This Is Your Law on Drugs

January 16, 2008

In presenting the government’s anti-drug plan in October, Prime Minister Stephen Harper never called it a "War on Drugs." But he talked tough about "breaking Canada’s drug habit," and Justice Minister Rob Nicholson punctuated that sentiment by proposing a bill aimed at invoking mandatory jail sentences for drug offenders. Immediately, critics sounded off on what they saw as a host of inherent flaws in the government’s whole approach to illicit drugs. One common strain of criticism pointed out that this is a familiar strategy once embraced by American policy-makers.

Ironically, with drug-related crime still rampant and overcrowding in prisons in some states, mandatory minimum sentencing for drug crimes is currently under review in the US. Yet, despite the failures of Washington’s drug policy, the Tories are determined that the American-styled law-and-order approach to drugs will work in Canada.

To help rid the country of "its complacent attitude toward illicit drugs," the Conservatives committed $63.8 million over two years to fund more enforcement, prevention and treatment programs, conspicuously dropping an important component known as harm reduction in the process. That’s a problem, say opponents of the government. The public-health alternatives derived from harm reduction, they say, would yield positive, long-term results for drug users — addicts who often deal drugs to support their dependency. Some of the different approaches being encouraged include treating drug use and abuse primarily as public health issues and not criminal ones; legalizing marijuana in order to emasculate a potent black market built on its illegal trade; and setting up harm-reduction initiatives similar to those that already exist for tobacco and alcohol. But if any of these alternatives are worth exploring, the Conservatives don’t appear keen on doing it.

The bill in question proposes amending the Controlled Drugs and Substances Act (CDSA) so that a range of minimum penalties for drug offences will give judges rigid sentencing guidelines. (Retired Quebec judge John Gomery likened the legislation to "a slap in the face" for the judiciary.) If the bill passes, a one-year mandatory prison sentence will be imposed for drug-related crimes involving a weapon or violence; a two-year penalty will be required for dealing drugs like cocaine, heroin and meth to youth, or dealing near areas frequented by children; and running a marijuana grow-op of at least 500 plants will lead to a mandatory minimum of two years. The maximum penalty for cannabis production would increase from seven to 14 years. Certain offenders who complete a Drug Treatment Court program will be exempted from facing mandatory prison time.

The new legislation is not going over well with Libby Davies, the NDP Deputy Leader and spokesperson on drug policy. She suggests the Conservatives’ focus on enforcement ("scare tactics") at the expense of proper education and harm reduction is "very much ideologically driven."
 "I think they’re trying to fool people. That somehow getting tough on crime and taking this kind of approach is going to make communities safer," Davies says. She thinks the opposite will happen. "Mr. Harper is clearly wanting to adopt the US model of a war on drugs."

And what a model it is, say the critics. Twenty-two years ago, the US Congress enacted severe mandatory minimum penalties for crack-related offences. What resulted was unrelenting organized crime, increasing incarceration of so-called lower-level drug offenders and, ultimately, a disproportionate number of poor people, mainly African-Americans, being given unduly harsh sentences. Last month, the US Supreme Court ruled in favour of a return to more individualized sentences in drug cases, a retreat from the 1986 national guidelines. The following day, the American Sentencing Commission voted unanimously to apply this leniency retroactively for almost 20,000 prisoners serving time on crack-related charges.

No one at the offices of the Health Minister Tony Clement or the Minister of Justice responded to requests for a telephone interview, but media officials provided written statements. Geneviève Breton, director of communications for the justice minister’s office, says the government’s approach is designed to target serious drug offenders. "The proposed set of mandatory minimum penalties simply does not target minor drug offenders," writes Breton. "Only those drug traffickers who have aggravating factors in their cases, such as using violence or selling drugs near schools, will be eligible to receive the mandatory minimum sentence."

Like Davies, the executive director of the Canadian HIV/AIDS Legal Network believes the Conservatives’ approach fails to recognize that many drug offenders resort to crime to support their habit. Richard Elliott says the root problem is one of addiction and the consequences of a market that supplies that addiction. "It’s a health issue, and we keep throwing all these criminal law provisions at it, thinking this is somehow going to address that," says Elliott. His organization opposes mandatory minimum sentencing, and warns of overcrowding prisons with non-violent drug offenders who are also addicts. Such a move, it says, will worsen a public-health problem by increasing the risks of HIV and Hepatitis C transmissions. "We’re not making a dent in drug markets: in fact, the sale and consumption of illegal drugs are steadily increasing. We are compounding the problems here and we’re impeding health services for people that are much more likely to have an impact."

Because the federal government excludes harm reduction — a component of the original national drug strategy — from its anti-drug plan, the status of certain health services remains in limbo. Last month Health Canada refused to grant Insite, the country’s lone supervised-injection site, its requested three-year renewal, opting instead on a six-month extension. In a September 2007 press release, Tony Clement said that "the best form of harm reduction is to help addicts break the cycle of dependency." At a Canadian Medical Association meeting the health minister was quoted as saying, "Harm reduction, in a sense, takes many forms. To me, prevention is harm reduction. Treatment is harm reduction. Enforcement is harm reduction."

Not so, said over 130 physicians and scientists who signed a petition the next day. It denounced the federal government for its "potentially deadly" misinformation on harm reduction programs. According to a report presented by a Toronto ad hoc committee for the Centre for Addiction and Mental Health, "Harm reduction is any policy or program designed to reduce drug-related harm without requiring the cessation of drug use."

Toronto criminal lawyer and Osgoode Law professor Alan Young says drug dependency is a complicated issue. "You can’t really use law to change the situation. People will always use drugs," he says. "So then the question becomes, what’s the most responsive governmental approach to a situation that most people handle responsibly and some people destroy their lives with?"

Young, who for years has advocated the legalization of marijuana, says by resorting to criminal prohibition, governments create a black market. "When you take a criminal approach to the drug issue, you bring in a whole other Pandora’s box of more serious crimes, and then the politicians blame the drugs, when in reality, it’s their approach that is creating violence within the drug trade."
Davies says there is a role in a national drug strategy for enforcement, but "not to the obliteration of other initiatives like harm reduction." Bill C-26 still has to pass second reading in the House of Commons and then be debated by a parliamentary committee before the Senate looks at it.

Meanwhile, Davies pledges to keep up the campaign to save Insite, and to push for harm reduction programs throughout Canada.

"Whether it’s alcohol, tobacco or substances that are illegal, the most important thing we can do for people is provide really solid education that is realistically frank," says Davies. "So when people do face substance-abuse issues like addiction or dependency, they actually receive medical help in a way that’s accessible and focused on the user."

By Saada Banker,
http://www.eyeweekly.com

Crown Drops Charges Against Former Red Cross Director
Official was one of several named in tainted-blood scandal

January 18, 2008

The Crown has dropped all criminal charges against the former national medical director of the Canadian Red Cross Society, who was one of several officials named in connection with Canada's tainted blood scandal.

