Next-generation oral preexposure prophylaxis: beyond tenofovir

by Bisrat K. Abraham and Roy Gulick

 

Purpose of review
Clinical trials of oral preexposure prophylaxis (PrEP) have focused on regimens of tenofovir (TDF) with or
without emtricitabine (FTC). However, TDF may be associated with toxicities (renal, bone), and FTC may
select for drug resistance. Both are also first-line drugs for HIV treatment. In this review, we discuss agents
that might serve as alternatives to TDF/FTC for HIV PrEP.
Recent findings
Several drug characteristics are important to consider when selecting agents for PrEP with the most critical
being safety, tolerability, adequate penetration into target tissues for prevention of HIV infection, and longlasting
activity with convenient dosing. With these factors in mind, we review five potentially useful agents
for PrEP. The first group includes drugs that are already Food and Drug Administration approved
(maraviroc, raltegravir) with attributes that make them attractive for PrEP. The second group includes
investigational agents with long-lasting activity that are being developed in parenteral form (rilpivirine-long
acting, S/GSK1265744, ibalizumab).

Download full review pdf here: [Download not found]
Summary
Future PrEP drugs may give clinicians the flexibility to select agents on the basis of individual patient needs
and preferences

New Resource Highlights Innovations in Oral Health Care for People Living with HIV/AIDS

blog.AIDS.gov     (10.17.12):: Ronald Valdiserri, M.D., M.P.H., Deputy Assistant Secretary for Health, Infectious Diseases, and Director, Office of HIV/AIDS Policy, U.S. Department of Health and Human Services

Dr. Ron Valdiserri, Deputy Assistant Secretary for Health, Infectious Diseases, and Director, Office of HIV/AIDS Policy, US Department of Health and Human Services, offers an excellent new resource published as a special supplement to the journal Public Health Reports. Called “Innovations in Oral Health Care for People Living with HIV/AIDS,” it presents findings from the Innovations in Oral Health Care Initiative, which involved 15, five-year demonstration projects supported by the Health Resources and Services Administration’s HIV/AIDS Bureau, in addition to resources from the Ryan White Care Act’s Special Projects of National Significance.

The findings showed that innovative program models can engage and retain people who are living with HIV/AIDS into oral healthcare services in both urban and non-urban settings. Valdiserri emphasizes oral health is crucial for a person’s general health and well-being throughout a lifespan, and it is especially critical for PLWHA. Inadequate oral health care can undermine the success of health outcomes, nutritional intake, and HIV treatment regimens. He notes that oral infections may also spread to other parts of the body, a particularly dangerous occurrence for individuals with compromised immune systems. View this resource at http://www.publichealthreports.org/issuecontents.cfm?Volume=127&Issue=8.

UNDP-led HIV/AIDS education programme for Thai police

by: http://www.nationmultimedia.com/

BANGKOK: — As many as 10,000 junior Thai police officers per year will soon receive education on HIV/AIDS stigma and discrimination due to a new partnership signed today, by the Royal Thai Police, the United Nations Development Programme (UNDP), the Foundation for AIDS Rights and the Department of Rights Protection of Ministry of Justice.

“The Royal Thai Police are committed to helping Thailand reduce and eliminate HIV/AIDS stigma and discrimination. This training will help our officers become a resource and a helping hand for people living with HIV/AIDS and key affected people,” said Police Lieutenant General Chanin Preechaharn, of the Royal Thai Police.

Stigma and discrimination remain a concern in Thailand and present barriers to access to HIV/AIDS prevention and treatments among key at-risk populations. The government has identified men who have sex with men (MSM) and transgendered persons (TG) as critical target populations to reversing a trend of new HIV infections.

In Thailand, MSM and TG are 20 times more likely to be living with HIV. Of those living with HIV in Thailand, over 16 percent come from the MSM community. For Thailand’s capital, Bangkok, it is as high as 31 percent.

The stigma and discrimination curriculum will be used to educate junior police officers who has passed examination and who will be appointed as non-commissioned police officers throughout the country. The training contains more than 22 hours of lessons, spread out over the course of five days.

A training of 40 trainers began right after the signing ceremony, with a pilot exercise to be held soon to further refine the new curriculum.

“The officers being trained here today will eventually train as many as 10,000 junior police students per year on basic HIV prevention, the principle of AIDS rights, to better understand what it means to live with stigma and discrimination when you’re living with HIV, and how this stigma can be addressed by police officers on the ground,” said Luc Stevens, UN Resident Coordinator and UNDP Resident Representative in Thailand.

