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Past Issues
Volume 21, numbers 1
January – March 2007
The End of Nandrolone
Critical wasting treatment dropped
The International Narcotics Control Board and HIV/AIDS
Secretive body undermines harm reduction and human rights
Money, Moralism, and Microbicides: Barriers in Microbicides Development
An opportunity to step up research and development
A Rare Moment in Time
A potential "revolution" on its way to pharmacy shelves for HIV-positive people who have developed a resistance to most available drugs
The End of Nandrolone
Nelson Vergel, Program for Wellness Restoration
The current terrain for wasting patients in the era of HAART
On March 20, 2007, Watson Laboratories stopped the production of nandrolone decanoate (old brand name: Deca Durabolin), a low-cost injectable anabolic steroid used for HIV wasting, citing the lack of raw-material suppliers for the product. Patients found out when they went to their pharmacies for a prescription a week later.
Although there are other makers of generic nandrolone internationally (easily located on the Internet), this offers little help to U.S. patients. Anabolic steroids and testosterone are designated by the Drug Enforcement Administration (DEA) of the U.S. Department of Justice as Class III drugs, which are illegal to import even for personal and medical uses.
Over the past 20 years, anabolic steroids have suffered from a lot of bad publicity and misconceptions due to their use in sports and bodybuilding. However, that did not stop activists in the 1990s from convincing doctors and researchers to look into these medicines to help those with HIV-related wasting syndrome. Since then, more than eight studies have been performed that showed nandrolone and oxandrolone (brand name Oxandrin, an oral anabolic steroid) to be effective and safe for increasing lean body mass (LBM) and strength in men and women with HIV. Many physicians quickly learned how to prescribe them and monitor their use for helping their HIV-positive patients to survive what used to be one of the main causes of AIDS mortality.
While Watson was abandoning nandrolone, another company was making a decision that would also limit options for HIV wasting patients. Savient Pharmaceuticals informed patients in April 2007 that it had stopped its 10-year-old patient assistance program (PAP) that gave free Oxandrin (oxandrolone) to HIV patients with no insurance or third-party payment sources. Oxandrin has been shown to be mildly effective in men, women, and children with HIV wasting. It can be taken by mouth daily, while nandrolone must be injected in the butt once a week. Whereas Oxandrin has been approved for the treatment of unintentional weight loss, nandrolone's use for HIV wasting was off-label (it was approved for the treatment of anemia in individuals with kidney problems). However, Oxandrin costs $1,300 a month for a 20 mg/day regimen, compared to around $200 a month for 200 mg/week for nandrolone.
Savient's PAP was set up by BTG Pharmaceuticals (bought out by Savient later on) in 1996 after activists pressured the company to provide the drug for free to those with no access or means. As with nandrolone, only 13 states include Oxandrin in their AIDS Drug Assistance Programs (ADAPs). The termination of Savient's PAP means many patients will have no way to afford this drug. The company informed patients that Watson would sell generic Oxandrin, thus eliminating the need for its PAP. Unfortunately, the generic price for Oxandrin sold by Watson is no different than that for the brand-name product, which will continue to be sold by Savient. Watson will not provide free Oxandrin via a PAP either. This is the first time in AIDS history that a company has stopped a PAP while still selling the drug.
Cost is not the only consideration. Unlike nandrolone, Oxadrin can increase liver enzymes and could be problematic for people with liver disease, or for people taking medications that heavily affect the liver, such as the HIV medication Reyataz, and drugs for those with hepatitis B and C. "The decisions of these two companies have a huge impact on many of my patients' health," says Dr. Richard Loftus, a San Francisco physician with a large HIV practice. "We use nandrolone extensively in patients who have problems gaining weight and who feel fatigued, even with undetectable viral loads. Many of my patients feel better and have experienced no side effects at the doses we use."
In the 1980s researcher Dr. Donald Kotler found that the loss of lean body mass can dramatically decrease survival in HIV-positive people.1 Even though the incidence of wasting syndrome has declined dramatically since protease inhibitors were introduced 10 years ago, many people still need extra help to hang on to their muscle to sustain health and productivity. A study performed at Tufts University School of Medicine reported that as many as 29% of people with HIV in the era of HAART are still losing weight or lean body mass, despite undetectable viral loads.2
Dr. Nathan Sherlock knows first hand about the importance of nandrolone for his health and that of his partner:
My partner has had a significant problem with wasting due to AIDS and the only way he has been able to stop the dangerous weight loss is to use anabolic steroids. He is also hepatitis B positive. His doctor first prescribed Oxandrin in 1998. Within a couple of weeks he had chemical induced hepatitis with the symptoms of nausea, vomiting, loss of appetite and jaundice. His liver enzymes were all elevated. He stopped Oxandrin and the symptoms promptly resolved. His doctor then prescribed nandrolone 200mg/week and he regained weight back to his norm with no side effects. When he stops taking it the wasting returns so he has been on nandrolone for close to 9 years now...I have been taking nandrolone for wasting due to AIDS for over 10 years. Every time I have stopped taking nandrolone I experience rapid weight loss that can only be reversed by resuming the use of nandrolone.