Six nuisance charges against Dr. Roger Perrault were withdrawn by the Crown in a Hamilton court Friday.

Crown prosecutor John Pearson said a review of the remaining charges against Perrault had been conducted and as a result "we have concluded that there no longer remains a reasonable prospect of conviction in this case."

The decision follows Perrault's acquittal last October on charges of criminal negligence causing bodily harm and common nuisance endangering the public in relation to the blood scandal.

In that 18-month trial, Superior Court Justice Mary Lou Benotto acquitted Perrault, along with former officials from Health Canada and New Jersey-based Armour Pharmaceutical Co.

Those counts of criminal negligence focused specifically on four victims — who cannot be named under a court order — who contracted HIV from tainted blood. Three of them have died.

The counts of common nuisance related to people living in Ontario, British Columbia, Manitoba and Alberta.

"There was no conduct that showed wanton and reckless disregard," Benotto said in delivering her verdict on Oct. 1.

But Perrault still faced a second criminal trial in Hamilton on several charges stemming from allegations that the Red Cross and senior officials failed to take adequate measures to screen donors.

After Friday's decision, Perrault's lawyer, Eddie Greenspan, said his client should never have been charged or named for the tainted blood crisis.

"Not every tragedy requires a scapegoat," Greenspan said.

But John Playter, of the Canadian Hemophiliac Society, said he was extremely disappointed in the Crown's decision to withdraw the charges.

"There are a lot of people out there that are hurting as a result of what happened," Playter said.

"They are going to walk away from this very confused, very upset with a lot of questions, and it's going to generate a lot of anger. People can say the system has failed them once again."

Some 20,000 people contracted hepatitis C and more than 1,000 were infected with HIV through transfusions of blood and blood products in the 1980s and 1990s.

It's not clear how many people have died as a result, but in 1997 the toll reached 3,000.

Krever Changed Blood Supply Management

In 1993, Ontario Justice Horace Krever looked into what went wrong with the country's blood supply during the 1980s and recommended at the conclusion of the inquiry that all victims, not just those covered by Ottawa's original package, be compensated.

The Krever royal commission also led to a change in how the blood supply is managed. Canadian Blood Services, a non-profit organization, now oversees the blood and blood products supply across the country, except in Quebec, where it's managed by Héma-Québec.

In May 2006, the Red Cross apologized to tens of thousands of Canadians infected with HIV or hepatitis C.

The Crown withdrew charges of criminal negligence causing bodily harm and common nuisance against the charity in exchange for a guilty plea under the federal Food and Drugs Act.

The Red Cross accepted responsibility, paying a $5,000 fine and dedicating $1.5 million to a scholarship fund and research project aimed at reducing medical errors

With files from the Canadian Press , www.cbc.ca

A After Linking New Strain of Staph to Gay Men, University Scrambles to Clarify

January 20, 2007

San Francisco - In a matter of days, it jumped from a routine press release to a medical controversy.

Divert AIDS Dollars to Basic Health Issues: Experts

January 18, 2008

In the two decades since AIDS began sweeping the globe, it has often been labelled as the biggest threat to international health.

But with revised numbers published last year downsizing the pandemic  — along with an admission that AIDS peaked in the late 1990s — some AIDS experts are now wondering if it might be wise to shift some of the billions of dollars of AIDS money to basic health problems like clean water, family planning or diarrhea.

"If we look at the data objectively, we are spending too much on AIDS," said Dr. Malcolm Potts, an AIDS expert at the University of California in Berkeley, who once worked with prostitutes in Ghana.

Problems like malnutrition, pneumonia and malaria kill more children in Africa than AIDS, he said.

"We are programmed to react quickly to small children with AIDS in distress," Potts said. "Unfortunately, we don't have that same reaction when looking at statistics that tell us what we should be spending on."

The world invests about $8 billion US to $10 billion US into AIDS every year, more than 100 times what it spends on clean water projects in developing countries.

Yet more than two billion people do not have access to adequate sanitation, and about one billion lack clean water.

In a recent series in The Lancet, experts wrote that more than one-third of child deaths and 11 per cent of the total disease burden worldwide are due to mothers and children not getting enough to eat — or not getting enough nutritional food.

"We have a system in public health where the loudest voice gets the most money," said Dr. Richard Horton, editor of The Lancet. "AIDS has grossly distorted our limited budget."

AIDS Activists Say Progress Would Be Lost

But some AIDS experts argue that cutting back on fighting HIV would be dangerous.

"We cannot let the pendulum swing back to a time when we didn't spend a lot on AIDS," said Dr. Kevin De Cock, director of the AIDS department at the World Health Organization. "We now have millions of people on treatment and we can't just stop that."

Still, De Cock once worked on AIDS projects in Kenya, his office just above a large slum.

"It did feel a bit peculiar to be investing so much money into anti-retrovirals while the people there were dealing with huge problems like water and sanitation," De Cock said.

Part of the issue is advocacy. From celebrity ambassadors to red ribbons, other diseases have been left by the wayside.

"No one is beating the drum for basic health problems," said Daniel Halperin, an AIDS expert at the Harvard University's School of Public Health.

Aside from southern Africa, most of the continent has relatively low rates of HIV, and much higher rates of easily treatable diseases like diarrhea and respiratory illnesses. Yet much of the money from the West, especially from the United States, goes into AIDS.

President George W. Bush has requested another $30 billion US for the next five years for AIDS, mostly to be spent in Africa, and the leading Democratic candidates have proposed that figure be bumped up to $50 billion US.

In comparison, the President's Malaria Initiative, launched in 2005, aims to reduce malaria deaths by half in 15 African countries. Its five-year budget is an estimated $1.2 billion US.

The Canadian Press, www.cbc.ca

Love and Hope for Children at AIDS School

January 14, 2008

Bhoogaon, India - In a smart blue tunic and red ribbons in her hair, 12-year-old Komal's laughing eyes hide a fear of death that stalks every student in her village school.

Within months or years she could be dead, but while she lives she is fulfilling a dream -- of going to school again after she was expelled from her previous one because she was infected with HIV.

"They used to throw water on me and tear up my books," Komal said as she reminisced about her days at a regular school. "Still, I wanted to go to school, but one day my teacher said don't come back."

At Gokul, a school for HIV-infected children in this dusty village north of India's commercial hub of Mumbai, each student has a heart-wrenching tale of discrimination and suffering.

The disease orphaned all of them, some were thrown out of school for their HIV status or abandoned by families. All got the virus from their mothers.

The school is among only a few across the country run by voluntary groups, where infected children expelled by "normal" schools receive education.

Rights groups and HIV/AIDS workers say conservative India's fight against the disease is being undermined by ignorance and prejudice. Sufferers are often denied treatment by hospitals, thrown out by families, evicted by landlords or fired.

