By Jennifer Gibson, PharmD | Editor Shaheen E Lakhan |
Currently, more than 33 million people worldwide are living with human immunodeficiency virus (HIV) infection. Each year, there are nearly 3 million new infections. The growing worldwide burden of this infection, which causes acquired immune deficiency syndrome (AIDS), has prompted researchers to investigate novel approaches to infection control and prevention. A recent investigation published by the New England Journal of Medicine, which will likely be known as a landmark study in HIV/AIDS research, reported that a daily dose of a prophylactic pill can prevent the spread of HIV before exposure to the virus.
The study, called the iPrEX (Preexposure Prophylaxis Initiative) trial, involved 2499 men and transgender women (born men) who have sex with men. All participants tested negative for HIV at the beginning of the study, but reported engaging in behavior that put them at high risk for exposure to HIV. Half of the subjects received a daily placebo pill, while the remaining half received a combination pill of 2 antiretroviral drugs: emtricitabine and tenofovir. (This combination pill is currently marketed as Truvada and is approved by the Food and Drug Administration to treat HIV infection.) All study participants also received HIV education and testing, as well as condoms, during the study period. They were followed for a median of 1.2 years.
Overall, the rate of HIV infection in the treatment group was 2.88% at the end of the study — 44% lower than the 5.13% infection rate in the placebo group. Participants who were most compliant with taking the prophylaxis pills — doing so on 90% or more of days — experienced a 70% decrease in risk of HIV infection. Medication adherence was reportedly low, though it is not clear why. Study participants who want to continue taking the prophylactic antiretroviral therapy (ART) will be able to do so as part of an 18-month open-label study of preexposure prophylaxis beginning in 2011. Researchers are hoping that an open-label design will improve medication adherence and strengthen the original findings.
An interesting secondary finding in iPrEX was that individuals enrolled in the study self-reported a decrease in high-risk sexual behavior. Whether taking a daily pill served as a reminder of safer sex practices, or the same result will be seen among larger populations or in the open-label study is not clear. Potentially, once the benefit of daily prophylaxis is confirmed, individuals will not engage in safer sex practices, a phenomenon of risk compensation. The authors of iPrEX warn that preexposure prophylaxis should still be considered a back-up plan, and not first-line defense against HIV infection. Additionally, high-risk sexual practices expose individuals to countless infections and conditions other than HIV, for which ART is not effective prophylaxis.
The iPrEX trial was conducted at 11 sites across the United States, South Africa, Thailand, Peru, Ecuador, and Brazil. The United States’ National Institute of Allergy and Infectious Diseases of the National Institutes of Health funded approximately two-thirds of the costs of the study. The Bill & Melinda Gates Foundation funded the remaining costs.
For the last several decades, HIV prevention efforts were basically limited to behavioral approaches: consistent use of barrier methods of protection during intercourse, a reduction in the prevalence of HIV in the blood supply, decreasing the use of dirty syringes among intravenous drug users, and awareness of HIV status. Safer sex practices with fewer partners have, thus far, proven to be the most effective prevention of the spread of HIV. Education efforts among high-risk groups, primarily men who have sex with men, must begin as early in life as possible to improve knowledge, negotiation, and communication regarding sexual practices.
Prevention of HIV infection for people exposed to the virus, after either occupational or nonoccupational exposure, involves a 28-day course of ART. In order to be effective, ART must be started within 72 hours of exposure to HIV-infected fluids, posing a significant barrier to postexposure prophylaxis.
The iPrEX trial is not the first to suggest preexposure prohylaxis of HIV as a viable infection control option. Early in 2010, South African researchers evaluated the use of a vaginal gel containing tenofovir, and found it decreased the risk of HIV infection among sexually active women by 39%. But, iPrEX is the first to suggest daily pill-popping as an effective mode of HIV prophylaxis. Unfortunately, ART does pose several risks: renal insufficiency and viral resistance. Renal insufficiency was reversible on discontinuation of ART during iPrEX, but this adverse effect could prove especially problematic among individuals with other diseases or chronic conditions. Viral resistance is the most significant concern regarding preexposure prophylaxis. The widespread use of antiretroviral agents has the potential to create new viral infections — not just HIV, but hepatitis, herpes, and other viruses — that are resistant to current treatments.
The cost of preexposure prophylaxis is also a huge concern. At an annual cost of up to $14,000 for ART, the cost-effectiveness of such modalities are in question, as well as who would pay these costs in the future, if prophylaxis is proved to be effective. As HIV infection rates continue to rise, preexposure prophylaxis may be one option for preventing the spread of infection, but behavioral modifications and education should accompany any such intervention in high-risk populations; the only truly effective prevention to any sexually-transmitted disease, including HIV, is abstinence from high-risk behavior. As clinicians evaluate preexposure prophylaxis to prevent the spread of HIV, they should be prepared for the highly-charged public debate that will accompany this issue.
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