prof Jean-Michel Molina Maladies Infectieuses et Tropicales, Hôpital Saint-Louis, Paris France Prof. Molina[/caption] MedicalResearch.com Interview with: Dr Jean-Michel Molina Department of Infectious Diseases Saint-Louis Hospital and University of Paris Diderot Paris France MedicalResearch: What is the background for this study? What are the main findings? Dr. Molina: Men who have sex with men (MSM) are disproportionately affected by HIV worldwide and represent the today in Europe the largest group in which new HIV infections are diagnosed with no decrease over the last 8 years. The first study assessing preexposure prophylaxis (PrEP) efficacy among MSM was published in 2010 (the Iprex study) which reported for the first time a 44% reduced incidence of HIV in those randomized to receive daily tenofovir/emtricitabine  TDF/FTC (one pill per day) as compared to placebo. Adherence to a daily pill regimen was found to be challenging however since only half of the participants (according to drug detection in blood) were taking their daily regimen. Post-hoc analyses suggested that among those with drugs detectable in plasma, PrEP efficacy could be as high as 92%. However, long term adherence to a daily regimen represents the Achille’s heel of daily PrEP, as shown later in other large PrEP trials among women in Africa (VOICE and Fem-PrEP). Based on data from animal models we wished to assess whether PrEP with TDF/FTC taken on demand, at the time of sexual activity, could improve adherence, thereby efficacy and also improve safety and cost. In this randomized double blind placebo controlled trial, on demand PrEP with TDF/FTC reduced the incidence of HIV by 86% in the intent to treat analysis as compared to placebo, and the only 2 participants who became infected in the TDF/FTC arm after more than a year of follow-up, had discontinued the use of PrEP months before infection. The ANRS Ipergay study reports therefore a very high efficacy of PrEP, similar to that also reported in another PrEP study carried out in the UK among MSM with daily TDF/FTC (PROUD), which results were disclosed at the same time. Both studies have increased awareness about the real potential of PrEP and have had a strong impact on WHO and European guidelines.
Author Interviews, Columbia, Compliance, HIV, JAMA, Pediatrics / 04.11.2015

[caption id="attachment_18947" align="alignleft" width="165"]Dr. Louise Kuhn PhD Professor, Epidemiology Sergievsky Center Columbia University Dr. Kuhn[/caption] MedicalResearch.com Interview with: Dr. Louise Kuhn PhD Professor, Epidemiology Sergievsky Center Columbia University  Medical Research: What is the background for this study? What are the main findings? Dr. Kuhn: Ritonavir-boosted lopinavir-based antiretroviral therapy is recommended as first-line treatment for HIV-infected infants and young children while efavirenz is recommended for adults and older children. There are several advantages of transitioning HIV-infected children to efavirenz-based treatment as they get older.  These advantages include the possibility of once-daily dosing, simplification of co-treatment for tuberculosis, avoidance of some metabolic toxicities, preservation of ritonavir-boosted lopinavir for second-line treatment, and alignment of adult and pediatric treatment regimens. However, there have been concerns about possible reduced viral efficacy of efavirenz-based treatment in children exposed to nevirapine for prevention of mother-to-child transmission.  This is because efavirenz and nevirapine are in the same drug class and the majority of children who become infected despite exposure to nevirapine used for prevention have mutations in their virus that usually predict resistance to this drug class. In this study, we randomized HIV-infected children to two different treatment strategies: In the control strategy they remained on their initial ritonavir-boosted lopinavir regimen; in the alternative strategy they transitioned to an efavirenz-based regimen.  All children had been exposed to nevirapine used (unsuccessfully) to prevent mother to child HIV transmission and were virologically-suppressed (HIV in blood < 50 copies/ml) at the time of enrollment into the study.  We observed excellent virological control in both groups with fewer than 3% of children having levels of HIV in their blood greater than 1000 copies/ml.  Sustained suppression of virus in blood below 50 copies/ml throughout follow-up was achieved in 82% of the children transitioned to efavirenz-based treatment compared to 72% of children remaining on the control treatment.
Author Interviews, CDC, HIV, Sexual Health / 25.09.2015

