FDA approves first drug to prevent HIV infection

The U.S. Food and Drug Administration has approved the prophylactic use of the antiviral drug Truvada to prevent healthy people from contracting HIV

While there are many methods for preventing HIV transmission that work in principle (abstinence, safe sex, monogamy to some extent), in practice efforts to prevent new HIV infections have reached a plateau - about 50 thousand new cases are reported every year in the United States and no progress has been made on reducing this number for at least 15 years, with the overall rate of infection remaining stable since at least 2004. In response to the almost complete lack of effective prevention methods, the U.S. FDA (Food and Drug Administration) has now approved the prophylactic use of the anti-retroviral combination drug Truvada, to reduce the risk of people acquiring HIV.

By 2000, hints had appeared that some antiviral drugs, if taken shortly following a potential exposure, might prevent HIV from becoming established in the body. Some thought had been given to seeking a "morning-after pill" that would be taken following a high-risk encounter, with the intent of preventing the HIV infection from becoming established. Unfortunately, the study participants would not follow the study protocols.

“That study brought home to me the fact that people have a hard time starting treatment after exposure,” says Dr. Robert Grant of the Gladstone Institute of Virology and Immunology. “You have to admit failure, admit that you failed to protect yourself in some way, and now you need to be rescued by some sort of pills. So for those reasons, we started thinking about pre-exposure prophylaxis as a possibility.”

Pre-exposure prophylaxis is probably most familiar in the prevention of malaria. Malaria is transmitted by the Anopheles mosquito, which is a host for the microorganism responsible for malaria. The trick is that, even in an area where malaria is endemic, you don't know if the mosquito that just bit you was infected. As a result, you are continually in "at-risk" status owing to the sheer number of mosquitoes in such areas.

People who can afford it now use a pre-exposure prophylactic regime that prevents malarial infection from taking hold in the body. It is difficult to cure malaria, but daily doses of antimalarial drugs taken before and during travel to locations where malaria is ever-present act to prevent infection.

The situation with HIV/AIDS is quite similar. There are people who, by choice or by necessity, are living with chronic exposure to HIV infection. However, one can't tell which exposure might actually result in infection. While physicians are able, in most cases, to hold off the progression of HIV to AIDS, the treatment regimen is difficult and very expensive. Taking a serious look at possible prophylactic treatments seemed a good direction for research.

Truvada (a combination of 300 mg tenofovir and 200 mg emtricitabine) was the first effective HIV antiviral drug combination which is taken once daily. Developed by Gilead Sciences, in 2004 it received FDA approval for treatment of HIV infection when combined with a non-nucleoside reverse transcriptase inhibitor such as Sustiva. Truvada's one-a-day dosing combined with a relatively small group of serious side effects suggested that large-scale clinical studies of Truvada's potential for prophylaxis were called for.

Two large clinical studies of at-risk populations clearly showed that a daily dose of Truvada is quite effective in reducing the risk of HIV infection. The first study was a U.S. National Institutes of Health (NIH) clinical study of some 2,500 HIV-negative gay, bisexual, and transgendered subjects. The second study was a University of Washington clinical study of 4,800 heterosexual couples in which only one partner was initially HIV-positive. Both studies were double-blind, and carried out in several countries. In both cases the prophylactic dosage was one Truvada each day.

The results were very encouraging. In the NIH study, for every subject who became HIV-positive in the Truvada-treated group, two became HIV-positive in the control group. Knowing that compliance was an uncontrolled factor, the researchers examined serum levels of Truvada in the treated group. Among those subjects showing measurable levels of Truvada on each check-in, HIV infection was thirteen times less likely than in the control group.

In the Washington study, the results indicated that a control participant was four times more likely to become HIV-positive than a treated participant. Independent smaller studies were also carried out, but with few exceptions the results were the same - if you take Truvada regularly, your chances of catching HIV are greatly reduced.

As a result of these findings, the FDA has now approve the use of Truvada for adults who do not have HIV but are at risk of becoming infected through sexual contact. The drug is to be taken once daily and used in combination with safer sex practices. The FDA stresses that the drug is not a substitute for safer sex practices.

Clearly Truvada is effective, but is it safe for prophylactic use? Like most drugs, there are a whole panel of relatively minor side effects, most of which are controllable (diarrhea, nausea, headache, disturbed sleep...). More seriously, Truvada is associated with liver and kidney damage, sometimes becoming life-threatening, and with bone thinning. Other problems include rapid progression of a preexisting hepatitis-B infection when Truvada is withdrawn.

While dangerous side effects are uncommon, it is clear that some evaluation is required to choose patients who will gain more from the anti-HIV properties than from the rare but serious side effects. Together with the FDA, Gilead Sciences has prepared a set of selection criteria for candidates for Truvada treatment.
Another issue is that candidates for prophylactic treatment must be HIV-negative. Otherwise, use of Truvada alone will suppress symptoms of HIV, but the level of infection may progress largely unchecked. It can take up to three months for tests to reveal a new HIV infection, so a period of abstinence before starting Truvada treatment seems advisable.

Truvada is expensive - a year of daily doses at present costs US$13,900. To Gilead's credit, it has a program to reduce this cost for people who cannot afford the treatment. It is also licensing Truvada to the Medicines Patent Pool Foundation, whose mission is to bring down the prices of HIV medicines and other products needed for the treatment and prevention of HIV, and to facilitate the development and production of improved formulations, by providing access to intellectual property relating to these products. Gilead is the first pharmaceutical company to cooperate with the patent pool.

HIV/AIDS, while largely treatable in First World countries, is still a massive scourge, especially in Africa. In addition to being one of the poorest countries in the world, the Kingdom of Lesotho, in Sub-Saharan Africa has nearly a 30 percent HIV/AIDS infection rate, with precious few resources to deal with this plague. Whole villages and families have been wiped out. It is to be hoped that we find a way to transfer the remarkable strides in fighting this scourge to those areas of the world that remain defenseless.

Source: FDA