Al Benson, an HIV treatment advocate in Los Angeles concurs. "Nandrolone is truly 'the Lazarus drug'... it has brought me back from the brink, restored my health and made all the difference in the quality of my life."
Other HIV Wasting drugs
The Food and Drug Administration (FDA) has approved other drugs for the treatment of HIV wasting or appetite loss. Megace (megestrol acetate), a female sex hormone-based product, tends to produce weight gain by increasing fat rather than lean body mass. Adding fat during AIDS wasting has not been shown to improve survival. Megace has also been associated with side effects such as diabetes, blood clots, impotence, and the development of female sex characteristics.
Serostim, a recombinant human growth hormone, requires daily injections and can cause joint aches, swelling, and diabetes. It can cost as much as $6,000 a month, so most insurance companies do not want to pay for it and many ADAPs can't. The kickback scandal Serostim's manufacturer was involved in hasn't helped matters either. FDA-approved appetite stimulants such as Marinol contain THC, the psychoactive ingredient in marijuana. This can be an issue for many people with HIV who are in recovery. It has also been suggested that Marinol may simply owe its ability to increase appetite and weight to a side effect of the THC high — "the munchies."
Compounding Pharmacies:
a Viable Option at Risk?
Many doctors and patients do not know that nandrolone and oxandrolone can also be obtained in smaller quantities legally by prescription and at a lower cost through compounding pharmacies (where drugs are not only dispensed but can be prepared according to a doctor's specifications). No one knows how much longer this option will remain available. One pharmacy owner reports that the DEA has raided several compounding pharmacies in the past few months, including his own. The Safe Compounding Drug Act of 2007, now under consideration, would place these sites under greater regulation and presumably greater surveillance. In the meantime, compounding pharmacies such as Applied Pharmacy, Kronos, the Compounding Shop, College Pharmacy, and others are still economical sources of nandrolone, oxandrolone, and testosterone gels and injections. However, they do not process insurance claims and are not equipped to supply ADAPs, insurance, Medicaid, or Medicare Part D vendors.
In this era when HIV/AIDS patients are living longer, it is just as critical to fight for safe, effective, and affordable "quality of life" drugs as it to advocate for accessible antiretrovirals. After all we have done as activists to secure antiwasting medications, we must not lose ground now and fall asleep when vital treatments such as nandrolone are dropped without notice and with little regard for patients' needs.
For more information or to find out how to get involved, please visit.
- Kotler DP, Tierney AR, Wang J, Pierson RN Jr., "Magnitude of body-cell-mass depletion and the timing of death from wasting in AIDS," Am J Clin Nutr. 1989 Sep; 50(3):444-7. "The impact of malnutrition on survival in AIDS was evaluated by examining the magnitude of body-cell-mass depletion as a function of time from death. Body cell mass was estimated as total body-potassium content and determined by whole-body counting. There was progressive depletion of body cell mass as patients neared death. The extrapolated and observed values for body cell mass at death were 54% of normal. Body weight had a similar relationship to death, with a projected body weight at death of 66% of ideal. We conclude that death from wasting in AIDS is related to the magnitude of tissue depletion and is independent of the underlying cause of wasting. The degree of wasting seen in this study is similar to historical reports of semistarvation, with or without associated infections. This observation suggests that successful attempts to maintain body mass could prolong survival in patients with AIDS."
- Mangili A, Murman DH, Zampini AM, Wanke CA, "Nutrition and HIV infection: review of weight loss and wasting in the era of highly active antiretroviral therapy from the nutrition for healthy living cohort,"
Clin Infect Dis. 2006 Mar 15;42(6):836-42. Epub 2006 Feb 7.
The International Narcotics Control Board and HIV/AIDS
Joanne Csete and Daniel Wolfe
Policies and programs to address the use of illicit drugs at both the national and the international level are fundamental to the success of government responses to HIV/AIDS. In countries where HIV transmission among people who inject drugs is very low, that outcome is usually the result of policies and programs that ensure ready access to sterile syringes (including in prisons in some countries); accessible and affordable opiate substitution therapy for people who inject heroin; and, in some cases, measures such as supervised injection facilities and decriminalization of syringe possession.
In contrast, in countries such as Russia where methadone therapy is illegal, needle exchanges are few, and people who use drugs have been subjected to arrest and imprisonment for the residue in used syringes, HIV/AIDS thrives. In the U.S., where there is a ban on federal funding of needle exchange, serious impediments to opiate substitution, and harsh drug laws that make it difficult to draw drug users into public health services, some 15% to 20% of new HIV transmissions and reported AIDS cases are linked to drug injection.1 Worldwide, about 30% of HIV transmission outside sub-Saharan Africa is linked to injection drug use. For many countries, this is the most difficult aspect of HIV/AIDS to address.