Philip J. Peters MD DTM&H (Diploma in Tropical Medicine & Hygiene) Medical Officer, Division of HIV/AIDS Prevention US Centers for Disease Control and Preventio Atlanta GeorgiaMedicalResearch.com Interview with: Philip J. Peters MD DTM&H (Diploma in Tropical Medicine & Hygiene) Medical Officer, Division of HIV/AIDS Prevention US Centers for Disease Control and Prevention Atlanta Georgia Medical Research: What is the background for this study? What are the main findings? Dr. Peters: We recruited participants from the STOP project, an existing multi-site study in North Carolina, New York City, and San Francisco, to analyze self-reported HIV-related risk behaviors among men who have sex with men (MSM). We found that newly diagnosed HIV-positive gay and bisexual men in North Carolina (predominately young and African American) did not always report male sex partners at the time of HIV testing.
Author Interviews, HIV, PLoS / 25.09.2015

MedicalResearch.com Interview with: Christine Bourgeois Unité UMR 1184 / Centre IMVA CR1 INSERM, Coordinatrice site Bicêtre Le Kremlin-Bicêtre Cedex Medical Research: What is the background for this study? What are the main findings? Response: Antiretroviral therapy (ART)  treatment in HIV infected patients had successfully reduced the development of AIDS (acquired immune deficiency syndrome). However, chronic HIV infection in ART treated patients exhibit rapid uprising of viral load following ART interruption indicating that the virus is not eradicated and persist in some cellular or anatomical sites that are called “reservoir”. Secondly, ART controlled HIV-infected patients exhibit low grade inflammation developing despite efficient viral control. This low grade inflammation has been associated with non AIDS related pathologies. The aim of our work was to identify site that may combine viral persistence and inflammatory potential. We believed that adipose tissue was a very promising candidate because it included the major targets of HIV infection (CD4 T cells, and macrophages) and exhibited a highly pro-inflammatory potential. Although adipose tissue has been extensively studied as a target of antiretroviral toxicity, we readdress the role of adipose tissue as a reservoir and a site of inflammation. We demonstrated that indeed, adipose tissue from  Antiretroviral therapy controlled HIV-infected patients contained infected CD4 T cells that upon in vitro reactivation were able to produce HIV RNA. These results are extremely important because adipose tissue represents 15%-20% of body weight and is diffusely located. We thus identify a large new reservoir.
Author Interviews, HIV, Pediatrics / 24.09.2015

MedicalResearch.com Interview with: Gayatri Mirani MD and Tulane University School of Medicine New Orleans, Louisiana Paige L. Williams, PhD Department of Biostatistics Harvard T. H. Chan School of Public Health Boston, MA 02115 Medical Research: What is the background for this study Response: Combination antiretroviral therapy (cART) has resulted in a dramatic decrease in HIV-related opportunistic infections and deaths in US youth, but both continue to occur. IMPAACT P1074, a long-term US-based prospective multicenter cohort study funded through NIH was conducted from April 2008 to June 2014. We reviewed complications and mortality rates in HIV-infected US youth enrolled in this study. Comparisons were made with a previous observational cohort study, P219C. While P219C was conducted from 2000 to 2007, we restricted our analysis to 2004-2007 in order to evaluate changes over the past decade. A total of 1201 HIV-infected youth were enrolled in the IMPAACT P1074 study, with most (1040, or 90%) infected with HIV at birth. The overall study population was 52% female, 58% black non-Hispanic and 28% Hispanic. Their mean age at the first chart abstraction was 17.4 (±5.4 Std. Dev.) years. The majority were on cART, had a stable CD4 count (baseline mean > 500 cells/mm3) and a suppressed viral load over a median follow-up of 3.7 years. The P219C group was younger, with a mean age of 11.9 (±5.0 Std. Dev.) years at the start of the 2004-2007 follow-up period.
Author Interviews, HIV, PLoS / 10.09.2015

MedicalResearch.com Interview with: Augustine T. Choko MSc Malawi–Liverpool–Wellcome Trust Clinical Research Programme Blantyre, Malawi Medical Research: What is the background for this study? Response: Despite rapid scale up of HIV testing in the sub Saharan African region, half of people living with HIV are unware of their status. We investigated a novel approach of HIV self testing as an additional strategy to existing HIV testing options. Medical Research: What are the main findings? Response: Population uptake of HIV self testing was high at the first offer and remained high at the second offer 12 months later. The approach saw high numbers of adolescents and men testing. Community participants with 8% illiterate were able to do the test and correctly interpret it on their own with minimal training. People who self-tested positive were able to link into the clinic for antiretroviral therapy eligibility assessment.
Author Interviews, HIV, Lancet, Sexual Health / 10.09.2015

