Key publications and weblinks providing important information regarding current and past research and expert commentary of biomedical, nonvaccine interventions for HIV prevention are grouped in the following categories:
General Biomedical Prevention
Future Directions for HIV Prevention Research; Charting a Prevention Science Research Agenda (Compton, W. et al.). J Acquir Immune Defic Syndr 2008;47(S1):S47-S48.
The authors stress the importance of collaboration between social/behavior and biomedical scientists to effectively evoke behavioral changes increasing the effectiveness of biomedical HIV prevention developments.
Challenges to HIV Prevention--Seeking Effective Measures in the Absence of a Vaccine (Lagakos, S.W. et al.). N Engl J Med 2008;358(15):1543-1545.
While an HIV vaccine is likely decades away from successful development, 20-60 million new HIV infections must be prevented through effective biomedical and behavioral interventions. Challenges to previous trials that have led to inconclusive results include inaccurate estimates of HIV incidence in target populations, high rates of nonadherence, and high pregnancy rates without adequate follow-up. The authors recommend key research and methodologic components that should be addressed when designing future prevention studies.
Methodological challenges in biomedical HIV prevention trials (Institute of Medicine). Washington, DC: National Academies Press, 2008.
The Bill and Melinda Gates Foundation asked the Institute of Medicine (IOM) to review the methodologic challenges of trials of nonvaccine biomedical interventions for HIV prevention and to recommend ways to improve the likelihood of success of future trials.
Recent Efforts in Biomedical Prevention of HIV (Landovitz, R.J.). Topics in HIV Medicine 2007;15(3):99-103.
The status of male circumcision, pre-exposure prophylaxis (PrEP), and use of anti-HIV microbicides summarized from Dr. Landovitz's presentation at an International AIDS Society--USA Continuing Medical Education course in Los Angeles, March 2007.
Biomedical HIV prevention--and social science (Imrie, J. et al.). Lancet 2007;370:10-11.
With a word of caution before the scale-up of efficacious biomedical developments, the authors encourage collaboration between trialists and social scientists to increase the effectiveness of interventions at a population level.
Diaphragm and lubricant gel for prevention of HIV acquisition in southern African women: a randomized controlled trial (Padian, N.S. et al.). Lancet 2007; 370(9583):251-61.
The MIRA study (Methods for Improving Reproductive Health in Africa) showed no added benefit for use of the diaphragm in lowering risk of HIV infection.
New Approaches to HIV Prevention: Accelerating Research and Ensuring Access, Global HIV Prevention Working Group, August 2006.
The report from the 2006 Global HIV Prevention Working Group, New Approaches to HIV Prevention: Accelerating Research and Ensuring Future Access summarizes the state of HIV prevention research, recommends accelerating research on promising new HIV prevention methods and ensuring rapid access to new tools and strategies.
After Toronto: Effective AIDS prevention requires far better understanding of why existing strategies do not succeed (editorial, no author). Nature 2006; 442(7105): 847.
This commentary points out barriers to successful HIV prevention including lack of research collaboration, and local resources.
HIV/AIDS Prevention and Treatment. Disease Control Priorities in Developing Countries (2nd Edition) 2006 (Jamison, D.T. editor, et al.): 331-369.
Chapter 18 discusses the necessity to tailor HIV prevention and treatment strategies to country specific HIV epidemics. It also supports the application of new interventions in the absence of definitive research.
Prevention Cocktails: Combining Tools to Stop HIV’s Spread (Cohen, J.). Science. 2005; 309 :1002-1005
This article gives a broad overview of the HIV prevention stratigies available and in development. Emphasis is on the combined potential of more than one approach. Male circumcision trials, HSV-2, novel vaccine approaches, PrEP, acute HIV infection identification, and traditional barrier methods are all discussed.
Other Useful Links
HIV Prevention Trials Network (HPTN)
The HIV Prevention Trials Network (HPTN) is a worldwide collaborative clinical trials network that develops and tests the safety and efficacy of primarily non-vaccine interventions designed to prevent the transmission of HIV.
AIDS Vaccine Advocacy Coalition "HIV Prevention Research: A Comprehensive Timeline"
The AVAC timeline summarizes major HIV prevention research trials that are currently underway. The research spans multiple strategies: from AIDS vaccines, to microbicides, to male circumcision, to behavioral interventions.