National drug policy is often caught up in the politics of the moment and politicians get considerable mileage by being "tough on crime" and "tough on drugs."
Many countries experiencing new and explosive HIV epidemics among drug users, often occurring at the same time as major economic or political transitions, look to the United Nations for guidance on how to respond both to drug use and HIV. International leadership, therefore, is critical and should reflect the lessons of effective public health — and not just law enforcement — responses to HIV/AIDS among drug users from over 20 years of accumulated experience and evidence. U.N. General Assembly resolutions2 and other U.N. documents have emphasized the importance of access to sterile injecting equipment and medications as methadone and buprenorphine for treatment of opiate addiction, and U.N. technical bodies have supported those resolutions with guidelines and reviews of programmatic evidence. The U.N. Office on Drugs and Crime has affirmed the importance of these strategies as part of a broader effort aimed at drug treatment and demand reduction.
One part of the U.N. machinery on illicit drugs, however, is out of step with these General Assembly resolutions and technical guidelines. The International Narcotics Control Board (INCB) is a 13-member self-described "quasi-judicial" body of experts whose work is paid for by the U.N. Its current members come mostly from the fields of psychiatry, pharmacology, psychopharmacology, forensic medicine, and toxicology. According to their published biographies, none of the current members have formal training in international law, and only one claims any formal expertise or experience on HIV/AIDS. A search of peer-reviewed medical, law, and public policy journals shows no contributions by any current member of the board on HIV/AIDS. Indeed, the board has become an obstacle to the establishment and implementation of effective programs to prevent and treat HIV and drug dependence.
INCB's Resistance to Harm Reduction
The INCB is responsible for monitoring countries' compliance with the U.N. drug conventions. The three drug conventions, developed 1961, 1971, and 1988, mostly predate the identification of AIDS as a disease or the explosive drug use–linked AIDS epidemics of the 1990s. The conventions encourage countries to criminalize the manufacture, sale, possession, and use of illicit drugs and do everything possible to limit the use of illicit drugs "exclusively to medical and scientific purposes." They also urge governments to ensure "treatment, education, after-care rehabilitation, and social reintegration" of people who use drugs and provide that treatment for drug dependence may be an alternative to criminal penalties in some cases.3 The INCB's duties include monitoring countries' estimates of their needs for illicit substances for "medical and scientific purposes" — such as methadone for treatment of heroin addiction — and ensuring that controlled substances are not diverted to illegitimate uses. The board makes about 20 country visits per year, issues an annual report where country-level developments are reviewed, and sends many letters to governments guiding or pressuring them into actions the board deems to be consistent with the drug conventions.
In theory, the INCB should therefore play a major role in ensuring that methadone and buprenorphine are available for opiate substitution therapy (OST). OST is a crucial part of national HIV/AIDS responses where opiate dependence is prevalent — not only because it provides an opportunity for people who inject heroin to stabilize their opiate cravings with opiates that are not injected, but also because OST is a determinant of success in antiretroviral treatment for people living with HIV. Instead, INCB reports regularly note the importance of drug injection in driving the AIDS epidemic but fail to take the next logical step and urge countries to ensure OST availability.
The INCB's failure to push countries to act on the heightened urgency of OST in the era of AIDS is especially egregious in other countries where methadone is banned (such as Russia) or effectively unavailable (as it is in many countries of the former Soviet Union). The board visited Russia in 2005 and noted with concern the country's fast-growing AIDS epidemic linked to heroin use. But rather than pressuring the Russian authorities to reverse their lethal ban on methadone, the INCB highlighted "the commitment of the government of the Russian Federation to addressing the problems of drug abuse and trafficking."4
The INCB's credibility and competence on the issue of OST were further undermined in 2005 when Russian board member Tatyana Dmitrieva — identifying herself as a member of the INCB — co-authored an article in a widely read Russian medical journal in which methadone therapy was condemned with numerous half-truths and inaccuracies.5 Addiction care specialists and scientists from twelve countries issued a heavily referenced, point-by-point refutation of the Russian article, correcting the multiple errors.6 Despite the use of its name in the article, the INCB has not published a correction. This incident calls into question the board's frequent assertions that its members are independent of the influences of their governments and are persons whose expertise in the field inspires confidence.
