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,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]
Author Interviews, HIV, PLoS, UC Davis / 31.07.2015

Dr. Satya Dandekar PhD Professor and Chair Department of Medical Microbiology and Immunology UC DavisMedicalResearch.com Interview with: Dr. Satya Dandekar PhD Professor and Chair Department of Medical Microbiology and Immunology UC Davis Medical Research: What is the background for this study? What are the main findings? Dr. Dandekar: Current anti-retroviral therapy is effective in suppressing HIV replication and enhancing immune functions in HIV infected individuals. However, it fails to eradicate the latent HIV reservoirs. Therapy interruption leads to a rapid viral rebound in these patients.  Eradication of latent HIV reservoirs is essential to achieve HIV cure. A “shock and kill” strategy for HIV cure has been proposed that involves reactivation of latent viral reservoirs using latency reversal agents (LRA) and eradication by the immune response. This highlights the need to identify potent LRAs to optimally activate latent HIV reservoirs so that immune surveillance and clearance mechanisms can be effectively engaged in the process of viral eradication. We have found that ingenol-3-angelate (PEP005), an anti-cancer drug can effectively reactivate latent HIV. It is a protein kinase C agonist that activates NF-kB and stimulates HIV expression. In combination with another compound, JQ1, a previously known p-TEFb agonist, the efficacy of PEP005 for HIV reactivation is markedly increased. In addition, ingenol-3-angelate decreases the expression of HIV co-receptors on immune cells, which potentially will help preventing further spread of the virus. The use of ingenol-3-angelate in combination with other latency reversal agents provides an excellent opportunity to optimally activate latent HIV reservoirs and target them for eradication.
Author Interviews, HIV, Sexual Health, UCSD / 05.06.2015

MedicalResearch.com Interview with: Dr. Martin Hoenigl Center for AIDS Research University of California, San Diego Medical Research: What is the background for this study? What are the main findings? Dr. Hoenigl: Although men who have sex with men (MSM) represent a dominant risk group for human immunodeficiency Virus, the risk of HIV infection within this population is not uniform. Characterizing and identifying the MSM at greatest risk for incident HIV infection might permit more focused delivery of both prevention resources and selection of appropriate interventions, such as intensive counseling, regular HIV screening with methods that detect acute infection (ie, nucleic acid amplification test), and antiretroviral preexposure prophylaxis (PrEP). By using data collected at a single HIV testing encounter from 8326 unique MSM were analyzed, including 200 with AEH (2.4%), we were able to create the San Diego Early Test (SDET) risk score. The SDET score consist of four risk behavior variables which were significantly associated with an AEH diagnosis (ie, incident infection) in multivariable: condomless receptive anal intercourse (CRAI) with an HIV-positive MSM (3 points), the combination of CRAI plus 5 or more male partners (3 points), 10 or more male partners (2 points), and diagnosis of bacterial sexually transmitted infection (2 points), all as reported for the prior 12 months. The SDET risk score is deployed as a freely available tool at http://sdet.ucsd.edu.
Author Interviews, CDC, HIV / 04.06.2015

MedicalResearch.com Interview with: Sandra Schwarcz, MD Senior HIV epidemiologist San Francisco Department of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Schwarcz: AIDS opportunistic illnesses continue to occur despite effective antiretroviral therapy. Although previous studies examined survival following a diagnosis of an opportunistic illness, there are few recent reports that are population-based. The San Francisco Department of Public Health has the only population-level data on the occurrence of and survival following opportunistic illnesses and use of antiretroviral therapy among persons reported with HIV in the United States. By measuring survival following the occurrence of opportunistic illnesses, we were able to document that survival following opportunistic illnesses has improved with better HIV treatment. However, opportunistic illnesses continue to occur and carry substantial mortality risk. Even in this era of effective HIV therapy, we found that 35% of persons who developed an opportunistic illness died within five years of their diagnosis and some opportunistic illnesses such as brain lymphoma and  progressive multifocal leukoencephalopathy remain highly lethal.
Author Interviews, HIV, NYU/NYMC, Race/Ethnic Diversity, Sexual Health / 22.05.2015