Children remain the hidden face of this suffering. When a parent is infected, children drop out of school to care for them, or go to work to replace the lost income, until they become orphans, health workers say.

Prejudice is so deep-rooted that a southern state, Kerala, failed to persuade schools to take in two infected children and was forced to bear the cost of their education at home.

Children do not figure on India's estimate of 2.5 million people infected with HIV, but the government says about 50,000 children below 15 years are infected by the virus every year.

Born Out Of Rejection

Among the students in Bhoogaon is Ramesh, whose father, his care-giver says, infected his mother because he wanted her to suffer his deadly fate.

All the students are aware of the fatal nature of their ailment. Seven children have died at the school in the past few years.

All of the school's 53 pupils are HIV positive, but none has AIDS yet and they are receiving expensive anti-retroviral treatment.

"When one of us falls sick and is taken to hospital we keep wondering if he or she is going to come back," says Ramesh.

Some of them remember cremating their parents and then being subjected to torture by their relatives and finally fleeing home.

"Gokul was born out of the social rejection of these children," says Ujwala Lawate, the school's managing trustee.

"Some of them were sent from government remand homes, some we picked up from villages and some were brought in by their families."

The residential school, the size of half a football field, has students ranging from two to 16 years.

"Villagers threatened us. They said our children were a risk," says Lawate. "In fact they said if our children bit their children they could get AIDS."

The locals relented after government health workers intervened and promised to keep the children within the confines of the school's high walls.

Institutionalising Stigma?

Lawate says her school is an effort to provide dignity and purpose to the lives of HIV-infected children, but she has critics as well.

"Instead of separate schools we should fight for equal rights of an HIV/AIDS child," says Meena Sheshu, whose state-based anti-AIDS group "Sangram" opposes Lawate's efforts.

"No child should be thrown out of a school. But a separate school only institutionalises the stigma and discrimination."

The government's stand is ambiguous. It provides financial aid to schools such as Gokul and says no school should turn away any student, but at the same time the government has yet to ban discrimination against those with HIV/AIDS.

Lawate says her critics are ignoring the "practical problems".

"While we debate what is right and wrong, children are being discriminated against," she says as groups of smiling students jostle around her, their "kaki" or aunt.

"What would happen if these 53 children were not here? Maybe they would just be lying sick somewhere by the streets and waiting to die."

By Krittivas Mukherjee, Reuters

Two XDR TB Cases Reported in Botswana

January 17, 2008

The government of Botswana announced yesterday that two cases of extensively drug-resistant tuberculosis (XDR TB) have been identified in the country. They are the first cases to be reported in sub-Saharan Africa outside South Africa.

Two patients with XDR TB have been quarantined at the Princess Marina Hospital in Gabarone.

Extensively drug-resistant TB is a form of TB that is resistant to the first-line drugs isoniazid and rifampicin, the fluoroquinilone class of antibiotics, and at least one of the injectable antibiotics used in the treatment of multi-drug resistant TB.

XDR TB is very difficult to treat and may have a very rapid disease course in people with HIV. It can only be diagnosed by laboratories equipped to carry out drug susceptibility testing, with the result that outside South Africa, its prevalence in sub-Saharan Africa is unknown. Nearly 500 cases of XDR TB have been diagnosed in South Africa since 2006, when an outbreak was first identified in KwaZulu Natal province.

Over 100 people were recently diagnosed with multi-drug resistant TB (MDR-TB) in Botswana and are now being treated as outpatients, Dr Julius Mboya, head of disease control at Princess Marina Hospital told the Botswana Press Agency.

"We know where all [MDR TB] patients are and we are monitoring their progress, but since they have all been educated on the dynamics of their condition, we feel they are not that risky to the public," said Dr Mboya.

The Botswana approach to MDR TB treatment contrasts with the approach in some South African provinces, where patients with MDR TB have been required to spend lengthy periods in specialist treatment facilities to receive supervised treatment.

The Permanent Secretary in the Ministry of Health, Ms Batatu Tafa yesterday released a press statement appealing to all people with chronic coughs and those who have been exposed to patients with active TB to visit the nearest health facilities for a check up.

By Keith Alcorn, www.aidsmap.com

Kenya: Drug Resistance Risk as Displaced HIV Patients Skip ARV Doses

January 17, 2008

After a fortnight of political violence during which an estimated 250,000 Kenyans were displaced, health workers are scrambling to ensure that HIV-positive people on life-prolonging anti-retroviral (ARV) therapy continue to receive their drugs and adequate food supplies.

"As of last week, only about 5 percent of our patients on ARVs had reported to refill their ARV prescriptions," Sylvester Kimaiyo, programme manager of the Rift Valley-based Academic Model for the Prevention and Treatment of HIV/AIDS (AMPATH), told IRIN/PlusNews. "We have 58,000 HIV-positive people under our care, 24,000 of whom are on ARVs."

Kimaiyo said AMPATH's 19 sites across the northern Rift Valley, Western and Nyanza provinces usually gave patients one month's supply of drugs, but habitually also a few days' extra in case patients failed to make it to the dispensaries in time.

"However, staff at our sites say many patients who have begun to report this week had missed some days of their medication," he said, noting that the Burnt Forest and Eldoret areas of the Rift Valley had been worst affected.

Interruption of ARV therapy risks patients developing resistance to the drugs. According to the UN World Health Organization, "The consequences of drug resistance include treatment failure, increased direct and indirect health costs associated with the need to start more costly second-line treatment for patients, the spread of resistant strains of HIV and the need to develop new anti-HIV drugs."

As tentative calm returns to the country, patients have begun making their way to the sites, Kimaiyo said, and by 15 January, only patients in IDP camps had not reported.

"We have sent our staff into the camps in the Rift Valley and they are tracing patients and delivering drugs to them," he added. "And for those patients able to make it to our clinics, we are providing food supplies from our stores, whether or not they were receiving food before the election."

In Nyanza Province, the Ministry of Health's provincial ART coordinator, Lennah Nyabiage, said it had been difficult to gauge the situation because the local population was extremely hostile to the government and its officials.

Nyanza, with an HIV prevalence rate of 12 percent, has an estimated 45,000 people on ARV treatment. Home to Raila Odinga, the opposition candidate contesting President Mwai Kibaki's December election victory, it has witnessed some of the worst violence in the country.

"Our officials have reported being harassed when they show up in GoK [Government of Kenya] vehicles and they are too scared to go to many areas because they are known to work for the government," she told IRIN/PlusNews. "I am in touch with our people at government hospitals, and they are reporting that most people have not run out of drugs yet."

She said her office was working with the local police to ensure that people were aware they could get treatment from any health centre, even if it was not their regular one, as long as they provided medical records that showed they were on ARVs. The ministry has also placed notices in national newspapers advising people on ARVs and tuberculosis medication to report to their nearest health centre for free treatment.

