Human Immunodeficiency Virus (HIV, AIDS) (cont.)
Eric S. Daar, MD
Eric S. Daar, MD
Dr. Daar received his undergraduate degree from UCLA and medical degree from Georgetown University School of Medicine. He completed an internship and residency in internal medicine at Cedars-Sinai Medical Center and his clinical and research fellowship in infectious diseases at Cedars-Sinai Medical Center and UCLA.
In this Article
What is in the future for preventing HIV transmission?
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Early advances in preventing HIV transmission resulted from educational programs describing how transmission occurs and providing barrier protection for those exposed to genital secretions and new needles or bleach to those exposed to blood by sharing needles. Despite these efforts, new infection in both the developed and developing worlds has continued at high rates.
Historically, the greatest success in preventing viral transmission has resulted from the development of preventative vaccines. Unfortunately, decades of research to develop an HIV vaccine has led to little hope for success. In 2007, a major setback in this area occurred when the STEP study investigating a promising vaccine candidate was prematurely stopped due to the lack of evidence that it produced any protection from HIV infection. In contrast, a glimmer of hope did emerge with the report in 2009 of the results of the RV 144 Thai HIV vaccine trial which demonstrated borderline effectiveness in the more than 16,000 recipients. While this vaccine demonstrated only limited evidence of protection, research is under way to further explore what can be learned for future vaccine development from this modest success.
In light of the limited ability of counseling and testing to curb the spread of the HIV pandemic, many researchers have moved toward other biologic strategies for preventing HIV that do not rely solely on people changing their behavior. It is in this area where there has been some success. During the last 10 years, there were several large studies showing that male circumcision along with behavioral counseling reduced the risk of heterosexual men acquiring HIV infection. This provides a novel prevention strategy for at-risk, HIV-uninfected heterosexual men. Another major advance on the prevention front came from the HPTN 052 study in which HIV-infected individuals with CD4 cells between 350 and 550 cells/mm3 who had uninfected partners were randomly assigned to initiate antiviral therapy or wait until their CD4 cells declined to less than 250 cells/mm3 or they developed symptoms consistent with disease progression. All enrolled individuals were aggressively counseled about continued safe sex practices, provided condoms and were monitored for sexual activities. The study ultimately showed that those treated early were more than 96% less likely to transmit to their partner than those who had antiviral treatment deferred. These data have added strong support to the universal initiation of therapy in all infected individuals, at least where such treatment is widely available, as well as enhancing effort for expanded HIV testing, linkage to care and early initiation of treatment, the so-called "test and treat" approach to curbing the spread of HIV. As opposed to treating infected people to protect their uninfected partners, another approach is to provide antiviral treatment to uninfected individuals, so-called pre-exposure prophylaxis (PrEP). The first success in this research arena came from the CAPRISA 004 study which showed that vaginal administration before and after intercourse of a gel containing the antiretroviral agent tenofovir reduced the risk of transmission of both HIV and herpes simplex virus to heterosexual women. Other studies are under way to confirm the results of this study as well as to determine whether the results are any different if the agent is administered daily rather than simply around the time of intercourse. One such study was not be able to show that once-daily tenofovir vaginal gel demonstrated protection from infection compared to placebo gel. The reasons for this finding are not completely known but it does appear that adherence with the therapy was very poor.
In the fall of 2010, the iPrEx study reported the results of the first large study testing the effectiveness of PrEP using orally administered therapy, as opposed to topical agents in the vaginal PrEP studies. In this study, HIV-uninfected men who had sex with men who took TDF/FTC once daily along with a comprehensive program to promote safe sex practices and early treatment of sexually transmitted diseases experienced a markedly reduced risk of acquiring HIV compared with those receiving similar prevention practice without TDF/FTC. There are several other studies under way testing the safety and effectiveness of PrEP in other at-risk groups such as heterosexuals and intravenous drug users. One such study was recently presented that assessed the protective effect of TDF or TDF/FTC compared to placebo, each given once daily to HIV-uninfected men and women in stable relationships with infected individual. This study demonstrated significant levels of protection for both drugs in this population. In contrast, two recent studies of high-risk HIV-uninfected women showed no benefit, with convincing data in both studies demonstrating extremely low levels of treatment adherence with study medications. Based upon the data available, the United States FDA has approved TDF/FTC for use in HIV-uninfected men who have sex with men and high-risk heterosexual women. When this therapy is utilized, it is clear that people need to be extensively counseled regarding the importance of continued use of condoms as well as diligent screening for HIV infection, acquisition of sexually transmitted diseases, as well as treatment adherence. Treated individuals also need to be made aware of potential side effects of treatment, including gastrointestinal symptoms, kidney damage, and decreases in bone mineral density.
Another potential way to consider the use of antiretroviral agents to prevent HIV transmission is by using them in infected individuals to reduce the levels of virus in blood and vaginal secretions and thus the transmissibility to others. Until recently, there were imperfect studies that strongly suggested that people on effective treatment are less likely to transmit to others. More recently, the results of a large study were published demonstrating unequivocally that those started on treatment are less likely to transmit to their stable HIV-uninfected partners than those who were not on treatment. In fact, it appeared to be approximately 96% protective. This type of data has increased interest in advancing studies to enhance testing for HIV, early engagement into care and initiation of therapy to reduce transmission in the community, so-called "test-and-treat" strategy. The feasibility of this approach and the potential impact on the epidemic of new infections is currently being explored. It is worth noting that although effective antiretroviral therapy almost certainly reduces the risk of HIV transmission, such individuals should still use standard precautions (for example, condoms to avoid transmission to partners).
A final prevention strategy of last resort is the use of antiretrovirals as post-exposure prophylaxis, so-called "PEP," to prevent infection after a potential exposure to HIV-containing blood or genital secretions. Animal studies and some human experience suggest that PEP may be effective in preventing HIV transmission, and it is based upon these limited data that current recommendations have been developed for health care workers and people in the community exposed to potentially infectious material. Current guidelines suggest that those experiencing a needle stick or who are sexually exposed to genital secretions of an HIV-infected person should take antiretrovirals for four weeks. Those individuals considering this type of preventative treatment, however, must be aware that post-exposure treatment cannot be relied upon to prevent HIV infection. Moreover, such treatment is not always available at the time it is most needed and is probably best restricted to unusual and unexpected exposures, such as a broken condom during intercourse. If PEP is to be initiated, it should occur within hours of exposure and certainly within the first several days. Updated guidelines are published and available at http://www.aidsinfo.nih.gov.
Reviewed by Jay W. Marks, MD on 4/3/2013
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