May 18th was HIV Vaccine Awareness Day, and we wanted to remind you of several posts we did last week on that subject.

On Friday, we featured a guest post, Moving Forward on HIV Vaccine Awareness Day, by Dr. Nelson Michael, director of the U.S. Military HIV Research Program. And then we posted this video interview with Dr. Carl Dieffenbach, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH). We ended the day with a cross-post of NIH’s bulletin for HIV Vaccine Awareness Day.

Today, we would like to share another video interview we did with Dr. Dieffenbach on the importance of vaccine research and on the HVTN 505 study, which was discontinued by NIH last month.

For more information about the HVTN 505 study, please see NIAID’s updated Questions and Answers and read the news release cross-posted on AIDS.gov. To learn about NIAID’s HIV vaccine research, please see the HIV vaccine section of the NIAID website.

The Food and Drug Administration (FDA) wants to talk to people living with HIV (PLWH) and HIV/AIDS advocates. On June 14, under its Patient-Focused Drug Development initiative, FDA will ask PLWH to join an open public discussion about:

• the impact of HIV on your daily life,
• experience with currently available therapies to treat HIV,
• your views on issues related to HIV cure research, including perceived benefits and acceptable risk for participating in HIV cure research, and
• how best to ensure clear communication of potential benefits and possible risks through informed consent.

This discussion is intended to help improve drug development and treatment, and get patients’ perspective into HIV cure research. The meeting takes place on June 14, 2013, from 9:30 AM – 5:30 PM at FDA’s White Oak Campus, located at:

10903 New Hampshire Avenue

Building 31, (in The Great Room)

Silver Spring, Maryland 20993

There is no cost to attend, but if you would like to attend, please register by June 5. Those who cannot attend will be able to view the meeting via webcast. However, the webcast will not be interactive, so viewers will not be able to actively participate in the discussion.

FDA has prepared a list of questions that we hope will frame and guide the discussion at this meeting. You can review those questions, read more about the meeting, and register at this link.

The implementation of scientifically proven HIV prevention strategies is helping to reduce the number of new infections — the annual HIV infection rate globally fell by 22 percent from 2001 to 2011 — but a great deal more must be done. Significant scale-up of proven HIV prevention strategies coupled with the discovery of new HIV treatment and prevention interventions are needed to achieve an end to the global HIV/AIDS pandemic. A safe, effective and durable HIV vaccine is an essential cornerstone to the long-term strategy to achieve this goal.

Developing a safe and effective HIV vaccine has been a long and difficult process largely because HIV has proven to be an especially tough target. Recent developments with the HVTN 505 clinical trial and analyses from the HVTN 503 “Phambili” vaccine study have been disappointing, but they also provided clear answers about investigational vaccine strategies that, ultimately, were not effective. Still, the new directions for HIV vaccines that have been recently initiated define our future path and will be pursued.

Among many projects, scientists continue to explore findings from the RV 144 HIV vaccine study in Thailand, which, in 2009, provided proof-of-concept that an HIV vaccine can afford a modest level of protection. Ongoing research related to the Thai trial is providing important information about human immune responses and other factors that may explain why the investigational vaccine protected some trial volunteers from HIV infection but not others. Such data will help advance researchers’ understanding of HIV’s structure and vulnerabilities and help guide the development of future HIV vaccine candidates. Large-scale investigational vaccine clinical trials designed to build on the RV 144 results and create a more robust and durable level of protection are expected to begin in two-to-three years in South Africa.

In basic research, scientists are making important discoveries about broadly neutralizing antibodies capable of disabling a wide range of HIV strains when tested in the laboratory setting. For example, NIAID scientists recently charted the co-evolution of HIV and a strong antibody response in an HIV-infected study participant, who is one of the 20 percent of HIV-infected individuals who naturally develops broadly neutralizing antibodies to the virus after several years of infection. Their findings could help identify which proteins to use in an investigational vaccine to induce broadly neutralizing antibodies more quickly. In another advance, a team of NIH scientists recently developed a new tool to identify broadly neutralizing antibodies from blood samples, which could help speed HIV vaccine research.

Other interesting basic research findings have included the identification of a new HIV-suppressing protein, called CXCL4, in the blood of HIV-infected individuals. NIAID scientists found that CXCL4 binds to HIV in such a way that the virus cannot attach or enter a human cell, leading to the conclusion that it may serve to regulate viral replication in an infected individual and, therefore, control the pace at which HIV disease progresses. Additionally, NIAID researchers found that even though HIV diversifies widely in infected individuals over time, the virus strains that are passed on through heterosexual transmission often resemble the strain that originally infected the transmitting partner. Learning more about the characteristics of these dominant strains could help inform HIV vaccine design.

