Once-Daily, Fixed-Dose Combination Tablet Containing Doravirine Achieved HIV-1 Viral Suppression

MedicalResearch.com Interview with:

Dr. Kathleen Squires MD Professor and Director of Infectious Diseases Thomas Jefferson University Philadelphia, PA 

Dr. Squires

Dr. Kathleen Squires MD
Professor and Director of Infectious Diseases
Thomas Jefferson University
Philadelphia, PA 

MedicalResearch.com: What is the background for this study? What are the main findings?

  • The pivotal Phase 3 DRIVE-AHEAD study evaluated the safety and efficacy of a once-daily, single tablet, fixed-dose combination containing doravirine, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV-1 infection, compared to a fixed-dose combination containing efavirenz.
    • After 48 weeks of treatment, 84 percent of the 364 treatment-naïve patients taking once-daily DOR/3TC/TDF achieved levels of HIV-1 RNA <50 copies/mL compared to 81 percent of the 364 patients taking once-daily EFV/FTC/TDF, with an estimated treatment difference of 3.5 percent.
    • Increases in mean CD4+ T-cell counts from baseline for the DOR/3TC/TDF and EFV/FTC/TDF groups were 198 and 188 cells/mm3, respectively, with an estimated treatment difference of 10.1.
    • In addition, comparable efficacy was observed across both treatment groups among individuals with high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, which consisted of 69 patients in the DOR/3TC/TDF group and 73 patients in the EFV/FTC/TDF group (Observed Failure approach).
      • Of those patients with a high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, 81 percent in the DOR/3TC/TDF group and 81 percent in the EFV/FTC/TDF group achieved the study’s primary endpoint of <50 copies/mL of HIV-1 RNA, with a treatment difference of 1.0 percent.
    • The study also met its primary safety endpoint, showing that treatment with DOR/3TC/TDF resulted in fewer patients reporting events of several pre-specified neuropsychiatric adverse events compared to EFV/FTC/TDF by Week 48, including dizziness (8.8 percent versus 37.1 percent); sleep disorders and disturbances (12.1 percent versus 25.5 percent); and inability to think clearly or concentrate (4.4 percent versus 8.2 percent).

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ONCEMRK Study: Once Daily Raltegravir In Combination With Other Antivirals Effective For Some HIV Patients

MedicalResearch.com Interview with:

Dr. Pedro Cahn Chief of the infectious disease unit at Juan A. Fernandez Hospital Buenos Aires, Argentina, and ONCEMRK lead study investigator

Dr. Pedro Cah

Dr. Pedro Cahn
Chief of the infectious disease unit at Juan A. Fernandez Hospital
Buenos Aires, Argentina, and
ONCEMRK lead study investigator

MedicalResearch.com: What is the background for this study? What are the main findings?

The ONCEMRK Phase 3 study was conducted to evaluate the efficacy and safety of once-daily ISENTRESS (raltegravir) HD 1200 mg (given as two 600 mg oral tablets) compared to twice daily raltegravir 400 mg, each in combination therapy with emtricitabine plus tenofovir disoproxil fumarate in previously untreated adults with HIV-1 infection with levels of HIV-1 RNA ≥ 1,000 copies/mL.

  • Week 96 data showed:
    • 5 percent of the 531 patients taking once-daily raltegravir 1200 mg (2 x 600 mg) achieved viral suppression of less than 40 copies/mL of HIV-1 RNA, compared to 80.1 percent of the 266 patients taking twice-daily raltegravir 400 mg, both in combination therapy with emtricitabine plus tenofovir disoproxil fumarate, with a treatment difference of 1.4 percent.
    • Increases in CD4+T-cell counts from baseline were comparable for the two treatment regimens, with an average increase of 261.6 cells/mm3 for once-daily raltegravir (1200 mg) and 262.2 cells/mm3 for twice-daily raltegravir (400 mg).
    • Efficacy was consistent across a variety of patient populations, including those with high viral load at baseline (HIV-1 RNA >100,000 copies/mL).
    • Treatment-emergent viral mutations leading to any drug resistance were detected in less than 1 percent of patients in both treatment arms, with 4/531 (0.8 percent) in the once-daily raltegravir (1200 mg) treatment arm, and 2/266 (0.8 percent) in the twice-daily raltegravir (400 mg) treatment arm through 96 weeks.
    • The rate of discontinuation of therapy due to adverse events through 96 weeks was low (1.3 percent in patients receiving once-daily raltegravir (1200 mg) and 2.3 percent in patients receiving twice-daily raltegravir (400 mg).

