Biopeer

Study finds explanation for some HIV drug side effects

Researchers at UCLA and Purdue University recently demonstrated that certain HIV protease inhibitors – crucial drugs for HIV treatment – block a cellular enzyme that is important to the structure of the cell nucleus. This link may explain some side effects for HIV treatment, such as metabolic syndrome and losing body fat in specific regions. “We show, for the first time, that certain HIV protease inhibitor drugs directly inhibit an enzyme called ZMPSTE24, which is important for generating the structural scaffolding supporting the cell nucleus,” said Catherine Coffinier, author of the study and an assistant researcher at the David Geffen School of Medicine at UCLA. The research team added HIV protease inhibitors to cultures of human and mouse fibroblast cells and found that the inhibition of ZMPSTE24 by the HIV protease inhibitor drugs led to an accumulation of prelamin A – a key molecule in the structural scaffolding for the cell nucleus. Progeria, an accelerated aging syndrome, can be caused by genetic defects that interfere with the conversion of prelamin A to lamin A. “Since HIV protease inhibitors interfere with the conversion of prelamin A to lamin A, we believe — at least at a biochemical level — that there is a link between progeria syndromes and HIV treatment regimens,” said Loren Fong, associate professor of medicine at the David Geffen School of Medicine.

Researchers at the San Diego HIV Neurobehavioral Research Center found that hepatitis C virus (HCV) can travel into the brain and replicate there causing cognitive impairment in people infected with both HIV and HCV. Researchers studied the brain tissue of 25 patients after their death and found HCV RNA in the brain tissue of all the HIV/HVC co-infected subjects, but none of the HCV negative individuals. The researchers also looked at the cognitive abilities of the subjects, assessed before death, and found that the presence of HCV RNA was significantly associated with considerable cognitive impairment as well as the presence of brain tissue inflammation, or encephalitis. The findings of this study suggest that HCV and HIV might be working together to block clearance of glutamate from the synapses of people with the co-infection, possibly leading to structural damage in the brain and therefore cognitive impairment.

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Substance in olive oil may slow spread of HIV infection in the body

Researchers at the University of Granada showed that maslinic acid, found in olive oil, inhibits the enzyme serin-protease, which is used by HIV to release itself from the infected cell into the extra cellular environment and, consequently, to spread to other cells and infect the whole body. The University of Granada's Bionat team carried out trials with the MT2 cell line using various concentrations of maslinic acid. The researchers determined that the use of olive-pomace oil could slow down the spread of HIV in the body by 80%.

A study published in the July 7 issue of The Lancet found that an experimental drug called etravirine has the potential to treat drug-resistant HIV as a part of an HIV drug cocktail that also includes the medication Prezista. The study included 600 patients with drug-resistant HIV, of which 300 patients were administered etravirine in addition to Prezista, Norvir and other HIV medications. After six months of treatment, most patients who were given etravirine had reduced to very low blood levels of HIV. "This study is one of the most significant worldwide HIV/AIDS clinical trials in recent years," said William Towner, M.D., of Kaiser Permanente in Southern California.

Peregrine Pharmaceuticals recently announced an opportunity for patients infected with both the hepatitis C virus (HCV) and HIV to enroll in a study of bavituximab. "This is an important study for the bavituximab HCV clinical program that is designed to evaluate an extended treatment schedule in an important HCV patient population," said Steven W. King, president and CEO of Peregrine. "We believe that bavituximab’s unique targeting mechanism has the potential to act on both HCV and HIV virus infections, and we look forward to working with Dr. Smith and his colleagues to assess the potential of bavituximab in this high need co-infected population."