Seeking Out Missing Patients

Across the country, NGOs are developing new ways to trace patients. The international medical charity, Médecins Sans Frontières (MSF), is setting up a toll-free national hotline, due to begin on 21 January.

"The hotline will run for six weeks and will be advertised in the national English and Kiswahili newspapers," said MSF's Anouk Delafortrie, who is coordinating the project. "We are asking patients to call for advice about the closest centre if they have had to relocate, and letting them know what their options are if they are no longer near an MSF health facility."

MSF has three centres in Nairobi's Kibera slum, scene of much of the violence, as well as a TB clinic in the city's Mathare slum and HIV projects in the western Kenyan towns of Homa Bay and Busia; the organisation has 12,000 patients on HIV treatment and care.

"When the unrest broke out after the election, many of our patients were displaced, so we have set up this mobile clinic in Jamhuri Park [in Nairobi, where 2,400 IDPs are living] to try and trace them and alert them to our presence - since we have been here, about 50 of our own patients have come to refill their ARV prescriptions," said Mohamed Hamid, coordinator of the mobile clinic. "We are not turning away patients from other health providers - if they have their medical records with them then we are providing them with drugs."

The Ministry of Health and several other health NGOs have also set up satellite centres at Jamhuri Park and in IDP camps in the Rift Valley to trace their patients, with particular emphasis on tracing those on ARVs and TB medication.

Uganda's New Vision Newspaper has reported that HIV-positive Kenyan refugees fleeing across the border will be able to get ARVs at camps through local NGOs.

Health workers have commended the speed with which emergency mechanisms have kicked in to locate patients nationally and keep them on their medication, but have also warned that only time will reveal the impact of interrupted treatment on thousands of patients across the country. More than 160,000 Kenyans receive free government ARVs.

Reproduced from PLUS NEWS, www.aidsmap.com

Cell Protein Found That Literally Nips HIV in The Bud

January 14, 2008

UCLA researchers have found that a key protein in the body's dendritic cells can stop the virus that causes AIDS from "budding" -- part of the virus' life cycle that is crucial to its ability to replicate and infect other cells.

"If we can block virus generation, then we can control the disease," said lead author Shen Pang, associate professor in the division of oral biology and medicine at the UCLA School of Dentistry and a member of the UCLA AIDS Institute.

Dendritic cells are specialized white blood cells in the skin, mucosa and lymph nodes that kick-start a primary immune response to foreign invaders by activating lymphocytes, including the T cells that HIV targets. Though dendritic cells can be infected with HIV -- and indeed play a crucial role in transmitting the virus to T cells -- studies have shown that viral generation from these cells is nearly a hundred times lower than from infected T cells, indicating that the cells may possess some inhibiting property.

Pang hypothesized that DC-SIGN, a protein expressed in dendritic cells, may be responsible for such inhibition. He and his colleagues found that DC-SIGN and a related protein, DC-SIGNR, both demonstrated 95 percent to 99.5 percent inhibition of viral production from host cells.

Very few cells are infected when HIV first enters the human body, but the virus rapidly creates new copies of itself, which in turn infect more cells. To achieve this, the virus, after infecting a cell, sends envelopes of protein to the cell's membrane. The viral genomes then combine with viral structural proteins and move into these envelopes. The envelopes bubble, or bud, outward, releasing viral particles that will infect more cells and start new viral life cycles.

According to the researchers, DC-SIGN appears to block HIV generation by efficiently neutralizing an HIV glycoprotein on the surface of the HIV envelope known as gp120, a key to viral infection. In such cases, while some viral particles may still be released from the infected dendritic cells, the lack of gp120 in their envelopes means they are not infectious to CD4-positive T-lymphocytes and macrophages. In other words, these viral particles have been rendered uninfectious.

Current methods to interrupt the life cycle of the virus are limited because they generally target HIV at the stages of viral entry, reverse transcription and post-translational protein cleavages. Once the virus passes through these stages, treatment fails. The UCLA researchers, therefore, focused on halting the virus' generation at different stages in its life cycle.

"The strong inhibition of viral production by DC-SIGN suggests the possibility of using this protein for treatment of HIV-infected patients," the researchers write. "Expression of this protein in various CD4-positive cells should inhibit viral production from infected cells. Because it can also enhance the immune response, DC-SIGN is expected to be useful for in vivo studies for developing an HIV vaccine."

The study, scheduled for publication in the April issue of the Federation of American Societies for Experimental Biology's FASEB Journal and may be available online at http://www.fasebj.org/cgi/rapidpdf/fj.07-9443comv3.pdf. Pang's co-author is Qiuwei Wang, a postgraduate researcher in the division of oral biology and medicine at the UCLA School of Dentistry.

This study was supported by the UCLA AIDS Institute, the UCLA School of Dentistry and a grant from the National Institutes of Health.

Adapted from materials provided by University of California - Los Angeles.

Science Daily

New Multi-Drug Resistant MRSA Strain Disproportionately Affecting Gay, HIV-PositiveMen

January 15, 2008

A recently-identified strain of methicillin-resistant Staphylococcus aureus (MRSA) resistant to most types of antibiotic is being seen more frequently amongst gay men, particularly in HIV-positive gay men, than in the general population, according to a new study released electronically yesterday and due to be published in the February 19th issue of Annals of Internal Medicine.

The investigators believe that this particular strain may sometimes be sexually transmitted and suggest that further studies examine the link between sexual behaviour and multidrug-resistant MRSA.

The mainstream press have widely reported the story today; however, at least one story in the London tabloid newspaper, Metro, has overstated both the risks of casual transmission and the seriousness of the infection, characterising it as the "new HIV".

The link between community-acquired MRSA, HIV-positive gay men and sexual transmission is not new. As early as 2005, it was reported that community-acquired MRSA infections were being observed with greater frequency among HIV-positive patients in San Diego, and that community-acquired MRSA in HIV-positive gay men in Los Angeles was associated with sex, drug use and environmental exposure.

A 2006 study tracking MRSA infections in patients admitted to an HIV hospital ward in San Francisco between 1996 to 2005, found that one community-acquired strain, USA300, first identified in 2002 made up 93% of MRSA by 2005.

The current study has found a multidrug-resistant genotype of this MRSA strain that is resistant to treatment with pencillins, erythromycin, clindamycin, tetracycline, mupirocin, and Cipro-like antibiotics. However, it is still susceptible to older antibiotics, such as co-trimoxazole and may also resolve by simply draining the infected boil without the use of any antibiotics. Only in the most extreme – and rare – cases is the infection life-threatening.