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Higher HIV Viral Loads Linked to Increased Squamous Cell Cancers of Skin

MedicalResearch.com Interview with:

Maryam M. Asgari, MD, MPH Department of Dermatology, Massachusetts General Hospital, Department of Population Medicine Harvard Medical School, Boston, Massachusetts Division of Research, Kaiser Permanente Northern California, Oakland

Dr. Asgari

Maryam M. Asgari, MD, MPH
Department of Dermatology
Massachusetts General Hospital,
Department of Population Medicine
Harvard Medical School, Boston, Massachusetts
Division of Research, Kaiser Permanente
Northern California, Oakland

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Nonmelanoma skin cancer – defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) – is a common malignant condition, affecting more than 2 million Americans every year. BCCs are more common than SCCs among individuals with healthy immune systems, while SCCs are more predominate than BCCs among people who are immunocompromised.

We examined how laboratory markers used to evaluate HIV disease progression may be associated with subsequent nonmelanoma skin cancer risk in white patients previously diagnosed with at least one such cancer from 1996 to 2008.  We measured CD4 count, viral load and subsequent nonmelanoma skin cancer. The study included 455 participants with HIV and 1,952 without HIV. All were members of the Kaiser Permanente Northern California health care plan.

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Opioid Agonist Therapy Found Cost Effective In Preventing HIV in People Who Inject Drugs

MedicalResearch.com Interview with:

Cora Bernard, MS, PhD candidate Pre-doctoral Student in Management Science and Enginnering Affiliate, Center for Health Policy and the Center for Primary Care and Outcomes Research Stanford Health Policy

Cora Bernard

Cora Bernard, MS, PhD candidate
Pre-doctoral Student in Management Science and Enginnering
Affiliate, Center for Health Policy and the Center for Primary Care and Outcomes Research
Stanford Health Policy

MedicalResearch.com: What is the background for this study?

Response: The US opioid epidemic is leading to an increase in the US drug-injecting population, which also increases the risks of HIV transmission. It is critical to public health that the US invests in a coherent and cost-effective suite of HIV prevention programs. In our model-based analysis, we considered programs that have the potential both to prevent HIV and to improve long-term health outcomes for people who inject drugs. Specifically, we evaluated opioid agonist therapy, which reduces the frequency of injection; needle and syringe exchange programs, which reduce the frequency of injecting equipment sharing; enhanced HIV screening and antiretroviral therapy programs, which virally suppress individuals and decrease downstream transmission; and oral HIV pre-exposure prophylaxis (PrEP), which is taken by an uninfected individual and lowers the risk of infection.

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Injectable Cabotegravir Holds Promise as HIV Prevention Stategy

MedicalResearch.com Interview with:

Martin Markowitz MD Clinical Director and Staff Investigator Aaron Diamond AIDS Research Center Aaron Diamond Professor at The Rockefeller University

Dr. Markowitz

Martin Markowitz MD
Clinical Director and Staff Investigator
Aaron Diamond AIDS Research Center
Aaron Diamond Professor at The Rockefeller University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Cabotegravir ((CAB) is an inhibitor of HIV-1 integrase and is amenable to formulation in both oral and long acting injectable forms. In preclinical studies injectable CAB protected against low dose intrarectal challenge using an HIV-like virus in the rhesus macaque model.

These results support the clinical development of CAB as prevention. This study was a first attempt to establish a dosing regimen and evaluate safety and acceptability of intramuscular injections of CAB. The study was a placebo controlled blinded study of approximately 120 subjects with a 5:1 randomization active/placebo. Subjects received 800mg CAB given as 2 2mL injections or placebo every 12 weeks for 3 injections after a 4 week safety lead in of oral therapy. Safety acceptability and PK were assessed.

The main findings were that injections were associated with injection site reactions in the vast majority of participants that were mild to moderate and of short duration. Only 4 subjects who entered the injection phase discontinued due to injection intolerance. There were no additional safety signals and the participants considered the injections acceptable when asked to complete questionnaires. PK analysis found that despite modeling that suggested that the 800mg q 12 week dose would be adequate, this was not the case. More rapid uptake and release from the depot resulted in lower than anticipated drug levels at trough. Alternate dosing regimens are under study.

Another finding is that there were participants (14%) who had detectable drug in plasma detected at 52 weeks after last injection suggesting the presence of a tail in some individuals.

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Community Targeting of High Risk Minority Males Improves HIV Detection and Treatment

MedicalResearch.com Interview with:

Robin Lin Miller, Ph.D. Professor, Ecological-Community Psychology Co-Director, MA in Program Evaluation Chair, Graduate Program in Ecological-Community Psychology Michigan State University East Lansing, MI 48824

Dr. Miller

Robin Lin Miller, Ph.D.
Professor, Ecological-Community Psychology
Co-Director, MA in Program Evaluation
Chair, Graduate Program in Ecological-Community Psychology
Michigan State University
East Lansing, MI 48824
MedicalResearch.com: What is the background for this study?

