Scientists develop two-drug combo pill to treat HIV

Scientists have developed a new delivery system for a combination of two HIV drugs that may serve as an effective treatment for the deadly virus. The discovery, which allows for a combination of decitabine and gemcitabine to be delivered in pill form, marks a major step forward in patient feasibility for the drugs, which previously had been available solely via injection or intravenous therapy (IV), researchers said.

 

"If you have a condition that requires you to take a medication everyday, as many patients with HIV do, you wouldn't want to have to take that medication via daily injection," said Steven Patterson, professor at the Center for Drug Design at the University of Minnesota.
"This finding is a big step in demonstrating this treatment could be taken as a pill, similar to other HIV drugs, and is suitable for eventual clinical translation," said Patterson. Researchers first announced decitabine and gemcitabine, both FDA approved drugs, could potentially combine to treat HIV in August 2010.
The drug combination was shown to work by lethal mutagenesis that could obliterate HIV by causing the virus to mutate to a point where it was no longer infectious. For some patients, human immunodeficiency virus (HIV)'s ability to quickly mutate and evolve can result in drug resistance, researchers said.
For patients who have developed resistance to currently available HIV treatments, the decitabine-gemcitabine drug combination could prove an effective alternative and secondary line of defence. In addition to a potentially effective treatment for humans with HIV, the combination also shows potential to treat cats with leukaemia, researchers said.
"There's still a lot of work that needs to be done to demonstrate the safety and efficacy of this drug combination before human clinical trials can begin," said Patterson. "But we're optimistic that we're moving forward," said Patterson.
The study, coauthored by Christine Clouser, Laurent Bonnac, Louis Mansky, and Steven Patterson, was published in the journal Antiviral Chemistry & Chemotherapy.

 

What Abnormal Results Mean

What Abnormal Results Mean

A positive result on the ELISA screening test does not necessarily mean that the person has HIV infection. Certain conditions may lead to a false positive result, such as Lyme disease, syphilis, and lupus.
A positive ELISA test is always followed by a Western blot test. A positive Western blot confirms an HIV infection. A negative Western blot test means the ELISA test was a false positive test. The Western blot test can also be unclear, in which case more testing is done.
Negative tests do not rule out HIV infection. There is a period of time (called the "window period") between HIV infection and the appearance of anti-HIV antibodies that can be measured.
If a person might have acute or primary HIV infection, and is in the "window period," a negative HIV ELISA and Western blot will not rule out HIV infection. More tests for HIV will need to be done.

ELISA/Western blot tests for HIV

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How the Test is Performed

A blood sample is needed. For information on how this is done, see: Venipuncture.

How to Prepare for the Test

No preparation is necessary.

How the Test Will Feel

When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing.

Why the Test is Performed

Testing for HIV infection is done for many reasons, including:

• Screening people who want to be tested
• Screening people in high-risk groups (men who have sex with men, injection drug users and their sexual partners, and commercial sex workers)
• Screening people with certain conditions and infections (such as Kaposi's sarcoma or Pneumocystis jirovecii pneumonia)
• Screening pregnant women to help prevent them from passing the virus to the baby
• When a patient has an unusual infection

Normal Results

A negative test result is normal. However, people with early HIV infection (termed acute HIV infection or primary HIV infection) often have a negative test result.

What Abnormal Results Mean

A positive result on the ELISA screening test does not necessarily mean that the person has HIV infection. Certain conditions may lead to a false positive result, such as Lyme disease, syphilis, and lupus.
A positive ELISA test is always followed by a Western blot test. A positive Western blot confirms an HIV infection. A negative Western blot test means the ELISA test was a false positive test. The Western blot test can also be unclear, in which case more testing is done.
Negative tests do not rule out HIV infection. There is a period of time (called the "window period") between HIV infection and the appearance of anti-HIV antibodies that can be measured.
If a person might have acute or primary HIV infection, and is in the "window period," a negative HIV ELISA and Western blot will not rule out HIV infection. More tests for HIV will need to be done.

Risks

Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others.
Other risks associated with having blood drawn are slight but may include:

• Excessive bleeding
• Fainting or feeling light-headed
• Hematoma (blood accumulating under the skin)
• Infection (a slight risk any time the skin is broken)

Considerations

People who are at high risk (men who have sex with men, injection drug users and their sexual partners, commercial sex workers) should be regularly tested for HIV.
If the health care provider suspects early acute HIV infection, other tests (such as HIV viral load) will be needed to confirm this diagnosis, because the HIV ELISA/Western blot test will often be negative during this window period.

Alternative Names

HIV testing

References

Dewar R, Goldstein D, Maldarelli F. Diagnosis of human immunodeficiency virus infection. In: Mandell GL, Bennett GE, Dolin R, eds. Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Elsevier Churchill Livingstone; 2009:chap 119.
Sax PE, Walker BD. Immunopathogenesis of human immunodeficiency infection. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, PA: Saunders Elsevier; 2007:chap 408.

Strategy developed that may help researchers design a future vaccine against HIV/AIDS

