The National Institutes of Health has awarded Albert Einstein College of Medicine of Yeshiva University a four-year, $7.2 million grant to develop a microbicide-releasing vaginal ring to prevent HIV transmission.

“While condoms are excellent at preventing the transmission of HIV, it’s often difficult for women to negotiate their use,” says principal investigator Betsy C. Herold, M.D., professor of pediatrics, of microbiology & immunology, and of obstetrics & gynecology and women’s health at Einstein. “It’s imperative that women have alternative strategies available to protect their own health. Our belief is that an intravaginal ring that delivers a combination of drugs is the best strategy.”

Vaginal rings are soft, plastic, doughnut-shaped devices designed to provide controlled release of drugs to the vagina over extended periods. At present, there are several models available for delivering contraceptives, but none for microbicides.

Dr. Herold and her colleagues will evaluate several anti-HIV microbicides, ultimately aiming for a two-drug combination. “Over the last decade, we’ve learned that when you expose HIV to a single drug, you make it easier to select for resistance,” she says. “So, we are trying to target HIV infection at two different steps very early in its life cycle, which should prevent the establishment of any infection.”

One of the drugs to be evaluated is tenofovir, which blocks reverse transcriptase, an enzyme crucial to HIV reproduction. Tenofovir is used currently as an oral systemic therapy against HIV, but it has also shown promise as a topical microbicide. The team will also test the efficacy of two so-called fusion inhibitors, including maraviroc and PIE12-trimer, which block the virus from entering target immune cells by different mechanisms.

The team will pay particular attention to choosing microbicides that preserve natural vaginal defenses against HIV. In recent years, supposedly safe microbicides were found to make women more susceptible to HIV infection. As Dr. Herold demonstrated in an earlier study, (http://www.einstein.yu.edu/home/news.asp?id=381) these microbicides most likely failed because they disrupted the vagina’s epithelial lining, which provides a protective barrier against infection.

“We want to preserve that protective barrier while adding drugs that will be at the right place at the right time when the virus presents,” says Dr. Herold. “That is why a ring, which can provide sustained delivery of the microbicide over three to four weeks, would be ideal. People wouldn’t have to remember to use it, which is a problem with gels and pills. Also, we don’t know if oral medications will get to the right place - some drugs get into the genital tract well, but some don’t.” The ring could be replaced monthly without a doctor’s supervision.

The microbicides will be incorporated into vaginal ring under development at the University of Utah, Department of Bioengineering, which is collaborating on the study.

“We’ve deliberately chosen to focus on drugs that have already been approved for systemic use or are far along in the regulatory process. This should shorten the time it takes to begin clinical trials. We know that every day that goes by, more people are getting infected with HIV,” says Dr. Herold. The researchers hope to start Phase I clinical testing within the next four years.

The need for a microbicide-releasing vaginal ring is especially urgent in sub-Saharan Africa, where the infection rate among 15 to 49 year-olds exceeds 23 percent in some countries. AIDS is the leading cause of death in sub-Saharan Africa and women account for six out of ten of those living with HIV. “But this is not just a global health problem,” says Dr. Herold. “This is a problem here in the U.S. The rates of HIV in certain regions in this country parallel the rates in many areas of developing world.”

According to the Centers for Disease Control and Prevention, the national infection rate in the United States is 1 percent; in D.C., it is 3 percent, and in the Bronx, 1.7 percent. While men still have higher rates of infection than women in the U.S., AIDS is a common killer for women - ranking third after cancer and heart disease. As of 2007, there were 9,000 women with HIV/AIDS living in the Bronx.

Marla J. Keller, M.D., associate professor of medicine and of obstetrics & gynecology and women’s health at Einstein is a co-investigator on the study. Dr. Keller is a leader in clinical studies on microbicide safety and the impact microbicides have on female genital tract mucosal immunity in HIV-infected and uninfected women. In addition to Dr. Herold, Patrick Kiser, associate professor of bioengineering at the University of Utah, is also a principle investigator on the study. Two biotechnology firms, ImQuest BioSciences, Inc. in Frederick, Maryland, and Particle Sciences, Inc. in Bethlehem, Pennsylvania, are also involved in the study.

Source
Albert Einstein College of Medicine of Yeshiva University

The U.S. Department of Health and Human Services (HHS) marked the recent approval of the 100th antiretroviral drug in association with the President’s Emergency Plan for AIDS Relief (PEPFAR), aimed at the prevention, treatment, and care of people infected with and affected by HIV/AIDS worldwide.

The PEPFAR program is a cooperative effort that involves the Food and Drug Administration (FDA) and other HHS agencies, the State Department’s Office of the U.S. Global AIDS Coordinator, U.S. Department of Defense, other federal agencies, host country governments, and many other international partners.

“This milestone exemplifies the dedication, caring, and hard work of all who strive to better the lives of those infected with or affected by HIV/AIDS,” said HHS Secretary Kathleen Sebelius.

To date, more than 100 products have been assessed by the FDA and either fully or tentatively approved in association with the PEPFAR program. Of these, 29 have been new products and 71 have been generic copies of previously authorized antiretroviral products in the United States. Twenty-two of these new products are new combinations or regimens that have not previously been authorized in the United States. In addition, there are seven new pediatric products considered innovative for patients in developing economies.

“As we recognize the 100th product authorized in this program, it is estimated that FDA’s actions are allowing PEPFAR to spend $150 million more each year on patient access to care,” FDA Commissioner Margaret A. Hamburg, M.D., told those attending an event marking the approval at the Pan American Health Organization (PAHO) headquarters in Washington, D.C. “I look forward to developing and expanding FDA’s international collaborations.”