Recent NIAID investments in basic research toward innovative HIV vaccine discovery research and vaccine immunology and immunogen discovery should also prove fruitful in the coming years for HIV vaccine research.

On this HIV Vaccine Awareness Day, NIAID thanks the thousands of men and women who have selflessly volunteered for clinical studies and the scientists and clinicians working to find an effective HIV vaccine. NIAID shares your commitment and will continue the important research needed to make a protective HIV vaccine a reality.

Editor’s note: Please see our National HIV Vaccine Awareness Day video with Dr. Carl Dieffenbach from NIAID, NIH.

May 18th is HIV Vaccine Awareness Day (HVAD), led by the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health. We spoke to Dr. Carl Dieffenbach at NIH, who had this to say about HIV Vaccine Awareness Day:

“[On Vaccine Awareness Day] we can take a moment to acknowledge the study participants who have given their time, their energy, . . .  to the study of HIV vaccines.”

Watch the HIV Vaccine Awareness Day video to hear the rest of his comments and visit the HIV Vaccine Awareness Day website for resources to help community members support the day. To learn more about HIV/AIDS and the Federal response, including information on federally funded research, visit AIDS.gov.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, will stop administering injections in its HVTN 505 clinical trial of an investigational HIV vaccine regimen because an independent data and safety monitoring board (DSMB) found during a scheduled interim review that the vaccine regimen did not prevent HIV infection nor reduce viral load (the amount of HIV in the blood) among vaccine recipients who became infected with HIV.

The HVTN 505 study began in 2009 and was testing an investigational prime-boost vaccine regimen developed by NIAID’s Vaccine Research Center. The Phase IIb study, conducted by the NIAID-funded HIV Vaccine Trials Network (HVTN) , was designed to determine whether the vaccine regimen could prevent HIV infection and/or reduce the amount of virus in the blood of vaccine recipients who became infected with HIV.

The investigational HIV vaccine regimen involved a series of three immunizations over the course of eight weeks, beginning with a DNA-based vaccine designed to prime the immune system. The DNA priming vaccine contained genetic material expressing antigens representing proteins from both the surface and internal structures of HIV. Immunizations with the priming vaccine were followed by a single injection at week 24 with a recombinant vaccine (the booster vaccine) based on a weakened adenovirus type 5 (Ad 5). The adenovirus was used as a vector, or carrier, of genetic material expressing a matching set of HIV antigens. Structures from all three major HIV clades, or subtypes, were included. Adenoviruses are a common cold virus, but the Ad5 virus used in the study’s vaccine regimen was disabled so that it could not cause a cold or other respiratory illness. The two investigational vaccines tested in HVTN 505 cannot cause HIV infection because neither contains live or weakened versions of HIV.

The HVTN 505 study enrolled 2,504 volunteers at 21 sites in 19 U.S. cities. The study population consisted of men who have sex with men and transgender people who have sex with men. In its April 22 interim review, the DSMB examined the information gathered from 1,250 volunteers who received the investigational vaccine regimen and 1,244 volunteers who received the placebo vaccine. The primary analysis looked at volunteers who were diagnosed with HIV infection after having been in the study a minimum of 28 weeks. This was done to enable enough time for the vaccine regimen to be given and stimulate an immune response. In this analysis, 27 HIV infections occurred among the vaccine recipients, and 21 HIV infections occurred among the placebo vaccine recipients. Among volunteers who became HIV-infected during the first 28 weeks of the study, 14 cases of HIV infection occurred among those who received the investigational vaccine regimen, and 9 HIV infections occurred among the placebo vaccine recipients. Overall in the study from the day of enrollment through the month 24 study visit, a total of 41 cases of HIV infection occurred in the volunteers who received the investigational vaccine regimen and 30 cases of HIV infection occurred among the placebo vaccine recipients.

Additionally, the DSMB found that the vaccine failed to reduce viral load among volunteers who acquired HIV infection at least 28 weeks after entering the study and who had been followed for at least 20 weeks after diagnosis. There were 30 participants with measurable viral load (15 vaccine recipients; 15 placebo recipients).