Prof-Sheena-McCormack.jpgMedicalResearch.com Interview with: Professor Sheena McCormack Clinical Epidemiology Medical Research Council Clinical Trials Unit University College London Medical Research: What is the background for this study? What are the main findings? Prof. McCormack: PROUD is the first study of pre-exposure prophylaxis (PrEP) to prevent HIV carried out in the UK. The results show that PrEP could play a major role in reducing the number of new infections among men who have sex with men who are at risk of catching HIV. Pre-exposure prophylaxis (PrEP) is a HIV prevention strategy that involves HIV-negative people taking some of the drugs we use for treatment of HIV to reduce the risk of becoming infected. The PROUD study (www.proud.mrc.ac.uk) looked at whether offering daily PrEP to men who have sex with men was an effective way to prevent HIV infection. The results show that pre-exposure prophylaxis is highly protective, reducing the risk of infection for this group by 86%. The drug used in the trial – the antiretroviral Truvada – was already known to reduce the incidence of HIV infection compared to placebo (a dummy pill).  The PROUD study was designed to see how good Truvada would be found as pre-exposure prophylaxis in a real world situation when participants knew they were taking an active drug.  It aimed to address outstanding questions such as whether taking PrEP would change sexual risk behaviour – for example increasing the number of partners they did not use condoms with and increasing the rate of other sexually transmitted infections (STIs) – and whether or not it would be cost-effective to make it available on the NHS.
Author Interviews, CDC, HIV, JAMA / 02.09.2015

Dr. John Weiser MD MPH Medical epidemiologist Division of HIV/AIDS Prevention CDC MedicalResearch.com Interview with: Dr. John Weiser MD MPH Medical epidemiologist Division of HIV/AIDS Prevention CDC  Medical Research: What is the background for this study? What are the main findings? Dr. Weiser: Ryan White was an Indiana teenager diagnosed with AIDS in the late 1980s. As a result of fear and stigma, he was barred from school and went on to become a national advocate for HIV education and acceptance. This year marks the 25th anniversary of his death and passage of the Ryan White CARE Act creating The Ryan White HIV/AIDS Program (RWHAP) which provides funding for healthcare facilities to deliver needed medical care and support services for hundreds of thousands of poor, uninsured, and underinsured Americans. While increased access to Medicaid and private insurance under the Affordable Care Act will provide coverage for medical care, it might not provide coverage for support services so it is likely that the RWHAP will continue to play a key role in providing these crucial services. Overall, 34.4 percent of facilities received Ryan White HIV/AIDS Program funding and 72.8 percent of patients received care at RWHAP-funded facilities. Many of the patients at Ryan White HIV/AIDS Program -funded facilities had multiple social determinants of poor health, with patients at RWHAP-funded facilities more likely to be ages 18 to 29; female; black or Hispanic; have less than a high school education; income at or below the poverty level; and lack health care coverage. Despite the greater likelihood of poverty, unstable housing and lack of health care coverage, nearly 75 percent of patients receiving care at RWHAP-funded facilities achieved viral suppression. The percentage of ART (antiretroviral therapy) prescribing was similar for patients at RWHAP-funded compared with non-funded facilities. Patients at RWHAP-funded facilities were less likely to be virally suppressed. However, individuals at or below the poverty level and those ages 30 to 39 who received care at a RWHAP-funded facility compared with those who received care at a non-RWHAP-funded facility were more likely to achieve viral suppression.
Author Interviews, HIV, NIH, Pediatrics, Vaccine Studies / 15.08.2015

George K Siberry, MD, MPH, Medical Officer Maternal and Pediatric Infectious Disease (MPID) Branch Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, MDMedicalResearch.com Interview with: George K Siberry, MD, MPH, Medical Officer Maternal and Pediatric Infectious Disease (MPID) Branch Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, MD Medical Research: What is the background for this study? Dr. Siberry:  Vaccines may not work as reliably in children with HIV infection, especially when their HIV is not under effective treatment. Today, most children in the United States who were born with HIV infection are receiving effective HIV treatment and have reached school age or even young adulthood. However, many received their childhood vaccines before they got started on their HIV treatment (because modern HIV treatments weren’t available when they were very young or their HIV infection was diagnosed late). So we wanted to see if these older children still had immunity from the vaccines they received when they were much younger. Medical Research:  What are the main findings? Dr. Siberry: We looked specifically at whether older children with HIV since birth were protected against measles, mumps, and rubella, the three viral infections covered by the measles-mumps-rubella (or MMR) vaccine. We found that 1/3 up to almost 1/2 of these children were not protected against these viruses, even though nearly all of the children had received at least 2 MMR doses, as recommended. And even if their HIV was currently under excellent control.  When we analyzed factors that were linked to being protected, we found that one of the most important factors was whether you got your MMR vaccine doses after you got on good treatment for your HIV infection.  For instance, over 85% of children who had gotten at least 2 MMR vaccine doses after being on effective HIV treatment were protected against measles compared to less than half of those who didn’t get both of their MMR vaccine doses while on effective HIV treatment.
Addiction, Author Interviews, HIV, Lancet / 10.08.2015