Treatment Action Group
TAG is an independent AIDS research and policy think tank fighting for better treatment, a vaccine, and a cure for AIDS. This site is frequenlty updated with new biomedical research and advocacy reports.
The Safety of Adult Male Circumcision in HIV-Infected and Uninfected Men in Rakai, Uganda (Kigozi, G. et al.). PLoS Medicine 2008;5(6):e116.
This study compared the rates of adverse events (AEs) after male circumcision (MC) in HIV-positive and HIV-negative men enrolled in two randomized controlled studies in Rakai, Uganda. Study results showed that rates of most surgery related AEs were similar among the two groups, early resumption of sexual activity increased the risk of surgery related AEs in both groups, and HIV-negative participants had more rapid wound healing. The results of this study are intended to assist MC programs that may provide services to HIV-infected and uninfected men.
PUBLIC HEALTH: Reassessing HIV Prevention (Potts, M. et al.). Science 2008;320(5877):749-50
There is strong evidence to support the shifting of prevention efforts from "established" interventions to male circumcision.
HIV Prevention Funding in Africa Should Be Shifted To Promote Male Circumcision, Partner Reduction Programs, Study Says (Kaiser)
MC studies provide compelling evidence that MC scale-up programs should receive more funding than many unproven HIV prevention efforts currently employed in the field. The growing number of new HIV infections demands a timely response with best methods available.
Male circumcision for HIV prevention: from evidence to action?(Weiss, H.A. et al.) AIDS 2008; 22:567-574.
The authors review the strength of biological and observational evidence that male circumcision reduces the risk of HIV infection then disucss implementation issues. Public health aspects including surgical complications, behavior change, cultural accepability, socioeconomic and impact predictions are included.
Male circumcision for HIV prevention in young men in Rakai, Uganda: a randomized trial (Gray, H. et al.). Lancet 2007;369:657-66.
Randomized controlled trial in Rakai, Uganda found approximately 55% efficacy of MC in preventing male HIV infection.
Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomized controlled trial (Bailey, R.C., et al.). Lancet 2007;369:643-56.
Randomized controlled trial conducted in Kenya found that MC resulted in approximately 53% reduction in the risk of acquiring an HIV in men.
The Potential Impact of Male Circumcision on HIV in Sub-Saharan Africa (Williams, B.G. et al.). Plos Medicine . 2006; 3(7): 1032-1040.
Based on Auvert's randomized clinical trial of male circumcision as an HIV prevention method, the authors modeled the impact of MC application in countries will low prevelance of MC. They project that MC could avert 2.0 (1.1-3.8) million new HIV infections and 0.3 (0.1-0.5) million deaths over the next ten years in sub-Saharan Africa.
Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial (Auvert, B. et al.). PLoS Med 2005;2(11):e298.
Randomized controlled trial stopped early when MC was found to provide approximately 60% protection of male acquired HIV infection in South African men.
HIV and male circumcision—a systematic review with assessment of the quality of studies (Siegfried, N. et al.). The Lancet Infectious Diseases. 2005, 5(3):165-173.
A literature review of 37 observational studies looking at the effect of MC on heterosexual HIV transmission. The author found the methodologies to range widely and it was difficult to interpret overall effects when studies used different models to account for confounding.
Forum for Collaborative HIV Research: Male Circumcision as an HIV Prevention Strategy Resouce Page
Updated MC resources including a timeline of meeting reports, websites and links, news and press releases, and additional informational documents assembled by the Forum.
Effect of Herpes Simplex Suppression on Incidence of HIV among Women in Tanzania (Watson-Jones, D. et al.). N Engl J Med 2008; 358(15): 1560-1571.
The results of a randomized, double-blind, placebo-controlled trial of suppressive treatment of HSV-2 with acyclovir (400 mg twice daily) show there was no significant difference in HIV incidence between the treatment and control arms out of a total sample of 812 Tanzanian women ages 16 to 35 years after a follow-up period of 12 to 30 months. The authors conclude there is no evidence that acyclovir as HSV suppressive therapy reduces HIV infection incidence.