The INCB's sad record on OST is nearly matched by its views in other areas of HIV prevention for people who use drugs. Although officially the board has recognized that governments are within their rights to ensure that sterile syringes are available to limit needle-sharing among people who use drugs, board president Philip Emafo suggested in a 2002 U.N. publication that "to promote drug use illicitly through the giving out of needles...would, to me, amount to inciting people to abuse drugs, which would be contrary to the provision of the conventions."7 Statements such as this, coming from an individual in a position of authority to whom countries turn for guidance on drug control carry considerable weight and have the potential to be extremely harmful. Although the board's report the following year recognized that needle exchange did not contravene the conventions, neither this nor subsequent INCB reports have raised concerns about countries where people who inject drugs have inadequate access to syringes, or about the many countries where police target syringe exchange sites to arrest or harass people who use drugs. This is supported in name only, with no leadership to back it up.
The INCB has repeatedly said that supervised injection facilities (SIFs), like the one in Vancouver, Canada and the many in Europe, which allow people to inject their own drugs under medical supervision, are in violation of the U.N. drug conventions. The board clings to this view even though the legal office of the U.N. Drug Control Program has stated that SIFs do not "aid, abet, or facilitate the possession of drugs" and are consistent with the drug conventions in that they "provide healthier conditions for IV drug abusers" and "[reach] out to them with counseling and other therapeutic options." Ignoring this advice from the U.N., the INCB makes it a habit every year to berate countries that run SIFs as violators of the drug conventions.
The INCB took its campaign against SIFs to new heights in 2006 when it confronted the then-U.N. special envoy for HIV/AIDS in Africa, Stephen Lewis of Canada. Lewis had visited the SIF in Vancouver and made a speech praising its services and encouraging the Canadian government to allow other such centers to open across the country. The INCB wrote to Lewis's boss, former U.N. secretary-general Kofi Annan, demanding that Lewis retract his positive statements about the SIF because they supported a practice that the board has judged to be prohibited by the drug conventions. While the INCB is in many ways out of step with the harm-reduction and HIV/AIDS policies and programs of other U.N. agencies, in this case the board went so far as to silence another U.N. actor. Speaking out later about this incident, Stephen Lewis noted that INCB secretary Koli Kouame, who called him before sending the letter to Annan, referred to the Vancouver SIF as an "opium den." Lewis said that Kouame's use of that term was a sign that Kouame was "incompetent to do his job."8
Not "Set Up" for Human Rights
Because drug use is so harshly criminalized in so many countries, it is challenging to ensure that HIV/AIDS prevention and treatment programs reach people who use drugs and who may have good reason to fear using established health services. United Nations documents and declarations have emphasized the importance of respecting the human rights of people who use drugs and others who are disproportionately affected by HIV/AIDS. But the INCB has been dismissive of this idea, referring more to the "human rights to be protected from drug abuse" than to the human rights of people who use drugs, whom it always refers to as "drug abusers."
This attitude can lead to missed opportunities and worse. In 2003, Thailand conducted one of the most brutal drug crackdowns in recent history, resulting in the arrest and/or internment of more than 50,000 citizens and the killing of more than 2,500 people in what human rights groups said were professionally executed assassinations. The INCB visited Thailand in 2004 to examine the impact of these "drug war" measures. While human rights organizations in the country and across the world were — and still are — calling for the government to allow an independent investigation of the crackdown, the INCB expressed appreciation of the government's investigation of the killings. It expressed no concern about the thousands arrested in the name of drug treatment or the impact of the crackdown on health services for people who use drugs.
Similarly, following the passage of one of the world's harshest drug laws in Bulgaria — a law questioned by the European Commission for leading to incarceration for very minor drug offenses — the board's visiting delegation congratulated the country for its "political commitment and the will to deal with drug abuse" and described the country's drug control framework as "well-developed." Though the board has made several visits to China in recent years, it has yet to comment on widespread reports that the country has regularly used the occasion of the U.N. International Day Against Drug Abuse and Illicit Trafficking to engage in show trials and executions, sometimes in public, of people charged with drug smuggling and trafficking. When asked at a press conference in March 2007 about the board's negligence regarding the human rights of people who use drugs, Kouame said the board was not "set up" for human rights and "therefore we will not talk about human rights."9
The press conference at which this statement was made provided an unusual opportunity for journalists to be able to question the INCB president and secretary. At a time when the United Nations is seeking more ways to engage with civil societies and with representatives of its member states, the INCB works in secrecy. Its meetings are closed, and no minutes are provided. It refuses to engage with nongovernmental organizations, saying that its business is with governments.
It is time that this small but influential body is brought into step with the resolutions and programs of the United Nations on HIV/AIDS and drug use. The curtains should be drawn on the INCB's secret deliberations, which should be made more open to civil society, U.N. member states, and independent technical experts. The board must start doing its job on OST by challenging countries to ensure adequate availability of opiate substitutes for this purpose. The U.N. Economic and Social Council and World Health Organization are jointly responsible for electing people to the INCB and must ensure that the board includes genuine experts on HIV/AIDS. Furthermore, the U.N. secretary-general should commission an independent evaluation of the INCB's work to see if the U.N. is spending its funds wisely in supporting this secretive body.