Response: We wanted to identify promising strategies for providing access to HIV-testing for gay and bisexual male youth. We were especially interested in testing strategies to reach gay and bisexual male youth of color, as they bear a disproportionate burden of the HIV epidemic and are the least likely to be aware of their HIV status. We also wanted to explore approaches to successfully link these youth with HIV-negative test results to diverse HIV prevention services, including pre-exposure prophylaxis, when warranted.

Although some argue that the ideal place to test adolescents and young adults is via emergency rooms and in routine medical care visits, we found that we were able test many more youth with previously undiagnosed HIV-infection through intensive, targeted community outreach efforts. We also tested a much higher proportion of young men of color through targeted outreach.

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Low CD4 Count Linked To Heart Failure in HIV Patients

MedicalResearch.com Interview with:
Matthew S Freiberg, MD, MSc
Associate Professor of Medicine, Division of Cardiovascular Medicine
Vanderbilt Translational and Clinical Cardiovascular Research Center

MedicalResearch.com: What is the background for this study?

Response:  HIV infected people are living longer and are at risk for cardiovascular diseases. While acute myocardial infarction has been studied and the increased risk of Acute Myocardial Infarction (AMI) among HIV+ people compared to uninfected people is well documented, there are less data describing the risk of HIV and different types of heart failure, including reduced and preserved ejection fraction heart failure. Understanding more about the link between HIV and different types of HF is important because reduced and preserved ejection fraction heart failure differ with respect to underlying mechanism, treatment, and prognosis. Moreover, as cardiovascular care has improved, HIV infected people who experience an AMI are likely to survive but may live with a damaged heart. Understanding more about the link between HIV and heart failure may help providers and their patients prevent or reduce the impact of HF on the HIV community.

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Adolescents Perinatally Infected with HIV Are At Increased Risk of Serious Physical and Mental Health Problems

MedicalResearch.com Interview with:

Anne M Neilan, MD,MPH Assistant In Medicine, Massachusetts General Hospital Research Fellow, Harvard Medical School Department: Medicine Service Division: Infectious Disease Department: Pediatric Service Massachusetts General Hospital Boston, MA 02114

Dr. Neilan

Anne M Neilan, MD,MPH
Assistant in Medicine and Pediatrics
Massachusetts General Hospital
Instructor at Harvard Medical School
Department: Medicine Service
Division: Infectious Disease
Department: Pediatric Service
Massachusetts General Hospital
Boston, MA 02114

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Adolescents infected with HIV – either at birth or later in life – experience poorer health outcomes compared to adults with HIV in nearly every respect. This study found that U.S. youth infected with HIV around the time of their birth are at higher risk throughout their adolescence and young adulthood for experiencing serious health problems, poor control of the HIV virus (having high levels of HIV virus in their bodies and fewer CD4 immune cells which protect the body from infection), or death. The study also found that among those with good HIV control, serious health problems are rare.

By combining data from two large, long-term U.S. studies – the Pediatric HIV/AIDS Cohort Study (PHACS, www.phacsstudy.org) and the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT, www.impaactnetwork.org) Network – we were able to study the health of more than 1,400 perinatally HIV-infected children, adolescents and young adults ages 7 to 30 years between 2007 and 2015. The study found that youth ages 13 to 30 were most likely to have poor HIV control AIDS-related illnesses, and death compared to younger participants. Among 18 – 30 year-olds, the study found that poor control of the HIV virus – meaning higher levels of HIV virus and lower levels of CD4 immune cells which protect the body from infection –35 percent of the time, increasing the risk that these youth would stop responding to certain HIV medications and could transmit HIV to others. These findings are consistent with other U.S. and European reports. Despite being engaged in health care, the number of deaths among youth born with HIV in the U.S. is 6 to12 times higher than for youth without HIV of the same age, sex and race.

Along with HIV-related health problems, the most commonly reported health conditions concerned mental health and brain and nervous system development. Many women in the study also had sexually transmitted infections, which was found to be associated with lower CD4 immune cell counts. This may suggest a biological mechanism or may reflect that patients who have difficulty with their medications are also engaging in more frequent risky sexual behaviors.

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High Risk Individuals Are Testing For HIV More Frequently

MedicalResearch.com Interview with:
Qian An, PhD

Epidemiologist/statistician
Division of HIV/AIDS Prevention
CDC

MedicalResearch.com: What is the background for this study?

