A close-up illustration of the Gonorrhea bacteria on a petri dish
Back in October, we told you that Gonorrhea could possibly become untreatable, well, unfortunately, the disease is closer to untreatable than it has been since doctors devised a way to treat it in the first place.
We’re down to just one antibiotic that can effectively fight the disease!
Gonorrhea is a major cause of serious reproductive complications in women and can facilitate human immunodeficiency virus (HIV) transmission. Effective treatment is a cornerstone of U.S. gonorrhea control efforts, but treatment of gonorrhea has been complicated by the ability of Neisseria gonorrhoeae to develop antimicrobial resistance.
In everyday terms, gonorrhea has gradually grown resistant to nearly every antibiotic we’ve created over the past several decades to destroy it. Nowadays, our last stand against the disease is injections of the antibiotic ceftriaxone, which then need to be be followed up with oral doses of either zithromycin or doxycycline. According to a statement from the CDC’s Director of STD Prevention, Dr. Gail Bolan, it is now “only a matter of time” until gonorrhea is resistant to our final, antibiotic regimen. After that, we’ll have nothing to stop it, which is not good news considering that gonorrhoea is a common STI in the UK.
It was diagnosed in over 16,500 people in 2010 and there are likely to be many more people who remain undiagnosed, because up to half of women and one in 10 men have no symptoms of gonorrhoea so don’t seek advice from a doctor.
So, in line with our advice in protecting yourself from contracting HIV, if you’re not using condoms already—(and, really, you should be using condoms if you’re having sex with people) maybe you should start now, there are other dangers out there besides HIV.
More information about gonorrhoea is available from the NHS and Bupa from the following links:
As we prepare to enter our 25th year, we are reflecting on the global HIV events from the last three decades. HIV has swept across the globe touching communities on every continent. Here’s an introduction to some of the key moments in the early global history of HIV. Catch up on the story using the ‘Recent Posts’ link to the right.
We focus on 1994 today, when The Centre for Disease Control (CDC) released 13 hard hitting AIDS advertisements which was a significant move from their more subdue approach. The prevention method was the use of condoms, which were rarely seen or even mentioned on television.
“One of the television ads, entitled Automatic, features a condom making its way from the top drawer of a dresser across the room and into bed with a couple about to make love. The voice-over says, ‘it would be nice if latex condoms were automatics. But since they’re not – using them should be. Simply because a latex condom, used consistently and correctly, will prevent the spread of HIV.’ (Library Reference)
In February, Secretary Shalala announced the eighteen members of the National Task Force on AIDS Drug Development, which includes experts in AIDS drug development issues from academia, industry, medicine, the HIV/AIDS-affected communities, and Government. The Chairman of the Task Force is the Assistant Secretary for Health. The FDA (Food & Drug Administration in America) provides administrative and managerial support for the Task Force.
In March, the actor Tom Hanks won an Oscar for playing a gay man with AIDS in the film Philadelphia.
Philadelphia was was the first big-budget Hollywood film to tackle the medical, political, and social issues of AIDS. Tom Hanks plays Andrew Beckett, a talented lawyer at a stodgy Philadelphia law firm. Andrew had contracted AIDS but fears informing his firm. The firm’s senior partner, Charles Wheeler (Jason Robards), assigns Andrew a case involving their most important client. Andrew begins diligently working on the case, but soon the lesions associated with AIDS are visible on his face.
I won’t tell you more in case you’ve not seen it yet, (spoilers are never nice)! Suffice to say it’s all about prejudice and discrimination in legal setting in the early 90’s. It’s nice to see that laws have since changed but today, 18 years on we still have a long, long way to go in order to stop the ignorance and stigma left behind!
On March 29, The FDA asked condom manufacturers to begin using the air-burst test on all brands of latex condoms. This new test measures a condom’s strength, and may be an indirect indicator of its resistance to breakage during use.
By July 1994 the number of AIDS cases reported to the WHO was 985,119. The WHO estimated that the total number of AIDS cases globally had risen by 60% in the past year from an estimated 2.5 million in July 1993 to 4 million in July 1994.
It was estimated that worldwide there were three men infected for every two women, and that by the year 2000 the number of new infections among women would be equal to that among men.
At the end of July, it was announced that the WHO’s Global programme on AIDS would be replaced. The UN Economic and Social Council approved the establishment of a new “joint and cosponsored UN programme on HIV/AIDS”. The separate AIDS programmes of the UNDP, World Bank, UN Population Fund, UNICEF and UNESCO would have headquarters with the WHO in Geneva. Later in the year it was announced that Dr. Peter Piot, the head of the research and intervention programme within the Global Programme on AIDS, would be the head of the new UN program.