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Ultra deep sequencing identifies previously undetectable HIV drug-resistant variants

Researchers at the Yale School of Medicine have identified previously undetectable, rare drug-resistant HIV variants using an innovative genome sequencing technology. The study analyzed 258 blood samples taken from HIV infected individuals before treating them with the drug. “We found that the fraction of HIV patients that harbored resistance mutations is at least twice as high as previously thought,” said Michael Kozal, M.D., Yale University School of Medicine. These low frequency resistant viral strains were not detectable by resistance testing methods currently used in the clinic. “Ultra Deep Sequencing provides an essential tool for research on viral diseases and their treatments," said Egholm Michael, vice president of research and development at 454 Life Sciences. "The ability to use 454 Sequencing to detect rare viral mutations is a crucial research tool to better understand the early stages of HIV drug resistance.” This finding will prove useful in the future to better understand the antiretroviral drug combinations that have the ability to suppress these resistant HIV strains, leading to better clinical responses in patients.

According to a study, published in the June 21 issue of the New England Journal of Medicine, patients suffering from both hepatitis B and HIV should not take the hepatitis-fighting drug Baraclude. Baraclude was approved as a drug to fight hepatitis B in early 2005. While Baraclude is very effective in treating hepatitis B, the study revealed that it also undermines the potency of combination drug therapies for HIV. “The active site (of drug action) – a polymerase enzyme – is similar on HIV and hepatitis B,” explained Chloe Thio, associate professor of medicine at Johns Hopkins University School of Medicine. “This means that if you are going to go ahead and treat for hepatitis B, you better be screening for HIV, too,” said. Michael Horberg, director of HIV/AIDS policy at Kaiser Permanente in Santa Clara, Calif.

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Fight against HIV gets a boost

Researchers from McGill University Health Centre, after a thorough reexamination, found an oral HIV test completely accurate. The US Food and Drug Administration had already approved the OraQuick HIV1/2 test, but reports of the test’s inaccuracy led to skepticism. Due to this, the scientists tried the oral test on 450 advanced HIV patients in rural India. They took saliva from the patients and also gave them a conventional blood test. The oral test was 100 percent accurate, while the blood test showed only 99.7 percent accuracy. Additionally, the oral test proved to be easier to use, gave less discomfort and provided quicker results. The researchers hope that this test could lead to the formulation of a home-based test.

Another group of scientists has announced the success of a new anti-HIV drug, raltegravir, in early clinical trials. They tested the drug on 178 patients who had been suffering from advanced HIV and had shown no reaction to antiretroviral medication for almost 10 years. During the trials, the patients were given the usual HIV drugs; in addition, some of them were given raltegravir while others were given a placebo. The team measured the HIV genetic material or RNA in the patients’ blood, 24 weeks post-treatment. They found that those who were given raltegravir showed a reduction of 98 percent in their RNA, on an average, while the placebo group saw a drop of only 45 percent. In addition, their CD4 cells had risen significantly, which indicated an improvement in their immunity. Most of these patients did not show any unfavorable responses. Researchers believe that there is a possibility that the drug may become a significant part of a combination treatment program.

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Research supports novel ways to prevent HIV

The latest in the fight against HIV involves announcements from WHO and UNAIDS, supporting researchers who claim that circumcision lowers the risk of HIV. The research conducted to prove the theory involved three trials in Africa. These trials showed that the operation reduced the chance of heterosexual men contracting the virus, to half. All three trials were halted sooner than expected, since the results were extremely positive. Researchers feel that certain cells and the skin under the foreskin, which are likely targets for HIV, become less sensitive after circumcision. However, experts strongly emphasize the fact that a higher rate of circumcision will not wipe out the need for the use of other preventive methods.

Meanwhile, researchers from USA and UK have jointly conducted a study to examine the benefits of green tea in the prevention HIV. The scientists conducted laboratory experiments on a flavanoid found in green tea, known as epigallocatechin gallate (EGCG). They found that EGCG combines with CD4 immune system T-cell receptors. In this way, it prevents the receptors from contracting the HIV infection. However, these results are only test-tube findings and may not lead to the same conclusions at the macro level. Further studies are being conducted to find the exact potential of green tea to prevent HIV.