Response: Since 2006, the Centers for Disease Control and Prevention (CDC) has recommended HIV testing for all persons aged 13-64 years old. Persons at high risk for HIV infection should be tested more frequently. Among sexually active men who have sex with men (MSM), repeat testing is recommended at least annually. An analysis in 2011 suggested that MSM might benefit from more frequent than annual testing.(1)

Among non-MSM, repeat testing is recommended at least annually for persons at high risk, including persons who inject drugs (PWID) and their sex partners, those who have sex in exchange for money or drugs, heterosexuals who have had more than one sex partner since their most recent HIV test, and those whose partners are living with HIV..

Using statistical models based on renewal theory, we estimate the mean HIV inter-test interval (ITI) — meaning the average time period (in months) between two successive HIV tests — to describe temporal trends in HIV testing frequency among MSM, PWID and high-risk heterosexuals (HRH) and differences in testing frequency by age and race/ethnicity. A decrease in ITI means individuals are testing more frequently.

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SWORD Study Demonstrates Two-Drug Control of HIV

MedicalResearch.com Interview with:

Kati Vandermeulen Senior Director, Global Regulatory Leader and Compound Development Team Lead IDV Janssen

Kati Vandermeulen

Kati Vandermeulen
Senior Director, Global Regulatory Leader and Compound Development Team Lead
IDV Janssen

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  SWORD is the first large trial program specifically conducted to look at the combination of dolutegravir and rilpivirine as a complete, two-drug antiretroviral regimen. Results of the two identical Phase III SWORD studies have been positive and demonstrate that the two-drug regimen of dolutegravir and rilpivirine is as effective, with comparable tolerability, to traditional three- or four-drug (integrase inhibitor-, non-nucleoside reverse transcriptase inhibitor-, or boosted protease inhibitor-based) antiretroviral regimens for the maintenance treatment of HIV.
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Educating Religious Leaders Improves Uptake of Male Circumcision in Tanzania

MedicalResearch.com Interview with:

Jennifer A. Downs, M.D., Ph.D. Assistant Professor of Medicine and Microbiology & Immunology Department of Medicine Weill Cornell Medicine Center for Global Health New York, NY 10065

Dr. Jennifer Downs

Jennifer A. Downs, M.D., Ph.D.
Assistant Professor of Medicine and Microbiology & Immunology
Department of Medicine
Weill Cornell Medicine
Center for Global Health
New York, NY 10065

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Between 2002 and 2006, three large randomized controlled trials in sub-Saharan Africa demonstrated that male circumcision reduces new HIV infections in men by approximately 60%. Based on these findings, the World Health Organization recommended male circumcision as an HIV prevention strategy in countries with high levels of HIV and a low prevalence of male circumcision. This led to prioritization of 14 countries in Eastern and Southern Africa for massive scale-up of male circumcision beginning in 2011.

In many of these countries, the uptake of male circumcision was lower than expected. In northwest Tanzania, where we work, there are a number of barriers to male circumcision. Some of these barriers are cultural, tribal, economic, and religious. We conducted focus group interviews in 2012 that showed that many Christian church leaders and church attenders in our region in Tanzania had major concerns about whether male circumcision was compatible with their religious beliefs. This led us to hypothesize that the uptake of male circumcision could be increased when religious leaders were taught about male circumcision, with the goal that they would then be equipped to discuss this issue with their congregations.
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Ibalizumab Immunotherapy Decreased Viral Load In Resistant HIV

MedicalResearch.com Interview with:

Brinda Emu MD Assistant Professor of Medicine (Infectious Diseases Yale University New Haven, CT

Dr. Brinda Emu

Brinda Emu MD
Assistant Professor of Medicine (Infectious Diseases
Yale University
New Haven, CT 

MedicalResearch.com: What is the background for this study?

Response: Ibalizumab is a fully humanized monoclonal antibody that targets the CD4 receptor.  This Phase III registrational study enrolled individuals with HIV infection that harbor high levels of multi-drug resistance, with limited treatment options.  At IDWeek in October, 2016, data was presented that demonstrated patients experienced a significant decrease in viral load after receiving a single loading dose of ibalizumab 2,000 mg intravenously (IV) in addition to their failing antiretroviral therapies (ART) (or no therapy). Seven days after this loading dose, 83% of patients achieved a ≥ 0.5 log10 decrease from baseline compared with 3% during the seven-day control period .These results were statistically significant (p<0.0001).

At CROI, additional data on the Week 24 results from this study are now presented.

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African American Women Remain Disproportionately Affected By HIV

MedicalResearch.com Interview with:
Donna Hubbard McCree, PhD MPH, RPh
Association Director for Health Equity/Division of HIV/AIDS Prevention
Centers for Disease Control and Prevention 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: HIV diagnosis rates among women declined 40% between 2005 and 2014 with the largest decline, 42%, occurring in black women. However, in 2015 black women represented 61% of HIV diagnoses among women. Our goal in this analysis was to determine whether the decline resulted in a decrease in the disparities among African American, Hispanic and white women between 2010 and 2014. There is currently not a standard method for measuring HIV-related disparity.