Perry N Halkitis, Ph.D., M.S., MPH Professor of Applied Psychology Global Public Health, and Population Health/Medicine New York University.MedicalResearch.com Interview with: Perry N Halkitis, Ph.D., M.S., MPH Professor of Applied Psychology Global Public Health, and Population Health/Medicine New York University. Medical Research: What is the background for this study? Dr. Halkitis: The P18 Cohort Study is a prospective cohort study of gay, bisexual and other young men who have sex with men (YMSM) which seeks to examine the development of health behaviors as these young men transition from adolescent to adulthood. Officially named “Syndemic Production among Emergent Adult Men”, this study was funded by the National Institute on Drug Abuse from 2009-2014 and renewed on March 1, 2014 for an additional five years. The original aims of the study were as follows:
  • 1) to develop and test theoretically informed measurement models of the covariance of illicit drug use, unprotected sexual behavior and mental health burden (multiple overlapping epidemics known as a syndemic) among emergent adult HIV-negative YMSM within and across time;
  • 2) to delineate the risk and protective bases- physical factors (e.g., pubertal onset, HIV status, etc.), relational and structural factors (e.g., family history of psychopathology, current romantic relationships, peer support, neighborhood factors, etc.), and psychosocial factors (e.g., sexual identity, internalized homophobia, hyper-masculine conceptions, etc.) that predict the development of syndemics; and
  • 3) to determine the extent to which the development of a syndemic varies by race/ethnicity, social class, and homelessness/housing instability.
  • In this current five year continuation we also seek
    • 1) to describe the social and sexual networks of YMSM, and to examine the relationship between social and sexual network-level structural characteristics, social support and normative influences on syndemic production (illicit drug use, unprotected sexual behaviors, and mental health burden) in YMSM, singly and in combination with the physical, psychosocial, and relational predictors, both within and across time;
    • 2) to describe the acquisition of sexually transmitted infections (STIs) in YMSM, specifically, urethral and rectal gonorrhea and chlamydia, pharyngeal gonorrhea as well as syphilis serology; and to determine the extent to which physical, relational, and psychosocial factors explain STI acquisition as part of the syndemic model within and across time.
    • A third exploratory aim was also added: 3) to describe HIV clinical treatment markers (i.e., HIV viral load, ART uptake and adherence, HIV care) among HIV+ YMSM, and to assess the extent to which physical, relational, and psychosocial factors are associated with differences in these clinical markers among HIV+ YMSM, both within and across time. The study is led by Drs. Perry N Halkitis and Farzana Kapadia at New York University’s Center for Health, Identity, Behavior & Prevention Studies.
Potential participants were recruited through both active (e.g., approaching individuals to solicit study participation) and passive (e.g., flyer posting, website advertisements) methods from June 2009 to May 2011. Eligibility criteria included being 18-19 years old, biologically male, residing in the NYC metropolitan area, having sex (any physical contact that could lead to orgasm) with a man in the last 6 months, and reporting a seronegative or unknown HIV status at baseline. We ensured the diversity of our sample by setting a fixed recruitment quota for participants in each targeted racial/ethnic group, such that African Americans, Latino (across race), Asian-Pacific Islander (API), and mixed race men comprised the majority of the sample. All participants provided written, informed consent before data was collected and were compensated for their time and effort upon completing the baseline assessment. The New York University’s Institutional Review Board (IRB) approved all study protocols and a federal Certificate of Confidentiality protects these data. A total of 2,068 participants were screened for eligibility to participate in the study, and 600 participants completed the baseline assessment in the first wave of the study. In 2014, we began the second wave and opened to cohort to recruit a baseline sample of 650 YMSM who will now be between the ages of 22-23; recruitment of participants is still underway. Medical Research: What are the main findings? Dr. Halkitis: Numerous publications have been generated from the P18 Cohort Study and can be accessed at www.chibps.org.  A recent publication, “Incidence of HIV infection in Young Gay, Bisexual, and other YMSM: The P18 Cohort Study” became available in the May 2015 of JAIDS, the Journal of Acquired Immune Deficiency Syndromes. This paper reports that over a 36 month follow-up period, during the first wave of the study, 7.2% of study participants seroconverted, with Black and Hispanic men much more likely to seroconvert over this time frame than White men. This finding aligns with epidemiological trends for HIV infection at the national and local, NYC, levels. Also, men reporting a lower familial socioeconomic status were more likely to seroconvert than men reporting high familial socioeconomic status, and Black men were more likely to report a lower socioeconomic status.  Moreover, the Black young men who seroconverted were more likely to reside in neighborhoods with higher area-level poverty and higher area-level HIV prevalence. Additionally we found that men who reported anal sex without a condom in the 30 days prior to assessment were no more likely to seroconvert than those who reported sex with a condom.  However, an earlier age of sexual debut was a predictor of HIV seroconversion.
Author Interviews, Diabetes, Endocrinology, HIV, Infections, JCEM / 18.05.2015