Based on these findings, the DSMB recommended that no further vaccinations with the investigational vaccine regimen be administered. As the trial’s sponsor, NIAID concurred with the DSMB’s recommendation and has instructed all HVTN 505 study sites to immediately cease administering injections but continue follow-up with study participants to further evaluate the trial data.

It should be noted that there was a non-statistically significant increase in HIV acquisition among volunteers in the investigational vaccine group compared to those in the placebo group. It is not clear why this occurred and further analysis is needed to draw any firm conclusions. Based on the finding, the DSMB recommended closer follow-up of participants beyond their month 24 study visit. NIAID concurred, and will, in concert with the study investigators, be amending the study protocol to allow for closer, extended follow up of the vaccine recipients.

As with all NIAID-sponsored HIV prevention trials, the HVTN 505 participants were offered extensive counseling on how to reduce their risk of becoming HIV-infected and provided free condoms. As an added precaution, study participants were required at time of enrollment to be circumcised and free of antibodies to Ad5. These precautions were taken in light of an HIV vaccine clinical trial, known as the Step Study, which found in 2007 an increased number of HIV infections among vaccine recipients, particularly those who were not circumcised and/or had Ad5 antibodies.

NIAID and the HVTN 505 study team are working to thoroughly analyze the study data to better understand why the vaccine did not work and to guide future vaccine development efforts. Detailed scientific findings will be made publicly available as soon as possible.

Study investigators at each of the 21 clinical trial sites have been informed of the decision to stop immunizations in the HVTN 505 study and are contacting study volunteers to inform them of the developments. Study volunteers are being asked to report to their specific clinic sites over the next few weeks to find out whether they received the investigational vaccines or placebo. Individuals who became HIV-infected during the trial were referred to local services for appropriate medical care and treatment. The study investigators will continue following all study participants for five years from the time of enrollment.

NIAID remains committed to the pursuit of a highly effective, preventive HIV vaccine as part of a multifaceted HIV prevention research program. For more information about the HVTN 505 study, please see the updated Questions and Answers. To learn about NIAID’s HIV vaccine research, please see the HIV vaccine section of the NIAID website.

Editor’s note: “Q&A: The HVTN 505 HIV Vaccine Regimen Study” from NIAID has more information.

A new grant award by the National Institute on Minority Health and Health Disparities (NIMHD) will support the development of new Health Information Technology (HIT) strategies that increase screening for chronic hepatitis B and reduce the impact of hepatitis B among high-risk Asian American and Pacific Islander (AAPI) populations.  Hepatitis B virus (HBV) infection is a major preventable health problem in the U.S. and the most pronounced health disparity among Asian Americans. Unfortunately, many HBV patients, especially immigrants and minorities, often do not receive recommended levels of care, indicating a critical need for developing culturally appropriate and effective strategies that can be incorporated into existing clinical practice. The investigator-initiated award was made to the Association of Asian Pacific Community Health Organizations (AAPCHO), a national association of 29 community health organizations dedicated to promoting advocacy, collaboration, and leadership that improves the health status of and access to health care for Asian Americans, Native Hawaiians, and other Pacific Islanders in the United States.

This new research grant advances multiple strategies identified in the Action Plan for the Prevention, Care and Treatment of Viral Hepatitis, first released in May 2011. To improve viral hepatitis testing, care, and treatment and prevent the long term consequences of untreated chronic viral hepatitis, including liver cancer, the Action Plan calls for the use of HIT to improve testing, access to and quality of viral hepatitis care and treatment in diverse clinical settings. It also highlights ongoing efforts to leverage resources across federal agencies participating in implementation of the Action Plan; in this case NIH investment in research to improve HBV screening in community health centers. The findings from this undertaking can then be disseminated through the other AAPCHO-affiliated health centers and the larger network of health centers supported by HRSA’s Bureau of Primary Health Care.

Approximately 1 in 12 AAPIs are living with chronic hepatitis B, but most do not know it, according to the Centers for Disease Control and Prevention (CDC). AAPIs make up 5% of the total U.S. population, but account for more than 50% of Americans living with chronic hepatitis B.  Despite these high rates, many AAPIs are not tested for hepatitis B. Unaware of their infection, they do not access medical services that can help save their lives and prevent transmission (the hepatitis B virus can be transmitted sexually, perinatally and through blood exposure.). As a result, chronic hepatitis B and associated liver cancer in AAPIs is one of the most serious health disparities in the United States: hepatitis B-related liver cancer incidence is highest among AAPIs and is a leading cause of cancer deaths in this population.

