Worldwide the HIV toll has been massive. During 2008 more than two and a half million adults and children became infected with HIV.The year also saw a further two million deaths from AIDS. Daily, that amounts to 7 400 new HIV infections.   And at last count just four million of the estimated 9.5-million people in low and middle-income countries who needed HIV drugs were getting them. The shortfall also tells us that for every two people who are put on ART today, an additional five are newly infected by HIV.  Many would say we are losing the war’€¦

The old adage ‘€œprevention is better than cure’€ was never more appropriate, yet to date prevention has fallen dismally short of the mark. Partly this is because the ‘€œold faithfuls’€ of abstinence, monogamy and condoms are not only ‘€œtired’€ but are limited by the need for human sexual behaviour change and consistent behaviour change at that.    Added to this, women, who are more biologically vulnerable to HIV infection than men, have no means of prevention that they can use independently of men.

Three months ago saw the first of the evidence that antiretrovirals used by HIV uninfected individuals could prevent HIV infection. The release of the Caprisa 004 trial results that showed that a 1% Tenofovir gel microbicide inserted vaginally by women at the time of sexual intercourse reduced HIV acquisition by 39%, resulted in a spontaneous standing ovation from the researchers, activists and scientists gathered at the World AIDS Conference in Vienna earlier this year.

And what a promising prevention year it has proved to be: last week it was the turn of the Global iPrEx study which showed that taking a daily antiretroviral pill can protect HIV-uninfected men who have sex with men from becoming infected.  The data is both exciting and challenging.

The antiretroviral drug chosen for this contains the same drug, Tenofovir, as the CAPRISA 004 study described above but also includes a second agent, Emtricitabine in a co-formulated once a day drug called TRUVADA.
Using the most rigorous analytical methods, men who were assigned to take the active medication were 43.8% less likely to become HIV-infected, whether they actually adhered to the regimen or not.   Among men who reported taking at least half their pills, the risk of becoming HIV-infected decreased by more than half.   More impressively, if Truvada drug was detected in blood samples from men assigned to take medication in a subgroup analysis, then the protective effect exceeded 90%.  
Now that we have proof that oral medication can partially protect against HIV, the first question is whether we can do better?   Will men who are now informed that the medication works become

more adherent, since previously the protective effect was only a theoretical possibility? What about women, heterosexual men, people at risk of becoming HIV-infected through unsterile syringes?    
There are multiple studies underway, looking at different populations, dosing strategies, modes of drug delivery. This includes a study in African women to see whether a gel or a pill is more protective. Very soon, there will be more than 20 000 men and women involved in studies of antiretroviral chemoprophylaxis or Prep.    
There has always been tension in Infectious Disease medicine around the use of treatment drugs for prevention. Yet none would dispute the use of chemoprohylaxis to prevent the life threatening effects of Malaria. The lives of almost three quarters of a million children in 34 African countries are estimated to have been saved in the past 10 years through the use of insecticide-treated mosquito nets, indoor residual spraying, and chemoprophylaxis of malaria using antimalarial agents during pregnancy.

But valid concerns have been raised that using the same drugs for treatment as prevention (in this case both Tenofovir and Emtricitabine-like agents are in South Africa’€™s first line of HIV treatment) could promote the spread of resistant HIV strains.   The CAPRISA 004 study showed no viral resistance mutations in the blood of individuals who became HIV infected whilst using Tenofovir gel and similarly in iPrEx, none of the men who became infected during the study developed resistance mutations in the virus found in their blood. The only resistance was seen in three men who were infected prior to the commencement of the study. Given this real concern, however it is salient that other trials are evaluating  different drugs, which might be able to be solely used for chemoprophylaxis.  

Most prevention researchers and public health officials hope that the use of antiretroviral drugs for prevention will be a stopgap, which could prevent millions of infections on the road to an effective AIDS vaccine.
Although  the iPrEx   study found the pill to be safe, long term monitoring will be necessary to anticipate later stage infrequent toxicities. Some of the next research questions will establish the frequency and extent of monitoring and the optimal dosing needed to prevent the maximal number of infections. There is no doubt that PrEP use will need strategizing ‘€“ it is likely that at least in the short term it will not be THE global panacea but may have great importance for specific individuals in specific settings. It adds diversity and depth to the prevention menu and dialogue and activism must go on until the right use in the right individuals in the right way is found. Encouraging testing and enabling recognition of risk remain a cornerstone and first step to any prevention modality.

What we learnt this week from iPrEx is that pre-exposure prophylaxis is a prevention concept which now has proven potential. This is a triumph to be celebrated. We now know that a drug already formulated and available can prevent a life threatening infection. We also learned that this approach will only be effective if it is part of a comprehensive prevention package that continues to promote condoms and safer sex (some of the men who took more than 50% of their pills still became infected), medication adherence, diagnosis and treatment of other sexually transmitted infections, and ongoing behavioral counseling.  

There is much we didn’€™t learn and there is much still to be done.
Living on a continent that has borne the brunt of this epidemic and having experienced the intolerable assumption that half of the world would be allowed to experience life saving treatments while the other half looked north, sickened and died, I would argue that now is the time that Africa must grapple with the possibilities that this medication may offer in reducing the incidence of HIV infection on our continent. Indeed, this may be prove to be a very real hope in the war on HIV.

Linda-Gail Bekker is Associate Professor of Medicine and the Deputy Director of the Desmond Tutu HIV Centre, University of Cape Town. She is also the South African Principle Investigator for the Global IPrEx study conducted at the Desmond Tutu HIV Foundation site in Cape Town.

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