Antiretrovirals: A significant role in preventing HIV infections in HIV-negative South Africans?

Prof Lynn Morris (left), Prof Helen Laburn, Dr Yogan Pillay, Prof Helen Rees and Prof Bev Kramer.

Researchers at the Wits' Faculty of Health Sciences fourth Prestigious Research Lecture endeavoured to initiate a dialogue on the role antiretrovirals (ARVs) could play in preventing HIV infections in HIV-negative people.

The audience at the lecture were told how offering ARVs to South Africans who have tested HIV-negative could take the battle against the scourge of HIV/AIDS to a new level by significantly reducing the spread of the virus

In order to concisely show all the issues relating to this strategy and indeed, make the audience think about the matter, Professor Lynn Morris and Professor Helen Rees created a debate on whether ARVs should be supplied to HIV negative people. Dr Yogan Pillay, a deputy director general of Strategic Health Programmes in the National Department of Health was the commentator on the debate.

The evidence

The concept of using medicinal drugs such as antimicrobials to prevent diseases is not a new one, and indeed, has been used in the treatment of infections such as malaria, where people entering a high-risk area would take the treatment before, during and after their visit. Similarly, ARVs could be used as a form of preventative prophylaxis, to help prevent the transmission of HIV to people who had tested HIV negative.

Already there are precedents in existence for the argument, in that ARVs are commonly used in South Africa to prevent mother to child transmission, where they are given to the mother during pregnancy or the infant at birth, greatly reducing the likelihood of the infant becoming infected with HIV. ARVs are also used as post exposure prophylaxis, where they are provided directly after high-risk potential exposure to HIV, where again it is thought to greatly reduce the likelihood of infection.

In 2010, two groundbreaking clinical trials have shown that supplying antiretroviral drugs to HIV negative people either as tablets or as a vaginal gel, could impact on HIV infection. These studies were CAPRISA 004 and iPrEx (Pre-Exposure Prophylaxis Initiative).

The two forms of prophylaxis so far tested for HIV prevention in HIV-negative individuals were orally administered as ARV tablets or were administered as a vaginal microbicide gel. The gel should be used about 12 hours before and no more than 12 hours after sex occurring while the oral formulation needs to be taken daily.

The iPrEx trial, which was conducted with 2499 volunteers at 11 sites in Peru, Ecuador, Brazil, Thailand, USA and South Africa, showed v positive results in preventing HIV infection in men who have sex with men and transgender women. The results showed that the oral drug Tenofovir/Emticitabine (FTC/TDF) is 43% effective in the overall group, 58% effective n those at very high risk of HIV infection and 73% effective in those who reported taking the medication >/= 90% of the time.

In the double blinded, randomized, placebo-controlled CAPRISA 004 trial conducted with 889 women in KwaZulu-Natal at high-risk of HIV infection, it was found that the infection rate among women using Tenofovir gel and contracting HIV was 39% lower than that of women who were using a placebo. if these results are confirmed then modelling suggest that the introduction of gel into South Africa could make a big impact on the HIV epidemic if the gel was widely used.

The challenges

With all the positive strides being made in research aimed at combating the current HIV crisis, the Professors also brought to the fore several factors to be considered before taking "the plunge".

The most pressing challenge would be that of resistance. It is well known that many people who are prescribed antibiotics do not complete their courses. This is increasingly leading to the emergence of antibiotic resistant bacteria that threatens our long-term ability to be able to treat bacterial infections. This misuse of what was once regarded as miracle drugs has led to many antibiotics becoming redundant because of resistance. In the case of ARVs, continuous exposure to the drugs could have similar results.

If patients use ARVs for prevention and contract HIV while taking the medication, something that is more likely to happen if they have poor adherence to the therapy, then the infecting HIV virus may develop resistance to the ARV being taken for prevention. This is a particular problem if the same ARV is being used for treatment as the widespread emergence of resistance could render the ARVs less effective for therapy. In the case of people using ARV regimens as an HIV preventative measure, it is imperative that those who do become infected with HIV be quickly identified and stop using the drugs immediately, as mono or dual therapies is sub-optimal treatment for HIV infection, and those that later become infected run the risk of resistance. This would require regular testing - at least four times a year - which is impractical at present.