This article is based on the report "Closed to Reason: The International Narcotics Control Board and HIV/AIDS" by these authors, published in February 2007 by the Canadian HIV/AIDS Legal Network and the International Harm Reduction Development Program of the Open Society Institute. The full report, including complete reference citations, is available at www.aidslaw.ca and www.soros.org.
- U.S. Centers for Disease Control, Cases of HIV infection and AIDS in the United States and dependent areas, 2005. Atlanta: U.S. Government, 2006. Available here.
- U.N. General Assembly, Declaration of commitment on HIV/AIDS (A/RES/S-26/2), August 2, 2001; and U.N. General Assembly, Political declaration on HIV/AIDS (A/RES/60/262), June 15, 2006.
- See, e.g., United Nations, Single Convention on Narcotic Drugs, March 30, 1961, 520 UNTS 204, amended by the Protocol amending the Single Convention on Narcotic Drugs, March 25, 1972, 976 UNTS 3.
- International Narcotics Control Board. Report of the International Narcotics Control Board for 2005 (Vienna, 2006), para 619.
- V Krasnov et al. "Nyet metadonovym programmam v Rossii" (No to methadone programs in Russia). Meditsinskaya Gazeta no. 29, 30 March 2005, 7. Slightly altered version available in Russian here.
- C Aceijas et al. "Say no to methadone" memorandum: Correcting the record (memo and open letter). Available here.
- Interview with Philip O. Emafo, MD. UNODC Update, December 2002. Available here.
- Stephen Lewis, Statements at press launch of "Closed to Reason" report, United Nations Correspondents Association room, U.N. Headquarters, New York, February 27, 2007.
- K Kouame (secretary of the INCB). Statement at INCB press conference, United Nations, New York, March 7, 2007.
Money, Moralism, and Microbicides:
Barriers in Microbicides Development
Gina Arias and Cornelia Adriana Jervis
Microbicides have been heralded as an "HIV prevention tool of the future,"1 and indeed, the last two decades have seen significant strides in their promotion. However, considerable challenges to microbicides research and development have emerged. One of the most consequential has been the lack of investment by the pharmaceutical industry and, to a lesser degree, by the U.S. government.2 Considering the exponential increase in seroprevalence rates for women who have sex with men, and men who have sex with other men, even a moderately effective microbicidal product could avert an estimated 2.5 million new cases of HIV in men, women, and infants over a three-year period.3
Microbicides are considered to be "public health goods" — products which would be of enormous benefit to society with regard to health, quality of life, and productivity. Particularly for individuals who traditionally have diminished bargaining power to negotiate when, where, and how sex takes place — women, gay men, and gender and sexual minorities — microbicides could be a user-controlled product of tremendous benefit. Various factors, including gender violence, place women in particular at increased risk for HIV. For many women who engage in sex with men, including within the context of marriage, it can be extremely difficult if not outright dangerous to insist on condom use.4 Likewise, abstinence and mutual monogamy are seldom viable options. Additionally, from a biological standpoint women are 2.5 times more susceptible than men to heterosexually transmitted HIV infection.5
The State of Microbicides Research
Researchers expect that a topical microbicide will likely come in the form of a cream, foam, gel, ring, or suppository delivery vehicle, which could be applied vaginally or rectally prior to sexual intercourse. In order to be considered effective the product must not cause irritation or activate a dangerous immune response for the majority of users.6 Most microbicides that are currently being researched are designed to do one or more of the following:
- Kill HIV and STI pathogens
- Strengthen the body's normal defenses
- Block or preventing viral entry
- Prevent viral replication
The process of bringing a microbicidal product to market has been long and arduous. The reality is that developing a safe and efficacious microbicide is much more difficult than originally anticipated. Currently, there are dozens of vaginal microbicides in various stages of laboratory testing. However, only ten are now in the clinical trials stage. Of these, three are in Phase III effectiveness trials, warranting guarded optimism about their viability as products marketable to the public within the next five to ten years. A cautionary approach is well placed, considering the fact that in the past year and half research difficulties have forced the closure of two Phase III trials.
In November of 2005, Family Health International (FHI), a nonprofit international public health organization, in cooperation with Cellegy Pharmaceuticals, announced the closure of the Phase III trial testing of a vaginal microbicide gel called Savvy. The Savvy trials were terminated after it was recognized that HIV incidence in the study population in Ghana was too low to conclusively demonstrate whether the Savvy microbicide was more effective in preventing the transmission of HIV than the placebo. A second Savvy trial, underway in Nigeria, was closed in September of 2006; HIV incidence in the trial community was also lower than initially expected. However, the decision to close this trial was primarily due to the lack of clear signals that the product was effective in reducing the risk of HIV transmission.