Through another study, South African researchers have discovered that breast milk could reduce the risk of postnatal HIV. They realized that the babies, who were fed formula milk as well as breast milk, had a two-fold chance of being infected with HIV, as compared to those who were only breastfed. Additionally, those who were given solid foods had an 11 times greater chance of contracting the virus. Also, foods other than breast milk, increased the mortality rate of babies at three months. These findings are extremely significant and call for the revision of the UN infant feeding guidelines.

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Fight against HIV/AIDS renews hope

In what could be a possible breakthrough in the fight against HIV/AIDS, researchers have concluded that circumcision protects men against HIV. The US National Institutes of Health researchers conducted two major trials in Kenya and Uganda wherein they followed more than 7,000 men, both circumcised and not, for two years. They found that circumcision brings about a 60 per cent reduction in men’s chances of contracting HIV. In fact, the results were so conclusive that the trials were stopped earlier than planned. However, experts are cautious about the feasibility of putting this into action, especially in Africa, due to health infrastructure, cultural and religious issues.

Meanwhile, researchers treating HIV positive women for herpes simplex virus have observed that the antiviral drug valacyclovir lowers HIV levels. The randomized, double-blind, placebo-controlled trial was conducted on 140 women with HIV-1 and HSV-2. The women were treated with either valacyclovir or placebo and followed for 12 weeks. Then they analyzed the impact of the drug on the genital and plasma viral loads of HIV-1 (RNA) and HSV-2 (DNA). They found that the level of HIV viral load came down in women who were on valacyclovir by an average of 50 per cent. The impact of the drug increased over a period of time. The researchers are hopeful that the findings will have “important implications for HIV control”.

Continuing their efforts to fight against HIV/AIDS, Germany, New Zealand, Sweden and the United Kingdom are coming together to donate USD 70 million to Zimbabwe. The funds will be used for the benefit of children who have lost their parents to HIV/AIDS. The orphans under this program will get access to vital education and health care services.

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Both setbacks and successes in HIV research

Researchers’ hopes to prevent the spread of HIV, suffered a severe setback after Phase III trials of an anti-HIV microbicide were stopped. The tests, conducted in Africa and India, involved 1300 women. Those in the experimental group were made to use the cellulose sulfate gel, which was meant to evade the transmission of HIV through sexual intercourse. Contradicting the hypothesis, more women in the cellulose sulfate group had contracted the virus in comparison to those in the placebo group. Although the scientists are extremely shocked and disappointed, they remain optimistic. They aim to figure out why the gel increases the risk of HIV transmission and use this information to back further research on microbicides.

Meanwhile, tests conducted on another AIDS vaccine saw positive results. An Atlanta-based company, GeoVax Labs, Inc, carried out Phase I trials to test their vaccine. In one test, one-tenth of the dose was given to 30 volunteers, while six volunteers were given a placebo. The results implied the safety of the vaccine and gave positive immune responses. A stronger dose, in the next test, also had a positive outcome. These findings suggest that a full dose of the vaccine will trigger an even better response. The researchers now plan to begin Phase II of the experiment on 300 volunteers earlier than expected.

Another interesting discovery points out loopholes in the antiretroviral drug therapy. Researchers from Rennes University on examining testicular tissue found that the antiretroviral drugs find it difficult to penetrate through the testes. This makes testicles the ideal breeding ground for the AIDS virus. According to the scientists, their findings will help them develop new drugs to combat the HIV in the testicles. Since sexual intercourse is one of the most common ways in which HIV is transmitted, this study is particularly significant.