Designing an effective HIV/AIDS vaccine is something of a paradox: a good vaccine would be safe and look enough like HIV to kick-start the immune system into neutralizing the virus - but the problem is that this is exactly what the human immune system has trouble doing even when it's exposed to the real thing.
Now a team of researchers led by scientists at The Scripps Research Institute in La Jolla, Calif. has developed a strategy for inducing a key part of an effective immune response to HIV. By tracing the evolution of HIV-recognizing molecules called antibodies taken from the blood of rare individuals whose immune systems are naturally able to target and neutralize the virus, they may have found a way to replicate this for everybody.
At a talk at the American Crystallographic Association meeting in Hawaii on July 24, the team will present multiple crystal structures, which like detailed architectural blueprints show how the virus interacts with components of the immune system. Examining these structures has allowed them to reverse engineer molecules that specifically activate the precursors of effective, neutralizing antibodies against the virus - molecules that may be components of a future vaccine against HIV.
"What we tried to do was to learn how those [effective] antibodies developed over the course of natural infection and attempt to guide the immune response in the direction of what we know works in certain HIV-infected individuals," said structural biologist Jean-Philippe Julien, who is presenting the work in Hawaii.
He conducted the research under the direction of Professors Ian Wilson and William Schief of The Scripps Research Institute. The work was funded by the International AIDS Vaccine Initiative Neutralizing Antibody Center, the Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, and the National Institute of Allergy and Infectious Diseases (one of the National Institutes of Health). Additional support was provided through a Canadian Institutes of Health Research fellowship.
Julien cautioned that the work might not, by itself, be the final answer that shows how to make an effective HIV/AIDS vaccine - but it is a step in the right direction. Most likely, Julien said, any future HIV/AIDS vaccine would combine multiple biological components in order to give the broadest possible protection against the virus.
He added that their candidate molecule was able to achieve the desired immune reactions in the test tube, and they are currently testing it in animals to see if it is able to kick start the desired immune response. If those experiments go well, he said, further studies will examine whether it can protect animals against infection, and human trials for safety and vaccine efficacy would be next - though it may be years before those results are known.
While designing a vaccine against any pathogen is a long, hard process, HIV has been particularly difficult, and despite decades of efforts and hundreds of millions of dollars spent in the process, we still do not yet have an effective vaccine that can prevent infection.

Failure Of Latest HIV Vaccine Test: A 'Huge Disappointment'

The green dots are HIV virus particles on a human white blood cell.

CDC

The largest current study of an AIDS vaccine, involving 2,500 people, is being stopped.
After an oversight committee took a preliminary peek at the results this past Monday, they concluded there was no way would show that the vaccine prevents HIV infection.
Nor would the vaccine suppress the wily virus among people who get infected despite being vaccinated.
So they on HVTN-505, as the study is called.
"It was a huge disappointment," says study leader , who learned the bad news at 1:45 Monday afternoon.
Hammer tells Shots the blow was all the more crushing because just a month earlier the had met its goal for participants.
"It was a big traumatic event to put all this effort in and then have the vaccine trial stop because of futility a month after we completed enrollment," Hammer says. He's chief of infectious diseases at Columbia University College of Physicians and Surgeons and a leading AIDS researcher who's been fighting the virus since the pandemic's beginning.
Participants are being notified that no more shots will be given. They will be followed for up to five more years to glean as much insight as possible from the $77 million, federally financed project.
It's another swerve into the ditch for AIDS researchers' on the long road to devise a vaccine that can prevent HIV infection, or at least blunt it, in a significant proportion of people at risk.
The only success so far has been in a involving 16,000 volunteers in Thailand. Published in late 2009, it showed a reduction in the rate of HIV infection by only 31 percent — not enough to deploy as a public health weapon, but a glimmer that encouraged researchers to think a protective vaccine is possible.
However, the latest big hope was dashed by these numbers: Among those in the just-halted study who got the vaccine, 41 people got infected with HIV, compared to 30 who got placebo shots.
That doesn't necessarily mean that the vaccine actually increased people's risk of HIV infection, because the difference is not statistically significant. But Hammer acknowledges that possibility.
"It's clear evidence the vaccine didn't work and may in some fashion put them at greater risk — we don't know that," he says. "The major message is they were not protected."
It may put the kibosh on the future use of an weakened cold virus, called , that was used as a vector — a vehicle carrying selected HIV genes that was used as part of the complicated four-shot vaccine regimen.
The possible riskiness of using the Ad5 vector was raised by results of an earlier HIV vaccine trial called back in 2007. That study was halted prematurely because of evidence that those who got the vaccine had higher risk of HIV infection.
The designers of the big HVTN-505 study hoped they'd avoided that problem by enrolling only people who had no evidence of prior exposure to the Ad5 cold virus. They reasoned that antibodies directed at the cold virus could have interfered with its efficacy as a vaccine vector and somehow increased the risk of HIV infection.
Other, early-phased HIV vaccine trials are using the Ad5 vector. Those will be reevaluated in light of the new findings, Hammer says.
"My own feeling is it's curtains for the Ad5 vector," Hammer says.
Even more ominous is the possibility is that it's not the vector that may be increasing the risk but rather any vaccine component that stimulates immune cells to attack HIV.
Since that's precisely what vaccines are supposed to do, that would be a catch-22 and a serious setback for AIDS vaccine research. But it's too soon to jump to that conclusion.
Leading AIDS researchers were disappointed by the failure of HVTN-505 – but not necessarily surprised, given the history of previous attempts.
"In a lot of ways, we're not much farther down the road than we were a number of years ago," of the University of California, San Diego MedPage Today.
"We understand a lot more about how (HIV-infected) people respond to the virus," Schooley says. "We don't know as much as we need to know about how to make uninfected people make the same kind of responses."
AVAC, an pushing the development of an HIV vaccine, said this latest failure "is a reminder of how challenging it is to develop an effective AIDS vaccine."
"This trial has provided a clear, swift answer about a specific vaccine strategy," says Mitchell Warren of AVAC. "It's not the answer we hoped for, but the search doesn't end here."
In fact, the search will continue with a careful dissection of the data gathered by the latest study.
Hammer says researchers will look at whether some people who got the vaccine were protected, and whether the vaccine produced the expected immune response. "Did it put pressure on the virus, but then the virus escaped?" he wonders. "We've got a bunch of things to do to figure this out."
To help with that task, the researchers are going to be talking with all 2,504 volunteers in the hope they can be persuaded to be poked and prodded for at least another couple of years to follow their responses and their risk of HIV infection.
The researchers will also redouble their efforts to get study volunteers to avoid risky behaviors that could expose them to HIV, given the clear evidence that the vaccine didn't protect them, and could have increased their risk of infection.
Meanwhile, this latest bad news "will throw the field into another round of discussion" about what to do next, Hammer says.
What it will not do, he says, is reduce the drive to keep trying until scientists come up with a vaccine "that gives us solid protection" against multiple strains of HIV.
"That will be a very joyous day," he says.