Thailand’s national AIDS strategy, ‘Getting to Zero’ is in line with the UNAIDS vision of zero new HIV infections, zero discrimination and zero AIDS-related deaths. The partnership is a product of the long-time development of a joint UN programme on stigma and discrimination under the Joint Team on AIDS in Thailand led by UNDP and UNAIDS.

HIV/AIDS is the third-leading cause of death in the world. More than 500,000 people are living with HIV in Thailand—including 14,000 children. Every year, 10,000 people are infected and over the next five years some 43,000 more are expected, many from at-risk populations such as MSM and TG.

Joining the Royal Thai Police in signing the partnership today were Luc Stevens, UN Resident Coordinator and UNDP Resident Representative; Supatra Nacapiew, Director of the Foundation for AIDS Rights; and Director-General Pitthaya Jinawat, Department of Rights and Liberty Protection, Ministry of Justice.

The Health Care Question: After the November election, what happens next?

Do you know what each candidate has planned for health care if elected, and how it’s relevant to the HIV/AIDS community?

David Ernesto Munar, President and CEO of the AIDS Foundation of Chicago, published an article in Positively Aware about Obama and Romney’s plans for national health care reform if elected. Munar’s article breaks down the candidates’ plans into simple, clear points so you can educate yourself about what will happen under each candidate’s plan.

 

CLICK HERE to read Munar’s article on positivelyaware.com

Munar’s article also includes in-depth information on HIV health care in Massachusetts, which under Governor Romney implemented a state plan similar to the Affordable Care Act.

Stopping the Spread of HIV Among Latinos

By Kevin Fenton, M.D., Ph.D., FFPH, Director, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC

In observance of National Latino AIDS Awareness Day Exit Disclaimer on October 15, the Centers for Disease Control and Prevention released today in the Morbidity and Mortality Weekly Report (MMWR) the results of a new study, “Geographic Differences in HIV Infection Among Hispanics or Latinos — 46 States and Puerto Rico, 2010.” Study authors looked at the characteristics of Hispanics or Latinos who were diagnosed with HIV in 2010 and the geographic distribution of HIV in Puerto Rico and the 46 states with long-term name-based HIV reporting.

The report found that HIV continues to pose a serious health threat to Latinos throughout the United States. In fact, the rate of new infections among Hispanics is three times higher than whites (26.4 vs. 9.1 per 100,000). The report also underscored significant regional differences in the Latino epidemic.

For example, Latinos in the Northeast United States had the highest HIV diagnosis rates in the nation and are more likely than those in other regions to be infected through injection drug use. Alternatively, Latinos in the South had the highest number of new diagnoses and were more likely than those in the Northeast to be infected through contact with men who have sex with men. These data once again showed that Latino gay and bisexual men are by far most affected, accounting for more than 80% of all infections among Latino men. Moreover, Latinas (Hispanic women) also are severely impacted – with rates of new HIV infections four times that of white women.

On National Latino AIDS Awareness Day and every day, there are actions we can take to address these health disparities. This day is a reminder that we have the power to take control of our health and protect ourselves against HIV by getting tested for HIV, getting treatment and staying on treatment if infected, and talking openly about HIV to reduce stigma and shed light on issues that if left unattended will continue to feed the epidemic.

Federal Programs to Fight HIV in Latinos
The National HIV/AIDS Strategy calls for the prioritization of U.S. HIV efforts on highly impacted populations, including Latinos. At CDC, one way we are supporting NHAS is though High-Impact Prevention strategies that will help us attain a higher level of impact with every prevention dollar.

At the community level, CDC is reaching Latinos through a three-year demonstration project in 12 U.S. cities with the highest burden of HIV. The project is aimed at reducing new HIV infections and disparities in Latino communities, and linking those infected to care and treatment. Furthermore, CDC has funded 34 community-based organization (CBOs) to expand prevention among young MSM and young transgender persons of color. Eighteen of the 34 CBOs reach out specifically to Hispanic MSM. CDC has also expanded the Act Against AIDS Leadership Initiative to include national Latino organizations with deep reach into the larger Latino communities.

There is no single solution to the epidemic among Latinos, and our work must be on all levels, national, state, community, and individual. Together we can begin to tackle the many social obstacles, ensure diversity awareness is part of our response, and work to tailor programs to fit the need. As an individual, start the dialogue, get the test, take the steps necessary to protect your health and the health of those you love. As a community, tackle social obstacles that keep many from seeking testing, care, and treatment. Start taking control today and stop the epidemic in the Latino community!

 

CLICK HERE to read the article by Kevin Fenton, M.D., Ph.D.

Methadone Treatment for Addicts Is Linked to Lower H.I.V. Risk

Offering methadone treatment to drug addicts substantially reduces the risk that they will get H.I.V. or give it to anyone else, a new study has found.