However, for this analysis we used three different measures – the absolute rate difference (the difference between the group with the lowest rate and the group with the highest rate); 2) the diagnosis disparity ratio (the ratio of the difference between the group rate and the overall population rate to the overall rate); and 3) the Index of Disparity (the average of the differences between rates for specific groups and the total rate divided by the total rate, expressed as a percentage). The absolute rate difference between black women and white women decreased annually, from 36.9 in 2010 to 28.3 in 2014. The diagnosis disparity ratio for black women compared to the total population decreased from 1.7 in 2010 to 1.2 in 2014. The Index of Disparity increased during 2010–2011, and then decreased each year during 2012–2014. Although disparities still exist, these findings indicate improvement.

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Does HAART Treatment for HIV Contribute To Rapid Rise in Syphilis Infections?

MedicalResearch.com Interview with:

Michael Rekart, MD, DTM&H Clinical Professor, Medicine and Global Health The University of British Columbia .... On behalf of my co-authors

Dr. Michael Rekart

Michael Rekart, MD, DTM&H
Clinical Professor, Medicine and Global Health
The University of British Columbia
…. On behalf of my co-authors

MedicalResearch.com: What is the background for this study?

Response: The background for this study is the observation that new syphilis cases over the last decade in British Columbia, Canada, have been escalating more rapidly than anyone could have predicted and that syphilis incidence has outpaced the incidence of other sexually transmitted diseases (STDs), including gonorrhea and chlamydia. This unexpected increase in syphilis has been almost wholly concentrated in men who have sex with men (MSM). Most of these MSM are HIV-1 infected and many are taking highly active antiretroviral therapy (HAART). In fact, the expansion in HAART coverage in MSM parallels the growth in syphilis in the same population. In addition, my co-authors and I had serious doubts as to whether ‘treatment optimism’, the generally accepted explanation for this phenomenon, was robust enough to account for such a dramatic increase in new syphilis cases. Treatment optimism posits that HAART availability and effectiveness have led to the perception in both HIV-1-infected and HIV-1-uninfected individuals that HIV-1 transmission has become much less likely, and the effects of HIV-1 infection less deadly. This is expected to result in increased sexual risk-taking, especially unprotected anal intercourse, leading to more non-HIV-1 STDs, including gonorrhea, chlamydia and syphilis.

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Types of Myocardial Infarction Among HIV–Infected Individuals

MedicalResearch.com Interview with:
Heidi M. Crane MD, MPH
Associate Professor of Medicine
Associate Director Clinical Epidemiology and Health Services Research Core
Center for AIDS Research
University of Washington

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Studies have suggested that rates of myocardial infarction (MI) are higher in those with HIV, likely for a variety of reasons. However, prior studies have not been able to distinguish MIs by type. The Universal Definition of MI has been recommended by cardiology societies and classifies MIs into types with Type 1 MIs resulting spontaneously from atherosclerotic plaque instability and Type 2 MIs occurring secondary to causes other than atherosclerotic plaque rupture, including hypotension, hypoxia, and stimulant induced spasm resulting in increased oxygen demand or decreased supply. Understanding MI types is likely important as they may indicate a different prognosis and need for different prevention approaches.

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Anti–HIV Drug Candidate Prevents Intestinal Inflammation

MedicalResearch.com Interview with:
Prof. Jamal Tazi

Director, Institute for Molecular Genetics
CNRS and University of Montpellier and Executive Committee Member
ABIVAX

MedicalResearch.com: What is the background for this study?

Response: Its long been established that people with HIV, even those treated successfully with antiretroviral treatment, exhibit significantly higher levels of chronic inflammation than HIV-negative people. The causes of this inflammation are many – ongoing viral replication, often in the so-called viral reservoirs, leaky gut syndrome, concomitant viral infections (eg CMV, hepatitis etc).

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Pubic Hair Grooming Linked To Increased Risk of STDs

MedicalResearch.com Interview with:

E. Charles Osterberg, M.D. Assistant Professor of Surgery Genitourinary Reconstruction and Trauma University of Texas- Dell Medical School Dell-Seton Medical Center / University Hospital

Dr. Osterberg

E. Charles Osterberg, M.D.
Assistant Professor of Surgery
Genitourinary Reconstruction and Trauma
University of Texas- Dell Medical School
Dell-Seton Medical Center / University Hospital

MedicalResearch.com: What is the background for this study?