In addition to Savvy, FHI was testing a cellulose sulfate (CS) vaginal microbicide. CONRAD, a not-for-profit reproductive health research organization, was also conducting CS trials until early 2007, when it terminated clinical studies at the recommendation of its Data Safety and Monitoring Board. Preliminary results from Benin, India, South Africa, and Uganda revealed a higher HIV incidence among females using the active microbicidal product than among those in the placebo group. It has not yet been determined why there was an increased risk of HIV transmission. Although no evidence of increased risk was found in the CS trial being conducted in Nigeria by FHI, that study was also halted as a precautionary measure.
More promising news came in March of 2007, when it was announced that another vaginal microbicide gel, PRO2000, would continue in Phase III trials. The Independent Data Monitoring Committee (IDMC) for the Microbicide Development Programme (a partnership of various African and European research institutions and academic organizations) met to review the information available on the PRO2000 trials. Just two months earlier IDMC decided that an additional examination of the data was needed in light of recent trial closures. Following a thorough review, the IDMC then determined that the PRO2000 trials could still continue with the understanding that another evaluation of the data would again take place in July of 2007.
In late March of 2007 the field reached a major milestone when data collection was completed for the Phase III trial of Carraguard, a vaginal microbicide being studied by various South African research institutions and the Population Council, a non-profit organization conducting biomedical, public health, and social science research. This Phase III trial began in March 2004 and was conducted at three different sites in South Africa. Results from the Carraguard trials are expected by the end of 2007, and if all goes well, they will produce the first data on the effectiveness of vaginal microbicides as a tool to reduce the risk of HIV infection.
Formulating microbicides for rectal use has proved to be even more complex than developing ones for vaginal use. This is due to the fact that the cells on the rectum are one layer thick, compared to most vaginal cells, which are approximately 40 layers thick. As a result, rectal tissue is much more susceptible to infection, irritation, and tearing during sex. In addition, there are more immune cells with CD4 receptors and more CD4 receptors per cell on the rectal tissue, making the rectum acutely vulnerable to HIV infection. Finally, because the rectum is an open-ended cavity, larger amounts of more potent microbicides may be required to ensure adequate coverage and protection.
Efforts to move rectal microbicides research forward must also be understood against a backdrop of pervasive moral and social stigmas associated with homosexuality and with the practice of anal intercourse — some of which have been enshrined in law. Even though data suggests that anal intercourse is commonly practiced by both homosexuals and heterosexuals (35% of heterosexual women report having had anal sex at some point in their lives), anal sex is still stigmatized as a deviant activity practiced exclusively by gay men.7 In response to initiatives to increase research and development funding for rectal microbicides, Bob Maginnis, former senior policy analyst for the Christian, right-wing Family Research Council and current Fox News analyst, declared, "We are facilitating, at taxpayer expense, an illegal and immoral activity that's abhorrent to most Americans... if we make homosexual sex safer, all we're going to do is promote promiscuity, which will lead to more STDs."8
Until the U.S. Supreme Court ruling in Lawrence v. Texas,9 anti-sodomy laws were still on the books in 13 states.10 Anal sex remains a criminal offense in many countries, often punishable by imprisonment; sometimes by death. Members of the U.S. military are still subject to criminal prosecution under the military's sodomy statute.11 The same sentiment that kept anti-sodomy laws on the books until the early 21st century continues to present obstacles to moving rectal microbicides research forward.
Funding Challenges
The disinclination by drug companies to invest in microbicides is directly related to the profit driven-nature of the "disease business."12 Some theorists have even gone so far as to suggest that for drug companies, maintaining and even expanding diseases is a precondition of growth that assures the Pharmaceutical Research and Manufacturers of America (PhRMA) an indefinite and limitless stream of profit-making potential.13 While this is not to suggest that the pharmaceutical industry is the lone culprit in the slow pace of microbicides development, PhRMA's relative inattention towards accelerating the development of desperately needed HIV/AIDS prevention drugs merits further examination.
PhRMA's unwillingness to invest in microbicides and other needed drugs for poorer countries is usually couched in terms of investment risk analysis, whereby research costs are weighed against potential profit margin. The industry has articulated other reasons for not investing in microbicides. Among the most salient are their lack of technological expertise in developing products applied intravaginally; regulatory hurdles in testing potential microbicidal candidates in high- risk areas in developing nations; and an uncharted terrain when it comes to anticipating the risk-benefit formulary which must be met for FDA licensure.