In addition, infection with multidrug-resistant MRSA can usually be avoided by washing with soap and water. "Taking a shower after sexual contact may minimise contamination," study co-author Dr Chip Chambers, told the San Francisco Chronicle. "Ordinary soap will do. It dilutes the concentration of bacteria. You don't need antibacterial soap."

About The Study

Investigators from California wanted to see how common multidrug-resistant MRSA infection is in San Francisco, and to identify risk factors for the infection. Of 2495 San Francisco residents found to have MRSA during a twelve month period in 2004-5 the investigators took a random sample of 532 (21%) in order to determine how many of these MRSA samples were multidrug-resistant.

In order to identify risk factors for multidrug-resistant MRSA, they studied two other groups of people with MRSA: 183 HIV-positive individuals attending an HIV clinic at a San Francisco hospital and 130 people, some of whom were HIV-positive, attending a health clinic in Boston.

Overall incidence of MRSA in San Francisco was estimated to be 275 cases per 100,000 people. However, overall the incidence of the newly-identified multidrug-resistant MRSA was much lower, at 26 cases per 100,000.

When the investigators examined the incidence of multidrug-resistant MRSA based on the area of residence within San Francisco, they found that the highest incidence of multidrug-resistant MRSA (170 cases per 100,000) was in the zip code that included the Castro district, which has a higher proportion of gay men than any other part of San Francisco.

They then examined the prevalence of multidrug-resistant MRSA in the 183 HIV-positive patients with MRSA at a San Francisco HIV clinic, and found that 30 (16%) were infected with multidrug-resistant MRSA. In multivariate analysis, sex between men was a highly statistically significant risk factor for having multidrug-resistant MRSA (relative risk, 13.2; p < 0.001).

Other statistically significant risk factors for multidrug-resistant MRSA included having had a previous MRSA infection (relative risk, 2.1; p = 0.007) or having previously used the antibiotic clindamycin (relative risk, 2.1; p = 0.007).

Finally, they examined the prevalence of multidrug-resistant MRSA in the 130 Boston clinic patients with MRSA infection, and found that 60 (46%) were multidrug-resistant MRSA. All 60 were gay men or other men who had sex with men, suggesting that the infection may have been acquired sexually.

A total of 45% of the patients with multidrug-resistant MRSA were HIV-positive, suggesting that although multidrug-resistant MRSA is not limited to people with HIV, it is more likely to be seen in HIV-positive people. When the investigators limited their analysis to the 121 gay men in the clinic with MRSA, 33 of 56 (59%) who were HIV-positive had multidrug-resistant MRSA infection compared with 27 of 65 (42%) who were HIV-negative (relative risk, 1.4; p = 0.056).

"These data suggest that although HIV infection is a risk factor for multidrug-resistant USA300 infection," write the investigators, "having male–male sex is also a risk factor independent of HIV infection."

They note that in San Francisco and Boston, multidrug-resistant MRSA most often manifested as an infection of the buttocks, genitals, or perineum, suggesting sexual transmission.

Previous studies have suggested that MRSA amongst HIV-positive gay men is associated with high-risk sexual behaviours, including use of methamphetamine and other illicit drugs, sex with multiple partners, participation in a group sex party, use of the internet for sexual contacts, skin-abrading sex, and history of sexually transmitted infections.

The investigators comment, however, that "it is not clear whether the behavior potentiating these infections among men who have sex with men is anal sex (that is, dissemination of rectal carriage of community-associated MRSA), skin-abrading sexual practices, or increased frequency of intimate skin-to-skin contact; prevention messages may therefore need to suggest caution in each of these practices."

They also found a gay man from Boston with the same genotype of multidrug-resistant MRSA infection as the gay men in San Francisco. Since he said he had often visited San Francisco for sex, the investigators believe that "the multidrug-resistant USA300 epidemic probably started in San Francisco and has been disseminated by the frequent cross-coastal travel of men who have sex with men."

However, there were several limitations to the study. Since relatively few multidrug-resistant MRSA infections were found, and because the researchers did not interview the people with multidrug-resistant MRSA, relying only on clinical records, their estimates of infection risk could be imprecise.

They conclude by summarising their findings thus: "we show that multidrug-resistant USA300 has emerged as an important source of disease among men who have sex with men in two geographically distinct communities."

"The high proportion of infection involving the buttocks, genitals, and perineum suggests that community-associated MRSA may be transmitted in the setting of sexual contact among men who have sex with men."

"The link among USA300, multidrug-resistant USA300, and unsafe sexual risk behaviors should be evaluated further in prospective studies."

Reference
Diep BA. Emergence of multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus clone USA300 in men who have sex with men. Annals of Internal Medicine 148 (4): 249-259, 2008.

By Edwin J Bernard, www.aidsmap.com

Probing the Problem of the HIV-1 Envelope

January 14, 2008  

New structural details illustrate how a promising class of antibodies may block human immunodeficiency virus (HIV)-1 infection and reveal valuable clues for design of an effective HIV-1 vaccine. The findings, published by Cell Press in the January issue of Immunity, are particularly significant as antibody induction appears to be a key and necessary component of an effective HIV vaccine, evidenced by the recent failure of vaccines that stimulated only the T cell arm of the immune system to protect humans from contracting HIV-1.

Profound challenges have interfered with creation of a preventative vaccination to halt the global spread of HIV-1. For example, the HIV-1 envelope protein, the only target for neutralizing antibodies, is highly variable among isolates and masked by sugar molecules, allowing the virus to escape antibody attack. "Not surprisingly, only a handful of broadly neutralizing antibodies (BNAbs) have been identified and they are rarely elicited during natural human infection," explains research leader Dr. Ellis L. Reinherz from the Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts.

The BNAbs that have been identified are directed against a portion of HIV-1 called the membrane proximal ectodomain region (MPER). This region lies at the base of the viral envelope protein comprised of the gp120 protein plus the membrane anchoring gp41 subunits adjacent to the viral membrane. A major conundrum has been the basis for the lack of human antibody response against the MPER segment since it is accessible to antibody and is highly conserved, even among different HIV-1 viral isolates around the world.

The present study reveals that much of the MPER is actually embedded in the viral membrane. As such, this stealthy segment appears to divert the immune attack elsewhere, namely to the exposed variable elements of the viral envelope and immunodominant regions which do not confer useful neutralization. The researchers also discovered a hinge in the middle of the MPER permitting segmental flexibility, an important feature in facilitating fusion of the virus with the human host immune cells.

BNAbs such as the monoclonal 4E10 antibody target this hinge area and cause the MPER to undergo dynamic changes that reveal key pieces of itself critical for viral fusion that were buried deep in the membrane. As a result, the antibody is then able to achieve a tighter hold on the virus, restrict hinge mobility and impede the ability of the virus to fuse to the membrane of the host cell.