The study, published online on Oct. 4 by the British journal BMJ, pooled data from studies done in nine countries. It concluded that making methadone available reduced H.I.V. risk by 54 percent.

Many countries, including Russia, have large H.I.V. epidemics among addicts but nonetheless outlaw methadone and buprenorphine treatment for political, religious or other reasons.

Methadone itself does not affect the virus; scientists believe it works because addicts on treatment become better able to stop sharing needles and selling sex for drugs. They are also better able to stay on antiretroviral drugs, which lowers the chance they will infect others. The authors speculated that opiate-substitution therapy was so effective because addicts who are motivated enough to seek treatment are also smart about protecting themselves in other ways.

Contaminated needles cause 5 percent to 10 percent of all the world’s H.I.V. infections, the study estimated. The problem is worst in Eastern Europe and in Central and Southeast Asia on the fringes of opium-growing areas.

Although more people have sex than inject drugs, the risk of catching H.I.V. is 1 in 125 from a syringe, about 1 in 122 from anal sex and less than 1 in 2,000 from vaginal sex, according to an editorial published with the study.

Another Use for Rapid Home H.I.V. Test: Screening Sexual Partners

NY Times By DONALD G. McNEIL Jr.

 

Some experts said the OraQuick test’s $40 price would prevent many people from using it to screen partners.

But some experts and advocates say that another use, unadvertised, for the OraQuick test – to screen potential sexual partners – may become equally popular and even help slow an epidemic stuck at 50,000 new infections each year in the United States.

There are reasons to think that screening might make a difference. Studies have found that a significant minority of people who are H.I.V.-positive either lie about their status or keep it secret, infecting unsuspecting partners.

And though the manufacturer, OraSure Technologies, is not promoting the use of the test for screening, 70 percent of the 4,000 men and women in the company’s clinical trials said they would either definitely or very likely use it that way. Some even suggested that the company sell boxes of two so couples could be tested together.

The only study of the practice – a small one involving 27 gay men who frequently had sex with virtual strangers without using condoms – found that it probably prevented some infections. The study was published online in August by the journal AIDS and Behavior.

“If it becomes a community norm, people may start testing their partners,” said Alex Carballo-Dieguez, the lead author of the study, who is a psychology professor at Columbia University and the associate director of the H.I.V. Center for Clinical and Behavioral Studies at the New York State Psychiatric Institute. “On sex sites now, men advertise themselves as ‘drug-and-disease-free.’ They could start saying ‘D-and-D-free, and willing to prove it.’ ”

Other AIDS experts had doubts. Some thought $40 was too much for people who need to screen multiple partners. Others said that men and women who are not comfortable demanding that their partners wear condoms would be unable to insist on a test.

And some, including Anthony S. Fauci, the country’s best-known AIDS doctor, worried that a negative test could lead partners to forgo condoms, removing the barrier to both H.I.V. and other diseases like gonorrhea.

The OraQuick test is imperfect. It is nearly 100 percent accurate when it indicates that someone is not infected and, in fact, is not. But it is only about 93 percent accurate when it says that someone is not infected and the person actually does have the virus, though the body is not yet producing the antibodies that the test detects.

The men in Dr. Carballo-Dieguez’s study were given 16 tests each and followed for three months. None of them had unprotected sex with anyone who tested positive.

Of the 101 partners they tested, 10 were positive. In six cases, it was how the partner first learned he was infected. (Ten percent is a very high success rate for H.I.V. testing, experts said.)

Twenty-three other partners refused testing. Two, after being asked, admitted knowing they were infected.

Seven men got angry, and one stomped on the kit. One man walked out saying he wanted to be alone and broke off contact.

Asking usually did not ruin the moment’s intimacy, the men said. Some pairs did the tests together, swabbing each other’s gums. Some passed the 20-minute wait talking, playing video games or in foreplay. One 47-year-old man found the wait helpful, telling the researchers, “It gives you that extra 20 minutes to decide, ‘O.K., if this comes back negative, am I really ready to bareback?’ ” – slang for having sex without a condom.

Dr. Carballo-Dieguez said people’s decision about whether to screen would depend on various factors, including the test’s price and how comfortable they were with its imperfect accuracy.

OraSure appears ambivalent about partner screening. AIDS experts said the company might fear lawsuits by people infected by partners who got false negatives – a possibility it declined to comment on. In an interview, its president, Douglas A. Michel, said, “We’re supportive, as long as it’s between consenting adults.”

But he also said the label would warn that the test “should not be used to make decisions that might put the user at risk of contracting H.I.V.”