Efavirenz in children: WHO dosing guidelines raise the risk of side-effects in Thai children

 Efavirenz in children: WHO dosing guidelines raise the risk of side-effects in Thai children


Taking efavirenz according to 2010 World Health Organization (WHO) guidelines ensures a higher proportion of children with HIV have drug levels in the blood above recommended therapeutic levels (1mg/L) compared to the US Food and Drug Administration (FDA) guidelines, but also results in a higher percentage with potentially toxic levels (above 4mg/L), according to a population pharmacokinetic (PK) model presented last week at the 7th International AIDS Society Conference (IAS 2013) in Kuala Lumpur.
This retrospective analysis looked at 623 blood samples from 190 Thai children with HIV. The children had a median age of 7.2 years (IQR 0.1-15.2), bodyweight of 16kg (IQR 5-42) and with efavirenz dose given according to FDA bodyweight band recommendations, 8% (16) had an efavirenz level below 1mg/L twelve hours after a dose (C₁₂) while 6% (12) had a level above 4mg/L. There were no adverse events reported among the children. 
Model simulations showed that the percentage of children with a drug concentration (C₂₄ – 24 hours after a dose) between 1mg/L and 4mg/L using FDA dosing guidelines was similar to 2010 WHO recommendations. While the percentage with sub-optimal levels was lower using WHO guidelines the percentage of children with levels above 4mg/L increased by 11%. 
Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI) together with a backbone of two nucleoside reverse transcriptase inhibitors (NRTIs) is the preferred ART regimen for children with HIV aged three and over weighing over 10kg.
Relatively little is known about how well efavirenz is absorbed in children. Some studies have shown sub-optimal as well as toxic levels in children and a greater variability compared to adults.
Between 1 and 4mg/L is a suggested concentration target 12 hours after efavirenz dosing to ensure efficacy and minimise the risk of toxicities, the majority of which are central nervous system disorders.
Dr Cressey cited two studies, both evaluating efavirenz levels according to WHO 2006 guidelines in African children, which reported high proportions of children with sub-therapeutic levels of efavirenz in the blood. One reported 40% of children and a sub-study of the ARROW trial reported 38% of children having efavirenz levels under 1mg/dl at C₂₄.
A poster presentation at the19th International AIDS Conference evaluating the 2010 WHO guidelines using scored generic 600mg efavirenz tablets among Zambian and Ugandan children (a sub-study of the CHAPAS-3 trial) showed more variability than adult data but similar to previously reported paediatric values “demonstrating the challenges of fixed-dosing when the therapeutic range is narrow”.
However, in Thailand, a study evaluating dosing according to FDA guidelines reported a lower percentage (15%) of children with sub-therapeutic efavirenz levels twenty-four hours after a dose (C₂₄).

Efavirenz dosing guidelines in HIV-infected children

                       Body weight (kg)

Dose (mg)	FDA dosing guideline	WHO 2006 dosing guideline	WHO 2010 dosing guideline
200	10 to <15	10 to <14	10 to <14
250	15 to<20	14 to<20	}
300	20 to <25	20 to<25	} 14 to <25
350	25 to <32.5	25 to <30	}
400	32.5 to <40	30 to <40	} 25 to <35
600	≥ 40	≥ 40	≥ 35

The investigators, wanting to evaluate current FDA and WHO 2010 efavirenz dosing guidelines, developed a population pharmacokinetic model to describe efavirenz absorption over time in Thai children with HIV.
Of the 190 children, 40 had 24-hour pharmacokinetic sampling data available.
Bodyweight affected efavirenz clearance.
The estimated median area under the concentration-time curve (AUC _0-24) was 49 (IQR 8-296) h.mg/L. The area under the curve (AUC) is a measure used to estimate the concentrations of active drug available to suppress HIV. If the AUC falls too low virus levels will increase, leading to virologic rebound and virologic resistance.
Some studies have suggested AUC in children above 50 h.mg/L is associated with virological efficacy.
A predicted efavirenz C₁₂ was 2.3 (0.07 to 11.9) mg/L.
FDA compared to WHO 2010 dosing guidelines, across all bodyweight bands, consistently showed higher percentages of those with sub-therapeutic levels (under 1 mg/dL) at C_12: from 14<15 , 15<20, 25<32.5 and 35<40 kg were 16 and 8%, 14 and 11%, 16 and 12% and 15 and 8%, respectively.
Conversely WHO 2010 guidelines compared to FDA guidelines showed consistently higher numbers, across all bodyweight bands, of those with potentially toxic levels (above 4 mg/dl) at C₁₂ : from 14<15 , 15<20, 25<32.5 and 35<40 kg were 39 and 25%, 33 and 24%, 28 and 21% and 42 and 21%, respectively.
Genotyping for CYP2B6 polymorphisms was not done. An estimated 11% prevalence of CYP2B6 TT (associated with high EFV exposure) in this population may explain higher levels in this group.
While the model suggests drug concentrations may be appropriate, safety data on EFV in children are needed for those getting WHO 2010 weight-band dosing.

Reference

Homkham et al. Plasma efavirenz concentrations in HIV-infected children in Thailand: comparison between FDA and WHO 2010 dosing guidelines. Seventh IAS Conference on HIV Pathogenesis, Treatment and Prevention, Kuala Lumpur, abstract MOAB0104, July 2013.
View this abstract on the conference website.
View details of the conference session, Expanding ARV Options for Children: First Line and Beyond, in which this abstract was presented, including some presentation slides and webcasting, on the conference website.

Two Men HIV-Free After Bone Marrow Transplants

Two HIV-positive men no longer have detectable virus in their blood after receiving bone-marrow transplants to treat Hodgkin's lymphoma. Timothy Henrich and Daniel Kuritzkes , from Brigham and Women's Hospital, Boston, USA, explained at the International AIDS Society Conference, Kuala Lumpur, Malaysia, that one patient has been off HIV medications for over fifteen weeks and the other seven weeks, and there are still no signs of the virus rebounding.