To address this disparity, AAPCHO will lead a community-scientific collaboration with its federally qualified health center member, International Community Health Services  in Seattle, Washington, as well as its scientific partners affiliated with the University of Washington  and Virginia Mason Medical Center  and members of a community-based organization, the Hepatitis B Coalition of Washington . The collaborators will use community-based participatory research (CBPR) approaches to conduct a needs assessment and develop a new culturally appropriate intervention to address HBV health disparities across Asian American communities. Methods including key informant interviews, focus groups, and surveys will be used to assess the needs for and impact of culturally proficient HIT strategies to improve HBV outcomes for underserved Asian Americans attending a community health center in Seattle.  The results from the needs assessment will then be utilized to develop and pilot an intervention that incorporates HIT strategies for HBV care with participation and ownership from community-based health centers, health care providers, patients, and their families.  The project will measure the effectiveness of this culturally proficient intervention in improving HBV vaccination, screening rates, and linkages to care. This project will serve as an important model for developing culturally proficient HBV care that includes key elements such as health services, HIT, and non-clinical support services for underserved communities in the United States.

“Given the significant impact of hepatitis B in the AAPI community, NIMHD is pleased to be supporting CBPR that will develop culturally competent interventions to reduce this health disparity,” observed Dr. Francisco Sy, Director of NIMHD’s Office of Extramural Research Administration. “The CBPR Initiative at NIMHD supports the development, implementation, and evaluation of intervention research and is a long-term commitment. It has three phases: a three-year research planning phase followed by a competitive intervention research phase. Afterwards, those with effective interventions compete for a three year research dissemination phase,” noted Dr. Sy, a member of the inter-agency group working to implement the Viral Hepatitis Action Plan.

In the final episode in my series of conversations from the 2013 Conference on Retroviruses and Opportunistic Infections (CROI) (held in Atlanta earlier this month), I had the opportunity to talk with Dr. Laura Cheever, HRSA’s Acting Associate Administrator for the HIV/AIDS Bureau. At CROI, she and her colleagues shared a new analysis of the continuum of HIV care for persons receiving services through the Ryan White HIV/AIDS Program (RW). Their analysis showed rates of retention in HIV care, ART prescription, and viral load suppression among RW clients to be higher than the national estimates developed by CDC for all people living with HIV (i.e., not just those who are enrolled in the Ryan White Care program).

Watch our conversation below.

To learn more about the continuum of care in the Ryan White Program, read the recent blog post on this topic by Dr. Cheever and her colleague, Dr. Rupali Doshi.  You can also read their abstract and view their poster on the CROI website.

To learn more about the HIV care cascade (or “continuum of care”), read my earlier blog post, watch my conversation with Dr. Kevin Fenton about CDC’s demographic analysis of the care cascade presented at AIDS 2012 last summer, or view this video animation.

This weekend, we observe World Tuberculosis (TB) Day (Sunday, March 24), a day to remember that the global burden of TB remains enormous, particularly among people with HIV/AIDS, among whom TB is the leading cause of death, worldwide. According to the World Health Organization  (WHO), in 2011, 1.4 million people died from TB, including 430,000 deaths among people who were HIV-positive. TB is also one of the top killers of women around the globe, with 300,000 deaths among HIV-negative women and 200,000 deaths among HIV-positive women in 2011.

TB is also a health threat among people living with HIV in the United States. In 2011, the Centers for Disease Control and Prevention (CDC) estimates that 6% of all TB cases in the U.S. and 10% of TB cases among people aged 25–44 occurred among people who are living with HIV.

Thankfully, the rate of TB is declining in the U.S. According to the CDC, the number of TB cases reported annually has decreased since its peak in 1992. In addition, most cases of TB disease in the U.S. now occur among immigrants; in 2011, a total of 62% of reported TB cases in the United States occurred in foreign-born persons (CDC). (Read more about TB trends in the U.S. in the March 22, 2013 issue of CDC’s Morbidity and Mortality Weekly Report (MMWR).)

However, tuberculosis remains a serious concern for people living with HIV/AIDS. That’s because a dangerous synergy exists between HIV and TB, such that people who have a suppressed immune system due to HIV infection are much more likely to develop active TB disease if they are exposed to the TB bacteria. Also, active TB infection appears to increase HIV replication among co-infected persons. Therefore, the populations of people who are infected with these two pathogens often overlap. Or, as an historical leader in the field of HIV (Dr. Jim Curran) once observed: “HIV and TB hang out together and they are a bad influence on each other!”