Herpes Simplex Virus Type 2 and Risk of Intrapartum Human Immunodeficiency Virus Transmission (Drake, A.L. et al.). Obstet Gynecol. 2007;109(4):1002-3.
This nested case control study, conducted within a perinatal cohort in Nairobi, Kenya, concludes that management of HSV-2 during pregnancy may enhance mother-to-child HIV-1 prevention efforts.
Management of Herpes Simplex Virus Type 2 Infection in HIV Type 1-Infected Persons (Strick, L.B. et al.). Clinical Infectious Diseases. 2006; 43: 347-356.
Treatment of HSV-2 (by nucleoside analogues: acyclovir, valacyclovir, and famciclovir) in HIV co-infected individuals results in decreased frequency and severity of HSV-2 symptomatic and asymptomatic recurrences along with decreased levels of HIV in the blood and genital tract.
Developments in STD/HIV Interactions: The Intertwining Epidemics of HIV and HSV-2 (Reynolds, S.J. et al.). Infectious Disease Clinics of North America. 2005; 19:415-425.
This is a thorough review of literature pertaining to the biological influences of HSV-2 on HIV acquisition, transmission, and its effect on biomedical prevention clinical trial outcomes. It concludes that treatment of HSV-2 would decrease HIV viral loads in HSV-2 coinfected populations and perhaps help to decrease HIV transmission.
Microbicide acceptability: insights for future directions from providers and policy makers (Hoffman, S. et al.). AIDS Educ Prev. 2008 Apr;20(2):188-202.
Opinions on microbicides from one New York City study and two South African studies with feedback contributed by patients, providers and policy makers. Top concerns included safety, messiness, and cost.
A Review of Current Intravaginal Drug Delivery Approaches Employed for the Prophylaxis of HIV/AIDS and Prevention of Sexually Transmitted Infections (Ndesendo, V.M. et al.). AAPS PharmSciTech. 2008 Apr 2 [Epub ahead of print]
Most recent review document of microbicide delivery systems including formulations that modify the genital environment (e.g. polyacrylic acid gels and lactobacillus gels), surfactants (e.g. sodium lauryl sulfate), polyanionic therapeutic polymers (e.g. carageenan and carbomer/lactic acid gels), proteins (e.g. cyanovirin-N, monoclonal antibodies and thromspondin-1 peptides), protease inhibitors and other molecules (e.g. dendrimer based-gels and the molecular condom).
Sexual pleasure, gender power and microbicide acceptability in Zimbabwe and Malawi (Woodsong, C. et al.). AIDS Educ Prev. 2008 Apr;20(2):171-87.
Though vaginal microbicides are intended to be woman-initiated and controlled, there is a need for male cooperation and acceptibility that should be addressed in both product development and roll-out strategies.
Scientists rethink approach to HIV gels (Check, E.). Nature 2007;446:12.
In light of the recent microbicide trail failures, scientists must prioritize the most promising new gels for large-scale trials and evaluate various preclinical testing methods. An impartial body of experts may be needed to guide research, avoid redundancy, and improve the probablity of successful field trials.
Microbicide research in developing countries: have we given the ethical concerns due consideration?(Moodley, K.) BMC Medical Ethics 2007; 8:10
The author addresses major ethical concerns including male partner involvement, pregnancy, and informed consent involving microbicide phase 3 trials. International consensus on ethical guidelines supported by various regulatory agencies is recommended.
Which Topical Microbicides for Blocking HIV-1 Transmission will work in the Real World? (Klasse, J. et al.) PLOS Medicine. 2006, 3(9): 0001-0007
Safety, acceptability, efficacy, and affordability aspects of microbicides in development.
Microbicides to Prevent HIV Transmission: Overcoming Obstacles to Chemical Barrier Protection (Dhawan, D. et al.). Journal of Infectious Disease. 2006, 193(2): 36-44
This review article draws from (2005) research on the mechanisms of HIV transmission and developments in the science of HIV prevention to provide an evaluation of the development of a safe and effective microbicide.
Dawn of non-nucleoside inhibitor-based anti-HIV microbicides (D'Cruz, O.J. et al.). Journal of Antimicrobial Chemotherapy. 2006; 57:411-423.