MedicalResearch.com Interview with: Dr. Keith Ahamad, a clinician scientist at the BC Centre for Excellence in HIV/AIDS and a Family Doctor trained and certified in Addiction Medicine.  He is Division Lead for Addiction Medicine in the department of Family and Community Medicine at Providence Health Care, and is also an addiction physician at the St. Paul’s Addiction Medicine Consult Service, the Immunodeficiency Clinic and Vancouver Detox. He is also Lead Study Clinician for CHOICES, a US National Institutes of Drug Abuse (NIDA) funded clinical trial looking at an opioid receptor blocker (Vivitrol) to treat opioid or alcohol addiction in HIV positive patients.Dr. Keith Ahamad, a clinician scientist at the BC Centre for Excellence in HIV/AIDS and a Family Doctor trained and certified in Addiction Medicine. He is Division Lead for Addiction Medicine in the department of Family and Community Medicine at Providence Health Care, and is also an addiction physician at the St. Paul’s Addiction Medicine Consult Service, the Immunodeficiency Clinic and Vancouver Detox. He is also Lead Study Clinician for CHOICES, a US National Institutes of Drug Abuse (NIDA) funded clinical trial looking at an opioid receptor blocker (Vivitrol) to treat opioid or alcohol addiction in HIV positive patients. MedicalResearch: What is the background for this study? Dr. Ahamad: Previous methadone research has mostly been done in restrictive settings, such as the USA, where methadone can only be dispensed through restrictive methadone programs and cannot be prescribed through primary care physician’s offices. Since a systematic review in 2012, randomised controlled trials have compared methadone treatment provided at restrictive specialty clinics with primary care clinics, which have shown the benefits of primary care models of methadone delivery on heroin treatment outcomes, but not on HIV incidence. MedicalResearch: What are the main findings? Dr. Ahamad: After adjusting for factors commonly associated with HIV, methadone remained independently associated in protecting against HIV in this group of injection drug users. Those study participants who were not prescribed methadone at baseline were almost four times more likely to contract HIV during study follow up. MedicalResearch: What should clinicians and patients take away from your report? Dr. Ahamad: Methadone is an effective medication in treating opioid addiction. Through international randomized control trials, we already know that when prescribed though primary care offices, access to this life-saving medication is increased, effective, and increases patient satisfaction. Now, through our study, we have evidence that when delivered in this manner, it also decreases the spread of HIV.
Author Interviews, CDC, HIV, Sexual Health / 06.08.2015

Adaora Adimora, MD, MPH Chair of the HIV Medicine Association Professor of Medicine School of Medicine University of North Carolina, Chapel Hill.MedicalResearch.com Interview with: Adaora Adimora, MD, MPH Chair of the HIV Medicine Association Professor of Medicine School of Medicine University of North Carolina, Chapel Hill. MedicalResearch: What is the current scope of the HIV epidemic? Dr. Adimora: The Centers for Diseases Control and Prevention (CDC) estimates that there are 1.2 million people living with HIV in the U.S. Nearly 13% are undiagnosed and unaware of their status. Men who have sex with men represented 54% of all people living with HIV in 2011. While new infection rates are stable, a majority of new infections (63%) are occurring among men who have sex with men. We have seen alarming increases among young black men who have sex with men who account for 55% of new infections among men who have sex with men. New infections among women have decreased slightly but black and Hispanic/Latina women represent 62% and 17% of new infections respectively among women.[i] While there have been decreases in new HIV infections among people who inject drugs in recent years, the serious outbreak largely among injection drug users in Scott County, Indiana identified this past spring[ii] puts us on high alert to improve access to preventive services and substance use treatment, including access to sterile syringes and equipment. My responses will generally focus on the U.S. epidemic but want to acknowledge that globally an estimated 36.9 million people were living with HIV at the end of 2014 with just 51% of them being diagnosed and more than 34 million deaths were attributed to HIV-related causes.[iii]