Kevin Yarasheski, PhD Assistant Director, Biomedical Mass Spectrometry Research Facility Professor of Medicine, Cell Biology & Physiology, Physical Therapy Washington University School of MedicineMedicalResearch.com Interview with: Kevin Yarasheski, PhD Assistant Director, Biomedical Mass Spectrometry Research Facility Professor of Medicine, Cell Biology & Physiology, Physical Therapy Washington University School of Medicine Medical Research: What is the background for this study? Dr. Yarasheski:   People living with HIV and taking combination antiretroviral therapy (cART) have successfully reduced the amount of HIV virus in their blood and have partially reconstituted their immune system (CD4+ T-cell count >250 cells/µL).  Despite this, many still experience residual immune cell activation and inflammation that is believed to increase HIV morbidity (non-AIDS conditions e.g., CVD, T2DM, obesity, liver fat, bone loss, dementia) and mortality.  Scientists are seeking safe and effective interventions for residual immune cell activation and inflammation, that have the potential to reduce non-AIDS complications that threaten quality and quantity of life among HIV infected adults. We have been testing the safety and efficacy of sitagliptin in people living with HIV; a dipeptidyl peptidase 4 inhibitor that is FDA approved for treating T2DM, and appears to have favorable anti-inflammatory and immune modulatory properties that might specifically benefit people living with HIV and experiencing cardiometabolic complications associated with residual immune cell activation and inflammation. Medical Research: What are the main findings? Dr. Yarasheski:   In a randomized, double-blinded, placebo controlled 8-wk trial, we found that sitagliptin had beneficial anti-inflammatory, immune regulatory, hematopoietic progenitor cell mobilizing, and glucose lowering effects in cART-treated virally suppressed HIV adults with impaired glucose tolerance.  Sitagliptin improved glucose tolerance (a risk factor for CVD), reduced circulating and adipose-specific inflammatory markers (risk factors for obesity, T2DM, liver fat accumulation, and CVD), and increased the number of blood stem cells that can repair damage and inflammation in the vascular walls.
Author Interviews, Compliance, HIV, NYU/NYMC / 06.04.2015

