DiversityNursing Blog

DONALD G. McNEIL Jr.

A major study testing whether Americans would take their H.I.V. drugs every day if they were paid to do so has essentially failed, the scientists running it announced Tuesday at an AIDS conference here.

Paying patients in the Bronx and in Washington — where infection rates are high among poor blacks and Hispanics — up to $280 a year to take their pills daily improved overall adherence rates very little, the study’s authors said.

The hope was that the drugs would not only improve the health of the people taking them, but help slow the spread of H.I.V. infections. H.I.V. patients who take their medicine regularly are about 95 percent less likely to infect others than patients who do not. The Centers for Disease Control and Prevention estimates that only a quarter of all 1.1 million Americans with H.I.V. are taking their drugs regularly enough to not be infectious.

Paying patients $25 to take H.I.V. tests, and then $100 to return for the results and meet a doctor, also failed, the study found.

“We did not see a significant effect of financial incentives,” said Dr. Wafaa M. El-Sadr, an AIDS expert at Columbia University and the lead investigator. But, she said, there is “promise for using such incentives in a targeted manner.”

Cash payments might still work for some patients and some poor-performing clinics, she said.

Other H.I.V.-prevention research released here Tuesday offered good news for gay men but disappointing results for African women.

Two studies — both of gay men, one in Britain and the other in France — confirmed earlier research showing that pills to prevent infection can be extremely effective if taken daily or before and after sex. Both were stopped early because they were working so well that it would have been unethical to let them continue with men in control groups who were not given the medicine.

But a large trial involving African women of a vaginal gel containing an antiviral drug failed — apparently because 87 percent of the women in the trial were unable to use the gel regularly.

The failure of the cash-incentives trial was a surprise and a disappointment to scientists and advocates. It had paid out $2.8 million to 9,000 patients in 39 clinics over three years, but the clinics where money was distributed did only 5 percent better than those that did not — a statistically insignificant difference.

Some small clinics and those where patients had been doing poorly at the start of the study did improve as much as 13 percent, however.

People in other countries have been successfully paid to stop smoking while pregnant and to get their children to school. In Africa, paying poor teenage girls to attend school lowered their H.I.V. rates; scientists concluded that it eased the pressure on them to succumb to “sugar daddies” — older men who gave them money for food, clothes and school fees in return for sex.

One study presented here at the annual Conference on Retroviruses and Opportunistic Infections estimated that every prevented H.I.V. infection saved $230,000 to $338,000. Much of that cost is borne by taxpayers.

Mathematical modeling suggested that paying people up to $5,000 a year could be cost effective, Dr. El-Sadr said, but $280 was settled on after a long, difficult debate.

Paying more than $280 at some clinics was not an option, she said; achieving statistical relevance would have meant signing up even more clinics. The study had already involved almost every H.I.V. patient in the Bronx and Washington.

“I don’t think anyone has an answer to what amount would be sufficient without being excessive,” Dr. El-Sadr said.

One advocate suggested that more money could work — in the right setting.

“In South Africa, $280 is a lot of money,” said Mitchell Warren, the executive director of AVAC, an organization that lobbies for AIDS prevention. “For that much, you’d definitely get some behavior change.”

The two studies among gay men looked at different ways to take pills. A 2010 American study, known as iPrEx, showed that taking Truvada — a combination of two antiretroviral drugs — worked if taken daily.

The British study, known as PROUD, used that dosing schedule, and men who took the pill daily were protected 86 percent of the time.

In the French trial, known as Ipergay, men were advised to take two pills in the two days before they anticipated having sex and two in the 24 hours afterward.

Those who took them correctly also got 86 percent protection.

“The problem,” Dr. Susan P. Buchbinder, director of H.I.V. prevention research for the San Francisco health department, said in a speech here commenting on the study, “is that studies have shown that men are very good at predicting when they will not have sex and not good at predicting when they will.”

The African study, known as FACTS 001, was a follow-up to the smaller trial from 2010, which showed that South African women who used a vaginal gel containing tenofovir, an antiviral drug, before and after sex were 39 percent better protected than women who did not.

But it also found that many women failed to use the gel because it was messy or inconvenient or because partners objected.

In this trial, there was virtually no effect.

One problem, said Dr. Helen Rees, the chief investigator, was that the women were very young — the median age was 23, and most lived with their parents or siblings.

“They had no privacy for sex,” she said. “They had to go outside to use the product.”

Mr. Warren, of AVAC, said: “The women wanted a product they could use. But this particular product didn’t fit into the realities of their daily lives.”

The development means that advocates are hoping even more that other interventions for women now in trials will work. They include long-lasting injections of antiretroviral drugs and vaginal rings that can be inserted once a month and leach the drugs slowly into the vaginal wall.

Another trial in Africa, the Partners Demonstration Project, conducted among couples in which one partner had H.I.V. and the other did not, found it was extremely effective to simultaneously offer treatment to the infected partner and preventive drugs to the uninfected one until the other’s drugs took full effect.

In the group getting the treatment, there were zero infections that could be traced to partners who were in the study.