As of Sept. 30, 2008, the most recent figure available, PEPFAR supported life-saving antiretroviral treatment for more than 2.1 million men, women, and children living with HIV/AIDS. In fiscal year 2008, PEPFAR provided nearly $1.6 billion in support of treatment programs, including antiretroviral drugs and services.

“PEPFAR is committed to supporting partner countries to build and maintain sustainable procurement and supply chain systems,” said U.S. Global AIDS Coordinator Eric Goosby.

Drug products used in PEPFAR receive a “tentative approval” and cannot be approved for marketing in the United States because of existing patents and marketing exclusivity. However, these products meet all the FDA’s manufacturing quality, clinical safety, and efficacy requirements to produce them using the same standards as required for marketing in this country.

FDA performs all of its reviews of applications received in association with the PEPFAR on an expedited basis. After receiving approval or tentative approval from FDA under this expedited process, a generic anti-retroviral passes quickly on to the pre-qualification list maintained by the Secretariat of the World Health Organization (WHO), because of a confidentiality agreement that allows FDA to share data from its evaluations with the WHO team in Geneva.

“Improving access to good quality medicinal products is a core objective of public health efforts and one with a direct and measurable impact on health,” said Margaret Chan, M.D., director-general of WHO.
The goal of PEPFAR is to work with host nations to support treatment of at least 3 million people, prevention of 12 million new infections, and providing care for more than 12 million HIV-infected and affected people by 2013. In addition, PEPFAR will support training of at least 140,000 health care workers in HIV/AIDS prevention, treatment, and care.

“We need to urgently and actively implement strategies to promote greater affordability of both first and second line HIV/AIDS antiretrovirals,” said Mirta Roses, M.D., director of PAHO, an international public health agency that works to improve health and living standards in the Americas. “PEPFAR has made a tremendous difference in the health of disadvantaged people.”

For more information

PEPFAR Web site

Improving Access to HIV/AIDS Drugs Abroad

FDA Office of Generic Drugs

Source
HHS

HIV prevalence among African Americans is ten times greater than the prevalence among whites. This racial disparity in HIV prevalence has persisted in the face of both governmental and private actions, involving many billions of dollars, to combat HIV. In the November 2009 issue of the American Journal of Preventive Medicine, researchers from the University of North Carolina at Chapel Hill examine factors responsible for the stark racial disparities in HIV infection in the U.S. and the now concentrated epidemic among African Americans.

The Centers for Disease Control and Prevention (CDC) estimates that 45% of new HIV infections in the U.S. in 2006 occurred among non-Hispanic blacks. Among the 13,184 adolescents and young adults in The National Longitudinal Study of Adolescent Health, a nationally representative study, HIV seroprevalence was almost 0.5% among blacks - 20 times that of whites.

While individual-level sexual behaviors can contribute to the disparity in HIV prevalence, these observed differences in individual behaviors do not fully explain the marked racial differences in HIV infection prevalence. Even when comparisons are stratified by education, poverty index, marital status, age at first sexual intercourse, lifetime number of sex partners, history of male homosexual activity, illicit drug use, injection drug use, and HSV-2 antibody positivity, HIV prevalence among African Americans exceeds that of whites, typically substantially.

The authors suggest a number of social factors that may contribute to the difference in infection rates. Because of racially segregated mixing patterns and the much higher HIV seroprevalence in African Americans, exposure to the virus is more likely among blacks than among whites for any given number of partners or frequency of sexual contacts. The prevalence of concurrent sexual partnerships (relationships that overlap in time) is higher among U.S. blacks than whites and this can spread infection through a sexual network faster than the same number of new, sequential relationships. Poverty, a reality of life for a disproportionately large number of African Americans, is strongly associated with HIV infection. The population gender ratio (number of men:women) is a major determinant of the structure of sexual networks and both high male mortality and disproportionate incarceration of black men reduce the gender ratio among African Americans. This likely influences not only marriage rates, but also participation in sexual risk behaviors and sexual mixing and other network patterns.

According to the authors, the overall impact of these factors constitutes structural violence; a social system characterized by inequalities in power and life chances of sufficient magnitude to restrict a group of people from realizing their full potential and put them “in harm’s way.” Although the link between social context and disease is increasingly recognized, with a few notable exceptions, the specific role of structural violence in the HIV epidemic among African Americans has received considerably less research attention.

Writing in the article, Adaora A. Adimora, MD, MPH, University of North Carolina at Chapel Hill, School of Medicine, states, “Continuing racial disparities in HIV infection more than 2 decades after the identification of the virus and availability of an accurate test are an indictment of the U.S. response to the epidemic. Existing interventions have failed to control the epidemic in African Americans in part because critical features of the socioeconomic context promote behaviors that transmit HIV and increase the risk of HIV infection even among those who do not have high-risk behaviors. Failure to address these structural determinants has allowed the epidemic to continue in the black community. There is a need for research and interventions that are informed by expertise in public health, medicine, basic science, and social sciences - along with expertise in economics, business and finance, education, criminal justice, political science, and other disciplines…Governments should be held accountable for progress or lack thereof in eliminating inequities.”

The article is “Ending the Epidemic of Heterosexual HIV Transmission Among African Americans” by Adaora A. Adimora, MD, MPH, Victor J. Schoenbach, PhD, and Michelle A. Floris-Moore, MD. It appears in the American Journal of Preventive Medicine, Volume 37, Issue 5 (November 2009) published by Elsevier.

Source:
AJPM Editorial Office

Elsevier Health Sciences