Asked about the price of the test, he said market research indicated that most users would buy it once or twice a year, so $40 was “appropriate.”

The technology is similar to that in home pregnancy kits, which sell for as little as $4 each.

Larry Kramer, the longtime AIDS activist, called screening “a potentially cool idea, but it depends on how the partner/date/trick/stranger takes it.”

If a test had been around 30 years ago, he added, “there would have been a lot more people alive today.”

Hunteur Vreeland, a professional party organizer who arranges “gay porn harbor cruises” and “underwear erotic parties” at Paddles, a dungeon-themed club in New York, said he would even consider selling home tests at his events. He now offers free H.I.V. testing at them in conjunction with the Men’s Sexual Health Project of Bellevue Hospital Center.

“Knowledge is never a bad thing,” he said. He added that if a potential partner unexpectedly pulled out a test kit, he would probably leave.

Then he reconsidered.

“But if the dude was hot, and maybe I was on the cusp of getting tested anyway – well, then, maybe I’d be, ‘All right, I’ll take it.’ ”

Justin Goforth, the director of medical adherence for Whitman-Walker Health, a clinic in Washington with many AIDS patients, said he doubted that screening would help his clientele.

“It’s expensive,” he said. “People who can afford it already have strategies for avoiding infection. It won’t help women whose men refuse to use condoms, because he’ll refuse to take the test, too. And the same for young black men – they usually get infected by older men, and the power dynamic is not in their favor.”

Steven Petrow, the author of “Complete Gay & Lesbian Manners,” argued against screening.

“Nobody should take this test and 20 minutes later go have unprotected sex,” he said. “The art of talking to a partner is the primary thing. You have to respect each other and tell the truth.”

But numerous studies have shown that many sexual partners do not.

In a large 2007 survey led by Dr. Robert Klitzman, also of Columbia University and the New York State Psychiatric Institute, nearly 20 percent of infected gay men admitted to having had unprotected sex with at least one partner without revealing their status.

Men made many excuses, saying they believed that they were not infectious or felt it was the partner’s duty to ask.

An equally large 2003 study led by Dr. Daniel H. Ciccarone of the University of California, San Francisco, found that about 9 percent of H.I.V.-positive heterosexual men and women and about 14 percent of infected gay or bisexual men had recently had unprotected sex with someone they either knew was uninfected or were unsure about, without revealing their own infection.

The authors estimated that in the six months their study covered, 17,000 infected gay men across the country and almost 5,000 infected heterosexual men and women had sex without telling the truth.

HIV Therapy Helps Reduce Risk of Non-AIDS Illnesses

Though non-AIDS-related health complications are still common among people living with HIV, data from a Spanish cohort suggest that the incidence of these problems has dropped and that CD4 cell gains and viral load reductions associated with antiretroviral (ARV) therapy use can be credited with reducing the risk, according to a new report published online ahead of print in the journal AIDS.  In the analysis of 5,185 people living with HIV participating in the CoRIS cohort, the incidence of non-AIDS-related illnesses dropped from 35 cases per 1,000 person-years between 2004 and 2007 to 25 cases per 1,000 person-years between 2007 and 2010. This decrease was largely attributed to the use of ARV therapy; detectable viral loads, low CD4 cell counts and age were all shown to be factors associated with an increased risk of non-AIDS-related illnesses, which included psychiatric problems, liver disease, cancers (lung cancer being the most common), kidney disease and cardiovascular disease.  The positive effects of ARV therapy were most pronounced in terms of reducing the incidence and risk of of psychiatric problems and kidney disease.

Cure-Focused Grants Support Intriguing New Research

A recurring theme in HIV cure research is the barrier presented by latent HIV infection. Current antiretroviral therapy (ART) can reduce active virus growth to undetectable levels. But there remains an extremely stable reservoir of virus invulnerable to attack by these drugs. 

One strategy to overcome this latent reservoir is to activate the latent cells, making the virus susceptible to ART. During the course of a prior ARCHE (amfAR Research Consortium on HIV Eradication) study, it was discovered that disulfiram, a drug that is approved by the FDA for the treatment of alcoholism, could activate latent HIV in the test tube. Dr. Julian Elliott of Monash University in Melbourne, Australia, along with Dr. Steven Deeks of the University of California, San Francisco, now plan to determine whether this concept could be effective in patients.

Drs. Elliot and Deeks will give different doses of disulfiram to four groups of 10 adult volunteers with stable HIV infection on ART, daily for three days. This is known as a dose escalation study. Apart from safety monitoring, they will evaluate the effect of this drug on the growth of HIV in T cells and plasma. They will also see if the size of a patient’s latent HIV reservoir is altered by treatment.

