Groundbreaking results of two large pre-exposure prophylaxis (PrEP) studies may lead to a new prevention option to reduce HIV transmission. Data released on two PrEP studies showed high levels of protection against HIV infection when tenofovir (Viread) or Truvada (tenofovir and emtricitabine) were taken daily by HIV-uninfected individuals at high risk for infection.
The Partners PrEP trial, the largest PrEP study to date, was conducted at nine centers in Kenya and Uganda. A total of 4,758 heterosexual couples, in which one partner was HIV infected and the other HIV uninfected, were enrolled. The HIV-uninfected partner was given either tenofovir, Truvada or placebo. The study was stopped a full 18 months before it was scheduled to end due to a demonstrated high rate of protection against HIV.
In the individuals who were given tenofovir, the risk of infection was reduced by 62%. For those receiving Truvada the rate of reduction was 73%. An adherence rate of 97% was seen. There were 78 infections reported in total, 18 in the tenofovir group, 13 in the Truvada group and 47 in the placebo group.
The TDF2 study was conducted by the U.S. Centers for Disease Control and Prevention (CDC) along with the Botswana Ministry of Health. A total of 1,200 HIV-uninfected men and women between the ages of 18 and 39 were enrolled in the study at two sites in Botswana. Participants were given either Truvada or placebo.
The primary analysis showed a 62.2% reduction in HIV infections in those who used Truvada. There were nine HIV infections among the 601 participants given Truvada and 24 among those who received placebo. A secondary analysis, which excluded any HIV infection that occurred among participants who stopped taking medication within 30 days of infection, indicated that tenofovir reduced the risk of HIV infection by 78%.
In contrast to these results, a third study, the FEM-PrEP trial, was ended prematurely as researchers could not show a significant benefit. Truvada was used in this study as well. Researchers suggest a lack of adherence may have contributed to poorer results.
It is important to view these new findings with a blast of fiscal and ethical reality. The cost of providing people at risk of HIV infection with PrEP far exceeds current financial capabilities.
In the U.S. alone, over 8,500 HIV-infected people are currently on ADAP waiting lists, awaiting desperately needed antiretrovirals (ARVs). Worldwide, 9 million people are in need of ARVs. The General Assembly of the United Nations' 2011 Political Declaration on HIV/AIDS proposed goal of providing 15 million people with treatment by 2015 (there are currently 6.6 million on treatment), although vital, is ambitious to say the least in the current financial environment.
With so many people living with HIV in need of ARVs, is PrEP, regardless of its effectiveness, a strategy currently worth entertaining on a local or global level? With 7,400 new HIV infections a day, it is prudent to discuss the possible application of all available evidence-based prevention modalities. With two new infections for every person who receives ARVs, as stated by Dr. Robin Shattock of St. George's, University of London, "the successful provision of universal access may be critically dependent on decreasing the number of new infections." However, is allocating much-needed resources for more clinical trials, particularly to provide HIV-uninfected people with ARVs when so many already infected are in desperate need of these life-extending medications, a reasonable debate? Should not all HIV-infected people be offered ARVs before considering the provision of these lifesaving medications to HIV-uninfected individuals?
With many donor countries cutting back or rescinding their commitments to the Global Fund to Fight AIDS, Tuberculosis and Malaria, the prospect of antiretrovirals for all people with HIV is a battle we will seemingly be waging on an ongoing basis as the number of HIV-infected people grows worldwide. Even if PrEP, along with other prevention modalities such as behavioral change, clean needles, PEP, circumcision and microbicides, was a guaranteed means of stopping the spread of HIV, would we be able to afford to implement it?
Another concern regarding the use of PrEP is the direct disregard for the premise on which all medical care is given: "Do no harm." With long-term use of ARVs possibly causing extensive physical damage, as well as daily side effects, can ARVs in the absence of HIV infection be justified by the benefit of possible protection against infection? Since it is still unclear what is caused by the virus itself and what is caused by extended use of ARVs, more long-term trials would be needed to determine whether the damaging effects many on ARVs experience would occur in HIV-uninfected individuals -- thereby further redirecting funding away from studies for HIV-infected people.
In the Partners PrEP study, a 97% adherence rate was seen among participants. With ongoing PrEP, could this adherence be maintained in the wake of persistent side effects and long-term use in HIV-uninfected people? It is likely that a lower rate of protection will be achieved by many, while risky behavior may increase under the guise of protection. Are some individuals then more at risk as their decision-making process on risk is affected by the belief that they are protected by PrEP?
These and other questions are sure to be key topics when discussing the possibility of widespread use of PrEP. For the moment, it is important to keep these pivotal study results in perspective as all options regarding PrEP are evaluated.