Source: www.nytimes.com

JESSICA FIRGER

Scientists have discovered a highly aggressive new strain of HIV in Cuba that develops into full-blown AIDS three times faster than more common strains of the virus. This finding could have serious public health implications for efforts to contain and reduce incidences of the virus worldwide.

Researchers at the University of Leuven in Belgium say the HIV strain CRF19 can progress to full blown AIDS within two to three years of exposure to virus. Typically, HIV takes approximately 10 years to develop into AIDS. Patients with CRF19 may start getting sick before they even know they've been infected, which ultimately means there's a significantly shorter time span to stop the disease's progression. 

The scientists began studying the cases in Cuba when reports began coming in that a growing number of HIV-infected patients were developing AIDS just three years after diagnosis with the virus. The findings of their study were published in the journal EBioMedicine.

Having unprotected sex with multiple partners can expose a person to numerous strains of the HIV virus. Research has found that when this occurs, the different strains can combine and form a new variant of the virus.

When HIV first enters the human body it latches on to anchor points of a certain protein, known as CCR5 on the cell membranes, which then allows it to enter human cells. Eventually the virus then latches onto another protein of the cell membrane, known as CXCR4. This marks the point when asymptomatic HIV becomes AIDS. In CRF19, the virus makes this move much sooner. 

For the study, the researchers analyzed blood samples of 73 recently infected patients. Among the group, 52 already had full-blown AIDS, while the remaining 21 were HIV-positive but the virus had not yet progressed. The researchers compared their findings to blood samples of 22 AIDS patients who had more common strains of the virus. 

The researchers found that patients with CRF19 had higher levels of the virus in their blood compared with those who had more common strains. 

They also had higher levels of the immune response molecules known as RANTES, which bond to CCR5 proteins in early stages of the virus. The abnormally high level of RANTES in patients infected with the new strain indicates that the virus runs out of CCR5 anchor points much earlier and moves directly to CXCR4 anchor points.

Thanks to advances in medical treatment and the development of highly effective antiretroviral drugs, HIV/AIDS is no longer a death sentence. But the researchers caution that patients with the new strain of the virus are more likely to be diagnosed when they already have full-blown AIDS and when damage from the disease has taken a toll.

The researchers suspect that this aggressive form of HIV occurs when fragments of other subsets of the virus cling to each other through an enzyme that makes the virus more powerful and easily replicated in the body.

There are currently 35 million people worldwide living with HIV/AIDS, according to the most recent data from the World Health Organization. Scientists have identified more than 60 different strains of the HIV 1 virus, with each type typically found predominantly in a specific region of the world.

Source: www.cbsnews.com

By Meera Senthilingam

"It only takes one virus to get through for a person to be infected," explained Dr. John Mascola. This is true of any viral infection, but in this instance, Mascola is referring to HIV and his ongoing efforts to develop a vaccine against the virus. "It's been so difficult to make an HIV/AIDS vaccine."

Those were the words of many working in HIV vaccine development until the results of a 2009 trial in Thailand surprised everyone. "The field is energized," said Mascola, director of the Vaccine Research Center at the U.S. National Institute of Allergy and Infectious Diseases, describing the change in atmosphere in the vaccine community.

The trial included over 16,000 volunteers and was the largest clinical trial ever conducted for a vaccine against HIV. It was also the first to show any protection at all against infection.

Two previously developed vaccines, known as ALVAC-HIV and AIDSVAX, were used in combination, with the first priming an immune response against HIV and the second used as a booster once the immunity waned. The duo reduced the risk of contracting HIV by 31.2% -- a modest reduction, but it was a start.

To date, only four vaccines have made it as far as testing for efficacy to identify their levels of protection against HIV. Only this one showed any protection.

"That trial was pivotal," Mascola said. "Prior to that, it wasn't known whether a vaccine could be possible."

In recent years, there have been parallel findings of an equally pivotal nature in the field of HIV prevention, including the discovery that people regularly taking their antiretroviral treatment reduce their chances of spreading HIV by 96% and that men who are circumcised reduce their risk of becoming infected heterosexually by approximately 60%.

Both improved access to antiretrovirals and campaigns to increase male circumcision in high-risk populations have taken place since the discoveries, and although numbers of new infections are falling, they're not falling fast enough.

In 2013, there were 35 million people estimated to be living with HIV globally. There were still 2.1 million new infections in 2013, and for every person who began treatment for HIV last year, 1.3 people were newly infected with the lifelong virus, according to UNAIDS. A vaccine remains essential to control the epidemic.

A complex beast

Scientists like Mascola have dedicated their careers to finding a vaccine, and their road has been tough due to the inherently complicated nature of the virus, its aptitude for mutating and changing constantly to evade immune attack, and its ability attack the very immune cells that should block it.

There are nine subtypes of HIV circulating in different populations around the world, according to the World Health Organization, and once inside the body, the virus can change continuously.

"Within an individual, you have millions of variants," explained Dr. Wayne Koff, chief scientific officer for the International AIDS Vaccine Alliance.

