A New Method of HIV Prevention in Africa
Rishi Rattan and Chris Curry discuss the medical and social impact of using microbicides to prevent HIV in low-income countries
Think of the birth control options you saw during reproductive health lectures. Imagine if those gels, rings, diaphragms and cervical caps were able to reduce the risk of sexually transmitted HIV. They’re effective, cheap, accessible and discreet. The desire to have children with one’s sero-discordant partner, or the inability to negotiate condom use, would no longer mean exposing oneself to HIV without protection. These are concerns that many women face daily. In sub-Saharan Africa, women make up the majority of those living with HIV; in some areas, they are three times more likely to be infected than men their age. (1)
Within the next decade, such a hope may exist. Microbicides currently in development, including one that finished Phase 3 clinical trials in 2007, are user-controlled substances that decrease HIV transmission. They have been hailed as a hope for people, usually women, unable to access condoms or negotiate condom use. Microbicides would change the landscape of HIV prevention, the ability of women to control their bodies and our prescribing and counseling efforts.
Remember your virology lectures on the HIV life cycle-people have sex, virus enters the vagina or rectum, passes through epithelial microtears, engages with and enters a CD4 positive cell. Reverse transcription of viral RNA allows subsequent integration of viral DNA into the cell’s chromosome. Each step in the viral life cycle provides a potential opportunity for a microbicide to disrupt infection. One strategy involves the creation of a physical barrier, in the form of gel or cream, between HIV and the vaginal or rectal epithelial cells. Carrageenan, a red seaweed derivative, prevents the infection of cervical epithelial cells by HIV. (2) Alternatively, the addition of buffers to the normally acidic vaginal environment (pH 3.5 - 4.5) maintains acidity in the face of semen-induced alkalinity, boosting the vagina’s natural defense mechanisms and decreasing the likelihood of HIV infection. (3)
Another method interferes with the lock-and-key mechanism between viral envelope proteins and the CD4 receptor and co-receptors that stud the surface of immune cells. (4) Alternatively, if HIV manages to get past these initial barriers and infects an immune cell, topical antiretroviral drugs could halt the infection while it is localized, preventing immune cells from migrating to lymphatic tissue and beyond.
The path to microbicides has more than scientific barriers. Cellulose sulfate clinical trials were shut down in 2006 after preliminary results suggested an increased risk of HIV infection in the trial’s microbicides arm.(5) Research ethics cannot ignore the potential exploitation of high-risk populations in developing countries. (6) Estimates of first generation efficacy being 60% are generous. (7) Questions of cost compared to condoms have arisen, as well as questions about funding the distribution of a less efficacious microbicide over condoms. Indeed, advocates acknowledge that microbicides would not eliminate the need for condoms. And if an infrastructure to distribute the cheaper and more effective condom is inadequate in many developing countries, how will microbicides distribution reach unsupplied populations?
But even as these challenges are being addressed, the changes microbicides have already wrought are significant enough to warrant committed efforts by health professionals to research, educate about and organize around microbicides.
Before organised research efforts began, women had demanded a user-controlled HIV prevention product usable within their sociocultural confines, spurring the research community into investigating options. (8) This collaboration has reshaped the way people think about science as advocacy and the way lay communities and research subjects can direct future research. Consequently, the women in microbicides trials have had a unique opportunity to determine the course of investigations. Through community advisory boards, UNAIDS, international non-governmental organizations and non-profit ventures, women participants in this research have ensured non-exploitative, culturally competent trial designs. As a result of this community participation, voluntary counseling and testing, condom distribution and sexual health education remain for the entire community long after researchers have left. (9)
Large, profit-driven pharmaceutical companies hesitated to invest in a questionably profitable product. Their concern was magnified given that lower income communities had the power to ensure that if a product were tested on them, it would also be affordable and accessible. (10) However, within this vacuum, several smaller, new biotech organizations have led the development of many products, signaling a change in how we think about developing prevention and treatment methods for all tropical and neglected diseases. Scientists, non-profit pharmaceutical companies, US medical students, women and activists continue to collaboratively advocate for microbicides development. In 2006, Gilead Sciences offered a royalty-free license to develop, manufacture and distribute tenofovir, a reverse transcriptase inhibitor, as a microbicide. (11)
But why should you pay attention to microbicides? The London School of Hygiene and Tropical Medicine estimates that a 60% efficacious microbicide could prevent 2.5 million infections over 3 years if used in 73 low-income nations. (12) But microbicides have already changed the reproductive health and women’s empowerment movements. Women who struggle to negotiate condom use have commanded the respect of Western scientists. They successfully demanded that investigators not use their bodies without offering their children, partners and them the infrastructure and continued sexual health resources that provide people the agency and knowledge to control their bodies and health. Microbicides are an exciting hope just around the corner, but demand our attention, our science and our advocacy now.
Rishi Rattan
3rd year medical studen
College of Medicine
University of Illinois
Chicago, IL, USA
rattan@uic.edu
Chris Curry
MD/PhD Candidate
Stritch School of Medicine
Loyola University
Maywood, IL, USA
clcurry@gmail.com
Conflicts of interest: The authors have pledged to accept no money, gifts or hospitality from the pharmaceutical industry under any circumstances and as such, have no conflicts of interest to declare.
(1) UNAIDS. Report on the global AIDS epidemic. [online] 2006. [cited 2008] http://www.unaids.org/en/KnowledgeCentre/HIVData/GlobalReport/Default.asp
(2) Pirovano A, Phillips DM. Carrageenan. Formulation prevents macrophage trafficking from vagina: Implications for microbicide development. Biol Reprod 2003 69:933-939.
(3) Olmsted SS, Khanna KV, Ng EM et al. Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model. BMC Infect Dis 2005 5:79-88.
(4) Balzarini J, Van Damme L. Microbicide Drug candidates to prevent HIV infection. Lancet 2007 369:787-797
(5) Van Damme L et al. Phase III trial of 6% cellulose sulfate (CS) gel for the prevention of HIV transmission. Fourth International AIDS Society Conference on HIV Treatment and Pathogenesis, Sydney, Australia. 2007.
(6) Lo B, Bayer R. Establishing ethical trials for treatment and prevention of AIDS in developing countries. BMJ 2003 327:337-9.
(7) Foss A, Vickerman P, Heise L. Shifts in condom use following microbicide introduction: should we be concerned? AIDS 2003 17:1227-1237
(8) Global Campaign for Microbicides. Microbicides: New hope for prevention of HIV and other STIs. [online] 2007. [cited 2007] http://www.global-campaign.org/clientfiles/Long-GCMMicrobicidesTalk-(E)Apr1-2007.ppt. .
(9) Ibid.
(10) UNAIDS. Financing the expanded response to AIDS: HIV vaccine and microbicides research and development. [online] 2005. [cited 2007] http://hivresourcetracking.org/
(11) CONRAD. Gilead grants intellectual property rights for tenofovir topical gel to the International Partnership for Microbicides and CONRAD. [online] 2006. [cited 2007]http://www.conrad.org/press/12112006.htm
(12) Foss A, Vickerman P, Heise L. Shifts in condom use following microbicide introduction: should we be concerned? AIDS 2003 17:1227-1237
Bookmark on delicious | Digg