Response: Pubic hair grooming has become an increasingly common practice among men and women. Perceptions of genital normalcy have changed as modern society’s definition of attractiveness and feelings of femininity and masculinity have changed. Pubic hair grooming has been shown to increase morbidity such as genital injuries, however little is known about the relationship between grooming practices and sexually transmitted infections.

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Dapivirine Vaginal Ring Helps Prevent HIV Infection in Women

MedicalResearch.com Interview with:
Ms. Neliëtte Van Niekerk M.Com
and Dr. Annalene Nel M.B., Ch.B., Ph.D.
From International Partnership for Microbicides
Silver Spring, MD

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Existing prevention methods have not done enough to stop the alarming rates of infection among women and girls, especially in sub-Saharan Africa, where young women are at least twice as likely to have HIV as young men. Rates of new infections among women aged 15-24 were more than four times greater than that of men the same age, and this age group accounted for 25 percent of new infections in South Africa. To provide women with more prevention options, the nonprofit International Partnership for Microbicides (IPM) developed a vaginal ring that contains an antiretroviral drug called dapivirine. Women insert the ring themselves and replace it every month.

The Ring Study was a Phase III clinical trial that assessed the safety and long-term efficacy of the monthly dapivirine ring among nearly 2,000 women in South Africa and Uganda. We found that the ring reduced the risk of HIV-1 infection in about one-third of the women in the trial, and it was safe, with no difference in adverse effects between the active and placebo ring groups.

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DTG-Based Medications May Allow Faster Suppression of HIV in Semen

MedicalResearch.com Interview with:
Arkaitz Imaz Vacas
HIV and STD Unit, Department of Infectious Diseases
Hospital Universitari de Bellvitge

MedicalResearch.com: What is the background for this study?

Response: Sexual transmission is the most common route of human immunodeficiency virus (HIV) acquisition in most regions of the world.

The male genital tract is a separate reservoir for HIV and may contribute to HIV shedding in seminal fluid even in individuals receiving antiretroviral (ARV) therapy (ART). Treatment of HIV-infected patients with currently available combined ART suppresses HIV in blood and also in genital fluids and reduces the risk of HIV acquisition by their sexual partners. However, sexual HIV transmission is possible even in patients on ART, especially if treatment was initiated recently. Thus, the ability of ARV drugs to penetrate into the male genital tract is a key factor for achieving HIV suppression in seminal fluid and preventing sexual transmission of the virus.

Dolutegravir (DTG) is a new integrase inhibitor (INI) with high antiviral potency and a high genetic barrier to resistance. In large phase III-a randomized clinical trials, DTG in combination with 2 nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) has shown noninferiority compared with raltegravir and superiority to efavirenz or ritonavir-boosted darunavir as first-line therapy in treatment-naive HIV-1 infected patients. A study in healthy volunteers showed that DTG penetration in seminal fluid was <7% of DTG exposure in blood plasma (BP), and the median seminal concentration at the end of the dosing interval (C24h) was lower than the in vitro protein-adjusted (PA) 90% inhibitory concentration (IC90) for wild-type HIV-1. However, information about protein unbound DTG fraction in seminal fluid is lacking and there is no information regarding DTG concentrations in the semen of HIV-1–infected patients or the antiviral activity of a DTG-based ARV combination in this compartment.

The aim of this study was to compare viral decay kinetics and DTG concentrations (total drug and unbound fraction) in the seminal plasma (SP) and BP in a group of treatment-naive HIV-1 infected patients starting DTG plus abacavir (ABC) and lamivudine (3TC) once daily.

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Penn Takes First Step in Development of Antibodies to HIV and Cure

MedicalResearch.com Interview with:

Katharine J Bar, MD Assistant Professor of Medicine Attending Physician, Infectious Diseases, Hospital of the University of Pennsylvania Physician, International Travel Medicine, Perelman Center for Advanced Medicine Director, Penn CFAR Viral and Molecular Core

Dr. Katharine J Bar

Katharine J Bar, MD
Assistant Professor of Medicine
Attending Physician, Infectious Diseases, Hospital of the University of Pennsylvania
Physician, International Travel Medicine, Perelman Center for Advanced Medicine
Director, Penn CFAR Viral and Molecular Core

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The passive administration of monoclonal antibodies has revolutionized many fields of medicine. Anti-HIV monoclonal antibodies are being explored as components of novel therapeutic and curative strategies, as they can both neutralize free virus and kill virus-infected cells. We sought to determine whether passive administration of an anti-HIV monoclonal antibody, VRC01, to chronically HIV-infected individuals on antiretroviral medications (ART) would be safe and well tolerated and could delay virus rebound after discontinuation of their ART.