Marya Viorst Gwadz, Ph.D Senior Research Scientist Director, Transdisciplinary Methods Core Center for Drug Use and HIV Research (CDUHR) New York University College of Nursing New York, NY 10010 MedicalResearch.com Interview with: Marya Viorst Gwadz, Ph.D Senior Research Scientist Director, Transdisciplinary Methods Core Center for Drug Use and HIV Research (CDUHR) New York University College of Nursing New York, NY 10010 Medical Research: What is the background for this study? Dr. Gwadz: HIV is a major success story in that the tolerability, convenience, and efficacy of antiretroviral medications have improved dramatically over the last decade. A number of years ago in the course of another research study with vulnerable individuals infected with HIV in New York City, and we noticed that a substantial proportion of study participants were medically eligible for HIV medications, and had access to medications, but had declined or stopped taking them. We then turned our attention to understanding why this is the case, that is, to identify the individual, social, and structural barriers that persons living with HIV/AIDS (PLHA) experience to antiretroviral therapy. We focused in particular on African American/Black and Latino/Hispanic PLHA, because the overall emphasis of our research group at the NYU College of Nursing is the development and evaluation of culturally targeted intervention approaches to address health disparities. Around 2011, studies of the “HIV cascade of care” began to emerge, which highlighted the problem of poor engagement in HIV care and antiretroviral therapy nationally. The ultimate goal of HIV treatment is viral suppression, but at present, the Centers for Disease Control and Prevention (CDC) estimates that we have achieved that goal with only 30% of PLHA. Medical Research: What kind of intervention approach that emerged from these background findings? Dr. Gwadz: We found that barriers to HIV medication are complex and multi-faceted for PLHA from African American/Black and Latino/Hispanic backgrounds. In particular, PLHA experience serious emotional barriers to the uptake of HIV medications, such as fear of side effects, stigma, and disclosure of HIV status. Further, high rates of substance use and mental health distress, and barriers to accessing services for these concerns, impede medication uptake. Moreover, PLHA who are wary of HIV medication tend to avoid HIV primary care, often because they do not want to feel pressured to take medications, or explain to their providers why they are not taking them. So poor engagement in HIV care, which is very common among PLHA, and low uptake of HIV medication are actually related problems. With funding from the National Institute of Mental Health (grant #R34MH093352), and in collaboration with Mount Sinai Beth Israel and Mount Sinai St. Luke’s-Roosevelt Hospital Center, we developed a multi-component culturally targeted intervention grounded in the Motivational Interviewing approach that included three individual sessions, 12-24 weeks of patient navigation (as needed), up to five support groups with other PLHA who had declined medication, which were co-led by a “successful” peer who was engaged in HIV care and were taking HIV medication with good adherence. One novel aspect of the intervention was its focus on emotional barriers to HIV medication, and the program’s “no pressure, no judgment” stance, congruent with the Motivational Interviewing approach, was key to engaging participants into the study to talk about these difficult issues.
Author Interviews, HIV, JAMA, Pediatrics, University of Pennsylvania / 02.04.2015

Elizabeth Lowenthal, MD MSCE Assistant Professor of Pediatrics Children's Hospital of PhiladelphiaMedicalResearch.com Interview with: Elizabeth Lowenthal, MD MSCE Assistant Professor of Pediatrics Children's Hospital of Philadelphia Medical Research: What is the background for this study? What are the main findings? Dr. Lowenthal: Between 2005 and 2012, HIV related deaths declined by 30% worldwide. However, during the same time period, HIV related deaths increased 50% among adolescents. Over 90% of HIV-infected children and adolescents live in sub-Saharan Africa and HIV is the leading cause of death among adolescents in Africa. Treatment is available that can allow babies born with HIV to live to be healthy adults. However, strict adherence to these medicines is necessary and often becomes a great challenge during adolescence. In our study of 300 adolescents (ages 10-19) in Botswana, my team found that adolescents who come to clinic without a parent or guardian have a 4.5X greater odds of failing their HIV treatment.
Author Interviews, HIV, Race/Ethnic Diversity / 31.03.2015

MedicalResearch.com Interview with: Catherine R. Lesko, MPH Department of Epidemiology UNC School of Global Public Health Chapel Hill, NC Medical Research: What is the background for this study? What are the main findings? Response: There is a lot of evidence out there that HIV-infected minorities, and in particular, African Americans, experience higher morbidity and mortality than do their white, HIV-infected counterparts. This study looked at whether there were still differences in mortality among treated, HIV-infected adults, which was a crude attempt to control for differences in access to HIV-testing, HIV-care, and antiretroviral therapy - all things previously shown to contribute to racial disparities among people infected with HIV. Even among people who had initiated HIV therapy, we still found that black patients had a 10-year risk of mortality that was 8 percentage points greater than white patients. Hispanic patients did marginally better than white patients, but not as much better as their non-HIV-infected counterparts.
Author Interviews, CDC, HIV, Race/Ethnic Diversity, Sexual Health / 05.03.2015