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Some hope, some concern regarding HIV

In a possible breakthrough in the fight against the human immunodeficiency virus (HIV), researchers from the Duke University Medical Center, USA, have formulated a test. This new HIV test pinpoints, in the patients’ bloodstream, those strains of the virus that are resistant to the currently available drugs. The researchers studied the accuracy of the test using blood samples of patients who had never received antiretroviral treatment, those who had received treatment earlier and those for whom the treatment was unsuccessful. Fluorescent tags were used to distinguish the mutated gene locations that are drug resistant from the non-mutated ones. With the help of a computer program, the researchers then calculated the number of molecules in each category in each sample. The test was proved to be highly precise in identifying genetic changes. It is hoped that with this tests, scientists will be able to better understand the complexities of HIV and develop new treatments.


Meanwhile, the spread of HIV is causing concern in Hong Kong. Recently, two large clusters of new infections have been detected in an area otherwise having a low incidence of the virus. The clusters consisted of 46 men who had been diagnosed with the virus after November 2003 and before September 2006. Local scientists found their samples to be similar in their genetic make-up and came to the conclusion that the virus had probably spread from one to another. Though such genetic similarity has not been detected in any woman yet, authorities are of the opinion that women too may have been infected. They are now calling upon the citizens to get themselves tested free for HIV in order to contain the spread of the virus.

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Nations up their fight against HIV/AIDS

In India, the Andhra Pradesh government is stepping up efforts to control the spread of AIDS. It is going to make it compulsory for prospective brides and grooms to get tested for HIV before they tie the knot. With Andhra Pradesh leading the Indian states in the number of affected people, the government wants to introduce the bill in the budget session of the Legislative Assembly in 2007. An all-party meeting will be called to discuss the bill but the Health Minister does not expect any opposition.

India’s neighbor China is also taking proactive steps to combat AIDS by targeting the prejudice that accompanies AIDS reporting. At a two-day workshop, publicity officials from municipalities, provinces and autonomous regions were taught to report on the disease in an accurate, balanced manner that does not discriminate against those suffering from this disease. Emphasizing the importance of reporting to create awareness, the organizers stressed that reports should also be detailed and accurate. The organizers hope that the course will help to make officials more sensitive to the human side of the disease.

Meanwhile, Bahrain too is gearing up to fight AIDS. The National Aids Committee has launched a program urging people to learn how to safeguard themselves from AIDS. While incorporating features from an earlier program, it will also include a public awareness drive to spread the message. The program will mainly be directed towards the youth, pregnant women and drug users. The estimated cost of the program is USD 40,000. The United Nations Development Program has lent its support to this initiative.

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Clinical trials boost hopes for those suffering from HIV and chronic ailments

Clinical trials for different types of drugs are in full swing in India. In Mumbai, research in microbicides is at the clinical stage at the National Institute for Research in Reproductive Health (NIRRH). A microbicide is any substance that can substantially reduce transmission of sexually transmitted infections, when applied either in the vagina or rectum.

Research in the area of microbicides is essential as 40 per cent of the total HIV/ AIDS affected population in India is women. Per the Director, NIRRH, Mumbai “The growing feminisation of the AIDS pandemic and the urgent need for a female-controlled method have made prevention of HIV infection through vaginal exposure the top priority for research. Although, trials till now have shown an efficacy of only about 40-60 per cent, even a partially effective microbicide could avert more than 2 million HIV infections over a three-year span.

Meanwhile, Glenmark Pharma, an Indian pharmaceutical company, has applied for Phase-I clinical trials in Europe, for GRC 6211, its leading vanniloid receptor [VR1] antagonist compound for a range of pain indications like osteoarthritis, dental pain, neuropathic pain and urinary incontinence. The Phase I study will be conducted using single and multiple oral doses with the objective of assessing safety and bioavailability of GRC 6211 in healthy human beings. Glenmark is also in discussions for licensing partners for this compound. The company is targeting 2011 as the year of launch and aims to be an early launcher in this class. Incidentally, other molecules in the same category currently under development include: Merck's lead molecule which has progressed to Phase II, GSK's molecule presently in Phase II and Pfizer's in-licensed compound from Renovis, which is undergoing pre-clinicals trials.

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