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Family-Centered Advanced Care Planning for Adolescents With HIV

MedicalResearch.com Interview with:

Maureen E. Lyon PhD Division of Adolescent and Young Adult Medicine, Center for Translational Science/Children’s Research Institute, Children’s National The George Washington University School of Medicine and Health Sciences Washington, District of Columbia

Dr. Maureen E. Lyon

Maureen E. Lyon PhD
Division of Adolescent and Young Adult Medicine,
Center for Translational Science/Children’s Research Institute, Children’s National
The George Washington University School of Medicine and Health Sciences
Washington, District of Columbia

MedicalResearch.com: What is the background for this study?

Response: Despite policy recommendations to include adolescents with chronic and life-limiting conditions in decision-making about their own end-of-life care, barriers continue in clinical practice, including fear of distressing vulnerable adolescents and providers’ beliefs that these conversations are potentially harmful.

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Ibalizumab Decreased Viral Load In Patients With Resistant HIV

MedicalResearch.com Interview with:

Jacob Lalezari, MD Quest Clinical Research San Francisco, CA

Dr. Jacob Lalezari

Jacob Lalezari, MD
Quest Clinical Research
San Francisco, CA 

MedicalResearch.com: What is the background for this study? What are the main findings?

  • Tremendous strides have been made since HIV-1 was first discovered 35 years ago. However, while many HIV patients can control the infection with currently-approved therapies, there is an urgent need for new treatments that can address viruses that are resistant to multiple antiretroviral treatment classes. With people starting treatments earlier and staying on them longer, some patients also face long-term safety and tolerability issues associated with current therapies.
  • Thousands of people are infected with HIV-1 with resistance to three classes of antiretroviral therapy (ART), and are in dire need of treatment. There are limited or no treatment options available for these patients.
  • As multi-drug resistant (MDR) HIV can be transmitted, it is imperative that it be controlled in order to prevent it from becoming a larger problem. It is important to not only focus on the patient being treated but also consider those they could infect.
  • Ibalizumab is the first biologic long-acting investigational ART to show efficacy in patients in just seven days. The Phase III TMB-301 results showed that patients with MDR HIV-1 and with limited treatment options experienced a significant decrease in viral load after receiving a loading dose of ibalizumab (2,000 mg intravenously) in addition to their failing ART therapies.
    •  A total of 40 patients were enrolled in the study.
    • Seven days after the loading dose, 83% of patients achieved a ≥ 0.5 log10 decrease from baseline compared with 3% during the seven-day control period.
    • These results were statistically significant (p<0.0001). Moreover, during that same period, 60% achieved a decrease of ≥1.0 log10.
    • The average viral load decrease for the total population was 1.1 log10
    • There were no treatment-related serious adverse events or discontinuations reported during the initial seven-day treatment period. 

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EHRs Can Help Identify Patients Who May Benefit From HIV PrEP Medications

MedicalResearch.com Interview with:

Douglas Krakower, MD Infectious Disease Division Beth Israel Deaconess Medical Center Boston, MA,

Dr. Douglas Krakower

Douglas Krakower, MD
Infectious Disease Division
Beth Israel Deaconess Medical Center
Boston, MA,

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There are 45,000 new HIV infections in the US annually, so effective HIV prevention strategies are needed. HIV pre-exposure prophylaxis (PrEP), whereby a person who is HIV-uninfected uses an HIV treatment medication on a daily basis to protect themselves from becoming infected with HIV, is over 90% effective when taken with high adherence. The Centers for Disease Control and Prevention estimates that there are 1.2 million Americans who are likely to benefit from using PrEP. However, only 80,000 persons have been prescribed PrEP. One of the barriers to implementing PrEP is that clinicians face challenges with identifying persons who are most likely to benefit from PrEP, given infrequent sexual health history assessments during routine clinical care. We thus sought to develop an automated algorithm that uses structured data from electronic health records (EHRs) to identify patients who are most likely to benefit from using PrEP. Our methods included extracting potentially relevant EHR data for patients with incident HIV and without HIV from nearly a decade of EHR data from a large ambulatory practice in Massachusetts. We then used machine learning algorithms to predict HIV infection in those with incident HIV and those without HIV. We found that some algorithms could offer clinically useful predictive power to identify persons who were more likely to become infected with HIV as compared to controls. When we applied these algorithms to the general population and identified a subset of about 1% of the population with risk scores above an inflection point in the total distribution of risk scores; these persons may be appropriate for HIV testing and/or discussions about PrEP.