A highly technical paper on the formulation and molecular structures of non-nucleoside inhibitor-based HIV microbicides.
Microbicides and other topical strategies to prevent vaginal transmission of HIV (Lederman, M.M. et al.). Nature Reviews. 2006; 6:371-382.
This article describes in detail the biological mechanisms targeted by new microbicides. An extensive list of the past/current (2006) microbicide trials is also provided.
Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women (Mayer, K.H. et al.). AIDS. 2006; 20(4):543-551.
A 2 week study of 84 women to determine the highest practical dose and frequency of tenofovir vaginal gel found that 1% tenofovir gel used twice daily was well tolerated in sexually abstinent and sexually active HIV-negative and HIV-positive women.
Safety and acceptability of cellulose sulfate as a vaginal microbicide in HIV-Infected women (El-Sadr, W.M. et al.). AIDS. 2006; 20:1109-1116.
A Phase 1 study of cellulose sulfate in 59 HIV-infected women enrolled in a randomized double-blind placebo-controlled study determined 6% CS gel to be safe and well tolerated.
Long term, controlled release of the HIV microbicide TMC120 from silicone elastomer vaginal rings (Malcolm, R.K. et al.). Journal of Antimicrobial Chemotherapy. 2005; 56:954-956.
This is a laboratory study providing scientific support for the use of TMC120 in vaginal rings to ultimately prevent or partially block HIV infection.
Preclinical Assessment of HIV Vaccines and Microbicides by Repeated Low Dose Virus Challenges (Regoes, R.R. et al.). PLOS Medicine. 2005; 2(8): 0798-0807
The authors have used statistical power analysis to determine that it may be feasible to increase the number of animals in vaccine studies to test efficacy under repeated low-dose HIV exposure scenarios, which is also a better model for real life HIV exposure in humans.
Global Campaign for Microbicides "Trial Results & Updates"
This site has the most recent information about microbicide trial results and trial closures.
Family Health International: Microbicides
FHI was responsible for the scientific management of the Microbicide Science Working Group of the HIV Prevention Trials Network (HPTN), an international network of researchers dedicated to the development and evaluation of nonvaccine methods of HIV prevention from 1999 to 2006. FHI currently manages operations for the Microbicide Trials Network (MTN), established in 2006.
Alliance for Microbicide Development
The latest research on microbicide research and development. The website also has a link to the 2006 Microbicide Development Strategy.
Population Council: Program Microbicides
Information on the Phase 3 clinical trial of the Population Council’s candidate microbicide Carraguard® (not shown to be effective in preventing male-to-female HIV transmission)
Press Releases from recent Microbicide Efficacy Trials:
Phase III trial of the vaginal microbicide Carraguard for the prevention of HIV infection in women-results announced Feb 2008
FHI Phase III trial of the vaginal microbicide Cellulose Sulfate gel for the prevention of HIV infection in women-stopped early (Jan 2007)
CONRAD Phase III trial of the vaginal microbicide Cellulose Sulfate gel for the prevention of HIV infection in women-stopped early (Jan 2007)
Phase 3 Trial in Nigeria Evaluating the Effectiveness of SAVVY Gel in Preventing HIV Infection in Women Will Close-stopped early (Aug 2006)
Pre-Exposure Prophylaxis (PrEP)
The impact of pre-exposure prophylaxis (PrEP) on HIV epidemics in Africa and India: a simulation study (Vissers, D.C. et al.). PLoS ONE. 2008 May 7;3(5):e2077.
Mathematic modeling of hypothetical PrEP impact scenarios in the epidemiological settings of Botswana, Nyanza Province in Kenya, and Southern India. Due to projected risk compensation behavior, PrEP should be introduced as an addition to condom campaigns, not as a substitution to established HIV prevention options.
Limited knowledge and use of HIV post- and pre-exposure prophylaxis among gay and bisexual men (Liu, A.Y. et al.). J Acquir Immune Defic Syndr 2008; 47(2):241-247.
In a cross-sectional survey of 1819 HIV- gay/bisexual men in California, 47% reported PEP awareness, and 16% reported PrEP awareness.