Official statistics for Brazil, with a population of about 154 million, indicated that some 46,000 cases of AIDS had been recorded, but estimates put the actual number at anywhere between 450,000 and 3 million cases. Two thirds of the known cases were in Sao Paulo state where AIDS was the leading cause of death of women aged 20-35.
In early August 1994, the Tenth International Conference on AIDS was held in Yokohama, Japan. It was the first of the International Conferences to be held in Asia. No major breakthroughs emerged, and it was announced that in future the international conference would be held every two years.
An exciting study, ACTG 076, showed that AZT reduced by two thirds the risk of HIV transmission from infected mothers to their babies. It was the most stunning and important result in clinical acquired immunodeficiency syndrome research to date because it was the first indication that mother-to-child transmission of HIV can be at least decreased, if not prevented. And it will provide a real impetus for identifying more HIV-infected women during pregnancies so that they could consider the benefit of AZT treatment for themselves and their children.”
Meanwhile in the Russian Federation, deputies in the Russian Parliament, the Duma, voted at the end of October to adopt a law making HIV tests compulsory for all foreign residents, tourists, businessmen and even members of official delegations.
India by this time had around 1.6 million people living with HIV, up by 60% since 1993 (identical to the global figure). Local and state governments were accused of underusing and misusing HIV prevention funds.
In December, President Clinton asked Joycelyn Elders to resign from the post of US Surgeon General, following a remark during a World AIDS Day conference that children could be taught about masturbation. She was asked whether it would be appropriate to promote masturbation as a means of preventing young people from engaging in riskier forms of sexual activity, and she replied, “I think that it is part of human sexuality, and perhaps it should be taught.”
This remark caused great controversy and resulted in Elders losing the support of the White House. White House chief of staff Leon Panetta remarked, “There have been too many areas where the President does not agree with her views. This is just one too many.”
Elders was fired by President Clinton as a result of the controversy in December 1994.
Perhaps this unfolds unhappy memories if you experienced this discrimination first hand but to our younger audience who may not have lived during these times, it’s important to understand that prejudice, stigma and discrimination remained significant obstacles for sex education, HIV prevention and AIDS awareness throughout the 1990s and into the new millennium.
In closing today, someone recently told me that Tim Radford (A freelance Journalist) wrote a special report “the progress being made in the fight against the cleverest and most malevolent virus scientists have ever seen”. The report also examines issues of stigma, discrimination, and the effect HIV/AIDS has on families. – I’m afraid I can’t link to it, but if anyone has a copy, please get in touch!
There’s no denying the life-extending benefits of antiretroviral therapy. While it has allowed many people living with HIV to plan for their golden years, it has also meant preparing to face age-related health problems. According to the CDC, 25 percent of those living with the virus are over 50 years old. In turn, there’s a growing need for comprehensive care to prevent and manage typical age-related maladies, such as heart disease, cancer, diabetes and osteoporosis—all of which can be complicated by HIV and its treatment.
You can find comprehensive information about treatment options from your GP and the people over at http://www.aidsmeds.com have written an excellent report into HIV & Ageing covering:
What is aging, and why do we become ill as we get older?
How does HIV affect the aging process?
Are people with HIV aging more rapidly?
Is it possible to slow down the aging process?
Are there experimental treatments to slow aging in people with HIV?
The good news is that most HIV-positive people can do quite a lot to slow the aging process and guard against the onset of age-related illness. So why not head over there and understand how aging works in the first place, and what you can do to help yourself..
The Red ribbon is a symbol for solidarity with HIV-positive people and those living with HIV. (Photo credit: Wikipedia)
We are here to to respond to the challenges of HIV, and over the next next few weeks, as we prepare to enter our 25th year, we’d like to take a moment to reflect on the past 25 years as HIV and AIDS have swept across the globe, touching communities on every continent. Here’s an introduction to some of the key moments in the early global history of HIV.
On 5 June 1981, the US Centres for Disease Control (CDC) published a report describing cases of a rare form of pneumonia among five gay men in Los Angeles. Soon after, there are a number of reports of a rare skin cancer, Kaposi’s sarcoma, increase among gay men living in California and New York.
In 1982, the term A.I.D.S. (Acquired Immune Deficiency Syndrome) is used for the first time. Prior to this, it was called G.R.I.D. (Gay Related Immune Deficiency) and was associated with homosexuality because it was first documented among gay men in New York and California. It was only in 1983 we began to get evidence that AIDS is caused by a virus (sic), this emerges from the Pasteur Institute in Paris. The US reports that more than 1,200 Americans have been affected by AIDS and more than one-third of them have died.