Importantly, the published structure of the lipid-embedded MPER also identifies those few residues poking out from the viral membrane. These may be ideal targets for vaccine design if properly configured in a synthetic lipid coat that conserves the native shape of the MPER and focuses production of antibodies against this Achilles' heel of the viral envelope.

While this research is still at an early experimental stage, it provides a plausible explanation as to why previous attempts, which neglected to preserve the native conformation of the MPER necessary for eliciting a broadly neutralizing antibody with 4E10-like specificity, were unsuccessful and offers a new approach to the design of antibody-eliciting vaccines to prevent HIV-1.

The researchers include Zhen-Yu J. Sun, Harvard Medical School, Boston, MA, USA; Kyoung Joon Oh, Harvard Medical School, Boston, MA, USA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Mikyung Kim, Harvard Medical School, Boston, MA, USA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Jessica Yu, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Vladimir Brusic, Harvard Medical School, Boston, MA, USA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Likai Song, Harvard Medical School, Boston, MA, USA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Zhisong Qiao, Harvard Medical School, Boston, MA, USA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Jia-huai Wang, Harvard Medical School, Boston, MA, USA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Gerhard Wagner, Harvard Medical School, Boston, MA, USA; and Ellis L. Reinherz, Harvard Medical School, Boston, MA, USA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Source: Cathleen Genova, Cell Press

Article adapted by Medical News Today from original press release. http://www.medicalnewstoday.com

HAART Significantly Lowers Risk of Non-Hodgkin's Lymphoma For Up To TenYears, Regardless Of Nadir CD4 Count

January 15, 2008

Antiretroviral therapy greatly reduces the incidence of non-Hodgkin’s lymphoma and its beneficial effect remains after ten years of treatment, according to the results of the largest, and longest, study into the effects of highly active antiretroviral therapy (HAART) on the incidence of this AIDS-defining cancer. The results were published in the January 11th edition of the journal, AIDS.

Following the advent and widespread use of HAART in wealthier nations more than a decade ago, a decrease in the incidence of AIDS-related illnesses was observed, including that of non-Hodgkin’s lymphoma. However, previous studies of non-Hodgkin’s lymphoma incidence in the post-HAART era included relatively small numbers of people diagnosed with non-Hodgkin’s lymphoma following HAART initiation. Consequently, there are few data on the incidence of non-Hodgkin’s lymphoma in the HAART era and the effects of long-term HAART on incidence over time.

Investigators for the Swiss HIV Cohort Study – which includes half of all people with HIV, and 68% of people with AIDS in Switzerland – analysed their database (which began in 1984 and included data until March 31st 2006) of 12,959 individuals, contributing a total of 75,222 person-years, of which 36,787 were spent on HAART.

They identified a total of 429 non-Hodgkin’s lymphoma cases between 1984 and 2006 (365 from the Swiss HIV Cohort Study dataset and a further 64 from the Swiss Cantonal Cancer Registries).

Of the approximately 3,870 cohort participants who developed AIDS during follow-up, non-Hodgkin’s lymphoma was the AIDS-defining illness for 201 (5.2%).

They found that the highest incidence of non-Hodgkin’s lymphoma (13.6 per 1000) took place in the pre-HAART era (1993-1995). During the period, 2002-2006, the incidence declined to a low of 1.8 per 1000.

The investigators found that individuals on HAART had a reduced risk (hazard ratio, HR) of non-Hodgkin’s lymphoma of 0.26 (95% CI, 0.20-0.33) compared with individuals not on HAART.

Significant factors that increased the risk of non-Hodgkin’s lymphoma for individuals not on HAART included being male (HR versus women = 1.94; 95% CI, 1.43-2.61); being over 45 years of age (HR ≥ 45 versus < 35 years = 2.71; 95% CI, 2.04-3.60), and acquiring HIV through sex between men (HR versus intravenous drug users = 1.81; 95% CI, 1.36-2.42).

A particularly important finding was that HAART use lowered the risk of non-Hodgkin’s lymphoma regardless of the individual’s CD4 count at enrolment. In other words, they found no association between CD4 cell count and non-Hodgkin’s lymphoma risk in people on HAART.

In contrast, as previous pre-HAART studies have found, non-Hodgkin’s lymphoma rates increased steeply as CD4 cell counts decreased for people not on HAART. This study found that individuals not on HAART with a CD4 count at enrolment of fewer than 50 CD4 cells/mm3 were more than twelve times more likely to be diagnosed with non-Hodgkin’s lymphoma than individuals enrolling with more than 350 cells/mm3.

The investigators also found that use of HAART reduced the risk of non-Hodgkin’s lymphoma by half within the first five months of use, and the risk continued to decline so that the hazard ratio after 36-59 months on HAART was 0.10 (95% CI, 0.06-0.17). Importantly, the risk remained extremely low after ten years of HAART: hazard ratio = 0.12 (95% CI, 0.05-0.25).

Although histological confirmation was available in the majority of cases, the histological subtype was often not available, and therefore this study only distinguished primary brain lymphoma from other types of non-Hodgkin’s lymphoma. When the investigators examined the incidence of primary brain lymphoma, they found that there was a stronger decline in incidence after 1995 than for other non-Hodgkin’s lymphomas. Specifically, primary brain lymphoma represented 31.6% of non-Hodgkin’s lymphomas before 1996, but only 13.3% in 1999-2006.

The investigators point out that although this is the largest, and longest, study on the incidence of non-Hodgkin’s lymphoma before and after HAART, there were several limitations to their study. These include a lack of information on the year of seroconversion; a lack of non-Hodgkin’s lymphoma histology; and no information on adherence to HAART.

The latter means that the investigators may have underestimated treatment efficacy since they included people who interrupted treatment as people on HAART. "Indeed," they write, "we found that 22% of non-Hodgkin’s lymphoma in HAART users arose in persons who were no longer on HAART at cancer diagnosis."

The investigators note that "the near complete disappearance of the association between CD4 cell count at enrolment or at initiation of antiretroviral treatment and [non-Hodgkin’s lymphoma] risk supports the strong efficacy of HAART regardless of the degree of immune impairment when follow-up or treatment begins.

"Thus," they conclude, "although it was already clear that HAART prevents [non-Hodgkin’s lymphoma] through improvement of immune status , this study shows that HAART avoids the majority of [non-Hodgkin’s lymphoma], even among the most severely immunosuppressed individuals."

Reference
Polesel, J et al. Non-Hodgkin’s lymphoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy. AIDS 22(2), 301-306, 2008.

By Edwin J Bernard, www.aidsmap.com

Researchers Report That Existing Antiretroviral Drugs May Thwart Vaginal HIV Transmission

January 15, 2008  

Prescription drugs now used to treat human immunodeficiency virus infection in adults may prevent the vaginal transmission of HIV, researchers at UT Southwestern Medical Center have found.