Completely ridding a patient of HIV is extremely difficult. The virus hides within human DNA in such a way as to become "untouchable". ART (anti-retroviral therapy) helps control the virus in the bloodstream. However, as soon as ART stops, HIV usually replicates rapidly.

The two patients had been HIV-positive for over thirty years. They had both developed Hodgkin's lymphoma, a blood cancer that requires a bone marrow transplant if chemotherapy and other treatments failed. Blood cells are made in the bone marrow - experts believe the bone marrow is a major HIV reservoir.

After undergoing the bone marrow transplants, one man has had no detectable HIV in his blood for four years, and the other for two years.

Lead researcher, Dr. Timothy Henrich warned against using the C-word (cure), saying it is still early days.

In an interview with the BBC, Henrich said:

"We have not demonstrated cure, we're going to need longer follow-up. What we can say is if the virus does stay away for a year or even two years after we stopped the treatment, that the chances of the virus rebounding are going to be extremely low."

Last year, Kuritzkes and Henrich announced that HIV was easily detected in the blood lymphocytes of the two patients before their transplants, but within eight months post- transplant the virus had become undetectable. At the time the patients were still on ART.

The two patients came off ART earlier this year. They are regularly monitored and have no detectable HIV virus. Henrich said "We demonstrated at least a 1,000 to 10,000 fold reduction in the size of the HIV reservoir in the peripheral blood of these two patients. But the virus could still be present in other tissues such as the brain or gastrointestinal track."

If the virus were to rebound, it would mean that the brain, GI tract, lymph nodes or some other sites are important reservoirs of infectious virus "(and) new approaches to measuring the reservoir at relevant sites will be needed".

Bone marrow transplant not the answer to HIV infection

Bone-marrow transplant as a way of curing people infected with HIV is unlikely to ever become standard clinical practice.

In this case, the two patients had blood cancer; the transplants were performed to treat the cancer, not the HIV infection.

Most HIV-positive people do not have blood cancer. Bone marrow transplants are costly and risky - patients face a 20% risk of death. Before undergoing a transplant, the patient's immune system needs to be weakened to minimize the risk of rejection.

A third patient, who also had lymphoma and was HIV-positive and had received the same transplant as the two Boston subjects, died from cancer.

With ART, a person with HIV can enjoy the same life expectancy as other people.

Doctors "cured" baby born with HIV infection

In March this year, doctors from Johns Hopkins Children's Center, the University of Mississippi Medical Center and the University of Massachusetts Medical School announced that an HIV-positive baby who was administered ART within 30 hours of being born had been "cured".

Deborah Persaud, M.D., explained that it is very uncommon to treat a baby for HIV-infection so soon after birth. She added that this was the first case of a functional cure in an HIV-positive infant. The medical team believes that the prompt administration of antiretroviral therapy led to the newborn's cure.

Dr. Persaud said "Prompt antiviral therapy in newborns that begins within days of exposure may help infants clear the virus and achieve long-term remission without lifelong treatment by preventing such viral hideouts from forming in the first place."

First apparent HIV-infection cure probably occurred in Germany, 2010

In December 2010, researchers from Charite - University Medicine Berlin, Germany, wrote in the journal Blood than an acute myeloid leukemia patient, Timothy Brown, who was also HIV-positive had been cured of HIV infection after receiving a bone marrow transplant.

The scientists wrote "Our results strongly suggest that cure of HIV has been achieved in this patient."

In 2007 Timothy Brown stopped receiving ART, had his own immune system effectively wiped out with high-dose chemotherapy and radiation therapy, and received a bone marrow transplant.

In this case, the donor had a very rare gene mutation - CCR5-delta32 - which protected him from HIV infection, meaning that Brown acquired that protection. In July 2012, scientists in California found traces of HIV in his tissue. However, Brown says that any virus that remains in his body is completely inactive ("dead") and cannot replicate.

Written by Christian Nordqvist
Copyright: Medical News Today

Yes, you can use pills to prevent AIDS, review finds

Maggie Fox

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July 10, 2012 at 7:25 PM ET

Drugs used to control the AIDS virus can also be used to protect uninfected people, researchers concluded on Tuesday in a “last-word” review of the data.
Their report, released in the Cochrane Library, bolsters calls for policies backing distribution of the drugs to people most at risk from the virus -- including gay and bisexual men, drug users, and women in some African-American communities as well as across the developing world.
The findings also underscore the debate over how best to use scarce resources to fight the pandemic of human immunodeficiency virus or HIV, which infects 33 million people globally, including more than a million in the United States. It has killed 25 million people. There is no cure and no vaccine.
But studies are showing hope on several fronts.
“We think we are at the beginning of the end of the AIDS epidemic,” Dr. Diane Havlir, an AIDS specialist at the University of California, San Francisco, and one of the organizers of a giant, international AIDS conference being held in Washington, D.C. later this month, told reporters on Tuesday. “Over the past three years, there has been a series of breakthroughs in interventions that can dramatically curb the rate of infections with HIV.”
Work on a vaccine is promising, it’s been shown clearly that circumcising men protects them from infection, and it’s also obvious that treating infected people not only keeps them alive and healthy, but it helps prevent them from infecting others. Work is also progressing on a microbicide -- a gel that women could use to protect themselves from infected husbands and partners. And now research is also showing that giving people a once-a-day dose of the pills used to treat HIV can keep them from becoming infected in the first place.
The studies on this last approach, called pre-exposure prophylaxis or PrEP, have been mixed. So Charles Okwundu of Stellenbosch University in South Africa and colleagues studied the studies.
They looked at experiments involving more than 9,800 people around the world at high risk of becoming infected with HIV, including gay or bisexual men and sex workers. The drug tenofovir alone -- sold under the brand name Truvada by Gilead Sciences -- cut the risk of HIV infection by nearly two-thirds, while trials using Truvada with a second drug called emtricitabine, brand name Emtriva, cut the risk by 49 percent, they reported in the Cochrane Library, a journal that seeks to find the “last word” on studies.
It’s not clear why using two drugs seemed to be less effective than using just one, but the trials were done very differently and using different groups of people.
"Our findings suggest that antiretroviral drugs can reduce the risk of HIV infection for people in high risk groups," Okwundu said in a statement. "However, in the search for highly reliable HIV prevention strategies, it is important to determine how pre-exposure prophylaxis can best be combined with existing programs, as no strategy is likely to be 100 percent effective."
Okwundu’s team noted controversy over using PrEP.
“One concern is the long-term side effects of antiretroviral drugs used over many years by uninfected individuals,” they noted.
These include possible kidney damage and bone loss. In addition, if people don’t take the drugs consistently, they could develop what is known as resistant virus -- infections that defy the use of drugs. This can hurt the patients themselves, and they can also pass this resistant and hard-to-treat virus to others.
“There also are concerns that PrEP will lead to an increase in high-risk behavior,” Okwundu’s team adds. “If PrEP is not completely effective, even a partial reduction in use of safer sex could lead to an increased rate of HIV transmission.”
And the drugs are expensive -- Truvada costs more than $1,000 a month in the United States, although Gilead allows for much cheaper generic versions to be made and distributed in the developing world.
Despite the concerns, in May a panel of Food and Drug Administration advisers recommended that the FDA approve the pills for this use. Already, doctors can and often do prescribe the pills as they like, but FDA approval would clear the way for U.S. insurance companies to pay for it and

