In 1983 in Paris, a virus was isolated. To this day it fills physicians and the public with fear. This small organic molecule has the power of progressive destruction of the body and, consequently, deprival of life. Will the pre –exposure prophylaxis (PrEP)- so keenly supported by the specialists from the Antiviral Drugs Advisory Committee – be accepted by the strict FDA committee?
In the period from 1983 to 2008, AIDS claimed 25 million lives. The disease develops over the period of many years from the moment of the invasion of HIV into the organism, often preventing an immediate diagnosis and an early treatment. Current methods of treatment undoubtedly prolong the lives of the infected patients, also post-exposure prophylaxis is becoming widely accepted, but sadly the dream of an effective vaccine still remains beyond the reach of the modern medicine. In recent years, however, there shined a glimmer of hope, which perhaps will have the power to stop the epidemic. Pre-exposure prophylaxis is to be a revolutionary method of preventing the spread of HIV and thus leading to its gradual eradication. Preliminary studies on macaques and also the advanced human studies that have been conducted in the US, Peru, South Africa and Thailand both have yielded promising results.
The pre-exposure prophylaxis is based on taking ART (antiretroviral therapy) prior to the expected exposure to HIV in order to prevent the infection –similarly as in the use of chloroquine in malaria prophylaxis. The ideal drug for the prevention of HIV should have a long half-life, ability of accumulation in the cells near the infection origin (vaginal, rectal and oral mucosa), simple dosing (for example once a day).
So far the greatest expectations regard the drug which is a combination of emtricitabine (FTC) and tenofovir (TDF). The effectiveness in preventing HIV infection has been demonstrated in phase III clinical trials and remained at 43.8% level. Supplementing the oral antiretroviral therapy through the introduction of the gel with a high content tenofovir, as a local precautionary measure may significantly increase the effectiveness of the prevention. All indications are that TDF or TDF / FTC has efficacy in the prevention of HBV as well, particularly important in the case of occupational exposure to contaminated blood.
Nevertheless, there are still many doubts concerning the chronic use of antiretroviral therapy. Concerns relate to, inter alia, the possible toxicity with the prolonged use, the overall effectiveness, enormous costs and a possibility of developing drug resistance. So far, the observed side effects are not significantly different from those observed in some over the counter drugs: nausea and weight loss and a slight reduction in bone mineral density were the only significant adverse effects noted. Nephrotoxicity and hepatotoxicity have not been detected so far in the studies. Because to date no trials have demonstrated 100% efficacy against the virus, there was a concern that the long-term use may contribute to the development of the resistance to the drug, making it even more problematic to treat the infected individuals (in PrEP studies tenofovir and emtricitabine -substances currently used in treatment of HIV infection are predominant). In order to dispel these doubts subsequent research projects are being prepared at the beginning of Autumn in the UK.
Answers to questions about the human nature, however, are harder to find. Will implementing the pre-exposure prevention give a false sense of security and consequently lead to an increased number of risky sexual behaviour? Will patients undergoing prophylaxis take the prophylaxis dosing seriously in order to prevent the formation of chains of drug-resistant virus? Time will tell if the newly chosen path in the war against HIV is the one leading to victory.
1. Preexposure Prophylaxis for HIV Prevention, Current HIV/AIDS Reports, Volume 8, Issue 2, June 2011, pp. 94 – 103, Kelesidis, Theodoros; Ladovitz, Raphael J.
2. Pre-exposure chemoprophylaxis of HIV infection: Quo vadis?; Biochemical Pharmacology, Volume: 83, Issue: 5, March 1, 2012, pp. 567-573; De Clercq, Erik
Want to know more? Watch on medtube.net: “Oropharynge-Esophagic Candidiasis HIV-positive female patient (1 of 5)”