MedicalResearch.com Interview with: Cyprian Wejnert Center For Disease Control MedicalResearch: What is the background for this study? What are the main findings? Cyprian Wejnert: Men who have sex with men (MSM) remain the risk group most severely affected by HIV in the United States, accounting for approximately two-thirds of new infections each year.  Understanding racial and age disparities among MSM is critical to tailor effective prevention efforts. Our study examined data from CDC’s National HIV Behavioral Surveillance system (NHBS) from 20 U.S. cities. We assessed changes in HIV prevalence, awareness of infection, and risk behavior among MSM, by age and race, from 2008 to 2011, finding that: o   Among black Men who have sex with men, 30 percent were HIV-infected overall, and 1 in 5 black MSM aged 18-24 were infected with HIV. Compared to 14 percent and 4 percent among white MSM. o   In all age groups younger than 40 years, black Men who have sex with men were significantly more likely to be HIV-positive compared to all other racial/ethnic groups. o   Disparities in HIV prevalence between black and white MSM were greatest among the youngest MSM, and increased between 2008 and 2011. o   Black MSM were less likely to be aware of their infection than their white counterparts (54 vs. 86 percent). o   Black Men who have sex with men did not report higher levels of condomless sex overall or condomless sex with partners of discordant or unknown HIV status.
Author Interviews, CDC, Gender Differences, HIV, Race/Ethnic Diversity / 05.03.2015

MedicalResearch.com Interview with: Dr. Ndidi Nwangwu-Ike Center Disease Control MedicalResearch: What is the background for this study? What are the main findings? Response: CDC data has shown encouraging signs of a decrease in new HIV infections among black women in recent years.  However, African American women continue to be far more affected by HIV than women of any other race or ethnicity, with a rate of new infection 20 times that of white women and nearly five times that of Hispanic women.  Ensuring people with HIV are diagnosed and remain in care is key to controlling HIV in the nation. When used consistently, antiretroviral medication can keep HIV controlled at very low levels in the body (known as viral suppression), allowing people with HIV to live longer, healthier lives and reducing the likelihood they will transmit HIV to others. Our study finds that viral suppression among women diagnosed with HIV is low, with young women and black women the least likely to achieve viral suppression. Specifically, we found that: o   Of women newly diagnosed with HIV in 2012, 83 percent were linked to care within three months of diagnosis. o   Retention in care varied by age and race/ethnicity; overall, just over half of women (52 percent) diagnosed and living with HIV in 2011 received ongoing HIV care. o   Overall, only 44 percent of women diagnosed and living with HIV in 2011 had a suppressed viral load.
Author Interviews, HIV, Nature, Scripps / 04.03.2015

Dr. Michael Farzan PhD Vice Chairman Department of Immunology and Microbial Science Florida Campus The Scripps Research InstituteMedicalResearch.com Interview with: Dr. Michael Farzan PhD Vice Chairman Department of Immunology and Microbial Science Florida Campus The Scripps Research Institute Medical Research: What is the background for this study? Dr. Farzan: The key points are that HIV-1 needs two receptors – CD4 and CCR5 – to infect cells.  CD4’s primary job is to initially bind the viral entry protein, which upon CD4 binding, uncloaks its CCR5 binding site.   A number of years ago we observed that CCR5 had an unusual modification that was really important to HIV-1.  We later showed that antibodies – protein your body makes to protect from pathogens – mimics CCR5 by incorporating this modification.  We develop a peptide from one of these antibodies that mimics CCR5. Medical Research: What are the main findings? Dr. Farzan: By combined a soluble form of CD4 with this CCR5-mimicking peptide, we created a protein that neutralizes all HIV-1 isolates tested, including the hardest-to-stop viruses, as well as distantly related viruses found in monkeys.  It does so better than the best HIV-1 antibodies.  We expressed this protein using a commonly used gene-therapy vector, and showed that after a one-time inoculation we could protect from doses much higher than most humans are likely to see, and we did so 34 weeks after the inoculation.
Author Interviews, Hepatitis - Liver Disease, HIV, JAMA, NIH / 28.02.2015

Shyamasundaran Kottilil MBBS, PhD University of MarylandMedicalResearch.com Interview with: Shyamasundaran Kottilil MBBS, PhD Division of Infectious Diseases, Institute of Human Virology, University of Maryland, Baltimore Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Kottilil:  Due to shared routes of transmission, almost half of all HIV-infected patients also have HCV infection. Traditionally, interferon based therapies have resulted in lower cure rates of HCV in HIV-infected subjects. Treatment for HCV is rapidly changing from an injection (interferon) based therapy to oral well tolerated pill based therapy for a shorter duration.Our intention was to test whether a treatment regimen without the use of interferon and ribavirin can be effective in HIV/HCV infected patients. Our study demonstrated that HIV/HCV connected patients without cirrhosis can be effectively treated with ledipasvir and sofosbuvir in 12 weeks. Overall 98% of patients were cured.
Author Interviews, CDC, HIV, Sexual Health / 14.02.2015