Once-a-day pill prevents HIV in drug users

 

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June 12, 2013 at 3:50 PM ET

Getty Images file /

Here's what the AIDS medication Viread, the brand name tenofovir is sold under, looks like.

A once-a-day pill can protect people who inject drugs such as heroin from the AIDS virus, lowering their risk by nearly 50 percent, researchers reported Wednesday.
The findings show that even people at the highest risk of being infected with the virus can protect themselves – and thus protect others. And it adds ammunition to arguments that HIV drugs should be made widely available to fight the epidemic that has killed more than 25 million people.
The study, published in the Lancet medical journal, demonstrates the value of pre-exposure prophylaxis, PrEP for short, the researchers say.
“Our trial is the first evidence that PrEP can reduce HIV risk among people who inject drugs,” said Dr. Amy Lansky of the Centers for Disease Control and Prevention. “It does become another strategy that we have to use in preventing HIV in this population,” Lansky said in a telephone interview.
PrEP has already been shown to protect people who are infected sexually, by far the most common way that the AIDS virus is transmitted. Doctors believe the once-a-day pills stop the virus from infecting immune system cells.
“This is an important study,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, who was not involved in the study. “There were people who said you couldn’t treat injecting drug users at all.”
There’s no cure for the human immunodeficiency virus (HIV) that causes AIDS. But cocktails of drugs can keep it under control and keep patients healthy for years, even decades. And the same drugs can be used to prevent infection. Newborn babies are given drugs such as nevirapine to prevent their mothers from infecting them, and several studies have shown the spouses and sexual partners of infected adults can take another drug, called tenofovir, and lower their risk by as much as 62 percent.
The virus can be spread sexually, in blood and in breast milk. About 11 percent of cases are in people who inject drugs; about 8 percent in the United States.
Injecting drug users are usually endangered in at least two ways – they often share needles, which can transmit the virus, and they often also indulge in risky sexual behavior. Drug users can spread the virus to non-drug users via sex.
Thai health officials, Bangkok city officials and the CDC collaborated on a study to see if these hard-to-reach people might be helped. They recruited 2,413 uninfected drug users in Bangkok, randomly assigning them to get either one pill a day of tenofovir, donated by Gilead Sciences, the company that makes it, or a placebo.
Tenofovir is the drug shown to protect people from sexual transmission and it’s a very safe drug, says Lansky. “It has a pretty long half-life,” she says. “It is staying in the body and having an effect over time.”
After an average of about four years, 17 of the volunteers who took tenofovir got infected with HIV, compared to 33 of those who got dummy pills. That’s a reduction of 49 percent. And among those who took the pill the most consistently, the reduction rate went up to 74 percent.
“It’s a really important finding. It provides that last piece of PrEP’s efficacy among popoulations at high risk,” Lansky says.
“This is a significant step forward for HIV prevention. We now know that PrEP can work for all populations at increased risk for HIV,” added Dr. Jonathan Mermin director of CDC’s Division of HIV/AIDS Prevention.
The researchers also got good compliance -- the volunteers in their study may have been drug users, but they showed up in the clinics, took their medications and stayed in touch for years.
Dr. Salim Karim, Director of the Centre for the AIDS Programme of Research in South Africa (CAPRISA), said it’s one more tool for fighting the virus, which infects 2.7 million people every year, including about 50,000 in the United States. “The introduction of PrEP for HIV prevention in injecting drug users should be considered as an additional component to accompany other proven prevention strategies like needle exchange programs, methadone programs, promotion of safer sex and injecting practices, condoms, and HIV counseling and testing,” Karim wrote in a commentary in the Lancet.
The CDC had updated its guidance on PrEP, and recommends that people who inject drugs such as heroin should get a once-a-day pill called Truvada, which contains both tenofovir and another HIV drug called emtricitabine.
“Nevertheless, while expanded HIV treatment for those with HIV infection is essential, it will not be sufficient to end the epidemic. Even if we can improve treatment outcomes for all of those diagnosed with HIV, individuals who do not know they are infected are likely to continue to unknowingly transmit HIV infection to others,” the CDC added in a statement.
Activists said the evidence was building up but not enough is being done to make use of proven methods to fight the epidemic.
“We now need to get serious about making PrEP available to those who can benefit,” said Mitchell Warren of the advocacy group AVAC. “More than two and a half years after the first positive results from a PrEP trial, little has been done to answer critical questions about the best ways to roll out daily oral PrEP to key populations worldwide. Within the next year, a comprehensive package of demonstration projects should be planned, funded and launched in countries around the world.”

What is the difference between HIV and AIDS?

HIV is the virus which attacks the T-cells in the immune system.

AIDS is the syndrome which appears in advanced stages of HIV infection.

HIV is a virus.

AIDS is a medical condition.

