In a speech at the National Institutes of Health in the United States of America (USA), on the 9th of November 2011, Secretary of State Hillary Clinton gave a speech which marks a pivotal moment in the fight against AIDS (1). She said: “…[creating an AIDS-free generation] would have been unimaginable just a few years ago. Yet today, it is possible because of scientific advances … and new practices…. While the finish line is not yet in sight, we know we can get there, because now we know the route we need to take. It requires all of us to put a variety of scientifically proven prevention tools to work in concert with each other. ….America’s … strategy focuses on … ending mother-to-child transmission, expanding voluntary medical male circumcision, and scaling up treatment for people living with HIV/AIDS.”
Scientists at SACEMA have been in the forefront of those arguing that the time to end AIDS is now (2) and the way to do this is through the strategic use of potent anti-retroviral therapy (ART). The road ahead will be long and hard and much still needs to be done. If we are to increase the number of people in the world who are on ART from the present 5 million to 15 million by, say, 2015 and to 30 million by 2020, many operational challenges will have to be understood and met. Here we outline the most important issues that need to be explored if treatment-as-prevention is to become a reality and if we are to end AIDS.
Drugs will have to be manufactured in sufficient quantity. This is a matter for negotiation between the funding agencies and the drug companies and the possibility of a large, guaranteed market should make it possible to reduce drug prices even further. Careful thought needs to be given to the optimal first and second line regimens in developing countries with special attention being paid to the needs of pregnant women and children.
Delivering 15 to 30 million daily doses of drugs will be challenging, but the drugs appear to be chemically stable and it will be important to ensure that adequate supply lines are in place. This will be a matter for negotiation between the funding agencies and national governments.
People need to be tested for HIV on average once every one to two years. There are many ways in which this can be done using provider initiated counselling and testing; snowball sampling; outreach/support groups; community workers; voluntary counselling and testing in mobile clinics; home based testing; couples counselling; methadone programmes; needle exchange programmes; and campaigns. How it is done will vary from place to place but given the will and the imagination this should not be an obstacle to rapidly scaling up ART. Success will depend on the extent to which local community members are actively engaged in supporting testing.
From testing to treatment
At present there is considerable attrition between testing positive and starting treatment and in some settings as many as 90% of those that test positive never start treatment. This happens mainly because of the complexity and difficulty of carrying out CD4+ cell counts, the reluctance in some places to use rapid tests, and the need for poor people to make repeated visits to distant clinics only to be told that their CD4+ cell count is still too high. By abandoning CD4+ cell counts, except for research and in so far as they may be used to monitor progress, the decision process for starting treatment can be simplified, streamlined, and cheaper, and the attrition can be avoided.
Once started on ART it is essential that people comply with their drug regimens (3); we need to reach levels of at least 80% to 90%. While many studies show that compliance in Africa is generally better than in developed countries, mainly because HIV positive people in Africa are often poor while people in developed countries may be intra-venous drug users, homeless, alcoholics or otherwise marginalized people, ways must be found to improve compliance above currently reported levels. This will depend largely on community awareness of the importance of compliance and on community support for those on ART.
Viral load suppression and viral rebound
Good compliance is needed for the benefit of the individual person taking ART, to minimize residual transmission and to reduce the development of drug-resistance. For this reason viral load monitoring, perhaps of a sub-set of patients, especially during the first year of ART, will be needed, and support should be given to scientists developing cheap, point-of-care viral load tests. In a drug trial (4) carried out in the USA the median viral load fell by 100 times after one month, 10 thousand times after one year and 100 thousand times after seven years to a level of between 2 and 20 virions per millilitre of plasma. Good viral load suppression can be achieved, but we need to find ways to achieve it in often marginalized communities.
While drug resistance was of great concern in the early days of triple therapy (5-7) the worst fears have not materialized (8) and there is strong evidence that with good coverage and compliance, and using appropriate drugs, drug resistance will decline rather than increase (9).
Population level impact
While there is evidence from observational studies that the increased availability of ART has led to population level declines in the incidence and prevalence of HIV (10-14) this needs to be confirmed and measured using both population level measures of incidence and measures of transmission among discordant couples. While a number of studies are being planned to explore this in detail (15), it should become part of routine monitoring of scale-up programmes.
Stigma and discrimination
Stigma and discrimination threaten the success of HIV-control programmes and these issues must be confronted. However, the widespread and ready availability of ART should make it possible to ‘normalize’ HIV infection especially if it is clearly understood that those on ART will not infect others, if they are fully compliant, and that they may be expected to live a full and productive life. Dealing with stigma and discrimination will depend largely on the extent to which community members are engaged and the programme is used in a positive way to create jobs and stimulate local economies. Fortunately, there is evidence that by making ART more widely available leads to a reduction in stigma (16).
Seventeen percent of all those living with HIV live in South Africa. The burden that this has placed on our still nascent democracy is almost beyond words. But we can now end the AIDS epidemic if we have the will, the commitment and the imagination to do it.