 A second ARCHE grant was awarded to Dr. Timothy Henrich of Harvard Medical School and Brigham and Women’s Hospital. He will study two HIV-positive individuals who had been on long-term ART when they developed lymphomas. To treat their cancer, both underwent typical stem-cell transplants from donors who had been selected only for tissue-type match. But Dr. Henrich found something extraordinary. Not only were these individuals cured of their cancer, but he could find no evidence of HIV infection. While the “Berlin patient” was cured of HIV following transplant with cells from a donor selected for the CCR5 delta32 mutation, and thus HIV infection, in a procedure involving highly toxic total body radiation and anti-T cell antibodies, no extraordinary measures were used here. For the moment, these two individuals remain on ART. But with amfAR funding, Dr. Henrich will interrupt their ART and search for HIV in their blood and other tissues. He will also assess the size of their HIV reservoir if any latent virus is uncovered.

A third grant was awarded to Dr. Deborah Persaud of Johns Hopkins and Dr. Katherine Luzuriaga of the University of Massachusetts. They will determine if it is possible to cure an HIV infection with ART alone in children in whom ART had been started soon after birth and continued for an average of 15 years. Drs. Persaud and Luzuriaga have a group of five such children with no detectable HIV, who remain HIV antibody negative. The researchers will use highly sophisticated tests to search for active and latent virus.

We are very excited about the prospects of these three new studies to advance our goal of finding a practical cure for HIV/AIDS.

 To view the press release click here. 

Secretary’s Minority AIDS Initiative Fund Supports $14.2 Million in Awards to 8 States to Improve HIV Testing and Engagement in Care

By Ronald Valdiserri, M.D., M.P.H., Deputy Assistant Secretary for Health, Infectious Diseases, and Director, Office of HIV/AIDS and Infectious Disease Policy, U.S. Department of Health and Human Services

CLICK HERE  to read the article on blog.AIDS.gov

The CDC announced that eight state health departments have been awarded a total of $14.2 million in first-year funding under a new, innovative, three-year cross-HHS demonstration project aligned with the National HIV/AIDS Strategy (NHAS). The eight states – Georgia, Illinois, Louisiana, Mississippi, Missouri, North Carolina, Tennessee, and Virginia – have a high burden of HIV among African-Americans and Latinos and the demonstration project is designed to reduce HIV-related morbidity, mortality, and related health disparities among racial and ethnic minorities by addressing social, economic, clinical and structural factors influencing HIV health outcomes.

“This new program funding represents a carefully planned movement that specifically joins together HIV prevention and treatment into a holistic statewide continuum of service. That is what people with HIV need and it is what we intend to deliver,” observed Dr. Jonathan Mermin, Director of CDC’s Division of HIV/AIDS Prevention

The Care and Prevention in the United States (CAPUS) Demonstration Project was open to 18 state/territorial health departments in the United States with disproportionately high burdens of HIV/AIDS among minority communities. Specifically, the eligible jurisdictions had more than 5,000 HIV cases among African Americans and Latinos and an AIDS diagnosis rate of over 6 per 100,000, which focuses this initiative on disproportionately affected geographic areas.

The primary goals of the project are three-fold:

  1. Increase the proportion of racial/ethnic minorities with HIV who have diagnosed infection by expanding and improving HIV testing capacity
  2. Optimize linkage to, retention in, and re-engagement with care and prevention services for newly diagnosed and previously diagnosed racial/ethnic minorities with HIV
  3. Address social, economic, clinical, and structural factors influencing HIV health outcomes

The demonstration project is funded by the Secretary’s Minority AIDS Initiative Fund (SMAIF), which is administered by my office, the Office of HIV/AIDS and Infectious Disease Policy (OHAIDP). (Read my earlier blog post about how the rest of the Fiscal Year 2012 SMAIF was allocated.) In keeping with the spirit and goals of the NHAS, and in recognition of the complex, interrelated, and multi-sectorial nature of the demonstration project’s goals, a multi-agency federal partnership will provide leadership for the activities. CDC serves as the lead agency, with participation from OHAIDP, Office of Minority Health, Office on Women’s Health, HRSA’s HIV/AIDS Bureau and Bureau of Primary Health Care, and the Substance Abuse and Mental Health Services Administration.

By concentrating these resources in communities that bear a disproportionate burden, providing assistance from multiple HHS agencies and offices, and requiring the grantees to use a minimum of 25% of the total award to fund community-based organizations serving racial/ethnic minority populations, we expect that the CAPUS project will contribute significantly to NHAS goals over the next three years.