HIV invades the body by attaching to, and killing, CD4 cells in the immune system. These cells are needed to send signals for other cells to generate antibodies against viruses such as HIV, and destroying those enables HIV to cause chronic lifelong infections in those affected.

Measles, polio, tetanus, whooping cough -- to name a few -- all have vaccines readily available to protect from their potentially fatal infections. But their biology is seemingly simple in comparison with HIV.

"For the older ones, you identify the virus, either inactivate it or weaken it, and inject it," Koff said. "You trick the body into thinking it is infected with the actual virus, and when you're exposed, you mount a robust immune response."

This is the premise of all vaccines, but the changeability of HIV means the target is constantly changing. A new route is needed, and the true biology of the virus needs to be understood. "In the case of HIV, the old empirical approach isn't going to work," Koff said.

Scientists have identified conserved regions of the virus that don't change as readily, making them prime targets for attack by antibodies. When the success of the Thai trial was studied deep down at the molecular level, the protection seemed to come down to attacking some of these conserved regions. Now it's time to step it up.

In January, the mild success in Thailand will be applied in South Africa, where over 19% of the adult population is living with HIV. The country is second only to bordering Swaziland for having the highest rates of HIV in the world.

"The Thai vaccine was made for strains (of HIV) circulating in Thailand," said Dr. Larry Corey, principal investigator for the HIV Vaccine Trials Network, which is leading the next trial in South Africa. The strain, or subtype, in this case was subtype B. "For South Africa, we've formed a strain with common features to (that) circulating in the population." This region of the world has subtype C.

An additional component, known as an adjuvant, is being added to the mix to stimulate a stronger and hopefully longer-lasting level of immunity. "We know durability in the Thai trial waned," Corey said. If safety trials go well in 2015, larger trials for the protective effect will take place the following year. An ideal vaccine would provide lifelong protection, or at least for a decade, as with the yellow fever vaccine.

A broad attack

The excitement now reinvigorating researchers stems not only from a modestly successful trial but from recent successes in the lab and even from HIV patients themselves.

Some people with HIV naturally produce antibodies that are effective in attacking the HIV virus in many of its forms. Given the great variability of HIV, any means of attacking these conserved parts of the virus will be treasured and the new found gold comes in the form of these antibodies -- known as "broadly neutralizing antibodies." Scientists including Koff set out to identify these antibodies and discover whether they bind to the outer coat of the virus.

The outer envelope, or protein coat, of HIV is what the virus uses to attach to, and enter, cells inside the body. These same coat proteins are what vaccine developers would like our antibodies to attack, in order to prevent the virus from entering our cells. "Broadly neutralizing antibodies" could hold the key because, as their name suggests, they have a broad remit and can attack many subtypes of HIV. "We will have found the Achilles heel of HIV," Koff said.

Out of 1,800 people infected with HIV, Koff and his team found that 10% formed any of these antibodies and just 1% had extremely broad and potent antibodies against HIV. "We called them the elite neutralizers," he said of the latter group. The problem, however, is that these antibodies form too late, when people are already infected. In fact, they usually only form a while after infection. The goal for vaccine teams is to get the body making these ahead of infection.

"We want the antibodies in advance of exposure to HIV," explained Koff. The way to do this goes back to basics: tricking the body into thinking it is infected.

"We can start to make vaccines that are very close mimics of the virus itself," Mascola said.

Teams at his research center have gained detailed insight into the structure of HIV in recent years, particularly the outer coat, where all the action takes place. Synthesizing just the outer coat of a virus in the lab and injecting this into humans as a vaccine could "cause enough of an immune response against a range of types of HIV," Mascola said.

The vaccine would not contain the virus itself, or any of its genetic material, meaning those receiving it have no risk of contracting HIV. But for now, this new area remains just that: new. "We need results in humans," Mascola said.

Rounds of development, safety testing and then formal testing in high-risk populations are needed, but if it goes well, "in 10 years, there could be a first-generation vaccine." If improved protection is seen in South Africa, a first-generation vaccine could be with us sooner.

Making an Impact

When creating vaccines, the desired level of protection is usually 80% to 90%. But the high burden of HIV and potentially beneficial impact of lower levels of protection warrant licensing at a lower percentage.

"Over 50% is worth licensing from a public health perspective," Koff said, meaning that despite less shielding from any contact with the HIV virus, even a partially effective vaccine would save many lives over time.

The next generations will incorporate further advancements, such as inducing neutralizing antibodies, to try to increase protection up to the 80% or 90% desired.

"That's the history of vaccine research; you develop it over time," Corey said. He has worked in the field for over 25 years and has felt the struggle. "I didn't think it would be this long or this hard ... but it's been interesting," he ponders.

But there is light at the end of tunnel. Just.

"There has been no virus controlled without a vaccine," he concluded when explaining why, despite antiretrovirals, circumcision and increased awareness, the need for a one-off intervention like a vaccine remains strong.

"Most people that transmit it don't even know they have it," he said. "To get that epidemic, to say you've controlled it, requires vaccination."

Source: www.cnn.com