HIV infection causes AIDS to develop. However, it is possible to be infected with HIV without developing AIDS. Without treatment, the HIV infection is allowed to progress and eventually it will develop into AIDS in the vast majority of cases.

HIV testing can identify infection in the early stages. This allows the patient to use prophylactic (preventive) drugs which will slow the rate at which the virus replicates, delaying the onset of AIDS.

AIDS patients still have the HIV virus and are still infectious. Someone with AIDS can pass HIV to someone else.

‘It is worse than the pain of contracting the disease’

‘It is worse than the pain of contracting the disease’

Shanthinath (name changed), who is undergoing treatment for AIDS in the city, has not been visited by his family for the past seven years.

“Whenever I try to meet my family members, the elders do not allow younger ones to touch me.”

Mr. Shanthinath, who is at Snehasadan — care and support centre for those infected and affected with HIV/AIDS — was isolated when his family learnt about his disease. “It was worse than the pain of contracting disease”. He is now serving as the caretaker for other patients in the centre.

Another patient was so humiliated when she was with her family found some solace only after she joined the centre.

A 37-year-old HIV positive from Koppal district has kept his and wife’s condition a secret because the situation would be “unimaginable” if people came to know about it.

Even as the district has made considerable strides in containing the spread of the disease, the stigma associated with the disease continues to haunt patients with even those in healthcare sector being ignorant about the way the disease spread.

A medical officer associated with Anti-Retroviral Therapy (ART) at Wenlock Hospital said, “Even some of the doctors and nurses hesitate to speak to HIV patients.”

She said there are cases of private hospitals refusing to treat persons with AIDS particularly if they have open wounds.

Kishore Kumar of the Dakshina Kannada AIDS Prevention Control Unit pointed out that lack of awareness among people about the disease was responsible for the stigma and the problems patients faced because of it.

He said Red Ribbon Clubs have been started in 32 colleges in Mangalore to create awareness through drama, street plays and demonstration. The fact that youths are more vulnerable to contract the disease brings the issue of stigma into greater focus.

Most persons registering at Snehasadan are in the age group of 20-35 years.

***

39-year-old Pooja (name changed) contracted HIV 12 years ago when she was in Mumbai. Soon she returned to her mother-in-law in Udupi.

Six months later she was shown the door forced to stay at her mother's place.

Her husband, also an HIV positive, committed suicide unable to fight the stigma. Pooja has been in the Snehasadan for nine years now along with her daughter, who is also an HIV positive.

HIV/AIDS Latest News: World Health Organization (WHO) announcement

HIV/AIDS Latest News: World Health Organization (WHO) announcement: World Health Organization (WHO) announced today at Treatment as Prevention conference in Vancouver, Canada that it will raise treatment...

World Health Organization (WHO) announcement

World Health Organization (WHO) announced today at Treatment as Prevention conference in Vancouver, Canada that it will raise treatment initiation guidelines for HIV-positive individuals from a CD4 count of less than 350 to a count of less than 500!

Vancouver, Canada (April 23, 2013) — AIDS Healthcare Foundation (AHF) today applauded the news that the World Health Organization (WHO) is set to raise its treatment initiation guidelines for HIV-positive individuals from a CD4 count of less than 350 to less than 500, allowing people to start treatment earlier.

Ahead of the official announcement of new treatment initiation guidelines which will be released in June at the IAS Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur, Malaysia, WHO's Treatment and Care coordinator Dr. Meg Doherty, offered a preview of the guidelines this morning at Treatment as Prevention workshop in Vancouver, Canada.

Today's announcement is a victory for people living with HIV around the globe," said Dr. Penninah Iutung, AHF's Africa Bureau Chief.

According to Dr. Meg Doherty, earlier treatment initiation will make 26 million people eligible to receive lifesaving antiretroviral medicine, an increase of 76% from the current 14.8 million.

"Today's announcement is a victory for people living with HIV around the globe – including Africa," said Penninah Iutung, M.D. AHF's Africa Bureau Chief. "WHO's decision to raise the treatment initiation guidelines removes a major roadblock to lifesaving treatment, as country AIDS programs often look to WHO recommendations when setting policy guidelines. This is a very significant step toward universal access to lifesaving antiretroviral treatment and, treatment-as-prevention."

"AHF has been vigorously and publicly advocating for WHO to raise the treatment initiation guidelines for many years. We applaud WHO for making this critical—and lifesaving—decision," said Michael Weinstein, President of AIDS Healthcare Foundation. "It's now more important than ever that we stop the current retreat from the global AIDS fight and restore U.S funding levels for PEPFAR and the Global Fund – which have been harmed by cuts proposed by the Obama administration. Even flat-lined funding will prevent this important WHO change from having an impact."

Studies have shown that earlier treatment initiation is associated with better clinical outcomes, lowering morbidity and mortality in patients. Additionally, a recent clinical trial HPTN 052 has shown that people on antiretroviral therapy are 96% less like to pass the infection to a partner.

Given this evidence, earlier treatment initiation, if sufficiently implemented, has the potential to significantly reduce the number of new infections.

Many CBOs- community based organizations in India have welcomed this move and have started their campaign requesting NACO to implement the same in the country as soon as possible. AHF India has already initiated steps to conduct community consultations in this regard and advocate the same to the Ministry of Health & Family welfare, Government of India. The AHF India cares project will soon roll out the treatment initiation of all PLHIV under CD4 <500 under the brand name Project SEETI-(STRATEGIC EFFORTS for EARLY TREATMENT INITIATION) and will follow the new WHO guidelines.

Latest World News - Dental Scare Leaves Thousands at Risk of HIV

HIV/AIDS Latest News: Researchers Identify New Approach for an Effective...

HIV/AIDS Latest News: Researchers Identify New Approach for an Effective...: Researchers Identify New Approach for an Effective HIV Vaccine American researchers have come up with a new approach to vaccine desi...