Tenofovir Disoproxil Fumarate for Prevention of HIV Infection in Women: A phase 2, double-blind, randomized, placebo-controlled trial (Peterson, L. et al.). PLoS Clinical Trials 2007.
While the treatment did not increase clinical or laboratory adverse events, the effectiveness of TDF as HIV prevention could not be evaluated due to the small number of HIV seroconversions observed during the study follow-up period.
Antiretroviral drug exposure in the female genital tract: implications for oral pre- and post-exposure prophylaxis (Dumond, J.B. et al.). AIDS 2007; 21:1899-1907.
This first study comprehensively evaluating antiretroviral prophylaxis drug exposure in the femal genital tract support the use of lamivudine, zidovudine, tenofovir and emtricitabine as excellent PrEP/PEP candidates.
Potential impact of antiretroviral chemoprophylaxis on HIV-1 transmission in resource-limited settings (Abbas, U.L. et al.). PLoS ONE. 2007 Sep 19;2(9):e875.
Different hypothetical PrEP effectiveness scenarios are modeled. A PrEP regimen with 90% effectiveness would prevent approximately 2.7 to 3.2 million new HIV-1 infections in southern sub-Saharan Africa over 10 years by targeting those at highest behavioral risk and by preventing sexual disinhibition.
Criteria for Drugs Used in Pre-Exposure Prophylaxis Trials against HIV infection (Derdelinckx, I. et al.). PLoS Medicine 2006.
Based on literature searches and the expert author opinions, an ideal PrEP candidate would meet criteria related to safety profile, ease of use, mode of action and pharmacology, antiviral profile, and cost-effectiveness. The article goes on to compare current (2006) PrEP drugs in trials based on these criteria.
Chemoprophylaxis of HIV Infection: Moving Forward with Caution (Grant, R.M. et al.). Journal of Infectious Diseases 2006; 194: 874-876.
Animal models do not provide a clear sense of PrEP efficacy due to species and exposure differences. Researchers should consider multi-drug therapies given the partial efficacy of tenofovir and drug resistance development.
Think Tank: Policy and Practical Implications of HIV Pre-Exposure Prophylaxis (PrEP) in the United States (Szekeres, G. et al.). UCLA Program in Global Health, Meeting Proceedings. May 11-12, 2006
Based on PrEP studies currently underway (2006), best-case, worst-case, and uncertain scenarios are described. Participants formulated research priorities, prevention programming, funding, community relations/communication, and media relations in response to each scenario along with recommendations to take action now to address these issues and assume leadership for moving the PrEP and larger HIV prevention agenda forward.
Promote HIV Chemoprophylaxis Research, Don’t Prevent it (Grant, R.M., et al.). Science. 2005, 309:2170-2171
A look at the ethical and community relations barriers to successful PrEP trials in vulnerable underserved international populations.
Building Collaboration to Advance HIV Prevention: Global Consultation on Tenofovir Pre-Exposure Prophylaxis Research, International AIDS Society (IAS), September 2005
A discussion of how to move forward with promising new PrEP drugs keeping in mind four key challenges that have emerged as particularly significant issues at tenofovir trial sites: provision of anti-retroviral therapy to trial participants who become infected with HIV during the course of a trial, delivery of proven effective HIV prevention interventions to participants, mechanisms to promote research literacy for host communities, and approaches to achieving meaningful community engagement in research.
Stakeholder Consultation to Address Issues Related to Tenofovir Prophylactic Research, Meeting Summary, International AIDS Society (IAS), May 19-20, 2005.
The fundamental goal of the meeting was to promote successful and ethical PREP research that is relevant, respectful, and acceptable to the host communities within which these trials are taking place.
Will a Pill a Day Prevent HIV? Anticipating the Results of the Tenofovir “PREP” Trials; A Special Publication of the AIDS Vaccine Advocacy Coalition (AVAC), March 2005.
Answers to many commen questions about tenofovir PrEP and trials written in broad non-technical terms. An overview of main pros and cons of tenofovir, common misconceptions, and ethical clinical trials issues.
A site developed and supported by the AIDS Vaccine Advocacy Coalition and the UCLA Program in Global Health. Frequent updates regarding PrEP research, trials, and advocacy.