MedicalResearch.com Interview with: Kristen Hess  ORISE Fellow Division of HIV/AIDS Prevention, National Center for HIV, Viral Hepatitis, STD and TB Prevention Centers for Disease Control and Prevention Atlanta, GA MedicalResearch: What is the background for this study? Response: Men who have sex with men (MSM) of all races continue to be the risk group most severely affected by HIV in the United States. CDC’s most recent HIV incidence data show that the number of new infections among MSM increased 12 percent between 2008 and 2010, with an even steeper increase among the youngest MSM. These data clearly show the urgent need to better understand the factors that affect their risk and to develop effective prevention interventions. One specific factor is excessive alcohol use, which is responsible for 88,000 deaths in this nation each year, and cost the U.S. about $224 billion in 2006. Binge drinking (consuming ≥5 drinks for men on an occasion; ≥4 drinks for women) is the most common form of excessive alcohol consumption. The association between excessive alcohol consumption, including binge drinking, and risky sexual behaviors among MSM has had mixed results in the literature with some studies finding an association and others not. One limitation of previous work is that the definition of excessive alcohol consumption varies between studies, so results are not easily compared between studies and populations. Our study examines the relationship between binge drinking and sexual risk behaviors among MSM who are current drinkers and who were either HIV-negative or unaware of their HIV status. MedicalResearch: What are the main findings? Response: We assessed the prevalence of binge drinking, using a standard definition, among a sample of MSM recruited from 20 cities across the U.S. We also examined the association between binge drinking and several risky sexual behaviors. The findings show that 6 in 10 MSM reported binge drinking. Those who binge drank, in comparison to non-binge drinkers, were more likely to engage in risky sexual behaviors such as sex with an HIV-positive or unknown status partner and exchange sex for money or drugs at last sex, as well as more likely to have concurrent partners and more condomless sex partners in the past year. We also found that the likelihood of risky sexual behaviors went up with increased frequency of binge drinking. In fact, MSM who reported 10 or more binge-drinking episodes in the past month were more likely to report risky behaviors. This is a critical point, especially given that, among those who binged, 22 percent reported 10 or more binge drinking episodes in the past month.
HIV, Kidney Disease, NEJM, Transplantation / 11.02.2015

Elmi Muller, M.B., Ch.B., M.Med. University of Cape Town–Surgery Groote Schuur Hospital Observatory Cape Town Cape Town, South Africa MedicalResearch.com Interview with: Elmi Muller, M.B., Ch.B., M.Med. University of Cape Town–Surgery Groote Schuur Hospital Observatory Cape Town Cape Town, South Africa Medical Research: What is the background for this study? Dr. Muller: South Africa currently offers dialysis and transplantation as a treatment option for patients with End Stage Renal Disease (ESRD). However, dialysis is not freely available to everyone, but severely limited and only available to a selected group of patients. This means that patients get assessed when they present with ESRD and they only get accepted onto a dialysis programme if they fulfill certain criteria. These criteria are criteria to assess the patient’s medical fitness in general as well as social criteria to assess whether the patient will be compliant with follow-up.  In most state hospitals, patients will only be accepted onto a dialysis program if they are also fit to receive a transplant in the long run.  The idea is that dialysis programs should naturally feed into transplant programs. Therefore a patient who is not a suitable transplant candidate will normally be turned down for dialysis. In 2008, when the HIV positive-to-positive program started, patients with ESRD and HIV would be turned down for dialysis. The reason was that they were seen as unfit for transplantation and therefore not suitable dialysis patients. This meant that anybody with HIV and ESRD was doomed to die. This situation remained unchallenged for a number of years, especially as the rollout of antiretroviral therapy was quite slow in the state sector. Because of very high HIV rates in the country, more and more HIV positive brain-dead donors presented to the Groote Schuur Hospital Transplant team. These donors were mostly braindead people who were worked up for organ donation (after consent was obtained from the family) and who then turned out to be HIV positive. In 2008 it made sense to try and marry this supply of donors with the group of HIV positive patients without any treatment options in the country.