While a few major pharmaceutical companies (Bristol-Myers Squibb, Merck, Gilead, and GlaxoSmithKline) have contributed compounds to the microbicides research field, most major drug companies have not participated in microbicides research. The reality is that for the average pharmaceutical company, a risky microbicidal product will never be as enticing an investment as popular top-sellers such as antidepressant, allergy, hypertension, and erectile dysfunction medications. Studies show that these aforementioned drugs are currently being developed and marketed to the virtual exclusion of most other desperately needed drugs for serious chronic and life-threatening conditions. As one Public Citizen study attests, "the drug industry is shifting the core of its business away from the unpredictable task of creating drugs and towards the steadier business of selling them."14
As for-profit institutions, pharmaceutical companies are largely focused on investment costs and returns. Additionally, the pharmaceutical industry continuously relies on a research and development "canard" which premises that pharmaceutical companies "need extraordinary profits...in order to conduct expensive and risky research into innovative new drugs."15 Certainly, microbicides research and development expenditures are not insignificant. Late stage Phase III clinical trials of microbicides generally range from US $30 million to US $50 million.16 Total costs for developing one microbicide, including all stages of research and registration of the product range from US $36–$65 million.17
Pharmaceutical companies also factor how product pricing will affect returns. If a product is to be accessible in lower-income countries the financial costs of developing the microbicide may outweigh the financial returns on the product. In fact it is often argued that pharmaceutical companies fear that the pressure to provide a microbicide free of charge in developing countries would further undermine the potential to yield profitable returns.18
The norms dictated by our global economic system lend justification to the pharmaceutical industry's lack of investment in microbicides research and development. However, with over US $550 billion in total global pharmaceutical sales per year19 and top executive pay packages that on average top tens of millions dollars, it is difficult to find a morally defensible argument for a continued lack of investment in such a critical public health good.
In the absence of a commitment by multinational pharmaceutical companies to sufficiently prioritize, participate in, and fund microbicides research and development, the onus has been placed on smaller-scale biotech firms and global health research NGOs to pick up the slack. Both the biotech firms and public sector non-profits conducting microbicides research and trials depend on competitive government and philanthropic grants or to a lesser degree on venture capital. The reliance on these institutions to conduct costly microbicides research has resulted in a slow pace of progress.
In 2004 global investment in microbicides research was approximately US $142 million, a figure nearly double that of microbicides investment in 2000.
Nevertheless need continues to outstrip existing funding levels. Experts calculate that in order to accelerate the development of microbicides and bring an effective microbicidal product to market within the next few years, global annual investment must be roughly doubled, to at least US $280 million.20
Advocates in the United States are trying to push policy makers to commit to increased public-sector funding and resources for microbicides research and development via the passage of the Microbicides Development Act (MDA). In an effort to move the microbicides agenda forward the legislation was re-introduced in early March 2007. Currently, the US Agency for International Development (USAID), the Centers for Disease Control and Prevention (CDC), and the National Institutes of Health (NIH), are all working on microbicides research and development. At the NIH, several institutes are conducting microbicides research. As it now stands, there is no single line of administrative accountability and no specific funding coordination. The MDA would establish a dedicated unit for microbicides research and development within the NIH's National Institute of Allergy and Infectious Diseases, streamlining administrative accountability and funding coordination. It would also authorize funding increases as needed at the CDC, NIH and USAID for the development of microbicidal products.
With the MDA, Congress has an opportunity to offset government and health care industry reluctance to adequately prioritize microbicidal development. Until now, the troubling inference has lingered that those most at risk of contracting HIV – the same likely consumer beneficiaries of microbicides — are not valuable enough to warrant a life-saving investment on their behalf. A decision to advance microbicides research and development will send a different message and may well alter the fate of millions of women worldwide.
- Kaethe M. Hoffer & Grisel Robles, "Microbicides: Prevention Tool of the Future," Positively Aware, Jan/Feb 2002, available here (last visited May 21, 2007).
- Microbicides receive only 3 percent of U.S. government funding allotted to HIV/AIDS research.
- Using epidemiologic models, researchers at the London School of Hygiene and Tropical Medicine have estimated that if only 20 percent of women in 73 developing countries used a 60-percent efficacious microbicide for half of all otherwise unprotected sex acts, 2.5 million HIV infections would be averted over three years in women, men, and infants. Visit (last visited May 21, 2007).
- Bauni EK, & Garimoi CO, et al. "Attitudes to Sexuality and Family Planning," Progress in Human Reproduction Research, No. 48, 1998, available here (last visited May 21, 2007).
- "Gender Equality in AIDS Prevention: Why We Need Prevention Options for Women," Global Campaign for Microbicides, May 2005, available here (last visited May 21, 2007).
- Bob Huff, "Women, Men and Microbicides," GMHC Treatment Issues, Vol. 17, No. 9, Sept. 2003, at 2.
- "All About Rectal Microbicides," Global Campaign for Microbicides, September 2006, available here (last visited May 21, 2007).
- Michael Scare, Smearing the Queer: Medical Bias in the Health Care of Gay Men, p. 104 (Haworth Press, Inc. 1999). Joyce Price, "Federal Study of Lubricant Blasted, Agency to Weigh Effect on Gay Men," The Washington Times, July 25, 1996.
- Lawrence v. Texas, 539 U.S. 558 (2003).
- "Supreme Court strikes down Texas sodomy law," CNN.com, Nov. 18, 2003, available here (last visited May 21, 2007).