Another issue that was brought to the attention of the audience was that presently only 55% of HIV-positive people in South Africa who really need the drugs receive them, a factor that should be considered before giving ARVs to HIV-negative people.

A concern about the possibility of rolling out ARVs for prevention is based on current results. Firstly, the trials only targeted specific high risk groups so the results of these studies cannot as yet be generalised to the broader population at risk if HIV infection. Secondly, both the study with oral ARVs and the study with ARVs containing vaginal gel, only showed partial effectiveness against HIV infection. There is a theoretical concern, not shown in the clinical trials, that the use of ARVs for prevention could produce a false sense of security amongst users who might stop using other preventative measures such as condoms.

Providing ARVs to HIV-negative people brings further challenges, which include programmatic issues such as service outlets, providers, training, screening for renal and hepatic problems, the logistics of large scale regular testing, which sections of the population to target and drug toxicity. Probably the most vexing challenge will be the allocation of budgets for treatment and preventative programmes.

So while the results of both studies provides real possibilities of using ARVs for prevention in future, more research needs to be undertaken to confirm these results, and to see if the use of ARVs for prevention can work in other populations beyond those who have participated in clinical trials to date. There are a number of other PrEP studies currently underway and the next few years will see the results of these trials being released. It is important for researchers, programme managers and policy makers to start to consider how we roll out these products should further studies be successful.

According to the Professors, the development of an HIV vaccine would be the first prize in HIV prevention but while some progress is being made in this field the reality of an effective HIV vaccine is still a long way off.

Completing the debate, Dr Pillay said that the Department of Health took cognisance of all HIV/AIDS research and was aware of the difficulties of rolling out antiretroviral programmes-difficulties that were common across the world. He agreed that the department would have to start considering the whether ARVs could be used for prevention as the oral ARV shown to be effective in the iPrEx study is already licensed for treatment and the private sector might start to use ARVs for prevention based on the newly available trial data. From the government's perspective, a major constraint will be the costs of the ARVs as currently the Department of Health cannot afford to purchase sufficient ARVs to be able to introduce the treatment policy that it would like to.

Professor Lynn Morris, a chief specialist scientist and head of the AIDS Unit at the National Institute for Communicable Diseases (NICD), holds a joint appointment at the University of the Witwatersrand's Division of Virology and Communicable Disease Surveillance. Professor Morris is a research professor in the Faculty of Health Sciences. She completed her BSc (Honours) degree at Wits and obtained her DPhil from the University of Oxford. One of her major areas of interest is the envelope glycoproteins of HIV-1agents, including antibodies that can inhibit this interaction. More recently, she has developed a programme to examine HIV-1 drug resistance, particularly in the setting of the prevention of mother-to-child HIV transmission. Professor Morris has been the recipient of a number of prestigious awards and participates in many committees and discussions on HIV research. She chaired the International AIDS Vaccine 2008 Conference in October 2008.

Professor Helen Rees is the director of the Wits Institute for Sexual and Reproductive Health, HIV and Related Diseases. She is also an ad hominem professor at the Wits School of Clinical Medicine and is an honorary professor at the London School of Hygiene and Tropical Medicine. Professor Rees received her medical degree and her Masters in Social and Political Sciences from Cambridge University. Professor Rees has a research interest in HIV/AIDS prevention, microbicides, HIV and HPV vaccines, and broader issues relating to women's health. She has won several awards for her work as a researcher and for her work within the global health community. Professor Rees serves on numerous international committees and Boards and is currently the chair of the World Health Organisation's Strategic Advisory Group of Experts on Immunization and Vaccines. She is the co-chair of South Africa's National AIDS Council's (SANAC) Programme Implementing Committee and the chair of the Research Sector sub-committee on HIV Prevention.