The number of cases doubles each six months, it is officially an epidemic and the deadliest since swine fever ravaged the US at the end of the first world war.
In Geneva, the World Health Organisation convenes the first meeting to discuss the international implications of AIDS, which has so far been found in dozens of countries, and has now been found in both women and men.
The Human Immunodeficiency Virus was isolated by scientists in the US and France (though it was not formally named as HIV until 1986). Later, a public controversy erupts over who first discovered HIV, and eventually over who would get the Nobel Prize for it.
Along with the discovery of the virus, the first diagnostic blood test, known as the Elisa test, is developed to screen for HIV infection.
This photo of Ryan White was taken in the spring of 1989 at a fund raising event in Indianapolis, Indiana. (Photo credit: Wikipedia)
Ryan White, a haemophiliac teenager who contracted HIV from contaminated blood products in 1985 is barred from school. He soon becomes one of the most bravest, and well-known advocates for AIDS research and awareness in America.
1985 also marks the year that Hollywood actor Rock Hudson dies of an AIDS related illness. He had recently publicly disclosed his AIDS diagnosis.
The first international Aids conference is held in Atlanta, Georgia and 1986 marks the discovery of a second type of HIV, eventually named HIV-2, it’s discovered by US and French research teams. Jon Parker, a former drug user, starts the first needle-exchange programme in the US to combat HIV among intravenous drug users and The World Health Organisation launches the Global Programme on Aids. The programme will later end and be replaced by UNAids, the UN Aids agency.
Stay tuned over the next few days for more information as we reveal more, of the history of HIV and AIDS.
A once-a-day pill to help prevent HIV infection could significantly reduce the spread of AIDS, but only makes economic sense if used in select, high-risk groups, Stanford University researchers conclude in a new study.
The researchers looked at the cost-effectiveness of the combination drug tenofovir-emtricitabine, which was found in a landmark 2010 trial to reduce an individual’s risk of HIV infection by 44 percent when taken daily. Patients who were particularly faithful about taking the drug reduced their risk to an even greater extent — by 73 percent.
The results generated so much interest that the Stanford researchers decided to see if it would be cost-effective to prescribe the pill daily in large populations, a prevention technique known as pre-exposure prophylaxis, or PrEP. They created an economic model focused on men who have sex with other men, or MSM, as they account for more than half of the estimated 56,000 new infections annually in the United States, according to the Centers for Disease Control and Prevention.
“Promoting PrEP to all men who have sex with men could be prohibitively expensive,” said Jessie Juusola, a PhD candidate in management science and engineering in the School of Engineering and first author of the study. “Adopting it for men who have sex with men at high risk of acquiring HIV, however, is an investment with good value that does not break the bank.”
For instance, using the pill in the general MSM population would cost $495 billion over 20 years, compared to $85 billion when targeted to those at particularly high risk, the researchers found. The study was published in the April 17 issue of the Annals of Internal Medicine.
Senior author Eran Bendavid, MD, assistant professor of medicine in the School of Medicine, said the results are a departure from a previous study, which found PrEP was not cost-effective when compared with other commonly accepted prevention programs. The new Stanford study differs in a few important respects, taking into consideration the decline in transmission rates over time as more individuals take the pill. The Stanford team also assumed individuals would stop taking PrEP after 20 years, not stay on the drug for life, as the previous study had assumed.
The pill combination, marketed under the brand name Truvada, is widely used for treating HIV infection. But it wasn’t until a landmark trial, published in the New England Journal of Medicine in November 2010, that individuals and their doctors began to seriously consider using the drug as a preventive therapy. The drug’s maker, Foster City, Calif.-based Gilead Sciences Inc., has filed a supplemental new drug application to market it for prevention purposes.
The CDC issued interim guidelines on the drug’s use in January 2011, suggesting that if practitioners prescribe it as a preventive measure, they regularly monitor patients for side effects and counsel them about adherence, condom use and other methods to reduce their risk of infection.
In developing their model, the Stanford researchers took into account the cost of the drug — about $26 a day, or almost $10,000 a year — as well as the expenses for physician visits, periodic monitoring of kidney function affected by the drug, and regular testing for HIV and sexually transmitted diseases.
“We’re talking about giving uninfected people a drug that has some toxicities, so it’s crucial to have them monitored regularly,” Bendavid said, who is also an affiliate of Stanford Health Policy, which is part of the Freeman Spogli Institute for International Studies.