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Pre-exposure Prophylaxis Use by Breastfeeding HIV-Uninfected Women

MedicalResearch.com Interview with:

Kenneth K. Mugwanya MBChB, MS Department of Epidemiology andDepartment of Global Health University of Washington, Seattle, Washington, USA Division of Disease Control, School of Public Health Makerere University Kampala, Uganda

Dr. Kenneth K. Mugwanya

Kenneth K. Mugwanya MBChB, MS
Department of Epidemiology andDepartment of Global Health
University of Washington, Seattle, Washington, USA
Division of Disease Control, School of Public Health
Makerere University
Kampala, Uganda

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Women living in regions with high HIV prevalence are at high risk of HIV acquisition in pregnancy and postpartum because they infrequently use condoms, do not know their partner’s HIV status, and have biologic changes or changes in their partner’s sexual partnerships that increase susceptibility. Moreover, acute HIV infection during pregnancy or breastfeeding period is associated with high rates of mother-to child HIV transmission because of high circulating level of HIV virus in blood. Oral antiretroviral pre-exposure prophylaxis (PrEP) is a powerful HIV prevention strategy recommended by both the World Health organization and US Centers for Diseases Control and Prevention. PrEP is an attractive prevention strategy for women as it can be used discreetly and independent of sexual partners. However, there is limited research about the safety of PrEP in HIV-uninfected pregnant or breastfeeding mothers and their infants.

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Meta-analysis finds that pre-exposure chemoprophylaxis for prevention of HIV infection may be associated with an increase in STDs among MSM

MedicalResearch.com Interview with:
Noah Kojima

David Geffen School of Medicine
University of California
Los Angeles, California

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: One of the most exciting new methods to prevent human immunodeficiency virus (HIV) type 1 infection is through the use of chemical pre-exposure prophylaxis (PrEP), which has been shown to be safe and effective in randomized-controlled trials and “real world” studies among men who have sex with men (MSM). However, reports of high incidence of sexually transmitted infections (STIs) and condomless sex in PrEP trials has led clinicians and public health advocates to be concerned that the use of PrEP for HIV might lead to higher STI incidence due to increased sexual risk behavior. We found that PrEP for HIV infection is associated with increased risk of STI acquisition among MSM in a meta-analysis of prior studies.

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HIV Patients With Depression Have Greater Risk of Myocardial Infarction

MedicalResearch.com Interview with:
Matthew S Freiberg, MD, MSc
Cardiovascular Medicine Division, Vanderbilt University School of Medicine
Tennessee Valley Geriatric Research Education and Clinical Center, Nashville  TN
Tasneem Khambaty, PhD
Department of Psychology, University of Miami, Coral Gables, Florida
Jesse C. Stewart, PhD
Department of Psychology, Indiana University–Purdue University , Indianapolis, Indianapolis

MedicalResearch.com: What is the background for this study?

Response: Due to highly effective antiretroviral therapy, people with HIV are living longer. Unfortunately, these HIV-infected individuals remain at a higher risk for other chronic diseases, with cardiovascular disease (CVD) being one of the leading cause of death in this population. In the general population, depressive disorders, such as major depressive disorder (MDD) and dysthymic disorder, are associated with increased risk of new-onset CVD. Given that roughly 24-40% of HIV-infected individuals have a depressive disorder, we examined whether MDD and dysthymic disorder are also associated with an increased risk of new-onset CVD in people with HIV.
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The Emergence of New HIV Strains That May Infect Humans Never Ends

MedicalResearch.com Interview with:

Zhe Yuan MS. MS. PhD Candidate Nebraska Center for Virology University of Nebraska-Lincoln

Dr. Zhe Yuan

Zhe Yuan MS. MS. PhD Candidate
Nebraska Center for Virology
University of Nebraska-Lincoln

MedicalResearch.com: What is the background for this study?

Response: AIDS causes millions of infections and deaths each year. Human immunodeficiency virus (HIV) is the cause of this detrimental disease of humans. Just like Ebola and Zika, AIDS is also a zoonotic disease at the beginning. For the origins of HIV, people believed that HIV originated from simian immunodeficiency virus from wild chimpanzees (SIVcpz). But until now, there has been no direct in vivo evidence for this assumption. Further, people cannot explain why only certain SIVcpz strains are thought to be the ancestors of already discovered HIV strains in humans. There is also a need to clarify what transmission risks might exist for those SIVcpz strains that have not already been found to infect humans. The answers to these questions are essential for a better understanding of cross-species transmission and predicting the likelihood of additional cross-species transmission events of SIV into humans.

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HIV Can Be Prevented in Monkeys With New Vaginal Ring That Dispenses Topical Meds

MedicalResearch.com Interview with:

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

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.

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HIV Lymphoma Patients Now Candidates For Stem Cell Transplants

MedicalResearch.com Interview with:

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

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.
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HIV Treatment Does Not Reduce Cardiovascular Risk of HIV Infection

MedicalResearch.com Interview with:

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

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.

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