- Art. 125 of the Uniform Code of Military Justice.
- "The Laws of the Pharmaceutical Industry," Dr. Rath Health Foundation, available here (last visited May 21, 2007).
- Ibid.
- Rx R&D Myths: The Case Against the Drug Industry's R&D "Scare Card", Public Citizen, 2001, available here (last visited May 21, 2007).
- Ibid.
- "The Economics of Microbicide Development: A Case for Investment," Rockefeller Foundation Microbicide Initiative, 2002, available here (last visited May 21, 2007).
- Ibid.
- "The Economics of Microbicide Development: A Case for Investment," Rockefeller Foundation Microbicide Initiative, 2002, available here (last visited May 21, 2007).
- Bill Trombetta, "2005 Industry Audit: For the fourth year in a row, Pharmaceutical Executive slices and dices the numbers to learn who's really on top," Pharmaceutical Executive, Sept. 1, 2005, available here (last visited May 21, 2007).
- "Microbicide development will require public subsidy," Global Campaign for Microbicides, available at http://www.global-campaign.org/economics.htm (last visited May 21, 2007).
A Rare Moment in Time
By Bob Huff
There are three new drugs coming to pharmacy shelves in the next 12 months that might conceivably herald a revolution for HIV-infected people who have developed resistance to many or most available drugs. (This group of so-called "salvage patients" also includes previously untreated people who were infected with drug resistant HIV).
Thousands of people live with unsuppressed HIV infection because they cannot benefit from or cannot tolerate enough of the currently approved drugs to construct an effective combination antiretroviral (ARV) regimen. During the ten years following the first flowering of HAART in 1996, whenever researchers developed a new drug that could help highly treatment-experienced people, there often were no other new drugs to add along with it, and treatment success was short lived. Eventually, HIV physicians and patients learned that simply adding one new drug to a failing regimen composed of previously prescribed drugs was virtually the same as using the new drug alone, the result being treatment failure due to resistance.
What is special about this time is that these toughest-to-treat patients will—if their doctors are smart about it—be able to combine several new drugs that have the power to knock down viral replication and keep it down for years to come.
Etravirine (TMC125), an NNRTI from J&J/Tibotec, seems to be effective against some (but not all) HIV that is resistant to efavirenz (Sustiva) and nevirapine (Viramune). Raltegravir (Isentress), from Merck, is the first drug to attack the HIV integrase protein, and it should be active against multidrug-resistant HIV by virtue of its first-in-class status. Raltegravir impressed the 2006 International AIDS Conference by showing it could knock down HIV viral loads twice as rapidly as efavirenz in a treatment-naïve study population. Its performance in studies with highly treatment-experienced patients has been equally impressive.
Because these two drugs do not interfere with one another pharmacologically, the sponsors allowed their combined use in expanded access protocols aimed at treatment-experienced patients. The response to the opportunity to add at least two new active drugs has been dramatic. Enrollment in the etravirine and raltegravir expanded access programs has been brisk. It is not yet clear if most expanded access patients are combining these two drugs or are incorporating darunavir or enfuvirtide (T20) as a second, third, or fourth drug in their combination. Regardless, even normally dour researchers have been uncharacteristically enthusiastic as reports trickle in about long-time salvage patients achieving undetectable viral loads for the first time. Indeed, if these people remain undetectable, then the talk may be justified.
The third new drug on the scene is the CCR5 antagonist, Maraviroc (Celsentri), from Pfizer. This first-in-class drug is capable of benefiting patients with long, troubled treatment histories, although a few limitations have held back enrollment in its expanded access protocol. The first problem is that blocking the CCR5 coreceptor molecules that HIV uses to infect new target T cells does not help every person who has HIV. Some forms of HIV use a different coreceptor, and the likelihood of having a virus that uses the alternate coreceptor increases the longer one is infected. Thus, perhaps only 50% of people with more advanced disease can benefit from maraviroc.
For those with CCR5-tropic virus, the maraviroc's antiviral efficacy has been impressive. Before someone starts taking the drug, though, it is highly advisable to undergo a viral tropism test to determine which kind of HIV the person has and to predict its susceptibility to CCR5 blocking. Currently, the tests are expensive and can take up to two months to obtain. Another possible deterrent is the concern of a few scientists about the safety of a drug that sticks to one of the body's own immune messenger proteins (all previous HIV drugs have targeted viral proteins). These issues—and the enthusiasm with which raltegravir has been received—suggest that maraviroc may not be as quickly accepted as a major player in the new salvage therapy paradigm, although it has already proved its worth in large studies in highly treatment experienced patients.
This is a rare moment of opportunity for people who have struggled to get their virus under control to finally become undetectable. At least that is the hope, and it represents a convergence of circumstances that could have a huge impact on the nature of the epidemic in the wealthy nations.
© 2007 Gay Men's Health Crisis
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