Without PrEP, the researchers calculated there would be more than 490,000 new infections among the MSM population in the United States in the next 20 years. If just 20 percent of these men took the pill daily, there would be nearly 63,000 fewer infections.
However, the costs are substantial. Use of the drug by 20 percent of the MSM population would cost $98 billion over 20 years; if every man in this group took PrEP for 20 years, the costs would be a staggering $495 billion.
Given these figures, the researchers looked at the option of giving PrEP only to men who are at high risk — those who have five or more sexual partners in a year. If just 20 percent of these high-risk individuals took the drug, 41,000 new infections would be prevented over 20 years at a cost of about $16.6 billion.
At less than $50,000 per quality-adjusted life year gained (a measure of how long people live and their quality of life), that strategy represents relatively good value, according to Juusola.
“However, even though it provides good value, it is still very expensive,” she said. “In the current health-care climate, PrEP’s costs may become prohibitive, especially given the other competing priorities for HIV resources, such as providing treatment for infected individuals.”
She said the costs could be significantly reduced if the pill is found to be effective when used intermittently, rather than on a daily basis. Current trials are examining the effectiveness of the drug when used less often.
Other co-authors are Margaret Brandeau, PhD, the Coleman F. Fung Professor
of Engineering, and Douglas Owens, MD, MS, the Henry J. Kaiser, Jr. Professor at Stanford and senior investigator at the Veterans Affairs Palo Alto Health Care System. Owens also is director of Stanford’s Center for Health Policy/Primary Care and Outcomes Research.
The study was funded by the National Institutes of Health and the Department of Veterans Affairs.
A pilot study in 14 European countries, in which groups of patients presenting with one of eight conditions strongly associated with HIV were routinely tested for HIV in various medical settings, found an HIV prevalence rate of 1.8%. This is far in excess of national rates and of the 0.1% prevalence rate suggested by the US Centres for Disease Control for routine HIV testing of the population, and suggests targeting people with these so-called indicator conditions (ICs) for HIV testing could be an efficient way of detecting infection.
The study found relatively high CD4 counts and a high prevalence in patients presenting with mononucleosis-like illness. These symptoms are usually caused by Epstein-Barr virus but may also be due to HIV seroconversion. This suggests that testing for indicator conditions might be a good way of detecting more people in early HIV infection.
The HIDES I study arose from the HIV in Europe conference in 2007, which debated how to improve HIV testing rates and reduce the amount of undiagnosed HIV in the region.
One method suggested was to draw up a list of indicator conditions (ICs) associated with HIV probability of HIV infection and recommend that people presenting of these should be routinely tested.
HIDES I drew up a shortlist of eight ICs and sent out a call to healthcare centres in Europe to participate in the study to test the feasibility and acceptability of routine IC-driven HIV testing.. This would involve them routinely test all patients consecutively presenting with a specific IC.
The eight conditions chosen were:
Acute STIs
Hepatitis B or C
Malignant lymphoma of any type
Anal or cervical intraepithelial neoplasia (HPV disease) grade 2 or above
Unexplained low platelets (thrombocytopenia) or neutrophils (neutropenia) for more than four weeks
Herpes zoster (shingles) in people under 65
Seborrhoeic dermatitis or exanthema (sudden rash)
Mononucleosis-like illness.
Results: demographics
Seventeen centres in 14 European countries spread over the whole continent from UK to Ukraine participated in HIDES I. They conducted 39 separate surveys on HIV testing in patients presenting with ICs between September 2009 and February 2011. There were one to six surveys conducted in each centre and between three to six surveys conducted for each indicator condition.
Altogether, 3588 patients were tested for HIV. They had an average age of 36, which varied according to condition from 24 for mononucleosis to 53 for lymphoma. Fifty-five per cent were men and a quite high proportion (36%) had had a previous HIV test.
Sex, age, sexuality and previous testing rates varied by European region. Patients were youngest (average 33) in northern Europe (UK, Netherlands, Denmark, Sweden) and oldest (43) in southern Europe (Italy and Spain). Roughly two-thirds were male in all European regions apart from northern Europe, where 44% were male.
Only two per cent of patients in eastern Europe (Belarus, Ukraine, Bosnia, Croatia, Poland) said they were gay compared with approximately 40% in south and west central Europe (Germany, Austria, Belgium) and 45% in northern Europe; and only 13% in eastern Europe had had a previous HIV test compared with 36% in southern, 45% in west central, and 60% in northern Europe.