In addition, while TB is curable with proper treatment, erratic or improper treatment can lead to drug resistance—one of the most serious problems facing people living with HIV who are coinfected with TB. Multidrug-resistant TB (MDR TB) is an extremely difficult to-treat and potentially fatal form of TB that is resistant to at least two of the best anti-TB drugs, isoniazid and rifampin. In addition, Extensively Drug-Resistant Tuberculosis (XDR TB) is rare type of MDR TB that is resistant to both the most powerful first-line drugs as well as to one of three second-line drugs. People living with HIV or AIDS are at greater risk of dying of MDR TB and XDR TB.

What You Can Do

To learn more about the intersection between TB and HIV infection, read our recently updated AIDS.gov Basics page, Tuberculosis and HIV. In addition, the Centers for Disease Control and Prevention’s Division of TB Elimination offers excellent resources on HIV and TB coinfection.

If you are an individual living with HIV, be sure to talk to your healthcare provider about tuberculosis and make sure you’ve been tested for TB.  CDC recommends that all people who are newly diagnosed with HIV infection should be tested for TB as soon as possible, regardless of their TB risk category. In addition, people living with HIV who remain in a “high risk” category for repeated or ongoing TB exposure should be tested annually to find out if they have latent TB infection (LTBI).  This includes individuals who have been incarcerated, those who live in group settings such as shelters or rehabilitation facilities, people who are active drug users, and those who have other risk factors for TB. People who are HIV-positive and who have a positive diagnostic test for LTBI should undergo additional clinical tests to rule out active TB disease.

If you are a clinical provider, please take this opportunity to review the CDC’s guidelines for the prevention, testing, treatment, and monitoring of TB infection among persons living with HIV.

For those of you who are interested in the most recent scientific advances, the Conference on Retroviruses and Opportunistic Infections (CROI) , held earlier this month, featured several sessions on TB and the challenges it poses to those living with HIV. The symposium “TB on the Verge” discussed the challenges of HIV-related TB and new approaches for the treatment of MDR TB. Researchers on TB and clinical care discussed recent advances in targeted TB prevention therapy and community-wide and combination prevention strategies; the changing TB diagnostic landscape; the treatment of TB in HIV-infected pregnant women and children; and the current state of MDR TB treatment. The webcast of this CROI symposium is available online .

Information about NIH-supported biomedical research on TB, including research on experimental drugs to treat MDR TB and support to help identify possible new candidate TB vaccines can be found at the National Institute of Allergy and Infectious Disease.

During the 2013 Conference on Retroviruses and Opportunistic Infections  (CROI) in Atlanta earlier this month, I had the opportunity to sit down with Dr. Jonathan Mermin, Director of CDC’s Division of HIV/AIDS Prevention. We discussed some of the important research findings being shared at the conference and their implications for our efforts to respond effectively to HIV/AIDS in the United States. Watch our conversation below about two important studies presented. We discuss the importance of medication adherence for people using antiretrovirals for pre-exposure prophylaxis (PrEP) as well as new CDC data indicating that far too few adults in care for HIV disease are receiving the recommended screening and prevention services related to other sexually transmitted infections (STIs), which can threaten their health and facilitate further HIV transmission.

To learn more about the findings from the VOICE study of pre-exposure prophylaxis shared at CROI, read the abstract ,watch the presentation  (beginning at 00:30:32) and review our related blog post.

To learn more about the CDC analysis related to receipt of STI screening services as part of HIV care, read the abstract  or view the poster .

Viral hepatitis was among the topics receiving significant attention at the 2013 Conference on Retroviruses and Opportunistic Infections  (CROI) in Atlanta this week. Sessions and posters explored a spectrum of topics ranging from virology to new frontiers in hepatitis treatments as well as examinations of HIV/HCV coinfection and its treatment.

Following his conference address, “Expanding the Individual and Public Health Benefits of Hepatitis C Virus Treatment ,” I sat down with my colleague Dr. John Ward, Director of CDC’s Division of Viral Hepatitis. We discussed viral hepatitis infection in the United States, new CDC recommendations about screening for the hepatitis C virus, and the Action Plan for the Prevention, Care and Treatment of Viral Hepatitis.

Watch our conversation below:

To read abstracts or view other presentations about viral hepatitis from CROI 2013, visit the conference website.