Researchers Identify New Approach for an Effective HIV Vaccine Read more: Researchers Identify New Approach for an Effective HIV Vaccine | Medindia http://www.medindia.net/news/researchers-identify-new-approach-for-an-effective-hiv-vaccine-

Researchers Identify New Approach for an Effective HIV Vaccine

American researchers have come up with a new approach to vaccine design that could help them overcome the difficulties faced in developing an effective HIV vaccine due to the rapidly changing structure of the HIV virus.





Now, a researcher team led by an Indian origin scientist has developed a new approach to vaccine design that may allow them to cut off those evolutionary escape routes. 

The researchers from the Ragon Institute of MGH, MIT and Harvard University have developed and experimentally validated a computational method that can analyze viral protein sequences to determine how well different viral strains can reproduce in the body. That knowledge gives researchers an unprecedented guide for identifying viral vulnerabilities that could be exploited to design successful vaccine targets. 

The team, led by Arup Chakraborty, the Robert T. Haslam Professor of Chemical Engineering, Chemistry, Physics and Biological Engineering at MIT, has designed protein fragments (peptides) that would target these weaknesses. 

Ragon Institute researchers are now developing ways to deliver the peptides so they can be tested in animals. 

"We think that, if it continues to be validated against laboratory and clinical data, this method could be quite useful for rational design of the active component of a vaccine for diverse viruses. Furthermore, if delivered properly, the peptides we have designed may be able to mount potent responses against HIV across a population," said Chakraborty, who is also the director of MIT's Institute for Medical Engineering and Science. 

Typically when a vaccine for a disease such as smallpox or polio is given, exposure to viral fragments primes the body's immune system to respond powerfully if it encounters the real virus. With HIV, it appears that when immune cells in a vaccinated person attack viral peptides that they recognize, the virus quickly mutates its protein sequences so immune cells no longer recognize them. 

To overcome this, scientists have tried analyzing viral proteins to find amino acids that don't often mutate, which would suggest that they are critical to the virus's survival. However, this approach ignores the fact that mutations elsewhere in the protein can compensate when those seemingly critical amino acids are forced to evolve, Chakraborty said. 

The Ragon Institute team focused on defining how the virus's ability to survive depends on the sequences of its proteins, if they have multiple mutations. This knowledge could enable identification of combinations of amino acid mutations that are harmful to the virus. Vaccines that target those amino acids would force the virus to make mutations that weaken it. 

With existing HIV protein sequence data as input, the researchers created a computer model that can predict the fitness of any possible sequence, enabling prediction of how specific mutations would affect the virus. 

In their study, the researchers focused on an HIV polyprotein called Gag, which is made up of several proteins that together are 500 amino acids long. The proteins derived from Gag are important structural elements of the virus. For example, a protein called p24 makes up the capsid that surrounds the virus's genetic material. 

Each position in HIV proteins can be occupied by one of 20 possible amino acids. Sequence data from thousands of different HIV strains contain information on the likelihood of mutations at each position and each pair of positions, as well as for triplets and larger groups. The researchers then developed a computer model based on spin glass models, originally developed in physics, to translate this information into predictions for the prevalence of any mutant. 

Using this model, the researchers can enter any possible sequence of Gag proteins and determine how prevalent it will be. That prevalence correlates with the fitness of a virus carrying that particular protein sequence, a relationship that the researchers demonstrated by using the model to predict the fitness of a few dozen Gag protein sequences, and verified by engineering those sequences into HIV viruses and testing their ability to replicate in cells grown in the lab. They also tested their predictions against human clinical data. 

The model also allows the researchers to visualize viral fitness using "fitness landscapes" - topographical maps that show how fit the virus is for different possible amino-acid sequences for the Gag proteins. In these landscapes, each hill represents sequences that are very fit; valleys represent sequences that are not. 

Ideally, vaccine-induced immune responses would target viral proteins in such a way that mutant strains that escape the immune response correspond to the fitness valleys. Thus, the virus would either be destroyed by the immune response or forced to mutate to strains that cannot replicate well and are less able to infect more cells. 

This would mimic the immune response mounted by people known as "elite controllers," who are exposed to the virus but able to control it without medication. Immune cells in those people target the same peptide sequences that the model predicted would produce the biggest loss of fitness when mutated. 

This general approach could also be used to identify vaccine targets for other viruses, Chakraborty added. 

The researchers have described their findings in latest issue of the journal Immunity.

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Early HIV drugs 'slow virus down'

Continue reading the main storyThe human immunodeficiency virus (HIV) attacks the immune system

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Giving a patient HIV drugs as soon as they are diagnosed could be the future of treatment, say researchers.

Currently, antiretroviral therapy is given only once the immune system has been seriously weakened by infection.

A trial, in the New England Journal of Medicine, showed that a year-long course of therapy after diagnosis helped preserve the immune system and keep the virus in check.

It is thought that early treatment may also reduce the spread of HIV.

The virus is no longer a death sentence for patients who get the best care and drugs. Treatment is given once their CD4 T-cell count, a part of the immune system, falls below 350 cells per cubic millimetre of blood.

However, there has been some speculation that starting as soon as a patient is diagnosed may be more beneficial.

The Spartac study, which involved 366 patients from eight countries around the world, tested the theory.

Continue reading the main story

“Start Quote

Questions remain about whether a longer course at an early stage could be more beneficial or whether early treatment should be continued for life”

Dr Jimmy WhitworthWellcome Trust

Some patients were given 12 weeks of drugs after being diagnosed, another group had drugs for 48 weeks after diagnosis and a third group were given no drugs until they reached the 350 level.

Prof Jonathan Weber, from Imperial College London, said those on the 48-week regime "end up with much higher CD4 cell count and a much lower viral load".

"Also, the benefit persists after you've stopped treatment," he added.

Who pays?

Keeping a strong immune system is important for preventing other "opportunistic" infections, such as tuberculosis, taking hold.

Prof Weber acknowledged that cost was a "massive question" that would represent "a real problem" in poorer parts of the world.

However, in richer countries if would mean "only a few extra years" on a lifetime of medication.

Dr Sarah Fidler, also from Imperial, pointed to the benefit of keeping levels of the virus low.