Results: HIV diagnoses
There were 66 new HIV diagnoses (1.8% of patients). Eighty-three per cent of those diagnosed were male, 58% of them were gay, 42% heterosexual and 9% had injected drugs. The prevalence of newly-diagnosed HIV varied widely from 0.6% in northern Europe to 6.5% in southern.
It also varied widely per IC. Not unexpectedly the highest HIV diagnosis rate was in surveys involving STIs (4%) but it was not much lower in mononucleosis-like illness (3.8%), neutro/thrombocytopenia (3.2%), shingles (2.9%) and dermatitis/rash (2.1%).
In contrast HIV prevalence was only 0.4% in cervical/anal dysplasia and hepatitis B/C and 0.3% in lymphoma, possibly because the individuals with these diseases who have HIV are more likely to have already been diagnosed. These rates are still above the 0.1% rate considered cost-effective for routine testing, though.
Over the whole group, more than half of those diagnosed with HIV(52%) had been tested for it before, with a median time from their previous HIV test of 19 months. Their average CD4 count was 400. This may indicate that offering an HIV test as standard when ICs are diagnosed may detect more cases of early HIV infection, though presenter Ann Sullivan of London’s Chelsea and Westminster Hospital did not split this analysis into European regions. It is possible that the relatively high amount of recent infections may be driven by tests given to people presenting with STIs who might have tested anyway.
HIDES 1 found that 20% of patients had presented to healthcare with one of the ICs in the preceding five years and 4.6% had presented more than once.
Next steps
The HIDES project now intends to conduct a larger HIDES 2 study involving 12 indicator conditions, in order to establish better HIV prevalence figures for each. It also intends to conduct a separate audit of whether patients in Europe who present with ICs are offered HIV tests. Finally they intend to develop, in collaboration with the European Centre for Disease Control and the World Health Organization, a set of guidelines for HIV testing targeted at indicator conditions.
HIDES investigator Jens Lundgren commented from the audience that although HIDES 1 was a pilot study, its results were important because many physicians had been sceptical that using ICs to guide HIV testing would find higher than average rates of HIV or be cost-effective. These results showed that it was an efficient way to find undiagnosed HIV.
Lab tests on gonorrhoea bacteria samples taken in 2010 showed that 17.4% had a reduced susceptibility to cefixime, up from 10.6% the year before.
The first cases of bacteria with reduced susceptibility to the antibiotic were noted in 2006. Doctors treating gonorrhoea patients are now advised to no longer use cefixime as their first choice.
Rather, they are recommended to use a mix of two drugs: ceftriaxone, an antibiotic which is injected, and azithromycin, which can be taken orally.
Prof Cathy Ison
Professor Cathy Ison, a gonorrhoea expert at the HPA, said: “Our lab tests have shown a dramatic reduction in the sensitivity of the drug we were using as the main treatment for gonorrhoea. This presents the very real threat of untreatable gonorrhoea in the future.
“We were so worried by the results we were seeing that we recommended that guidelines on the treatment of gonorrhoea were revised in May this year, to recommend a more effective drug.
“But this won’t solve the problem, as history tells us that resistance to this therapy will develop too. In the absence of any new alternative treatments for when this happens, we will face a situation where gonorrhoea cannot be cured.”
“Many patients may feel anxious about having an injection, but this is now the best way of avoiding treatment failure. Patients who refuse the jab will be offered oral antibiotics instead”.
“This highlights the importance of practising safe sex, as, if new antibiotic treatments can’t be found, this will be only way of controlling this infection in the future.”
PrEP is short for PreExposure Prophylaxis and may be part of comprehensive HIV prevention services in which HIV negative people who are at high risk, take antiretroviral medication daily to try to lower their chances of becoming infected with HIV if they are exposed to it.
To date, PrEP has been shown to be effective in men who have sex with men (MSM) and heterosexual men and women.
The effectiveness of biomedical approaches to prevent HIV infection was a key theme of the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011), held July 17-20, 2011, in Rome.
Among the major studies presented, Robert Grant from the Gladstone Institute of the University of California at San Francisco described final data from the iPrEx trial, which showed that pre-exposure prophylaxis (PrEP) using tenofovir/emtricitabine (Truvada) reduced new HIV infections by 42% overall, and by more than 90% among people who demonstrated good adherence.
The US Centers for Disease Control and Prevention (CDC) has recommended testing patients for HIV before they begin taking the drugs and again at two- to three-month intervals. The FDA could also require drug companies to set up a registry of patients taking the drugs and ask that patients provide proof of a negative HIV test before getting their medications refilled.