Using a highly sophisticated human/mouse chimera or "humanized mouse" model, the UT Southwestern researchers discovered that anti-retroviral drugs given daily before and after exposure to HIV can prevent vaginal transmission of the virus that causes AIDS. Worldwide, the vast majority of newly acquired HIV infections occur through unprotected vaginal sex with an infected partner.

The study, appearing online in PLoS Medicine, used human/mouse chimeras that have fully developed human immune systems and produce the infection-fighting cells that are specifically targeted by HIV in humans.

While almost 90 percent of the humanized mice inoculated vaginally with HIV became infected with the virus, none of the humanized mice given the anti-retroviral drugs emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) displayed any evidence of infection.

"Our motivation is to look for interventions that can be implemented rapidly and have the potential to make a big difference," said Dr. J. Victor Garcia-Martinez, professor of internal medicine at UT Southwestern and the study's senior author. "We don't want something in 10 years. We want female-controlled prevention measures now. Our observations support the potential for antiviral drugs to function as an effective pre-exposure prophylaxis against the further spread of AIDS."

HIV is predominantly transmitted by unprotected sexual contact with an infected partner. Women are more susceptible than men to HIV infection, and vaginal exposures result in a majority of the estimated 6,800 transmission events a day.

"There are 33 million people infected with HIV. This study is a highly significant breakthrough because it offers proof-of-principle that pre-exposure prophylaxis with currently available anti-retroviral drugs can potentially prevent vaginal HIV transmission, empowering women throughout the world to protect themselves from this deadly disease," Dr. Garcia said.

"More women are being infected by HIV now than at any other time during the history of the AIDS epidemic," Dr. Garcia said. "Over 15 million women worldwide are infected. Our findings should provide further impetus to continue clinical trials using oral anti-retroviral drugs as a preventive measure, particularly in areas with the highest rates of HIV infection."

Dr. Garcia said one potential caveat is that the experiments were conducted on humanized mice and not humans.

"This is a human/mouse chimeric model that clearly recapitulates very important aspects of humans, but at the end of the day, these are mice," he said. "It will take additional work to translate these observations to humans."

Investigators have long used mouse models to study human physiology and to test new drugs. But differences in mouse and human immune systems - and the fact that normal mice can't be infected with human-specific pathogens or produce human immune cells needed to fight them - have limited this type of research.

In 2006 Dr. Garcia, along with colleagues at UT Southwestern and researchers from the University of Minnesota, created humanized mice that developed fully functional human immune systems and infection-fighting cells, such as T cells, throughout their bodies. These humanized mice, known as Bone Marrow Liver Thymic mice (BLT mice), can develop T cells the same way as humans and can be infected vaginally with HIV.

In this latest study, the BLT mice were given the anti-retroviral drugs once a day for seven consecutive days starting 48 hours before being challenged intravaginally with HIV. None of the mice that had been given the anti-retroviral drugs contracted HIV; however, seven of the eight mice that didn't receive the anti-retroviral drugs tested positive for the infection as early as two weeks post-infection.

If this pattern proves to be true in subsequent trials, women someday might have to take one pill a day in order to potentially prevent vaginal transmission of HIV, Dr. Garcia said.

"One important issue to keep in mind is that pre-exposure prophylaxis is not something that would be advantageous or cost-effective to use in areas where there's a very low incidence of HIV infection," he said. "If you take this pill on a regular basis, but you're not exposed to this virus, then the drugs are not doing any good and could potentially do harm. But, in parts of the world where the likelihood of exposure is significantly higher, the risk of contracting HIV may warrant taking these medications."

Dr. Garcia said it's possible that other more cost-effective drug combinations or concentrations could have the same effect. What this research does, he explained, is demonstrate that existing anti-retroviral drugs can help curtail the spread of the HIV/AIDS epidemic.

Other UT Southwestern researchers involved in the study were lead author and student research assistant Paul Denton; research assistants Daniel Powell and Florence Othieno; postdoctoral researchers Dr. Zhifeng Sun and Dr. Anja Wege; former postdoctoral researcher Dr. Bangdong Wei; and Dr. Deborah Payne, associate professor of pathology. Drs. Jacob Estes and Ashley Haase from the University of Minnesota also participated.

Source: Kristen Holland Shear, UT Southwestern Medical Center
adapted by http://www.medicalnewstoday.com from original press release.

Low Testosterone Increases Bone-Fracture Risk

January 15, 2008

Low blood testosterone levels in men over 60 significantly increased their risk of having a bone fracture, according to the authors of a study published in the January 14 issue of the Archives of Internal Medicine. Though the study did not include HIV-positive men, low testosterone levels, also known as hypogonadism, is a condition that frequently affects people living with the virus. Weakened bone density, also known as osteoporosis, is also affecting increasing numbers of people with HIV.

Christian Meier, MD, of the bone research program at the ANZAC Research Institute at the University of Sydney in Australia, and his colleagues examined data collected through the Dubbo Osteoporosis Epidemiology Study, which since 1989 has enrolled all men and women 60 years of age and older living in the Australian city of Dubbo. By 2004 there were 868 men enrolled in the study, of whom 609 had blood samples available from the time of their enrollment and from follow-up visits. The average age of the men was 73 years old.

During the period of observation, 113 men had a low-trauma bone fracture. Nearly 80 percent of the fractures occurred in men who were 70 or older. After accounting for traditional risk factors that can negatively affect bone health, such as age, bone mineral density, calcium intake and history of smoking, having a low testosterone level was independently associated with an increased risk of bone fracture. With every degree that testosterone dropped, the risk of fracture increased significantly.

Though Meier’s team is recommending testosterone replacement therapy only for those with the most severe testosterone deficiencies, they are encouraging other physicians to view low testosterone levels in older men as a potential risk for bone fracture. Though it is not possible to extrapolate the results of this study directly to people living with HIV, particularly men under 60 or HIV-positive women with testosterone deficiency, people who have other risk factors for poor bone health may want to discuss the results of this study with their health care provider.

http://www.aidsmeds.com

Virus Linked to Development of Deadly Skin Cancer: Study

January 17, 2008

A newly discovered virus has been linked to the development of Merkel cell carcinoma, a dangerous skin cancer.

Researchers at the University of Pittsburgh Cancer Institute spent 10 years developing a way of isolating the virus, named Merkel cell polyomavirus (MCV).

Polyomaviruses have been linked to cancer in animal studies.

"This is the first polyomavirus to be strongly associated with a particular type of human tumour," said Dr. Moore, professor of microbiology and molecular genetics at the University of Pittsburgh School of Medicine and leader of the molecular virology program at UPCI, in a release.

"Although polyomaviruses have been studied in relation to cancer development for years, the weight of scientific evidence had been leaning toward the view that these viruses do not cause human cancers."

Merkel cell carcinoma is a fast-moving skin cancer that develops from nerve cells and quickly invades other tissues and organs in the body. This incidence of this type of cancer has increased dramatically over the 20 years and now averages 1,500 cases per year.