"This could be very important for helping reduce the risk of passing on the virus to a sexual partner," she said.

Dr Jimmy Whitworth, from the Wellcome Trust, which funded the study, said: "This study adds to increasing evidence that early initiation of HIV treatment is of benefit to the individual in preventing severe disease and in reducing infectiousness to his or her partners.

"Questions remain about whether a longer course at an early stage could be more beneficial or whether early treatment should be continued for life."

However, one of the biggest problems remains identifying people who have been infected. In the UK, one in four people with HIV are thought to be completely unaware they have the infection.

Centres run out of anti-HIV drugs

Centres run out of anti-HIV drugs

         People battling the human immunodeficiency virus (HIV) in the city are having a tough time finding drugs for opportunistic infections, which can be life-threatening. Most centres providing anti-retroviral therapy (ART) have run out of drugs for opportunistic infections since last year, despite repeated requests to the Mumbai District Aids Control Society (MDACS).

The virus primarily targets the immune system, causing a gradual decline in the immunological response of patients. This makes the patient highly susceptible to tuberculosis, pneumonia, diarrhoea and meningitis blindness. Most of those infected come from middle and lower-middle classes.

People living with HIV are extremely susceptible to infection, which can prove fatal if not treated on time. At least 30% patients develop opportunistic infection(s), with 8% getting tuberculosis, th e most common infection in HIV cases. The mortality in HIV patients due to TB hovers around 5% for Mumbai.

A medical officer from an ART centre in a civic hospital told TOI that even medicines to treat common symptoms have not been supplied for over six months. "The symptoms hint at the presence of infections like tuberculosis, cryptosporidial diarrhoea, serious meningitis or pneumonia," said the doctor, adding that several requests have been made to higher-ups to arrange for medication.

Another medical officer from a centre in a suburban hospital said medicines prescribed to patients with low CD4 counts (indicates stage of HIV) have also been out of stock for over two months. "We tell patients to buy them from chemist shops but most cannot afford them. Patients are reluctant to collect medications from civic hospitals," he said. 
The National Aids Control Organization (NACO) attaches significant importance to the control of opportunistic infections as they can push up morbidity and mortality. The unavailability of medicines can push up mortality from HIV, which is on a steady decline.

Former head of JJ Hospital's ART centre, Dr Alaka Deshpande, said early diagnosis and treatment of opportunistic infections are imperative to improve expectancy and quality of a patient's life. The programme is grappling with compliance issues and unavailability of drugs will only compound the situation, she said.

"At least 15-30% patients stop taking ART treatment and it weakens their immune system. At least one-third of these patients have very high chances of developing opportunistic infections," she said.

Deshpande busted the myth that patients on ART usually have a healthy CD4 count and thereby may not get opportunistic infections. She said in the last one month she has treated three cases of cryptococcal meningitis, a serious fungal infection, in patients who were regular with ART medication. She cautioned that the authorities cannot take chances with resistance to tuberculosis medicines on the rise.

MDACS additional project director Dr Balkrishna Adsul said, "We will float a tender for the drugs and make them available to patients. They can always take drugs from medical college dispensaries." 

Preventing HIV Infection With Anti-HIV Drugs In People At Risk Is Cost-Effective

An HIV prevention strategy in which people at risk of becoming exposed to HIV take antiretroviral drugs to reduce their chance of becoming infected (often referred to as pre-exposure prophylaxis or PrEP), may be a cost-effective method of preventing HIV in some settings, according to a study by international researchers published in this week's PLOS Medicine. 

In an analysis of 13 modelling studies led by Gabriela Gomez from the Department of Global Health, Academic Medical Centre, University of Amsterdam/AIGHD in The Netherlands, the authors evaluated the impact of pre-exposure prophylaxis in different populations (heterosexual couples, men who have sex with men, and people who inject drugs) in different regions and countries, such as southern Africa, Ukraine, the US, and Peru. 

They found that in every setting, the cost of antiretroviral drugs was an important factor influencing the affordability of effective prevention programmes but delivery of pre-exposure prophylaxis to populations at higher risk of HIV exposure appeared to be the most cost-effective strategy. The authors also found that both behavioural changes and adherence to the pre-exposure prophylaxis drug regimens affected programme effectiveness. 

The authors say: "Our findings show that pre-exposure prophylaxis has the potential to be a cost-effective addition to HIV prevention programmes in some settings." 

They continue: "However, the cost-effectiveness of pre-exposure prophylaxis is likely to depend on considerations such as cost, the epidemic context, pre-exposure prophylaxis programme coverage and prioritisation strategies, as well as individual adherence levels and pre-exposure prophylaxis efficacy estimates." 

The authors add: "Given that our review shows that both the setting and which population is prioritised for pre-exposure prophylaxis are critical drivers of cost-effectiveness, the next step is to conduct context-specific demonstration studies, including comprehensive cost analyses, of different prioritisation and adherence promotion strategies to ensure that the maximum benefit from the introduction of pre-exposure prophylaxis is realised within combination HIV prevention programmes." 

Government moots anti-AIDS measures in 8 districts

The State Government has identified eight districts where it plans to involve corporate houses to address the issues of HIV and AIDS. Mineral rich and industrial hubs, these districts have different sets of vulnerabilities to the dreaded infection which prompted the Health and Family Welfare Department to seek help of its Industries counterpart for a joint initiative.

The Health Department had asked the Odisha State AIDS Control Society (OSACS) to flag the major issues faced by the eight districts where mining and industrial activities are intensive leading to prevalence of high risk groups such as migrants, transporters, alcoholics and drug users.

In its report, the OSACS pointed out the concerned areas in each of the districts which included Angul, Jharsuguda, Jajpur, Keonjhar, Sundargarh, Rayagada, Koraput and Jagatsinghpur. It also suggested that massive IEC campaigns, health camps, counselling-cum-therapy centres could be set up in the districts basing on their needs with support from the corporate social responsibility (CSR) wings of the industrial houses. Industries Department will hold a meet with the corporate houses so that an action plan can be charted out for giving the plan a working shape.