Deciding who to treat with PrEP could also be a challenge. The CDC reported on 3 August that rates of new HIV infection in the United States are stable overall, but are rising in young men who have sex with men. Yet if these men aren’t using the prevention measures already available, there’s little reason to think doctors will have an easier time convincing them to take a daily pill.
The question of who should get PrEP is more difficult in many developing nations, which cannot even afford to treat everyone currently infected with HIV. PrEP would cost hundreds of dollars per patient per year in developing countries, and many thousands of dollars in rich nations.
Even with regimens costing less than £1 per day, developing nations will be forced to choose between providing more treatment for those who already need it and potentially preventing new infections. Myron Cohen, a doctor and researcher at the University of North Carolina at Chapel Hill, points out that half of young girls in some parts of sub-Saharan Africa become infected with HIV by their mid-twenties. “That’s unacceptable, so I see that as one potential population for PrEP,” says Cohen.
Although the cost-effectiveness of PrEP increases in higher-risk populations, it will be politically dicey for financially strapped countries to justify distributing drugs to those in these groups. “Even if you thought the best use of the pills would be for sex workers, it would be very difficult to take a limited supply of pills and give them to high-risk populations at the expense of people who are dying of infection,” says Cohen.
In the past year, three landmark clinical trials have shown that a daily dose of the antiretroviral medication Truvada can protect individuals from infection with H.I.V.— a significant discovery, given the failure so far of all efforts to develop a vaccine against the virus.
Now researchers in San Francisco and Miami are planning to test this prevention strategy, called pre-exposure prophylaxis, or PrEP, in a pilot study supported by the National Institutes of Health. The researchers will soon recruit up to 500 uninfected men who have sex with men, especially those considered to be at greatest risk of infection, such as younger gay men and, in particular, African-Americans.
The men will be asked to take Truvada daily, and the researchers will monitor their compliance with the regimen, their sexual behavior and their health status. Already, though, the prospect of antiretroviral drugs’ being used for prevention as well as treatment is raising complex questions for researchers and advocates.
Will healthy uninfected people consistently take an expensive and powerful drug that can cause a range of side effects? Is it fair to provide medications to H.I.V.-negative individuals when so many of those already infected do not have access? Will those receiving the drug be more likely to engage in risky sex because they believe they are protected — even if they do not always take it as prescribed?
The issues are more than academic: According to anecdotal reports, some doctors are already prescribing the medications to some H.I.V.-negative patients, said Dr. Kenneth Mayer, a chairman of the Fenway Institute, a research and advocacy center for gay, lesbian, bisexual and transgender health in Boston, who has been involved in research into PrEP.
“I think that’s going to increase, but it’s very incremental,” said Dr. Mayer, who believes PrEP is an important new weapon in the H.I.V. prevention arsenal. “People have a lot of questions.”
AIDS advocates have generally expressed optimism that the strategy, if applied carefully, could help reduce the approximately 50,000 new H.I.V. infections that occur annually in the United States. But one major provider of services to people with H.I.V., the AIDS Healthcare Foundation in Los Angeles, has initiated a media and ad campaign raising serious concerns.
The foundation’s president, Michael Weinstein, noted that participants in the first round of PrEP research were counseled extensively that not following the protocol could reduce any protective effect, and yet many still failed to take their pills as prescribed. Adherence to the regimen is likely to be even worse under real-world conditions, he said.
“We deal with tens of thousands of patients here who are positive, and a high percentage of them have adherence issues,” said Mr. Weinstein. “So the idea that young gay men who don’t have this disease are going to take this routinely is highly questionable.”
Mr. Weinstein is particularly concerned that the Food and Drug Administration could soon approve Truvada for use in H.I.V. prevention as well as treatment, which would undoubtedly lead to greater use of the drug. Gilead Sciences, the company that makes the drug, has said it is likely to file such an application with the F.D.A. early next year.
Once the F.D.A. approves a drug for any use, doctors can legally prescribe it “off-label” for other purposes. Drug companies, however, are allowed to promote their products only for indications specifically approved by the agency.
In one of the three earlier clinical trials, among men who have sex with men, PrEP reduced new infections by 44 percent over all. Among men who adhered closely to the prescribed daily regimen, however, protection against infection was greater than 90 percent.
Some researchers worry that sexually active individuals who only sporadically adhere to the PrEP regimen may not realize that they are still at risk for infection; at the same time, feeling “protected,” they may be less vigilant about practicing safe sex and getting regular H.I.V. testing.
And inconsistent use of medications among those who do not realize they are infected could encourage new drug-resistant forms of H.I.V., some experts fear.