Those vulnerable to this form of cancer are immune-suppressed individuals — such as those taking drugs to prevent the rejection of a transplant — and AIDS patients.

The survival rate isn't high, with 50 per cent of patients succumbing to the disease within nine months.

In the study, researchers discovered that many people carry MCV, though in many it never develops into cancer.

Moore says the discovery opens the door to further exploration into how the virus targets cell pathways. "Information that we gain could possibly lead to a blood test or vaccine that improves disease management and aids in prevention," he said.

He likens the possible future treatments to the HPV vaccine that protects against certain strains of human papillomavirus, which is linked to cervical cancer.
Corrections and Clarifications

    * Merkel cell polyomavirus is a newly discovered virus. It has not been linked to Kaposi's sarcoma as this story originally reported. The HPV vaccine protects against certain strains of human papillomavirus, not cervical cancer as was originally reported in this story. Jan. 18, 2008 | 12:39 p.m. ET

www.cbc. ​​​​​ca

Balance of Evidence Continues To Show: Undetectable Viral Load In BloodDoes Not Equal Zero Infection Risk

January 18, 2008

The level of HIV viral load in blood and semen is related, but studies looking at the correlation between HIV in blood and semen have yielded a wide variety of results, according to a review article analysing the results of 19 studies examining this issue published in the January 2008 edition of Sexually Transmitted Diseases. The review article’s authors found that the association between viral load in blood and semen was affected by a number of factors, with successful antiretroviral therapy strengthening the association and sexually transmitted infections weakening it.

Prevention messages should stress the importance of condoms and other risk reduction strategies, regardless of whether a patient is taking effective anti-HIV therapy, recommend the investigators, as HIV transmission is possible even if a patient has an undetectable viral load in their semen.

HIV is mainly transmitted by unprotected anal and vaginal sex. Since the earliest days of the HIV epidemic it has been known that the virus is present in both blood and genital fluids. Infection with HIV is dependent upon the exposure of susceptible cells to an infectious quantity of HIV and it is known that concentrations of HIV in genital fluids, such as semen can vary.

HIV viral load levels in blood and semen are related but are not equal. It is not possible to determine how infectious an HIV-positive individual is on the basis of their blood viral load unless the extent of the association between viral load in blood and semen is determined.

Understanding the relationship between viral load in blood and semen is essential for estimating the potential benefit for antiretroviral therapy to reduce the risk of HIV transmission.

Investigators from the University of Connecticut therefore reviewed studied that measured viral load in blood and semen at the same time. The investigators examined the correlation between viral load in the two and the factors affecting this.

A PubMed search in January 2007 together with a search of abstracts of research presented to the Conference on Retroviruses and Opportunistic Infections (CROI) and the conferences of the International AIDS Society yielded 19 eligible studies.

The investigators caution that most of these studies had a small sample size. Furthermore 17 had a cross-sectional design and only two were prospective.

Correlations between levels of HIV in blood and semen in the 19 studies ranged between 0.07 and 0.64.

But one study found an almost perfect (94%) concordance between viral load in blood and semen. The authors note that this was the most rigorously designed study, with all the men taking potent anti-HIV therapy and none having sexually transmitted infection.

A consistent finding of the study was that viral load was lower in semen than blood. In most of the studies, men who had undetectable virus in their semen also had an undetectable viral load in their blood. But two studies identified individuals who had levels of HIV in their semen that were equal to or greater than in their blood.

Four factors were identified that could potentially influence the relationship between viral load in blood and semen: sexually transmitted infections; anti-HIV therapy and adherence; drug resistance; and the stage of HIV infection.

Infections such as gonorrhoea and chlamydia (which cause inflammation in the urethra) were found to significantly increase levels of HIV in semen. Some studies also suggested that a greater numbers of sex partners and higher rates of sexual intercourse also increased genital shedding of HIV.

Because sexually transmitted infections increase viral load in semen but not in blood, the correlation between viral load in the two is lowered. The investigators stress, "in fact, the studies with the lowest correlations between blood plasma viral load and semen viral load are those that are most likely to have included men with co-occurring sexually transmitted infections."

Most of the studies showed that anti-HIV therapy suppressed viral load in semen. But there was also evidence that some anti-HIV drugs did not penetrate the blood and semen with equal efficiency. But in ideal conditions, when men were taking an effective antiretroviral regimen, were fully adherent to their therapy, and did not have a sexually transmitted infection, then there was a 95% certainty that below 4% of men with an undetectable viral load in their blood would have a detectable viral load in their semen. However, the investigators note, "these optimal conditions are rarely met outside of research settings."

Poor adherence to anti-HIV therapy was associated with detectable HIV in semen in some studies, and another study showed that the men who missed the fewest treatment doses had the greatest degree of HIV suppression in semen over time.

Men who are treated with anti-HIV therapy can develop drug-resistant virus in their semen, and there is evidence of multi-drug resistant strains of HIV developing in the genital tract but not blood. The investigators note, "there is considerable alarm about the potential spread of multiple drug-resistant HIV from men with resistant HIV in their semen who contract a co-occurring sexually transmitted infection…when HIV is poorly controlled, the risk of transmitting treatment-resistant variants is particularly high."

There were conflicting findings about the relationship between CD4 cell count and the level of viral load in semen, but no study found that the presence of symptoms of HIV disease influenced the association between viral load in blood and semen.

The investigators note that there is research evidence that some men (HIV-positive and uninfected) who believe an undetectable viral load means a lower risk of transmission are more likely to have unprotected sex. The investigators are concerned that this could lead to an increase in the number of men who have risky sex, offsetting the "protective benefits of reductions in semen infectivity."

Furthermore, the investigators note that semen that has an undetectable viral load is still potentially infectious, and that cells in semen can contain HIV proviral DNA and can act "as vehicles for sexual transmission of HIV."

They also note that the antiretroviral-treated men most likely to report unprotected sex are those most likely to have poor adherence to antiretroviral therapy. Treatment non-adherence increases viral load and unprotected sex involves a risk of sexually transmitted infections. The investigators are concerned that unprotected sex occurring in the context of poor adherence and sexually transmitted infections could result in the transmission of drug-resistant virus.

The investigators recommend that "HIV prevention messages targeted to both infected and uninfected persons should communicate the importance of condoms and other risk reduction strategies regardless of HIV treatment status and at all stages of HIV disease. Perhaps most crucially, HIV prevention for people living with HIV…must include regular monitoring and aggressive treatment of co-occurring sexually transmitted infections."

Reference

Kalichman SC et al. Human immunodeficiency virus load in blood plasma and semen: review and implications of empirical findings. Sexually Transmitted Diseases 35: 55 – 60, 2008.

By Michael Carter, www.aidsmap.com