Dr. Grant Colfax, director of H.I.V. prevention and research at the San Francisco Department of Public Health, said he hopes that the new research will yield important information about how best to use the emerging strategy.
“The question is, will people be able to maintain the regimen?” said Dr. Colfax, whose agency is a major partner in the study. “What are the risks and benefits outside of a randomized clinical trial? Will they want to take the pill, will there be changes in their risky behavior, will they come back to get H.I.V. testing on a quarterly basis?”
Dr. Howard Jaffe, chairman and president of the Gilead Foundation, acknowledged that adherence was a problem in earlier studies. But he said that participants in the upcoming research, unlike those in the trials, will all know that they are receiving the actual drug, not a placebo, and that the drug can prevent H.I.V. infection if taken as directed. That critical new information, he said, could help motivate them to stick to the prescribed regimen.
The three recent PrEP trials focused on different populations: heterosexual couples in East Africa in which one person was H.I.V.-positive and the other was not; sexually active young adults in Botswana; and men who have sex with men in the United States and five other countries. (A fourth trial, among African women, was stopped early because PrEP was not found to be working.)
The trial involving the East African couples reported that the infection rate was 73 percent lower in the group taking Truvada; among the group in Botswana, there was a 63-percent drop.
“Now that it’s been proven to be effective, the discussion is a much different discussion than when you’re enrolling people for a placebo-controlled trial,” Dr. Jaffe of the Gilead Foundation said.
Truvada combines two antiretroviral drugs, Viread and Emtriva, both also made by Gilead. Besides the upcoming study in the United States, results from additional research into the use of Truvada as H.I.V. prevention are expected over the next few years.
The drug currently costs thousands of dollars a year. A recent editorial in the medical journal Lancet Infectious Diseases raised ethical concerns about the new approach, noting that many people with H.I.V. do not have access to the lifesaving medications.
“How can these drugs be provided as prevention to those high-risk populations, while people with the disease in need of treatment continue to go without?” said the editorial.
In response, proponents of PrEP say that it would be unethical not to explore the new approach, given its potential to reduce infection rates, especially among vulnerable populations whose members have often found it difficult to consistently practice safe sex.
Earlier this month, we posted a video containing data from the iPrEx trial from the IAS 2011 conference stating that tenofovir/emtricitabine (Truvada) reduced new HIV infections by 42% overall, and by more than 90% among people who demonstrated good adherence.
When the US Food and Drug Administration approved Viagra in 1998, officials never considered one possible side effect of the drug: higher rates of sexually transmitted diseases among men who, thanks to Viagra, would become more sexually active. A powerful tool in the fight against HIV is raising similar questions about the possibility of unintended public-health consequences if drugs are approved for use in healthy people and cause them to alter their behaviour.
Several studies in the past year have reported that the very drugs used to treat people with HIV can also stop healthy people from becoming infected (see table below).
People taking the drugs may adopt riskier behaviours because they feel protected — a phenomenon known as ‘risk disinhibition’ — undermining the benefit of the drugs and potentially infecting others. Moreover, those who become infected while taking the preventive regimen might develop drug-resistant viruses that they could then transmit to others. “You have this wonderful scientific breakthrough,” says Kevin Frost, chief executive of the Foundation for AIDS Research in New York City. “But what are the practical implications?”
Researchers will mull over these issues today at a meeting convened by the Forum for Collaborative HIV Research in Washington DC. The questions have become more urgent since January, when the drug firm Gilead of Foster City, California, announced that it plans this year to ask the Food and Drug Administration (FDA) to approve its HIV drug Truvada for use in healthy people — in what is known as pre-exposure prophylaxis, or PrEP. Truvada, which contains the antiretroviral drugs tenofovir and emtricitabine, has been used in many of the PrEP trials. In the three clinical trials that have reported benefits for PrEP so far, once-a-day pills have cut a person’s risk of acquiring HIV by between 44% and 73%, a variation that is due primarily to differences in how strictly patients stuck to the daily regimen.
Asking the FDA to evaluate questions about risk disinhibition and drug resistance might push the agency into uncharted territory. “When you’re talking about a population issue, is that something that the FDA should be looking at at all?” asks Jur Strobos, deputy director of the Forum for Collaborative HIV Research.
The clinical trials don’t offer clear guidance. Some of the successful trials found that people on PrEP actually used condoms more frequently while receiving PrEP treatment, countering the risk-disinhibition argument. And only a few instances of drug resistance occurred, and these did not compromise patients’ treatments.
But the controlled setting of a clinical trial, in which participants received intensive prevention counselling and were tested monthly for HIV, is very different from the real world. “We think of PrEP as a pill, but we all recognize that PrEP is about a much broader programme,” says Mitchell Warren, director of the AIDS Vaccine Advocacy Coalition in New York City. “How you would deliver the kind of testing and monitoring that would go into that programme is a very important question.”
The US Centers for Disease Control and Prevention (CDC) has recommended testing patients for HIV before they begin taking the drugs and again at two- to three-month intervals. The FDA could also require drug companies to set up a registry of patients taking the drugs and ask that patients provide proof of a negative HIV test before getting their medications refilled.
Deciding who to treat with PrEP could also be a challenge. The CDC reported on 3 August that rates of new HIV infection in the United States are stable overall, but are rising in young men who have sex with men. Yet if these men aren’t using the prevention measures already available, there’s little reason to think doctors will have an easier time convincing them to take a daily pill.
The question of who should get PrEP is more difficult in many developing nations, which cannot even afford to treat everyone currently infected with HIV. PrEP would cost hundreds of dollars per patient per year in developing countries, and many thousands of dollars in rich nations.
Even with regimens costing less than £1 per day, developing nations will be forced to choose between providing more treatment for those who already need it and potentially preventing new infections. Myron Cohen, a doctor and researcher at the University of North Carolina at Chapel Hill, points out that half of young girls in some parts of sub-Saharan Africa become infected with HIV by their mid-twenties. “That’s unacceptable, so I see that as one potential population for PrEP,” says Cohen.
Although the cost-effectiveness of PrEP increases in higher-risk populations, it will be politically dicey for financially strapped countries to justify distributing drugs to those in these groups. “Even if you thought the best use of the pills would be for sex workers, it would be very difficult to take a limited supply of pills and give them to high-risk populations at the expense of people who are dying of infection,” says Cohen.
The review of a major national population HIV study has found that the HIV infection rate among low-income heterosexuals in 24 American cities with a high prevalence of AIDS is 10 to 20 times greater than in the general U.S. population.
The link between high HIV rates and low socio-economic status couldn’t be attributed to factors typically associated with HIV infection risk in heterosexuals such as crack cocaine use, being diagnosed with a sexually transmitted disease, or having an exchange sex partner.
While major racial disparities are a feature of the HIV/AIDS epidemic in the United States, the researchers found no racial/ethnic-related differences in HIV infection rates among low-income heterosexuals in cities either.
The U.S. Centers for Disease Control and Prevention surveys persons in selected metropolitan statistical areas (MSAs), using the National HIV Behavioral Surveillance System (NHBS). This report summarizes data collected from heterosexuals in 24 MSAs with a high prevalence of acquired immunodeficiency syndrome (AIDS) that participated in NHBS during 2006 and 2007.
NHBS is an annual cross-sectional survey of three populations at high risk for HIV infection: men who have sex with men (MSM), injection-drug users (IDUs), and heterosexuals at increased risk for HIV infection. Data are collected in annual cycles from one risk group per year, with each population surveyed once every 3 years.
Twenty-five MSAs with high AIDS prevalence were selected for the survey. In each MSA, NHBS project staff members recruited participants using either respondent-driven sampling (15 MSAs) or venue-based sampling (10 MSAs).
Recruitment efforts targeted residents of census tracts with high rates of poverty and HIV diagnoses, referred to as high-risk areas. For respondent-driven sampling, a small number of initial participants were recruited by project staff members or referred by community-based organizations. Initial and subsequent participants who lived in high-risk areas were then asked to recruit up to five other persons using a coded coupon to track their referrals. Recruitment continued for multiple waves of peer referral.
In summary, of 14,837 heterosexuals aged 18 to 50 years who were interviewed and tested, 2% were HIV infected. HIV prevalence was higher among those with lower socioeconomic status (SES). For example, HIV prevalence was 2.8% among participants with less than a high school education compared with 1.2% among those with more than a high school education, 2.6% among participants who were unemployed compared with 1.0% among those who were employed, and 2.3% among participants with annual household incomes at or below the poverty level compared with 1% among those with incomes above the poverty level.
As mentioned above, this association between HIV prevalence and SES could not be attributed to factors commonly associated with HIV infection risk in heterosexuals, such as using crack cocaine, exchanging sex for things such as money or drugs, or being diagnosed with a sexually transmitted disease (STD). Based on the association observed between HIV prevalence and SES, HIV prevention activities targeted at heterosexuals in urban areas with high AIDS prevalence should be focused on those with lower SES.
Based on their findings, the CDC authors recommended that HIV prevention programs aimed at heterosexuals should focus on those in low-income areas.
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